MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Antimicrobial Agents and Chemotherapy' source. Fri, 19 Mar 2010 17:36:14 +0100 http://www.medworm.com/index.php?rid=3372911&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231388%26dopt%3DAbstract Authors: Colombo AL, Ngai AL, Bourque M, Bradshaw SK, Strohmaier KM, Taylor AF, Lupinacci RJ, Kartsonis NA Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins. We identified 212 patients with invasive candidiasis due to non-albicans Candida species (>/=5 cases per species) in 5 clinical trials of caspofungin monotherapy from the pharmaceutical Sponsor's (Merck and Co., Inc.) database: 71 C. parapsilosis, 65 C. tropicalis, 54 C. glabrata, 10 C. krusei, 9 C. guilliermondii, and 5 C. lusitaniae; 167 cases caused by C. albicans were also identified. Efficacy was assessed at the end of caspofungin therapy. Success (... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372911 Mon, 15 Mar 2010 00:00:00 +0100 3372911 http://www.medworm.com/index.php?rid=3372910&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231389%26dopt%3DAbstract Authors: Deshpande D, Srivastava S, Meek C, Leff R, Gumbo T Ethambutol, together with a macrolide, is the backbone for the treatment of disseminated Mycobacterium avium. However, at the standard 15 mg/kg/day dose ethambutol efficacy is limited. In addition, susceptibility breakpoints have consistently failed to predict clinical outcome. We performed dose-effect studies against extracellular M. avium as well as against bacilli within human macrophages. The maximal kill (Emax) by ethambutol against extracellular bacilli was 5.54 log10 cfu/ml, compared to 0.67 log10 cfu/ml against intracellular M. avium, after 7 days exposure. Thus, extracellular assays demonstrated high efficacy. We created a hollow fiber system model of intracellular M. avium, and performed microbial pharmacokinetic-pha... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372910 Mon, 15 Mar 2010 00:00:00 +0100 3372910 http://www.medworm.com/index.php?rid=3372909&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231390%26dopt%3DAbstract Authors: Blango MG, Mulvey MA Numerous antibiotics are proven effective at ameliorating the clinical symptoms of urinary tract infections (UTIs), but recurrent and chronic infections continue to plague many individuals. Most UTIs are caused by strains of uropathogenic Escherichia coli (UPEC), which can form both extra- and intracellular biofilm-like communities within the bladder. UPEC also persist inside of host urothelial cells in a more quiescent state, sequestered within late endosomal compartments. Here, we tested a panel of 17 different antibiotics, representing seven distinct functional classes, for their effects on survival of the reference UPEC isolate UTI89 within both biofilms and host bladder urothelial cells. All but one of the tested antibiotics prevented UTI89 growth in ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372909 Mon, 15 Mar 2010 00:00:00 +0100 3372909 http://www.medworm.com/index.php?rid=3372908&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231391%26dopt%3DAbstract Authors: Shakya T, Wright GD Antibiotic kinases, which include aminoglycoside and macrolide phosphotransferases (APHs and MPHs), pose a serious threat to currently used antimicrobial therapies. These enzymes show structural and functional homology with Ser/Thr/Tyr kinases, suggestive of a common ancestor. Surprisingly, recent in vitro studies using purified antibiotic kinase enzymes have revealed that a number are able to utilize GTP as the antibiotic phospho-donor; either preferentially or exclusively when compared to ATP, the canonical phosphate donor in most biochemical reactions. To further explore this phenomenon, we examined three enzymes: APH(3')-IIIa, APH(2'')-Ib and MPH(2')-I using a competitive assay that mimics in vivo nucleotide triphosphate (NTP) concentrations and usage b... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372908 Mon, 15 Mar 2010 00:00:00 +0100 3372908 http://www.medworm.com/index.php?rid=3372907&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231392%26dopt%3DAbstract This study assessed the spectrum of activity of torezolid (TR-700), the active moiety of torezolid phosphate (TR-701) and proposes tentative MIC and disk diffusion breakpoints as well as quality control ranges. The in vitro susceptibilities of 1,096 bacterial isolates, representing 23 different species or phenotypic groups, were determined for torezolid, linezolid, cefotaxime and levofloxacin using Clinical and Laboratory Standards Institute (CLSI) broth microdilution minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), agar dilution and disk diffusion testing methods. Torezolid was very active against the majority of gram-positive strains including methicillin-susceptible and -resistant Staphylococcus aureus (MIC50 =0.25 mug/ml, MIC90 </=0.5 mug/ml), co... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372907 Mon, 15 Mar 2010 00:00:00 +0100 3372907 http://www.medworm.com/index.php?rid=3372906&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231393%26dopt%3DAbstract Authors: Goren MG, Navon-Venezia S, Chmelnitsky I, Carmeli Y All carbapenem resistant Escherichia coli (CREC) isolates identified in our hospital during 2005-2008 (n=10) were studied. CRECs were multidrug resistant and all carried blaKPC-2, of which, six were also ESBL-producers. PFGE indicated six genetic clones; within the same clone similar transferable blaKPC-2-encoding plasmids were found whereas between clones plasmids differed. Tn4401 elements were identified in all these plasmids. PMID: 20231393 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372906 Mon, 15 Mar 2010 00:00:00 +0100 3372906 http://www.medworm.com/index.php?rid=3372905&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231394%26dopt%3DAbstract Authors: Somé AF, Séré YY, Dokomajilar C, Zongo I, Rouamba N, Greenhouse B, Ouédraogo JB, Rosenthal PJ Artemether-lumefantrine (AL), dihydroartemisinin-piperaquine (DP), and amodiaquine/sulfadoxine-pyrimethamine (AQ/SP) offer excellent antimalarial efficacy, but may select for parasite polymorphisms that decrease drug sensitivity. We evaluated the selection of known polymorphisms in genes encoding putative transporters (pfcrt and pfmdr1) and SP targets (pfdhfr and pfdhps) in parasites that caused new infections within 42 days of therapy for uncomplicated falciparum malaria in Burkina Faso. In 559 children in 2006, 42-day genotype-uncorrected failures were seen in 31.2% with AL, 11.8% with AQ/SP, and 7.6% with DP. After prior AL, selection of wild type sequence was s... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372905 Mon, 15 Mar 2010 00:00:00 +0100 3372905 http://www.medworm.com/index.php?rid=3372904&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231395%26dopt%3DAbstract Authors: Salomão K, de Souza EM, Carvalho SA, da Silva EF, Fraga CA, Barbosa HS, de Castro SL From a series of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol screened in vitro against Trypanosoma cruzi, eight (S1 to S8) were selected for in vivo screening by a single oral administration (200 mg/kg) to infected mice at 5 dpi. Based on both significant decrease of parasitemia and mortality, S2 and S3 were selected for further assays. Despite having no in vivo effect, S1 was included since it was twofold more potent in vitro against trypomastigotes than megazol. Trypomastigotes treated with S1, S2 or S3 showed alterations of the flagellar structure and of the nuclear envelope. When assayed on intracellular amastigotes, the SI for macrophages was in the range of >27 to &g... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372904 Mon, 15 Mar 2010 00:00:00 +0100 3372904 http://www.medworm.com/index.php?rid=3372903&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231396%26dopt%3DAbstract Authors: Opatowski L, Mandel J, Varon E, Boëlle PY, Temime L, Guillemot D Streptococcus pneumoniae is a major pathogen in the community presenting high resistance rates to available antibiotics. To prevent antibiotic failure caused by highly resistant bacteria, increasing the prescribed antibiotic dose has recently been suggested. The aim was to assess the influence of beta-lactam prescribed doses on resistance emergence and selection in the community. A mathematical model was constructed, combining S. pneumoniae pharmaco- and population-dynamic approaches. Received-dose heterogeneity in the population was specifically modelled. Simulations over a 50-year period were run to test the effects of dose-distribution and antibiotic-exposure-frequency changes on community resistance patt... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372903 Mon, 15 Mar 2010 00:00:00 +0100 3372903 http://www.medworm.com/index.php?rid=3372902&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231397%26dopt%3DAbstract Authors: Feola DJ, Garvy BA, Cory TJ, Birket SE, Hoy H, Hayes D, Murphy BS Infection with mucoid strains of Pseudomonas aeruginosa in chronic inflammatory diseases of the airway is difficult to eradicate and can causes excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiologic process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotype in vitro. Here we test whether azithromycin affects macrophage activation status and migration in the lungs of P. aeruginosa-infected mice. C57Bl/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain of P. aeruginosa. Properties of macrophage activation, immune... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372902 Mon, 15 Mar 2010 00:00:00 +0100 3372902 http://www.medworm.com/index.php?rid=3372901&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231398%26dopt%3DAbstract Authors: Molina-Torres CA, Ocampo-Candiani J, Rendón A, Pucci MJ, Vera-Cabrera L In this work we describe the activity of ACH-702 against clinical isolates of Mycobacterium tuberculosis and six different non tuberculous mycobacteria (NTM). The MIC50 and MIC90 of both susceptible and drug resistant M. tuberculosis strains tested were 0.0625 and 0.125 mug/ml. The MIC50 and MIC90 values for M. fortuitum isolates were 0.0625 mug/ml in both cases; M. avium complex isolates showed MIC50 and MIC90 values of 0.25 and 4 mug/ml respectively. PMID: 20231398 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372901 Mon, 15 Mar 2010 00:00:00 +0100 3372901 http://www.medworm.com/index.php?rid=3372900&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231399%26dopt%3DAbstract Authors: Panagiotidis G, Bäckström T, Asker-Hagelberg C, Jandourek A, Weintraub A, Nord CE Ceftaroline is a new broad-spectrum cephalosporin being developed for the treatment of serious bacterial infections including those caused by aerobic Gram-positive and Gram-negative bacteria. The purpose of the present study was to investigate the effect of administration of ceftaroline on the intestinal flora of healthy subjects. Twelve healthy subjects (6 males and 6 females) 20-41 years of age received ceftaroline 600 mg by intravenous infusion q12h for 7 days. Plasma and faeces were collected for determination of ceftaroline concentration and analysis of faecal flora. Faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated i... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372900 Mon, 15 Mar 2010 00:00:00 +0100 3372900 http://www.medworm.com/index.php?rid=3372899&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231400%26dopt%3DAbstract Authors: Thakkar N, Pirrone V, Passic S, Keogan S, Zhu W, Kholodovych V, Welsh W, Rando R, Labib M, Wigdahl B, Krebs FC We previously demonstrated that the biguanide-based compound NB325 inhibits human immunodeficiency virus type 1 (HIV-1) infection by interacting with the CXCR4 viral co-receptor. This interaction also appeared to be persistent, since HIV-1 infection was inhibited even when the virus was introduced subsequent to the removal of NB325 from the cell culture media. The present studies were conducted to determine the extent and mechanism of this prolonged antiviral activity. Persistent inhibition of HIV-1 infection by NB325 was concentration-dependent and was apparent up to 8 h after compound removal. Flow cytometric analyses of stimulated CD4(+) T lymphocytes exposed to NB... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372899 Mon, 15 Mar 2010 00:00:00 +0100 3372899 http://www.medworm.com/index.php?rid=3372898&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231401%26dopt%3DAbstract Authors: Wang Q, Sun FJ, Liu Y, Xiong LR, Xie LL, Xia PY Biofilm formation in Staphylococcus epidermidis is mediated by icaADBC-dependent and -independent pathways. Subinhibitory erythromycin, azithromycin and clarithromycin markedly enhanced, in vitro in a dose-dependent manner, biofilm formation of 20% (21/105) macrolide-resistant ica-positive and -negative isolates tested. Yet, the ica presence apparently produced an enhanced effect on biofilm formation. Expression of biofilm-related icaA, atlE, fruA, pyrR, sarA and sigB genes was increased in response to erythromycin. The results likely underscore the potential clinical relevance of macrolide-induced biofilm growth. PMID: 20231401 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372898 Mon, 15 Mar 2010 00:00:00 +0100 3372898 http://www.medworm.com/index.php?rid=3372897&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231402%26dopt%3DAbstract Authors: Simor AE, Louie L, Watt C, Gravel D, Mulvey MR, Campbell J, McGeer A, Bryce E, Loeb M, Matlow A, We determined the in vitro antimicrobial susceptibilities of 7,942 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients hospitalized in 48 Canadian hospitals from 1995-2008. Regional variations in susceptibilities were identified. Dissemination of community-associated strains in Canada appears to have contributed to increased susceptibility of MRSA to several non-beta-lactam antimicrobial agents in the past decade. Reduced susceptibility to glycopeptides was not identified. PMID: 20231402 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3372897 Mon, 15 Mar 2010 00:00:00 +0100 3372897 http://www.medworm.com/index.php?rid=3354955&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211885%26dopt%3DAbstract In this study, we sought to design and synthesize a large number of STAMPs targeting Streptococcus mutans, the primary etiologic agent of human dental caries, in order to identify candidate peptides with increased killing speed and selectivity when compared with their unmodified antimicrobial peptides (AMP) precursors. We hypothesized that a combinatorial approach utilizing a set number of AMP, targeting, and linker regions, would be an effective method for the identification of STAMPs with the desired level of activity. STAMPs composed of the S. mutans binding peptide Sm6 and the AMP PL-135 displayed selectivity at minimal inhibitory concentrations after incubation for 18-24 h. A STAMP where PL-135 was replaced by the B-33 killing domain exhibited both selectivity and rapid killing within... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354955 Mon, 08 Mar 2010 00:00:00 +0100 3354955 http://www.medworm.com/index.php?rid=3354954&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211886%26dopt%3DAbstract Authors: Manageiro V, Ferreira E, Albuquerque L, Bonnet R, Caniça M Inhibitor resistant TEM (IRT) beta-lactamases derive from TEM-1 or TEM-2 enzymes by point mutations in the corresponding coding gene (http://www.lahey.org/studies). ... PMID: 20211886 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354954 Mon, 08 Mar 2010 00:00:00 +0100 3354954 http://www.medworm.com/index.php?rid=3354953&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211887%26dopt%3DAbstract Authors: Reddy T, Chopra T, Marchaim D, Pogue JM, Alangaden G, Salimnia H, Boikov D, Navon-Venezia S, Akins R, Selman P, Dhar S, Kaye KS A phenotypic and genotypic analysis of Acinetobacter baumanni was conducted from 2003-2008 in Detroit, MI. Incidence of A. baumannii increased from 1.7 to 3.7/1,000 patient days during the study period. Susceptibility to ampicillin-sulbactam and imipenem decreased from approximately 90% to approximately 40%. Genotyping revealed polyclonality, suggesting either emergence of multiple resistant strains or spread of a common genetic element. The sharp rise mandates major multidisciplinary interventions to optimize management of this multi-drug resistant pathogen. PMID: 20211887 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chem... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354953 Mon, 08 Mar 2010 00:00:00 +0100 3354953 http://www.medworm.com/index.php?rid=3354952&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211888%26dopt%3DAbstract Authors: Wener KM, Schechner V, Gold HS, Wright SB, Carmeli Y Antibiotic exposure exerts strong selective pressure and is an important modifiable risk factor for antibiotic resistance. We aimed to identify the role of various antibiotics as risk factors for the isolation of extended-spectrum ss-lactamase (ESBL) -producing Klebsiella spp. in hospitalized patients at a tertiary care hospital. A parallel multivariable model was created to compare two groups of cases with either nosocomially-acquired ESBL- or non-ESBL-producing Klebsiella spp. to a common control group of hospitalized patients (a case-case-control design). 78 ESBL cases, 358 non-ESBL cases and 444 controls were analyzed. Significant factors associated with the isolation of Klebsiella spp. were age >65 years, transfer fr... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354952 Mon, 08 Mar 2010 00:00:00 +0100 3354952 http://www.medworm.com/index.php?rid=3354951&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211889%26dopt%3DAbstract In this study, we report that overproduction of NlpE increases multidrug and copper resistance through activation of the genes encoding the AcrD and MdtABC multidrug efflux pumps in Escherichia coli. PMID: 20211889 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354951 Mon, 08 Mar 2010 00:00:00 +0100 3354951 http://www.medworm.com/index.php?rid=3354950&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211890%26dopt%3DAbstract Authors: Nannini EC, Stryjewski ME, Singh KV, Rude TH, Corey GR, Fowler VG, Murray BE Using 98 clinical MSSA isolates of known beta-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), mild for cephalothin (especially type B and C), and nonexistence for ceftriaxone and cefuroxime. Ceftobiprole showed the lowest MICs at high inoculum but with a slight increase for Bla-positive versus Bla-negative strains. Since a potential therapeutic effect associated with a cephalosporin inoculum effect has been described, further studies are warranted. PMID: 20211890 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354950 Mon, 08 Mar 2010 00:00:00 +0100 3354950 http://www.medworm.com/index.php?rid=3354949&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211891%26dopt%3DAbstract Authors: Coombs GW, Monecke S, Ehricht R, Slickers P, Pearson JC, Tan HL, Christiansen KJ, O'Brien FG Clonal complex (CC) 59 community-associated MRSA (CA-MRSA) were characterized using pulsed-field gel electrophoresis, spa typing, multilocus sequence typing, diagnostic DNA microarrays, and PCRs targeting SCCmec elements and Panton Valentine leukocidin (PVL). Six distinct groups within CC59 were characterized. At least seven different variants of SCCmec elements were identified (IVa [2B], IVb [2B], IVd (2B), IVvariant [2B], IVa [2B&5], Vvariant [5C2] and V [5C2&5]). The first group is similar to the American ST59-MRSA-IV CA-MRSA strain "USA1000". The second group includes, a PVL-negative ST87 strain with a SCCmec element subtype IVb (2B). The third group comprises PVL-variable ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354949 Mon, 08 Mar 2010 00:00:00 +0100 3354949 http://www.medworm.com/index.php?rid=3354948&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211892%26dopt%3DAbstract Authors: Kaniga K, Flamm R, Tong SY, Lee M, Friedland I, Redman R The worldwide increase in fluoroquinolone-resistant and extended-spectrum beta-lactamase-(ESBL) producing Enterobacteriaceae pathogens has led to doripenem and other carbapenems assuming a greater role in the treatment of serious infections. We analyzed data from 6 phase 3 multinational doripenem clinical trials on ciprofloxacin-resistant Enterobacteriaceae consisting of all genera (CIPRE) and ESBL-producing Enterobacteriaceae isolates consisting of Escherichia coli, Klebsiella spp., and Proteus spp. with ceftazidime MICs >/=2 mug/mL (ESBLE) for: prevalence by geographic region and disease type; in vitro activity of doripenem and comparator agents; clinical or microbiologic outcome in doripenem- and comparator-treated... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354948 Mon, 08 Mar 2010 00:00:00 +0100 3354948 http://www.medworm.com/index.php?rid=3354947&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211893%26dopt%3DAbstract Authors: Folster JP, Pecic G, Krueger A, Rickert R, Burger K, Carattoli A, Whichard JM Shigellosis is a major source of gastroenteritis throughout the world (14). ... PMID: 20211893 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354947 Mon, 08 Mar 2010 00:00:00 +0100 3354947 http://www.medworm.com/index.php?rid=3354946&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211894%26dopt%3DAbstract In this study, we investigated the interaction of the prototypic cyclotide, kalata B1, with the external surface of H. contortus larval and adult worms. We have shown that cyclotides do not need to be ingested by the worms to exert their toxic effects, but that an interaction with the external surface alone is toxic. Evidence for this was toxicity towards adult worms in the presence of a chemically induced pharyngeal ligature, and toxicity of cyclotides towards non-feeding larval life stages. Uptake of tritiated inulin in ligated adult worms was increased in the presence of cyclotide, suggesting that cyclotides increase the permeability of the external membranes of adult nematodes. Polyethylene glycols of various sizes showed protective effects on the non-feeding larval life stage, as well... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354946 Mon, 08 Mar 2010 00:00:00 +0100 3354946 http://www.medworm.com/index.php?rid=3354945&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211895%26dopt%3DAbstract Authors: Pérez-Roth E, Kwong SM, Alcoba-Florez J, Firth N, Méndez-Álvarez S We have sequenced the conjugative plasmid pPR9 that carries the ileS2 gene, which had contributed to the dissemination of high-level mupirocin resistance at our institution. The plasmid backbone shows extensive genetic conservation with plasmids belonging to the pSK41/pGO1 family, but comparative analyses have revealed key differences that provide important insights into the evolution of these medically important plasmids and high-level mupirocin resistance in staphylococci, and highlight the role of insertion sequence IS257 in these processes. PMID: 20211895 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354945 Mon, 08 Mar 2010 00:00:00 +0100 3354945 http://www.medworm.com/index.php?rid=3354944&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211896%26dopt%3DAbstract Authors: Ando H, Kondo Y, Suetake T, Toyota E, Kato S, Mori T, Kirikae T Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 8 novel KatG mutants with a single amino acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild-type, and each mutant showed various levels of activity. Isolates having mutations with relatively lower activities showed high-level INH resistance. Based on our results and known mutations associated with INH resistance, we developed a new hybrid... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354944 Mon, 08 Mar 2010 00:00:00 +0100 3354944 http://www.medworm.com/index.php?rid=3354943&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211897%26dopt%3DAbstract Authors: Rhee JY, Park YK, Shin JY, Choi JY, Lee MY, Ran Peck K, Song JH, Ko KS Prevalence of extended-spectrum beta-lactamases (ESBLs) has limited the available therapeutic options and necessitated the increased use of carbapenems against Klebsiella pneumoniae infections. ... PMID: 20211897 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354943 Mon, 08 Mar 2010 00:00:00 +0100 3354943 http://www.medworm.com/index.php?rid=3354942&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211898%26dopt%3DAbstract Authors: Warren TK, Warfield KL, Wells J, Enterlein S, Smith M, Ruthel G, Yunus AS, Kinch MS, Goldblatt M, Aman MJ, Bavari S There exists an urgent need to develop licensed drugs and vaccines for treatment or prevention of filovirus infections. FGI-103 is a low-molecular weight compound that was discovered through an in vitro screening assay utilizing a variant of Zaire ebolavirus (ZEBOV) that expresses green fluorescent protein. In vitro analyses demonstrated that FGI-103 also exhibits antiviral activity against wild-type ZEBOV, Sudan ebolavirus as well as marburgvirus (MARV) strains Ci67 and Ravn. In vivo administration of FGI-103 with a single intraperitoneal dose of 10 mg/kg delivered 24 h after infection is sufficient to completely protect mice against a lethal challenge with eith... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354942 Mon, 08 Mar 2010 00:00:00 +0100 3354942 http://www.medworm.com/index.php?rid=3354941&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211899%26dopt%3DAbstract Authors: Ruiz C, Levy SB Multidrug resistance (MDR) in clinical isolates of Escherichia coli can be associated with overexpression of marA, a transcription factor that up-regulates multidrug efflux and down-regulates membrane permeability. Using random transposome mutagenesis, we found that many chromosomal genes and environmental stimuli affected MarA-mediated antibiotic resistance. Seven genes affected resistance mediated by MarA in an antibiotic-specific way; these were mostly genes encoding unrelated enzymes, transporters and unknown proteins. Other genes affected MarA-mediated resistance to all antibiotics tested. These were acrA, acrB and tolC, which encode the major MarA-regulated multidrug efflux pump AcrAB-TolC; crp, cyaA, hns and pcnB, four genes involved in global regulation... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354941 Mon, 08 Mar 2010 00:00:00 +0100 3354941 http://www.medworm.com/index.php?rid=3354940&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211900%26dopt%3DAbstract Authors: Bulitta JB, Yang JC, Yohonn L, Ly NS, Brown SV, D'Hondt RE, Jusko WJ, Forrest A, Tsuji BT Colistin is increasingly being utilized against gram-negative pathogens including Pseudomonas aeruginosa resistant to all other antibiotics. As limited data exist regarding killing by colistin at different initial inocula (CFUo), we evaluated killing of Pseudomonas aeruginosa by colistin at several CFUo and developed a mechanism-based mathematical model accommodating a range of CFUo. In vitro time-kill experiments were performed using >/=8 concentrations up to 64 xMIC of colistin against PAO1 and two clinical P. aeruginosa isolates at CFUo of 10(6), 10(8) and 10(9) CFU/mL. Serial samples up to 24h were simultaneously modeled in NONMEM VI (results shown) and S-ADAPT. The mathematical mo... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354940 Mon, 08 Mar 2010 00:00:00 +0100 3354940 http://www.medworm.com/index.php?rid=3354939&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20211901%26dopt%3DAbstract Authors: Rogers SA, Huigens RW, Cavanagh J, Melander C 2-Aminoimidazoles are an emerging class of small molecules that possess the ability to inhibit and disperse biofilms across bacterial order, class and phylum. Herein, we report the synergistic effect between a 2-aminoimidazole/triazole conjugate and antibiotics toward dispersing pre-established biofilms, cumulating with a three orders of magnitude increase of biofilm dispersion towards Staphylococcus aureus biofilms. Furthermore, we document that the 2-aminoimidazole/triazole conjugate will also re-sensitize multi-drug resistant strains of bacteria to the effects of conventional antibiotics, including MRSA and multi-drug resistant Acinetobacter baumannii. PMID: 20211901 [PubMed - as supplied by publisher] (Source: Antimicrobial... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3354939 Mon, 08 Mar 2010 00:00:00 +0100 3354939 http://www.medworm.com/index.php?rid=3336214&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194689%26dopt%3DAbstract This study describes the results of antimalarial in vitro susceptibility assays and molecular polymorphisms of Plasmodium falciparum isolates from Cambodia. The samples were collected from patients enrolled in therapeutic efficacy studies (TES) conducted by the Cambodian National Malaria Control Program for the routine efficacy monitoring of artemisinin-based combination therapy or ACT (artesunate-mefloquine and artemether-lumefantrine combinations). The isolates (n=2041) were obtained from nine sentinel sites during 2001 - 2007. Among these, 1,588 were examined for their in vitro susceptibility to four antimalarials (artesunate, mefloquine, chloroquine and quinine) and 851 isolates were genotyped for single nucleotide polymorphisms (SNP). The geometric means of the IC50 (GMIC50) were sign... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336214 Mon, 01 Mar 2010 00:00:00 +0100 3336214 http://www.medworm.com/index.php?rid=3336213&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194690%26dopt%3DAbstract Authors: Berg M, Kohl L, Van der Veken P, Joossens J, Al-Salabi MI, Castagna V, Giannese F, Cos P, Versées W, Steyaert J, Grellier P, Haemers A, Degano M, Maes L, de Koning HP, Augustyns K In this paper we present the biochemical and biological evaluation of N-arylmethyl-substituted iminoribitol derivatives as potential chemotherapeutic agents against trypanosomiasis. Previously, a library of 52 compounds was designed and synthesized as potent and selective inhibitors of Trypanosoma vivax IAG-NH. However, when tested against bloodstream form Trypanosoma brucei brucei, only one inhibitor, N-(9-deaza-adenin-9-yl)methyl-1,4-dideoxy-1,4-imino-D-ribitol (UAMC-00363), displayed a significant activity (IC50 = 0.49 +/- 0.31 muM). A validation in an in vivo model of African trypanosomiasis... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336213 Mon, 01 Mar 2010 00:00:00 +0100 3336213 http://www.medworm.com/index.php?rid=3336212&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194691%26dopt%3DAbstract Authors: Li L, He L, Tan S, Guo X, Lu H, Qi Z, Pan C, An X, Jiang S, Liu S Heterosexual transmission is the primary route for women to acquire HIV/AIDS. Thus, development of woman-controlled topical microbicides for prevention of sexual transmission of HIV is urgently needed. Here we report that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibits potent antiviral activity against a broad spectrum of HIV-1 isolates with different genotypes and biotypes. Its antiviral activity is correlated with the percentage of the chemically modified and unmodified lysines and arginines in OVA. HP-OVA inhibits HIV-1 fusion and entry through multiple mechanisms of action, including (i) blocking gp120 binding to CD4 and (ii) interfering with gp41 six-helix bundle formation. Because ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336212 Mon, 01 Mar 2010 00:00:00 +0100 3336212 http://www.medworm.com/index.php?rid=3336211&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194692%26dopt%3DAbstract Authors: Gupta S, Fransen S, Paxinos EE, Stawiski E, Huang W, Petropoulos CJ Recent reports have described the effect of mutations in the connection and ribonuclease H (RNase H) domains of RT on nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI respectively) resistance in the presence of thymidine analog resistance mutations (TAMs) and NNRTI mutations (5, 7, 18, 19, 36). In the present study, novel mutations in the connection domain of RT (T369I/V), first identified in patient-derived viruses, were characterized, and their effects on NNRTI and NRTI susceptibility were determined. Furthermore, the effect of N348I on NRTI and NNRTI resistance was confirmed. HIV-1 with either N348I or T369I/V demonstrated reduced susceptibility to nevirapine (NVP), efavirenz (E... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336211 Mon, 01 Mar 2010 00:00:00 +0100 3336211 http://www.medworm.com/index.php?rid=3336210&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194693%26dopt%3DAbstract Authors: Tomas M, Doumith M, Warner M, Turton JF, Beceiro A, Bou G, Livermore DM, Woodford N Expression of ampC, oprD, mexA, mexC, mexE, and mexX was studied in 25 Pseudomonas aeruginosa from cystic fibrosis patients, including 14 isolates of the 'Liverpool' epidemic strain. Overexpressed mexA or ampC and reduced oprD were associated with beta-lactam resistance. A specific combination of mexR, nalC and nalD mutations occurred in 11 'Liverpool' strain isolates, including 7 with up-regulated mexA. PMID: 20194693 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336210 Mon, 01 Mar 2010 00:00:00 +0100 3336210 http://www.medworm.com/index.php?rid=3336209&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194694%26dopt%3DAbstract Authors: Gamarra S, Rocha EM, Zhang YQ, Park S, Rao R, Perlin DS The antiarrhythmic drug amiodarone has been found to have fungicidal activity. In S. cerevisiae, its antifungal activity is mediated by calcium overload stress, which leads to a rapid nuclear accumulation of the calcineurin-regulated transcription factor CRZ1. In addition, low doses of amiodarone have been reported to be synergistic with fluconazole in fluconazole-resistant C. albicans. To establish its mechanism of toxicity in C. albicans, we used expression profiling of key pathway genes to examine cellular responses to amiodarone alone and in combination with fluconazole. Gene expression profiling of 59 genes was done in five C. albicans strains (3 fluconazole-susceptible and 2 fluconazole-resistant strains) after amio... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336209 Mon, 01 Mar 2010 00:00:00 +0100 3336209 http://www.medworm.com/index.php?rid=3336208&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194695%26dopt%3DAbstract Authors: Loregian A, Mercorelli B, Muratore G, Sinigalia E, Pagni S, Massari S, Gribaudo G, Gatto B, Palumbo M, Tabarrini O, Cecchetti V, Palù G WC5 is a 6-aminoquinolone that inhibits potently the replication of human cytomegalovirus (HCMV) but has no or significantly less activity against other herpesviruses. Here we investigated the nature of its specific anti-HCMV activity. Structure-activity relationship studies on a small series of analogues showed that WC5 possesses the most suitable substitutions pattern around the quinolone scaffold to give potent and selective anti-HCMV activity. Studies performed to identify the possible target of WC5 indicated that it prevents viral DNA synthesis but does not significantly affect DNA polymerase activity. In yield reduction experiments ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336208 Mon, 01 Mar 2010 00:00:00 +0100 3336208 http://www.medworm.com/index.php?rid=3336207&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194696%26dopt%3DAbstract A NOVEL AZOLO-1,2,4-TRIAZINE-DERIVED INHIBITOR OF INFLUENZA A AND B VIRUS REPLICATION: ANTIVIRAL PROPERTIES, METABOLISM, AND PHARMACOKINETICS. Antimicrob Agents Chemother. 2010 Mar 1; Authors: Karpenko I, Deev S, Kiselev O, Charushin V, Rusinov V, Ulomsky E, Deeva E, Yanvarev D, Ivanov A, Smirnova O, Kochetkov S, Chupakhin O, Kukhanova M Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated a novel effective inhibitor of human influenza A and B virus triazavirine (2-methylthio-6-nitro-1,2,4-triazolo[5,1-C]-1,2,4-triazine-7(4H)-one, TZV). TZV suppressed replication of influenza virus in cell culture, chicken chorioallantoic membranes, prote... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336207 Mon, 01 Mar 2010 00:00:00 +0100 3336207 http://www.medworm.com/index.php?rid=3336206&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194697%26dopt%3DAbstract Authors: Kiraz N, Dag I, Yamac M, Kiremitci A, Kasifoglu N, Oz Y The combination of voriconazole, fluconazole, itraconazole with caspofungin was evaluated against 50 Candida glabrata isolates by the time-kill, disk diffusion and Etest methods. The majority of antifungal combinations were indifferent. By the time kill method, synergistic activity was detected at eight (16%) of caspofungin-voriconazole and seven (14%) of caspofungin-fluconazole combinations, but synergy was not seen in caspofungin-itraconazole combination. Further comparisons of the Etest and disk diffusion synergy techniques with the time kill method are warranted. PMID: 20194697 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336206 Mon, 01 Mar 2010 00:00:00 +0100 3336206 http://www.medworm.com/index.php?rid=3336205&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194698%26dopt%3DAbstract Authors: Shekalaghe SA, Ter Braak R, Daou M, Kavishe R, van den Bijllaardt W, van den Bosch S, Koenderink JB, Luty AJ, Whitty CJ, Drakeley C, Sauerwein RW, Bousema T The current interest in malaria elimination has led to a renewed interest in drugs that could be used in mass administration to minimise malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature P. falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the haematolytic effect of... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336205 Mon, 01 Mar 2010 00:00:00 +0100 3336205 http://www.medworm.com/index.php?rid=3336204&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194699%26dopt%3DAbstract Authors: Tuohy MJ, Reja V, Park S, Perlin DS, Wnek M, Procop GW, Yen-Lieberman B A High-resolution melt (HRM) assay using the Rotor-Gene 6000(TM) was developed to characterize the codon for glycine 54 in the cyp51A gene from 13 reference and 12 clinical isolates of Aspergillus fumigatus. Mutations in this codon confer reduced susceptibility to itraconazole and posaconazole. The assay is simple to perform and a result of wildtype or mutant is available after approximately one hour following DNA extraction using commercially available reagents and conventional primers. PMID: 20194699 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336204 Mon, 01 Mar 2010 00:00:00 +0100 3336204 http://www.medworm.com/index.php?rid=3336203&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194700%26dopt%3DAbstract Authors: Okomo-Adhiambo M, Demmler-Harrison GJ, Deyde VM, Sheu TG, Xu X, Klimov AI, Gubareva LV The clinical use of the neuraminidase inhibitor (NAI) oseltamivir is associated with emergence of drug resistance resulting from subtype-specific neuraminidase (NA) mutations. The influenza A/Texas/12/2007 (H3N2) virus isolated from an oseltamivir-treated immunocompromised patient exhibited reduced susceptibility to oseltamivir in the chemiluminescent neuraminidase inhibition (NI) assay ( approximately 60-fold increase in IC50 compared to a control virus). When further propagated in cell culture, the isolate maintained reduced susceptibility to oseltamivir in both chemiluminescent and fluorescent NI assays ( approximately 50- and 350-fold increases in IC50, respectively). Sequencing analysis... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336203 Mon, 01 Mar 2010 00:00:00 +0100 3336203 http://www.medworm.com/index.php?rid=3336202&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194701%26dopt%3DAbstract Authors: Lin YC, Hsia KC, Chen YC, Sheng WH, Chang SC, Liao MH, Li SY Multidrug-resistant (MDR) Acinetobacter spp. have emerged as a threat in public health. We investigated the various antibiotic-resistant genes involved in fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems resistance in 75 Acinetobacter spp. clinical isolates from a Taiwanese hospital. All isolates were detected for the mutations of gyrA, the presence of integrons, blaAmpC, and carbapenem-resistant genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolones resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not amikacin. The presence of an ISAba1 element on the upstream of blaAmpC was correlated with... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336202 Mon, 01 Mar 2010 00:00:00 +0100 3336202 http://www.medworm.com/index.php?rid=3336201&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194702%26dopt%3DAbstract Authors: Krishna G, Beresford E, Ma L, Vickery D, Martinho M, Yu X, Komjathy S, Tavakkol A A randomized, single-center, open-label study of posaconazole (POS) was performed to determine the concentration of POS in the skin of 30 healthy adult human subjects receiving 400 mg POS twice daily for 8 days with a high-fat meal. Blood samples for plasma POS level determination were collected at prespecified times on day 1 and day 8. From each subject, two 4-mm skin punch biopsy samples were obtained, one immediately before or after both the first and last doses of POS. A MIC90 value of 250 ng/ml, which encompasses the majority of common dermatophytes, was used to calculate the time-above-MIC90 in plasma and skin. On days 1 and 8, POS attained peak plasma concentrations at a median Tmax of 8 a... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336201 Mon, 01 Mar 2010 00:00:00 +0100 3336201 http://www.medworm.com/index.php?rid=3336200&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194703%26dopt%3DAbstract In this study we analyzed 118 penicillin-non-susceptible Streptococcus pneumoniae (PNSP) isolates (MICs, >/=0.12 mug/ml), recovered in Poland in 2003-2005 from respiratory tract diseases and invasive infections. Seven different serotypes (14, 9V, 23F, 19F, 6B, 19A and 6A, in the order of descending frequency), seven alleles of the murM gene (murMA, murMB6 and the new murMB12-16 alleles), and 31 multilocus sequence types (STs) were observed. The vast majority of the PNSP (90.7%) belonged to the international multiresistant clones and among these, the Spain(9V)-ST156 clonal complex was the most prevalent (56 isolates) and significantly overrepresented in invasive infections. The clone has been evolving rapidly, as it was demonstrated by the observed number of STs, the diversity of the MLV... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336200 Mon, 01 Mar 2010 00:00:00 +0100 3336200 http://www.medworm.com/index.php?rid=3336199&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194704%26dopt%3DAbstract Authors: Kosowska-Shick K, McGhee PL, Appelbaum PC We compared the affinity to all penicillin-binding proteins (PBPs) of ceftaroline with those of ceftriaxone and cefotaxime in 6 Staphylococcus aureus and 7 Streptococcus pneumoniae isolates of varying resistance phenotypes. Ceftaroline MICs were </=1 mug/ml against all S. aureus isolates, and were </=0.25 mug/ml for 4 of 7 isolates of S. pneumoniae. Ceftaroline affinities for penicillin-susceptible S. pneumoniae strain were PBP2X, 3 > 1A, 1B, 2A > 2B and ceftaroline had >/=4-fold higher IC50 (0.1-4 mug/ml) for PBP2X, 2A, 2B, and 3 compared to other cephalosporins tested. Among 3 penicillin-resistant S. pneumoniae strains, ceftaroline had high affinity to PBP2X (IC50 0.1-1 mug/ml), a primary target for cephalosporin PBP b... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336199 Mon, 01 Mar 2010 00:00:00 +0100 3336199 http://www.medworm.com/index.php?rid=3336198&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20194705%26dopt%3DAbstract Authors: Vediyappan G, Rossignol T, d'Enfert C Candida albicans can form biofilms that exhibit elevated intrinsic resistance to various antifungal agents, in particular azoles and polyenes. The molecular mechanisms that are involved in the antifungal resistance of biofilms remain poorly understood. We have used transcript profiling to explore the early transcriptional responses of mature C. albicans biofilms exposed to various antifungal agents. Mature C. albicans biofilms grown under continuous flow were exposed for up to 2h to concentrations of Fluconazole (FLU), Amphotericin B (AMB) and caspofungin (CAS) that, while lethal for planktonic cells, were not lethal for biofilms. Interestingly, FLU exposed biofilms did not show any significant changes in gene expression over the course of... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3336198 Mon, 01 Mar 2010 00:00:00 +0100 3336198 http://www.medworm.com/index.php?rid=3303225&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176892%26dopt%3DAbstract Authors: Farowski F, Cornely OA, Vehreschild JJ, Hartmann P, Bauer T, Steinbach A, Rüping MJ, Müller C A rapid turn-around is a pre-requisite of therapeutic drug monitoring (TDM). For antifungals this need is still unmet, since hardly any method has been established to simultaneously quantitate concentrations of different antifungal classes. A liquid chromatography tandem mass spectroscopy (LC-MS/MS) was developed allowing quantitation of anidulafungin (ANF), caspofungin (CSF), isavuconazole (ISC), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). Quantitation was successful in diluted plasma, peripheral blood mononuclear cells (PBMC), polymorphonuclear leucocytes (PMN), and erythrocytes (RBC). A triple quadrupole mass spectrometer in selected reaction monitoring ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303225 Mon, 22 Feb 2010 00:00:00 +0100 3303225 http://www.medworm.com/index.php?rid=3303224&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176893%26dopt%3DAbstract Authors: Wang YP, Liu F, He HW, Han YX, Peng ZG, Li BW, You XF, Song DQ, Li ZR, Yu LY, Cen S, Hong B, Sun CH, Zhao LX, Kreiswirth B, Perlin D, Shao RG, Jiang JD Heat-stress cognate 70 (Hsc70) is a host protein associated with hepatitis B viral (HBV) replication. The goal of this study is to investigate whether Hsc70 could be an anti-HBV drug target. Our results showed that introducing Hsc70 increased HBV replication in the HBV(+) human hepatocytes (HepG2.2.15 cells). The coiled coil region on Hsc70 (nt 1533-1608, aa 511-536) was the key sequence for HBV replication. Knockdown of Hsc70 expression by RNAi largely inhibited HBV replication with no cytotoxicity to the host. Using Hsc70 mRNA screening assay, natural compound oxymatrine (OMTR) was found to be a selective inhibitor for Hsc70 ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303224 Mon, 22 Feb 2010 00:00:00 +0100 3303224 http://www.medworm.com/index.php?rid=3303223&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176894%26dopt%3DAbstract In this study, we investigated the frequency and mechanism of resistance to cyclosporin A (CsA), NIM811, and a structurally unrelated cyclophilin inhibitor, SFA-1, in replicon-containing Huh7 cells. Cross-resistance between all clones was observed. NIM811 resistant clones were selected only after obtaining initial resistance to either CsA or SFA-1. The time required to select resistance against cyclophilin inhibitors was significantly longer than that required for resistance selection against viral protein inhibitors and the achievable resistance level was substantially lower. Resistance to cyclophilin inhibitors was mediated by amino acid substitutions in NS3, NS5A, and NS5B with NS5A mutations conferring the majority of resistance. Mutation D320E in NS5A mediated most of the resistance c... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303223 Mon, 22 Feb 2010 00:00:00 +0100 3303223 http://www.medworm.com/index.php?rid=3303222&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176895%26dopt%3DAbstract Authors: Chen H, Liu Y, Jiang X, Chen M, Wang H The incidence of methicillin-resistant Staphylococcus aureus (MRSA) has been increasing yearly at Peking Union Medical College Hospital (PUMCH). In order to understand the molecular evolution of MRSA at PUMCH, a total of 466 nonduplicate S. aureus isolates including 302 MRSA and 164 methicillin susceptible (MSSA) isolates recovered from 1994 to 2008 were characterized by staphylococcal cassette chromosome mec (SCCmec) typing, spa typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). The 302 MRSA isolates were classified into 12 spa types and 9 STs. During the years of 1994-2000, the most predominant MRSA clone was ST239-MRSA-III-spa t037. Since 2000, ST239-MRSA-III-spa t030 has rapidly replaced t037, and ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303222 Mon, 22 Feb 2010 00:00:00 +0100 3303222 http://www.medworm.com/index.php?rid=3303221&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176896%26dopt%3DAbstract Authors: Reynolds NL, De Cecco M, Taylor K, Stanton C, Kilanowski F, Kalapothakis J, Seo E, Uhrin D, Campopiano D, Govan J, Macmillan D, Barran P, Dorin JR beta-defensins are known to be both antimicrobial and able to chemoattract various immune cells. Although the sequences of paralogous genes are not highly conserved, the core-defensin structure is retained. Defb14-1C(V) has similar bactericidal activity to its parent peptide (murine beta-defensin Defb14) despite all but one of the canonical six cysteines being substituted with alanines. The twenty three amino acid N-terminal half of Defb14-1C(V) is a potent antimicrobial where the C-terminal region half is not. Here we use a library of peptide derivatives to demonstrate that the antimicrobial activity can be localised to a particula... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303221 Mon, 22 Feb 2010 00:00:00 +0100 3303221 http://www.medworm.com/index.php?rid=3303220&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176897%26dopt%3DAbstract Authors: Anantharaman A, Rizvi MS, Sahal D By choosing membranes as targets of action, antibacterial peptides offer the promise of providing antibiotics to which bacteria would not become resistant. However, there is need to increase their potency against bacteria along with reduction in toxicity to host cells. Here, we report that three de novo designed antibacterial peptides (DeltaFm, DeltaFmscr and Ud) with poor to moderate antibacterial potencies and kill kinetics, improved significantly in all these aspects when synergized with rifampicin and kanamycin against E.coli. In synergy with rifampicin, the MIC of DeltaFmscr showed a 34 fold decrease (67.9 mug/ml when alone to 2 mug/ml in combination). A 20-fold improvement in Minimum Bactericidal Concentration of Ud was observed, when us... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303220 Mon, 22 Feb 2010 00:00:00 +0100 3303220 http://www.medworm.com/index.php?rid=3303219&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176898%26dopt%3DAbstract Authors: Lenz O, Verbinnen T, Lin TI, Vijgen L, Cummings MD, Lindberg J, Berke JM, Dehertogh P, Fransen E, Scholliers A, Vermeiren K, Ivens T, Raboisson P, Edlund M, Storm S, Vrang L, de Kock H, Fanning GC, Simmen KA TMC435 is a small-molecule inhibitor of the NS3/4A serine protease of HCV currently in Phase 2 development. The in vitro resistance profile of TMC435 was characterized by selection experiments using HCV genotype 1 replicon cells and the genotype 2a JFH-1 system. In 80% (86/109) of the sequences analyzed from genotype 1 replicon cells, a mutation at NS3 residue D168 was observed, with changes to V or A being the most frequent. Mutations at NS3 positions 43, 80, 155 and 156, alone or in combination, were also identified. A transient replicon assay confirmed the relevance of ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303219 Mon, 22 Feb 2010 00:00:00 +0100 3303219 http://www.medworm.com/index.php?rid=3303218&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176899%26dopt%3DAbstract Authors: Sánchez-Hidalgo M, Núñez LE, Méndez C, Salas JA Streptomyces lydicus NRRL2433 and S. spectabilis NRRL2494 produce two inhibitors of bacterial RNA polymerase: the 3-acyltetramic acid streptolydigin and the naphthalenic ansamycin streptovaricin, respectively. Both strains are highly resistant to their own antibiotics. Independent expression of S. lydicus and S. spectabilis rpoB and rpoC genes, encoding the beta- and beta'-subunits of RNA polymerase respectively, in S. albus showed that resistance is mediated by rpoB with no effect of rpoC. Within the beta-subunit, resistance was confined to an amino acid region harboring the "rif region". Comparison of the beta-subunit amino acid sequences of this region from the producer strains and those of other streptomyc... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303218 Mon, 22 Feb 2010 00:00:00 +0100 3303218 http://www.medworm.com/index.php?rid=3303217&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176900%26dopt%3DAbstract Authors: Betriu C, Morales G, Rodríguez-Avial I, Culebras E, Gómez M, López-Fabal F, Picazo JJ The in vitro activity of TR-700 (torezolid) was evaluated against a collection of 660 staphylococcal blood isolates. TR-700 showed excellent activity against all the staphylococci tested. The MIC50/MIC90 values of TR-700, linezolid, daptomycin, and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) isolates were 0.25/0.5, 2/4, 0.5/0.5, and 1/2 mug/ml, respectively. TR-700 demonstrated greater in vitro potency than linezolid against staphylococci, including linezolid-resistant and vancomycin-nonsusceptible strains and was 32-fold more active than linezolid against the 7 cfr-positive MRSA strains tested. PMID: 20176900 [PubMed - as supplied by publisher] (S... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303217 Mon, 22 Feb 2010 00:00:00 +0100 3303217 http://www.medworm.com/index.php?rid=3303216&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176901%26dopt%3DAbstract Authors: Propst KL, Troyer RM, Kellihan LM, Schweizer HP, Dow SW Burkholderia pseudomallei is a soil bacterium endemic to southeast Asia and northern Australia that can cause both acutely lethal pneumonia as well as chronic systemic infections in humans. Effective treatment of infection with B. pseudomallei requires rapid diagnosis and prolonged treatment with high doses of antimicrobials, and even with appropriate antibiotic therapy, patient relapse is common. Thus, new approaches to treat B. pseudomallei infection are needed. In the present study, we asked whether active immunotherapy with IFN-gamma, a key cytokine regulating intracellular replication of B. pseudomallei, could increase the effectiveness of conventional antimicrobial therapy for B. pseudomallei infection. Macrophage i... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303216 Mon, 22 Feb 2010 00:00:00 +0100 3303216 http://www.medworm.com/index.php?rid=3303215&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176902%26dopt%3DAbstract Authors: Aiello D, Williams JD, Majgier-Baranowska H, Patel I, Peet NP, Huang J, Lory S, Bowlin TL, Moir DT The type III secretion system (T3SS) is a clinically important virulence mechanism in Pseudomonas aeruginosa that secretes and translocates up to four protein toxin effectors into human cells, facilitating the establishment and dissemination of infections. To discover inhibitors of this important virulence mechanism, we developed two cellular reporter assays and applied them to a library of 80,000 compounds. The primary screen was based on the dependence of transcription of T3SS operons on T3SS-mediated secretion of a negative regulator and consisted of a transcriptional fusion of the Photorhabdus luminescens lux CDABE operon to the P. aeruginosa exoT effector gene. Secondary ass... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303215 Mon, 22 Feb 2010 00:00:00 +0100 3303215 http://www.medworm.com/index.php?rid=3303214&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176903%26dopt%3DAbstract Authors: Schulz Zur Wiesch P, Engelstädter J, Bonhoeffer S Strains of bacterial pathogens that have acquired mutations conferring antibiotic resistance often have a lower growth rate and are less invasive or transmissible initially than their susceptible counterparts. However, fitness costs of resistance mutations can be ameliorated by secondary site mutations. These so-called compensatory mutations may restore fitness in the absence and/or in the presence of antimicrobials. We review literature data and show that the fitness gain in absence and presence of antibiotic treatment need not be correlated. The aim of this study is to get a better conceptual grasp of how compensatory mutations with different fitness gains affect evolutionary trajectories - in particular reversibility. T... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303214 Mon, 22 Feb 2010 00:00:00 +0100 3303214 http://www.medworm.com/index.php?rid=3303213&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176904%26dopt%3DAbstract Authors: Muller AE, Mouton JW, Oostvogel PM, Dörr PJ, Voskuyl RA, Dejongh J, Steegers EA, Danhof M The study was performed to describe the pharmacokinetics of intravenously administered clindamycin in pregnant women. 7 pregnant women treated with clindamycin were recruited. Maternal blood, arterial and venous umbilical cord blood samples were obtained. Maternal clindamycin concentrations were analyzed with nonlinear mixed-effects modeling using NONMEM. Data were best described by a linear three-compartment model. Clearance and volume of distribution at steady state were 10.0 L/h and 6.32 x 10(3) L. Monte Carlo simulations were performed to determine the area under concentration curve for the free (unbound) drug in maternal serum for 24 hours over the MIC (fAUC0-24h/MIC). At a MIC ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303213 Mon, 22 Feb 2010 00:00:00 +0100 3303213 http://www.medworm.com/index.php?rid=3303212&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176905%26dopt%3DAbstract We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and protein-coated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5), but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-kappa B (NF-kappaB) p65 pathway. ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303212 Mon, 22 Feb 2010 00:00:00 +0100 3303212 http://www.medworm.com/index.php?rid=3303211&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176906%26dopt%3DAbstract In this study, we examined the ability of the peptides to inhibit the growth of Salmonella in mammalian cells. J774A.1 macrophage-like cells and murine peritoneal macrophages were infected with Salmonella enterica serovar Typhimurium and grown in the presence or absence of peptide. We found that peptide wrwycr reduced the number of Salmonella recovered after 24 hours growth in J774A.1 cells by 100X - 1000X, depending on the multiplicity of infection. The peptide also inhibited Salmonella growth in peritoneal macrophages and although higher doses were required, these were not toxic to the host cells. The apparent lower potency of the peptide paralleled the lower replication of Salmonella and lesser permeability of the peptide in the peritoneal macrophages compared to the J774.1 cells. Treat... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303211 Mon, 22 Feb 2010 00:00:00 +0100 3303211 http://www.medworm.com/index.php?rid=3303210&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176907%26dopt%3DAbstract Authors: Lunde CS, Rexer CH, Hartouni SR, Axt S, Benton BM The cellular binding patterns of fluorescent conjugates of telavancin and vancomycin were evaluated in Staphylococcus aureus using fluorescence microscopy and ratio imaging analysis. Telavancin showed enhanced binding at the division septum compared to vancomycin. This result is consistent with observations that telavancin binds with higher affinity to lipid II than D-Ala-D-Ala residues in cell wall, thus demonstrating the preferential binding of telavancin to the site of active cell wall biosynthesis. PMID: 20176907 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303210 Mon, 22 Feb 2010 00:00:00 +0100 3303210 http://www.medworm.com/index.php?rid=3303209&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176908%26dopt%3DAbstract In conclusion, the standard cefotaxime dose regimen provides sufficiently long periods of supra-MIC concentrations to provide adequate treatment of infants on ECMO. PMID: 20176908 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303209 Mon, 22 Feb 2010 00:00:00 +0100 3303209 http://www.medworm.com/index.php?rid=3303208&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176909%26dopt%3DAbstract Authors: Gobin P, Lemaître F, Marchand S, Couet W, Olivier JC A rapid high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for routine quantification of colistins A and B and their prodrugs colistin methanesulfonate (CMS) A and B in human plasma and urine, using polymyxin B1 as internal standard (IS). CMS concentrations were determined indirectly by substracting colistin concentrations determined in biological samples from the whole colistin concentrations determined after sample treatment with sulfuric acid in order to hydrolize CMS into colistin. After extraction on SPE column, colistins were separated on an XBrigde(R) C18 column with isocratic elution (3.8 min runtime). The mobile phase was 0.1% (v/v) formic acid in acetonitrile : 0.1% ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303208 Mon, 22 Feb 2010 00:00:00 +0100 3303208 http://www.medworm.com/index.php?rid=3303207&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176910%26dopt%3DAbstract Authors: Woosley LN, Castanheira M, Jones RN In vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of MIC and MBC, timed-killing, single-step and multistep mutation rates, erythromycin induction of resistance, post-antibiotic effect (PAE) and drug interactions were performed for CEM-101 and results compared to telithromycin, macrolides and lincosamides. CEM-101 MBC results remained overall lower than those of telithromycin and CEM-101 displayed a two-fold greater potency compared the ketolide. Timed-killing curve testing resulted in CEM-101 having greater bactericidal activity than telithromycin (>/=3 log10 CFU/ml decrease of initial inoculum at 24 hours) for th... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303207 Mon, 22 Feb 2010 00:00:00 +0100 3303207 http://www.medworm.com/index.php?rid=3303206&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20176911%26dopt%3DAbstract In conclusion, JNJ-Q2 exhibits a range of antibacterial activity in vitro that is supportive of its further evaluation as a potential new agent for the treatment of skin and respiratory tract infections. PMID: 20176911 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3303206 Mon, 22 Feb 2010 00:00:00 +0100 3303206 http://www.medworm.com/index.php?rid=3284772&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160045%26dopt%3DAbstract Authors: van 't Klooster G, Hoeben E, Borghys H, Looszova A, Bouche MP, van Velsen F, Baert L The next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200 nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentr... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284772 Tue, 16 Feb 2010 00:00:00 +0100 3284772 http://www.medworm.com/index.php?rid=3284771&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160046%26dopt%3DAbstract Authors: Blumer J, Rodriguez A, Sánchez PJ, Sallas W, Kaiser G, Hamed K A multicenter, open-label, study evaluated single-dose pharmacokinetics and safety of a pediatric oral famciclovir (prodrug of penciclovir) formulation in infants aged 1 to 12 months with suspicion or evidence of herpes simplex virus (HSV) infection. Individualized single doses of famciclovir based on the infant's body weight ranged from 25 to 175 mg. Eighteen infants were enrolled (1 to <3 months [n = 8], 3 to <6 months [n = 5], and 6 to 12 months [n = 5]). Seventeen infants were included in the pharmacokinetic analysis; one infant experienced immediate emesis and was excluded. Mean Cmax and AUC0-6h values of penciclovir in infants <6 months of age were approximately 3- to 4-fold lower vs. those in t... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284771 Tue, 16 Feb 2010 00:00:00 +0100 3284771 http://www.medworm.com/index.php?rid=3284770&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160047%26dopt%3DAbstract LACK OF A CLINICALLY RELEVANT EFFECT OF AN ANTACID ON THE PHARMACOKINETICS OF LERSIVIRINE. Antimicrob Agents Chemother. 2010 Feb 16; Authors: Vourvahis M, Banerjee S, Labadie R, Gore D, Mayer H Lersivirine (UK-453,061) is a next-generation non-nucleoside reverse transcriptase inhibitor, which displays potent antiviral activity. Lersivirine solubility is pH-dependent; therefore, the effect of co-administration of antacid on the pharmacokinetics of lersivirine was investigated in healthy subjects. The ratio of adjusted geometric means (lersivirine 750 mg + Maalox Max(R) 20 mL/lersivirine 750 mg) for AUCinf was 101.86% showing that co-administration of an antacid had no effect on lersivirine exposure. Co-administration appeared to be safe and relatively well-tolerated. PMID: 2... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284770 Tue, 16 Feb 2010 00:00:00 +0100 3284770 http://www.medworm.com/index.php?rid=3284769&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160048%26dopt%3DAbstract ANTISTAPHYLOCOCCAL ACTIVITY OF TELAVANCIN TESTED ALONE AND IN COMBINATION BY TIME-KILL ASSAY. Antimicrob Agents Chemother. 2010 Feb 16; Authors: Lin G, Pankuch GA, Ednie LM, Appelbaum PC Synergy time-kill studies against 40 methicillin-resistant Staphylococcus aureus (MRSA) strains of differing resistance phenotypes were conducted. Subinhibitory concentrations of telavancin were combined with subMIC concentrations of other antimicrobial agents that might be used in combination with telavancin to provide Gram-negative coverage. The highest incidence of synergy was found after 24 h with gentamicin (90% of strains), followed by ceftriaxone (88%), rifampin and meropenem (each 65%), cefepime (45%), and ciprofloxacin (38%) for combinations tested at or below the intermediate breakpoi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284769 Tue, 16 Feb 2010 00:00:00 +0100 3284769 http://www.medworm.com/index.php?rid=3284768&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160049%26dopt%3DAbstract In this study, we used Tn5 transposon mutagenesis to identify genes that may affect PB resistance in P. mirabilis. Two genes, ugd and galU, which may encode UDP-glucose dehydrogenase (Ugd) and UDP-glucose pyrophosphorylase (GalU), respectively, were identified. Knockout mutants of ugd and galU were found to be extremely sensitive to PB, presumably because of alterations in lipopolysaccharide structure and cell surface architecture in these mutants. These mutants were defective in swarming, expressed lower level of virulence factor hemolysin, and had lower cell invasion ability. Complementation of the ugd or galU mutant with full-length ugd or galU gene, respectively, led to restoration of wild-type phenotypic traits. Interestingly, we found that the expression of Ugd and GalU was induced b... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284768 Tue, 16 Feb 2010 00:00:00 +0100 3284768 http://www.medworm.com/index.php?rid=3284767&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160050%26dopt%3DAbstract In conclusion, combination empiric antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection. PMID: 20160050 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284767 Tue, 16 Feb 2010 00:00:00 +0100 3284767 http://www.medworm.com/index.php?rid=3284766&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160051%26dopt%3DAbstract Authors: Kuete V, Ngameni B, Tangmouo JG, Bolla JM, Alibert-Franco S, Ngadjui BT, Pagès JM Isobavachalcone and diospyrone are two naturally occurring compounds and their respective activities were evaluated on documented strains and multidrug resistant (MDR) Gram-negative isolates. The results indicated that the two compounds exhibited an intrinsic antibacterial activity on several Gram-negative bacteria and their activity was significantly improved in presence of an efflux pump inhibitor (MIC values decreased below 10 mug/ml). In addition, the activity of isobavachalcone and diospyrone significantly increased when tested on various strains exhibiting deletions of the major efflux pump components (AcrAB, TolC). The overall results indicate that isobavachalcone and diospyrone could... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284766 Tue, 16 Feb 2010 00:00:00 +0100 3284766 http://www.medworm.com/index.php?rid=3284765&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160052%26dopt%3DAbstract Authors: Lim SP, Nikaido H Multidrug efflux transporter AcrAB-TolC is known to pump out a diverse range of antibiotics, including beta-lactams. However, kinetic constants of the efflux process, needed for the quantitative understanding of resistance, were not available until those accompanying the efflux of some cephalosporins were determined recently by combining efflux with the hydrolysis of drugs by the periplasmic beta-lactamase. Here we extend this approach to the study of a wide range of penicillins, from ampicillin and penicillin V to ureidopenicillins and isoxazolylpenicillins, by combining efflux with hydrolysis with the OXA-7 penicillinase. We found that penicillins had much stronger apparent affinity to AcrB and higher Vmax values than cephalosporins. All penicillins showed ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284765 Tue, 16 Feb 2010 00:00:00 +0100 3284765 http://www.medworm.com/index.php?rid=3284764&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160053%26dopt%3DAbstract Authors: Lackovic K, Parisot JP, Sleebs N, Baell JB, Debien L, Watson KG, Curtis JM, Handman E, Street IP, Kedzierski L Current treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity and lack of efficacy in endemic regions. Therefore, development of new, effective and affordable antileishmanial drugs is a global health priority. Leishmania synthesize a range of mannose-rich glycoconjugates that are essential for parasite virulence and survival. A prerequisite for glycoconjugate biosynthesis is the conversion of monosaccharides to activated mannose donor, GDP-mannose, the product of a reaction catalysed by GDP-mannose pyrophosphorylase (GDP-MP). The deletion of the gene encoding GDP-MP in Leishmania le... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284764 Tue, 16 Feb 2010 00:00:00 +0100 3284764 http://www.medworm.com/index.php?rid=3284763&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160054%26dopt%3DAbstract Authors: Rullas J, García JI, Beltrán M, Cardona PJ, Cáceres N, García-Bustos JF, Angulo-Barturen I Murine models of M. tuberculosis are essential tools in drug discovery. Here we describe a fast standardized 9-day acute assay intended to measure the efficacy of drugs against M. tuberculosis growing in the lungs of immunocompetent mice. This assay is highly reproducible, allows good throughput and was validated for drug lead optimization using isoniazid, rifampicin, ethambutol, pyrazinamide, linezolid, and moxifloxacin. PMID: 20160054 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284763 Tue, 16 Feb 2010 00:00:00 +0100 3284763 http://www.medworm.com/index.php?rid=3284762&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160055%26dopt%3DAbstract This study shows that conventional RIF/INH/PZA chemotherapy significantly decreased numbers of the highly virulent strain [Erdman K01] of Mycobacterium tuberculosis, with most of the bacilli eliminated in a month. Despite this, bacteria could still be detected in the lungs and other tissues for at least another 3-4 months. Resolution of the non-necrotic granulomas in the lungs and lymph nodes could be clearly visualized using magnetic resonance imaging at the macroscopic level. Microscopically, the majority of the pulmonary and extra-pulmonary inflammation resolved spontaneously, leaving residual lesions composed of dystrophic calcification and fibrosis marking the site of primary lesion necrosis. Residual calcified lesions, which were also associated with pulmonary lymphangitis, contained... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284762 Tue, 16 Feb 2010 00:00:00 +0100 3284762 http://www.medworm.com/index.php?rid=3284761&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20160056%26dopt%3DAbstract This study highlights a new phenomenon in Plasmodium response to ART that may explain the delayed clearance of parasites after artesunate treatment observed on the Thai-Cambodia border and that provides important information for better understanding of the mechanisms of antimalarial resistance. PMID: 20160056 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3284761 Tue, 16 Feb 2010 00:00:00 +0100 3284761 http://www.medworm.com/index.php?rid=3263204&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145076%26dopt%3DAbstract Authors: Docquier JD, Benvenuti M, Calderone V, Giuliani F, Kapetis D, De Luca F, Rossolini GM, Mangani S Class D beta-lactamases represent a heterogeneous group of active-site serine-beta-lactamases that show an extraordinary panel of functional features and substrate profiles, thus representing relevant models for biochemical and structural studies. OXA-46 is a narrow spectrum enzyme belonging to the OXA-2 subgroup which has been found in a Pseudomonas aeruginosa clinical isolate from Northern Italy. In this work, we obtained the 3D structure of OXA-46 which shows the overall fold of active serine-beta-lactamases and a dimeric quaternary structure. Significant differences with currently available structures of class D beta-lactamases were found in the loops located close to the activ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263204 Tue, 09 Feb 2010 00:00:00 +0100 3263204 http://www.medworm.com/index.php?rid=3263203&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145077%26dopt%3DAbstract Authors: Rodríguez MM, Pastor FJ, Sutton DA, Calvo E, Fothergill AW, Salas V, Rinaldi MG, Guarro J We have evaluated the in vitro activity of posaconazole (PSC) against 50 clinical strains of Rhizopus oryzae using a broth microdilution method, the Neo-Sensitabs(R) tablet diffusion method, and the minimal fungicidal concentration (MFC) determination. In general, PSC showed low minimal inhibitory concentrations (MICs) against this fungus, which correlated with inhibition zone diameters. Most of the MFCs, however, were from 1 to 4 dilutions higher than their corresponding MICs. We then investigated the efficacy of several different doses of PSC in a murine model. All treatments began 24 h after challenge, and lasted for 7 days. The drug was administered twice a day against three stra... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263203 Tue, 09 Feb 2010 00:00:00 +0100 3263203 http://www.medworm.com/index.php?rid=3263202&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145078%26dopt%3DAbstract Authors: Ben-Ami R, Lewis RE, Leventakos K, Latgé JP, Kontoyiannis DP Cutaneous models have proven useful in studies of the pathogenesis and treatment of Gram-positive bacterial infections. Because cutaneous invasive aspergillosis (IA) occurs in the clinical setting, we sought to develop a non-lethal murine cutaneous model of IA. We induced cutaneous IA in cyclophosphamide-treated BALB/c nude mice by subcutaneous injection of Aspergillus fumigatus conidia. Skin lesion areas correlated well with tissue fungal burdens, allowing dynamic visual monitoring of cutaneous infections. The cutaneous model accurately reflected alterations in A. fumigatus pathogenicity resulting from deletions of recognized virulence genes (pabaA, sidA and pksP). Moreover, analysis of the roles of conidial an... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263202 Tue, 09 Feb 2010 00:00:00 +0100 3263202 http://www.medworm.com/index.php?rid=3263201&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145079%26dopt%3DAbstract Authors: Crémet L, Caroff N, Giraudeau C, Dauvergne S, Lepelletier D, Reynaud A, Corvec S Extended-spectrum AmpC beta-lactamase (ESAC) E. coli producers were investigated over a 5-year period. Eleven isolates presenting a strong ampC promoter and different strategic AmpC mutations, including two new described modifications (A292V and 295 L-A-A insertion) were characterized. All the isolates belonged to the phylogenetic group A and to the ST23 complex. PMID: 20145079 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263201 Tue, 09 Feb 2010 00:00:00 +0100 3263201 http://www.medworm.com/index.php?rid=3263200&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145080%26dopt%3DAbstract Authors: Hoehamer CF, Cummings ED, Hilliard GM, Rogers PD The yeast Candida albicans is an opportunistic human fungal pathogen and cause of superficial and systemic infections in immunocompromised patients. The classes of antifungal agents most commonly used to treat Candida infections are the azoles, polyenes, and echinocandins. In the present study, we identified changes in C. albicans protein abundance using 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF MS) following exposure to representatives of azole (ketoconazole), polyene (amphotericin B), and echinocandin (caspofungin) antifungals in an effort to elucidate the adaptive responses to these classes of antifungal agents. We id... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263200 Tue, 09 Feb 2010 00:00:00 +0100 3263200 http://www.medworm.com/index.php?rid=3263199&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145081%26dopt%3DAbstract In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between faropenem free drug (f) plasma concentrations and efficacy against B. anthracis in a murine post-exposure prophylaxis inhalation model. Plasma PK and PK-PD of faropenem were evaluated in BALB/c mice following intra-peritoneal (IP) administration of doses ranging from 2.5 to 160 mg/kg. For evaluation of efficacy, mice received aerosol inhalation of B. anthracis (Ames strain, faropenem MIC 0.06 mug/mL) at 100 times the LD50. Faropenem dosing regimens (10, 20, 40 and 80 mg/kg/day) were administered IP 24 hours post-challenge at 4, 6, and 12 hour intervals for 14 days. The sigmoid Emax effect model fit the survival data, where free-drug (f) AUC:MIC, fCmax:MIC ratios and f %T>MIC were each evaluated.... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263199 Tue, 09 Feb 2010 00:00:00 +0100 3263199 http://www.medworm.com/index.php?rid=3263198&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145082%26dopt%3DAbstract Authors: Pinho MD, Melo-Cristino J, Ramirez M, Quinolone resistance is an emerging problem in Streptococcus pyogenes and recombination with Streptococcus dysgalactiae DNA has been implicated as a frequent mechanism leading to resistance. We have characterized a collection of S. dysgalactiae subsp. equisimilis responsible for infections in humans (n = 314) and found a high proportion of levofloxacin resistant isolates (12%). Resistance was associated with multiple emm types and genetic lineages, as determined by pulsed-field gel electrophoretic profiling. Since we could not find evidence for a role of efflux pumps in resistance, we sequenced the quinolone resistance-determining regions of gyrA and parC of representative resistant and susceptible isolates. We found a much greater divers... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263198 Tue, 09 Feb 2010 00:00:00 +0100 3263198 http://www.medworm.com/index.php?rid=3263197&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145083%26dopt%3DAbstract Authors: Cantón E, Espinel-Ingroff A, Pemán J, Del Castillo L Anidulafungin, micafungin and caspofungin in vitro activity was evaluated by MIC and time-kill methods against Candida metapsilosis, C. orthopsilosis and C. parapsilosis. All echinocandins showed lower MICs (mean MICs 0.05-0.71 mg/L) and the highest killing rates (-0.06 to -0.05 CFU/mL/h) for C. metapsilosis and C. orthopsilosis than for C. parapsilosis (mean MICs 0.59-1.68 mg/L). Micafungin and anidulafungin killing rates were greater than that of caspofungin. None of the echinocandins had fungicidal activity against C. parapsilosis. PMID: 20145083 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263197 Tue, 09 Feb 2010 00:00:00 +0100 3263197 http://www.medworm.com/index.php?rid=3263196&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145084%26dopt%3DAbstract Authors: Garcia-Effron G, Chua DJ, Tomada JR, Dipersio J, Perlin DS, Ghannoum M, Bonilla H We studied three clinical isolates of Candida spp. (1 C. tropicalis and 2 C. glabrata ) isolated from patients with invasive candidiasis. The first isolate emerged during echinocandin treatment while the others after the same treatment. These strains harbored an amino acid substitution in Fksp never linked before with reduced echinocandin susceptibility in C. tropicalis or in C. glabrata. The molecular mechanism of reduced susceptibility was confirmed using a 1,3-beta-D-glucan synthase inhibition assay. PMID: 20145084 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263196 Tue, 09 Feb 2010 00:00:00 +0100 3263196 http://www.medworm.com/index.php?rid=3263195&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145085%26dopt%3DAbstract Authors: Girlich D, Poirel L, Nordmann P An Aeromonas allosaccharophila environmental isolate, recovered from the Seine river (Paris, France) produced a novel extended-spectrum beta-lactamase, PER-6, that shared 92% amino-acid identity with the closest beta-lactamase PER-2. The kinetic properties of PER-6 showed a slightly increased affinity for carbapenems. The blaPER-6 gene was chromosomally-located and bracketed by non-transposon related structures. PMID: 20145085 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263195 Tue, 09 Feb 2010 00:00:00 +0100 3263195 http://www.medworm.com/index.php?rid=3263194&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145086%26dopt%3DAbstract Authors: Ma C, Tran J, Gu F, Ochoa R, Li C, Sept D, Werbovetz K, Morrissette N The human parasite Toxoplasma gondii is sensitive to dinitroaniline compounds which selectively disrupt microtubules in diverse protozoa but which have no detectable effect on vertebrate host cell microtubules or other functions. Replication of wild type T. gondii is inhibited by 0.5-2.5 muM oryzalin, but mutant parasites harboring amino acid substitutions in the predicted dinitroaniline binding site confer resistance up to 40 muM oryzalin. However, the precise interaction between dinitroanilines and the binding site in alpha-tubulin remains unclear. We have investigated the activity of 12 dinitroanilines and the related compound amiprophos methyl on wild-type and dinitroaniline-resistant parasite lines that... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263194 Tue, 09 Feb 2010 00:00:00 +0100 3263194 http://www.medworm.com/index.php?rid=3263193&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145087%26dopt%3DAbstract We examined pfmdr1 and pfcrt in samples from Sifontes, Venezuela and integrated our findings with earlier work describing dhfr and dhps in these samples. We characterized pfmdr1 genotypes and copy number variation, pfcrt genotypes, and proximal microsatellites in 93 samples originating from 2003-2004 surveillance. Multicopy pfmdr1 was found in 12% of the samples. Two pfmdr1 alleles, Y184F/N1042D/D1246Y (37%) and Y184F/S1034C/N1042D/D1246Y (63%), were found. These alleles share ancestry and no evidence of strong selective pressure on mutations was found. Chloroquine resistant pfcrt alleles are fixed with two alleles: StctVMNT (91%) and SagtVMNT (9%). These alleles are associated with strong selection. There was also an association between pfcrt, pfmdr1, dhfr, and dhps genotypes/haplotypes. ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263193 Tue, 09 Feb 2010 00:00:00 +0100 3263193 http://www.medworm.com/index.php?rid=3263192&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145088%26dopt%3DAbstract ANTISTAPHYLOCOCCAL ACTIVITY OF ACHN-490 TESTED ALONE AND IN COMBINATION WITH OTHER AGENTS BY TIME-KILL ASSAY. Antimicrob Agents Chemother. 2010 Feb 9; Authors: Lin G, Ednie LM, Appelbaum PC Synergy time-kill studies of 47 MRSA strains with differing resistance phenotypes showed that combinations of sub-inhibitory concentrations of ACHN-490 and daptomycin yielded synergy against 43/47 strains at 24 h, while the combination was indifferent against the remaining 4 strains. ACHN-490 and ceftobiprole showed synergy in 17/47 strains tested at 24 h, while 6/47 strains showed synergy for sub-inhibitory combinations of ACHN-490 and linezolid. PMID: 20145088 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263192 Tue, 09 Feb 2010 00:00:00 +0100 3263192 http://www.medworm.com/index.php?rid=3263191&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20145089%26dopt%3DAbstract Authors: Toth M, Frase H, Chow JW, Smith C, Vakulenko SB Directed evolution by random PCR-mutagenesis of the gene for the aminoglycoside 2"-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes resulting in elevated levels of resistance to amikacin and isepamicin but not to other aminoglycoside antibiotics. Increases in the activities of the mutant phosphotransferases for isepamicin are the result of decreases in Km values, while improved catalytic efficiency for amikacin is the result of both a decrease in Km values and an increase in turnover of antibiotic. Enzymes with R92H, D268N, and D268N single amino acid substitutions did not result in elevated MICs for aminoglycosides. PMID: 20145089 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3263191 Tue, 09 Feb 2010 00:00:00 +0100 3263191 http://www.medworm.com/index.php?rid=3236839&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20123998%26dopt%3DAbstract Authors: Galarza PG, Abad R, Fernández Canigia L, Buscemi L, Pagano I, Oviedo C, Vázquez JA Although azithromycin (1 g orally in a single dose) is not recommended for treating gonorrhea, it is still used in some parts of the world and it is widely used either to treat Chlamydia trachomatis infections or in combination with expanded expectrum cephalosporins to treat simultaneous infections by both chlamydia and gonococci (7).... PMID: 20123998 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236839 Mon, 01 Feb 2010 00:00:00 +0100 3236839 http://www.medworm.com/index.php?rid=3236838&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20123999%26dopt%3DAbstract Authors: Jiang SS, Liu MC, Teng LJ, Wang WB, Hsueh PR, Liaw SJ Proteus mirabilis is naturally resistant to polymyxin B (PB). To investigate the underlying mechanisms, Tn5 mutagenesis was performed and a mutant exhibiting increased PB susceptibility was isolated. The mutant was found to have Tn5 inserted into the pmrIp gene, a gene which may encode a UDP-glucuronic acid decarboxylase. In other bacteria, pmrI belongs to the seven-gene pmrF operon which is involved in a lipopolysaccharide (LPS) modification. While the pmrIp-knockout mutant had a wild-type LPS profile and produced similar amounts of LPS as did the wild type, LPS of the knockout mutant had higher PB-binding activity than that of the wild type. PB could induce alterations of LPS in the wild type but not in the pmrIp-knockout... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236838 Mon, 01 Feb 2010 00:00:00 +0100 3236838 http://www.medworm.com/index.php?rid=3236837&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124000%26dopt%3DAbstract Authors: Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ Attenuated activity of echinocandin antifungals at high concentrations, known as the "paradoxical effect", is a well-established phenomenon in Candida albicans and Aspergillus fumigatus. In the yeast C. albicans, upregulation of chitin biosynthesis via the PKC, HOG, and Ca(2+)/calcineurin signaling pathways is an important cell wall stress response that permits growth in the presence of high concentrations of echinocandins. However, nothing is known of the molecular mechanisms regulating the mould A. fumigatus and its paradoxical response to echinocandins. Here we show that laboratory strain of A. fumigatus and five of seven clinical A. fumigatus isolates tested display varying magnitudes of paradoxical g... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236837 Mon, 01 Feb 2010 00:00:00 +0100 3236837 http://www.medworm.com/index.php?rid=3236836&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124001%26dopt%3DAbstract Authors: Gatanaga H, Ode H, Hachiya A, Hayashida T, Sato H, Oka S Etravirine (ETV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) introduced recently for salvage antiretroviral treatment after the emergence of NNRTI resistant human immunodeficiency virus type 1 (HIV-1). Following its introduction, two naturally-occurring mutations in HIV-1 reverse transcriptase (RT); V106I and V179D, were listed as ETV resistance-associated mutations. However, the effect of these mutations on the development of NNRTI resistance has not been analyzed yet. To select high NNRTI resistant HIV-1 in vitro, monoclonal HIV-1s harboring each of V106I and V179D (HIV-1V106I and HIV-1V179D) were propagated in the presence of increasing concentrations of efavirenz (EFV). Interestingly... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236836 Mon, 01 Feb 2010 00:00:00 +0100 3236836 http://www.medworm.com/index.php?rid=3236835&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124002%26dopt%3DAbstract Authors: Cuesta I, Bielza C, Cuenca-Estrella M, Larrañaga P, Rodríguez-Tudela JL EUCAST and CLSI have established different breakpoints for fluconazole and Candida spp. However, the reference methodologies employed to obtain the MICs provide similar results. The aim of this work was to apply supervised classification algorithms to analyze the clinical data used by CLSI to establish fluconazole breakpoints for Candida infections and compare them with the results obtained with the dataset used to set up fluconazole EUCAST breakpoints where the MIC value for detecting failures was > 4 mg/L with sensitivity of 87%, false-positive rate of 8% and area under the ROC curve of 0.89. Five supervised classifiers (J48, CART, OneR, Naïve Bayes and Simple Logistic) were used to ana... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236835 Mon, 01 Feb 2010 00:00:00 +0100 3236835 http://www.medworm.com/index.php?rid=3236834&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124003%26dopt%3DAbstract Authors: Endimiani A, Bethel C, Choudhary Y, Bonomo RA The widespread dissemination of blaKPC-possessing Klebsiella pneumoniae (KpKPC) isolates represents a serious threat for hospitalized patients (4, 8).... PMID: 20124003 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236834 Mon, 01 Feb 2010 00:00:00 +0100 3236834 http://www.medworm.com/index.php?rid=3236833&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124004%26dopt%3DAbstract Authors: De Luca F, Giraud-Morin C, Rossolini GM, Docquier JD, Fosse T Aeromonas enteropelogenes (formerly A. tructi) was described as an ampicillin-susceptible and cephalothin-resistant Aeromonas species, suggesting the production of a cephalosporinase. Strain ATCC 49803 was susceptible to amoxicillin, cefotaxime and imipenem but resistant to cefazolin (MICs 2, 0.032, 0.125 and >256 mug/ml, respectively) and produced an inducible beta-lactamase. CTX-resistant mutants (MIC, 32 mug/ml) could be selected in vitro that showed a constitutive beta-lactamase production. The gene coding for the cephalosporinase of A. enteropelogenes ATCC49803 was cloned and its biochemical properties investigated. E. coli transformants showing resistance to various beta-lactams carried a 3.5-kb plasmid ins... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236833 Mon, 01 Feb 2010 00:00:00 +0100 3236833 http://www.medworm.com/index.php?rid=3236832&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124005%26dopt%3DAbstract Conclusions In the presence of K65R, zidovudine and tenofovir are associated with similar reductions in HIV RNA levels. Given its tolerability, tenofovir may be the preferred agent over zidovudine even in the presence of the K65R mutation. PMID: 20124005 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236832 Mon, 01 Feb 2010 00:00:00 +0100 3236832 http://www.medworm.com/index.php?rid=3236831&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20124006%26dopt%3DAbstract Authors: Pannecouque C, Szafarowicz B, Volkova N, Bakulev V, Dehaen W, Mély Y, Daelemans D The human immunodeficiency virus type 1 (HIV-1) nucleocapsid p7 (NCp7) protein holds two highly conserved 'CCHC' zinc finger domains that are required for several phases of viral replication. Basic residues flank the zinc fingers and both determinants are required for high affinity binding to RNA. Several compounds were previously found to target the NCp7 by reacting with the sulfhydryl group of cystein residues from the zinc fingers. Here, we have identified an N,N'-bis(1,2,3-thiadiazol-5-yl)benzene-1,2-diamine (NV038) that efficiently blocks the replication of a wide spectrum of HIV-1, HIV-2 and SIV strains. Time-of-addition experiments indicate that NV038 interferes with a step of the vir... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3236831 Mon, 01 Feb 2010 00:00:00 +0100 3236831 http://www.medworm.com/index.php?rid=3213139&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100873%26dopt%3DAbstract Authors: Majchrzykiewicz JA, Lubelski J, Moll GN, Kuipers A, Bijlsma JJ, Kuipers OP, Rink R Recent studies showed that the nisin modification machinery can successfully dehydrate serines and threonines and introduce lanthionine rings in small peptides that are fused to the nisin leader sequence. This opens up exciting possibilities to produce and engineer larger antimicrobial peptides in vivo. Here, we demonstrate the exploitation of the class I nisin production machinery to generate, modify and secrete biologically active, previously not yet isolated and characterized class II two-component lantibiotics that have no sequence homology to nisin. The nisin synthesis machinery, composed of the modification enzymes NisB and NisC and the transporter NisT, was used to modify and secrete a pu... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213139 Mon, 25 Jan 2010 00:00:00 +0100 3213139 http://www.medworm.com/index.php?rid=3213138&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100874%26dopt%3DAbstract Authors: Morello J, Soriano V, Barreiro P, Medrano J, Madejón A, González-Pardo G, Jiménez-Nácher I, González-Lahoz J, Rodríguez-Novoa S The influence of ribavirin trough concentrations (RBV Ctrough) on the risk of HCV relapse was retrospectively analysed in 99 HIV/HCV-coinfected patients who achieved end of treatment response with pegylated interferon-alpha plus weight-based RBV. The independent predictors (OR [CI95%]) of HCV relapse were RBV plasma Ctrough<2.5 mug/mL (4.5 [1.3-15.5]), baseline serum HCV-RNA (2.5 [1.2-5.1]), and HCV genotypes 1/4 (13.3 [2.6-66.7]). Monitoring of RBV Ctrough may permit early adjustment fo RBV dosage to avoid HCV relapse. PMID: 20100874 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherap... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213138 Mon, 25 Jan 2010 00:00:00 +0100 3213138 http://www.medworm.com/index.php?rid=3213137&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100875%26dopt%3DAbstract Authors: Bortolaia V, Guardabassi L, Trevisani M, Bisgaard M, Venturi L, Bojesen AM We characterized 67 Escherichia coli isolates with reduced susceptibility to cefotaxime or ceftiofur obtained from healthy broilers housed in five Italian farms. The blaCTX-M-1, blaCTX-M-32 and blaSHV-12 beta-lactamase genes were identified on IncI1, IncN or IncFIB plasmids. Considerable genetic diversity was detected among the ESBL-producing isolates, and we identified indistinguishable strains in unrelated farms and indistinguishable plasmids in genetically unrelated strains. The detection of highly mobile plasmids suggests a potential animal reservoir for beta-lactamase genes. PMID: 20100875 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213137 Mon, 25 Jan 2010 00:00:00 +0100 3213137 http://www.medworm.com/index.php?rid=3213136&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100876%26dopt%3DAbstract Authors: Miyazaki T, Yamauchi S, Inamine T, Nagayoshi Y, Saijo T, Izumikawa K, Seki M, Kakeya H, Yamamoto Y, Yanagihara K, Miyazaki Y, Kohno S A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell-wall damaging agents, and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress. PMID: 20100876 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213136 Mon, 25 Jan 2010 00:00:00 +0100 3213136 http://www.medworm.com/index.php?rid=3213135&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100877%26dopt%3DAbstract Authors: Citron DM, Tyrrell KL, Merriam V, Goldstein EJ The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and 4 comparator antimicrobials were determined against anaerobic bacteria. Against gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin/clavulanate and 4 to 8 times greater than ceftriaxone. Against gram-negative organisms, ceftaroline showed good activity against beta-lactamase-negative strains, but not against the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft-tissue infections. PMID: 20100877 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213135 Mon, 25 Jan 2010 00:00:00 +0100 3213135 http://www.medworm.com/index.php?rid=3213134&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100878%26dopt%3DAbstract In conclusion, linezolid was consistently efficient against S. aureus strains. Emergence of E. faecalis resistant mutants was probably favored by the rapid decline of linezolid concentrations against a strong mutator, a phenotype less exceptional in E. faecalis than in S. aureus. PMID: 20100878 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213134 Mon, 25 Jan 2010 00:00:00 +0100 3213134 http://www.medworm.com/index.php?rid=3213133&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100879%26dopt%3DAbstract This study compared the activity of finafloxacin, a novel fluoroquinolone which shows enhanced activity under acidic pH, and ciprofloxacin, against Acinetobacter baumannii under standard conditions (pH 7.2) and at a pH of 5.8. Overall, finafloxacin demonstrated superior activity to ciprofloxacin under acidic conditions. Furthermore, finafloxacin showed comparable activity to ciprofloxacin at pH 7.2. Hence, finafloxacin could be a promising new antimicrobial agent for the treatment of A. baumannii infections at acidic body compartments. PMID: 20100879 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213133 Mon, 25 Jan 2010 00:00:00 +0100 3213133 http://www.medworm.com/index.php?rid=3213132&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20100880%26dopt%3DAbstract Authors: Yoneyama H, Akiba K, Hori H, Ando T, Nakae T Pseudomonas aeruginosa is equipped with the Sec and Tat protein secretion systems, which translocate the xenobiotic transporter, MexAB-OprM, and the pathogenic factor, phospholipase C (PlcH), respectively. When the signal sequence of MexA was substituted with that of PlcH, the hybrid protein was successfully expressed and recovered from the periplasmic fraction, suggesting that the hybrid protein had been translocated across the inner membrane. MexA-deficient cells harboring the plasmid carrying the plcH-mexA fusion gene showed antibiotic resistance comparable to that of the wild-type cells. This result suggested that MexA secreted via the Tat-machinery was properly assembled and functioned as a subunit of the MexAB-OprM efflux pump... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3213132 Mon, 25 Jan 2010 00:00:00 +0100 3213132 http://www.medworm.com/index.php?rid=3194691&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086140%26dopt%3DAbstract Authors: Najafzadeh MJ, Badali H, Illnait-Zaragozi MT, De Hoog GS, Meis JF Clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested in vitro against eight antifungal drugs. The resulting MIC90s across all strains (n=55) were in increasing order posaconazole (0.063 mug/ml), itraconazole (0.125 mug/ml), isavuconazole (0.25 mug/ml), voriconazole (0.5 mug/ml), amphotericin B (2mug/ml), caspofungin (2mug/ml), anidulafungin (2mug/ml), and fluconazole (32 mug/ml). PMID: 20086140 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194691 Tue, 19 Jan 2010 00:00:00 +0100 3194691 http://www.medworm.com/index.php?rid=3194690&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086141%26dopt%3DAbstract Authors: San Millan A, Garcia-Cobos S, Escudero JA, Hidalgo L, Gutierrez B, Carrilero L, Campos J, Gonzalez-Zorn B Plasmid pB1000 is a mobilizable replicon bearing the blaROB-1 ss-lactamase gene that we have recently described in Haemophilus parasuis and Pasteurella multocida animal isolates. Here, we report presence of pB1000 and a derivate plasmid, pB1000', in four H. influenzae clinical isolates from human origin. Pulsed-field gel electrophoresis showed unrelated patterns in all strains, indicating that existence of pB1000 in H. influenzae isolates is not the consequence of clonal dissemination. The replicon can be transferred both by transformation and conjugation into H. influenzae, giving rise to ampicillin (MIC > 64 mug/ml) and cefaclor (MIC > 64 mug/ml) resistant recipien... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194690 Tue, 19 Jan 2010 00:00:00 +0100 3194690 http://www.medworm.com/index.php?rid=3194689&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086142%26dopt%3DAbstract Authors: Nguyen KT, He X, Alexander DC, Li C, Gu JQ, Mascio C, Van Praagh A, Mortin L, Chu M, Silverman JA, Brian P, Baltz RH Daptomycin is a cyclic lipopeptide antibiotic approved for treatment of skin and skin structure infections caused by Gram-positive pathogens, and bacteremia and right-sided endocarditis caused by Staphylococcus aureus. Daptomycin failed to meet non-inferiority criteria for treatment of community acquired pneumonia, likely due to sequestration in pulmonary surfactant. Many analogues of daptomycin were generated by combinatorial biosynthesis, but only two displayed improved activity in the presence of bovine surfactant, and neither was as active as daptomycin in vitro. In the present study, we generated hybrid molecules of the structurally related lipopeptide A541... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194689 Tue, 19 Jan 2010 00:00:00 +0100 3194689 http://www.medworm.com/index.php?rid=3194688&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086143%26dopt%3DAbstract Authors: Imboden M, Riggs MW, Schaefer DA, Homan EJ, Bremel RD At the current time there are no completely effective treatments available for Cryptosporidium parvum infections in humans and livestock. Based on previous data showing the neutralizing potential of a panel of monoclonal antibodies developed against C. parvum, and innate immune peptides and enzymes having anticryptosporidial activity, we engineered several of these antibodies into antibody-biocide fusions. We hypothesized that the combination of high affinity antibody targeting with innate immune molecule-mediated killing would result in a highly effective new antiprotozoal agent. To test this we expressed antibody-biocide fusions in a mammalian cell culture system and used the resulting products for in vitro and in vivo ef... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194688 Tue, 19 Jan 2010 00:00:00 +0100 3194688 http://www.medworm.com/index.php?rid=3194687&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086144%26dopt%3DAbstract Authors: De Leo L, Di Toro N, Decorti G, Malusà N, Ventura A, Not T The pharmacokinetics of the aminoglycoside tobramycin was evaluated after oral administration to fed or fasting (15 h) mice. As expected, in normal feeding conditions, oral absorption was negligible, however, fasting induced a dramatic increase in tobramycin bioavailability. The dual sugar test with lactulose and L-rhamnose confirmed an increased small bowel permeability via the paracellular route in fasting animals. When performing experiments aimed at increasing the oral bioavailability of hydrophilic compounds, timing of fasting should be extremely accurate. PMID: 20086144 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194687 Tue, 19 Jan 2010 00:00:00 +0100 3194687 http://www.medworm.com/index.php?rid=3194686&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086145%26dopt%3DAbstract Authors: Shamir ER, Warthan M, Brown SP, Nataro JP, Guerrant RL, Hoffman PS Enteroaggregative Escherichia coli (EAEC) strains have emerged as a common cause of persistent diarrhea and malnutrition among children and HIV-infected persons. During infection, EAEC typically adheres to the intestinal mucosa via fimbrial adhesins that results in a characteristic aggregative pattern. Here we investigated whether the broad spectrum antiparasitic and anti-diarrheal drug nitazoxanide (NTZ) might be active against EAEC in vitro. While E. coli strains were resistant to NTZ in rich LB medium (MIC >64 mug/ml), the drug was slightly inhibitory in a minimal medium supplemented with glucose (MinA-G medium, MIC approximately 32 mug/ml). NTZ also inhibited biofilm production by strain EAEC 042 in both... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194686 Tue, 19 Jan 2010 00:00:00 +0100 3194686 http://www.medworm.com/index.php?rid=3194685&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086146%26dopt%3DAbstract Authors: Drawz SM, Bethel CR, Doppalapudi VR, Sheri A, Pagadala SR, Hujer AM, Skalweit MJ, Anderson VE, Chen SG, Buynak JD, Bonomo RA OXA beta-lactamases are largely responsible for beta-lactam resistance in Acinetobacter spp. and Pseudomonas aeruginosa, two of the most difficult to treat nosocomial pathogens. In general, the beta-lactamase inhibitors used in clinical practice (clavulanic acid, sulbactam, and tazobactam) demonstrate poor activity against class D beta-lactamases. To overcome this challenge, we explored the efficacy of beta-lactamase inhibitors of the C2/3-substituted penicillin and cephalosporin sulfone families against OXA-1, extended-spectrum (OXA-10, -14 and -17), and carbapenemase-type (OXA-24/40) class D beta-lactamases. Three C2-substituted penicillin sulfone comp... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194685 Tue, 19 Jan 2010 00:00:00 +0100 3194685 http://www.medworm.com/index.php?rid=3194684&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086147%26dopt%3DAbstract Authors: Tsubakishita S, Kuwahara-Arai K, Baba T, Hiramatsu K Macrococcus is a bacterial genus closely related to Staphylococcus, which is typically isolated from animal skin and products. Genome analysis of a multidrug-resistant Macrococcus caseolyticus strain JCSC5402 isolated from chicken previously led to the identification of plasmid pMCCL2 carrying a transposon containing an unusual form of mec-gene complex (mecAm-mecR1m-mecIm-blaZm). In M. caseolyticus strain JCSC7096, this mec-transposon containing the mec-gene complex (designated Tn6045 in this study) was found integrated downstream of orfX on the chromosome. Tn6045 of JCSC7096 was bracketed by the direct repeat sequences (DR) specifically recognized by cassette chromosome recombinase (CCR). A non-mecA-containing staphylococca... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194684 Tue, 19 Jan 2010 00:00:00 +0100 3194684 http://www.medworm.com/index.php?rid=3194683&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086148%26dopt%3DAbstract Authors: Maccallum DM, Coste A, Ischer F, Jacobsen MD, Odds FC, Sanglard D Principal resistance mechanisms to azole antifungals include the upregulation of multidrug transporters and modification of the target enzyme, a cytochrome P450 (Erg11) involved in the 14alpha-demethylation of ergosterol. These mechanisms are often combined in azole-resistant Candida albicans isolates recovered from patients. However, the precise contribution of individual mechanisms to C. albicans resistance to specific azoles has been difficult to establish because of the technical difficulties in genetic manipulation of this diploid species. Recent advances have made genetic manipulations easier and we therefore undertook the genetic dissection of resistance mechanisms in an azole-resistant clinical isolate. ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194683 Tue, 19 Jan 2010 00:00:00 +0100 3194683 http://www.medworm.com/index.php?rid=3194682&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086149%26dopt%3DAbstract Authors: Ptak RG, Gentry BG, Hartman TL, Watson KM, Osterling MC, Buckheit RW, Townsend LB, Drach JC Triciribine (TCN) is a tricyclic nucleoside that inhibits human immunodeficiency virus type 1 (HIV-1) replication by a unique mechanism not involving inhibition of enzymes directly involved in viral replication. This activity requires phosphorylation of TCN to its 5'-monophosphate by intracellular adenosine kinase. New testing against a panel of HIV and SIV isolates including low passage clinical isolates of selected subgroups of HIV-1, multi-drug resistant HIV-1, and HIV-2 has demonstrated that TCN has broad anti-retroviral activity. It was active in cell lines chronically infected with HIV-1 isolates in which the provirus was integrated into chromosomal DNA thereby indicating TCN inhi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194682 Tue, 19 Jan 2010 00:00:00 +0100 3194682 http://www.medworm.com/index.php?rid=3194681&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086150%26dopt%3DAbstract Authors: Gumbo T Arguably, one of the most common and consequential laboratory tests performed in the world is Mycobacterium tuberculosis susceptibility testing. M. tuberculosis resistance is defined by growth of >/=1% of bacillary inoculum on critical concentration of an antibiotic. The critical concentration was chosen based on inhibition of >/=95% of wild type isolates. Critical concentrations of isoniazid are either 0.2 or 1.0 mg/L, rifampin 1.0 mg/L, pyrazinamide 100 mg/L, ethambutol 5.0 mg/L, and fluoroquinolones 1.0 mg/L. However, the relevance of these concentrations to microbiologic and clinical outcomes is unclear. Critical concentrations were identified using the ability to achieve the antibiotic area under the concentration-time curve to minimum inhibitory concentrati... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194681 Tue, 19 Jan 2010 00:00:00 +0100 3194681 http://www.medworm.com/index.php?rid=3194680&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086151%26dopt%3DAbstract Authors: Pasca MR, Degiacomi G, Ribeiro AL, Zara F, De Mori P, Heym B, Mirrione M, Brerra R, Pagani L, Pucillo L, Troupioti P, Makarov V, Cole ST, Riccardi G The new antitubercular drug candidate, benzothiazinone (BTZ043), targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-beta-D-ribose 2'-epimerase. To monitor the potential development of BTZ resistance, a total of 240 sensitive and multi-drug resistant Mycobacterium tuberculosis clinical isolates, from four European hospitals, were surveyed for the presence of mutations in the dprE1 gene and for BTZ susceptibility. All 240 strains were susceptible thus establishing the baseline prior to the introduction of BTZ043 in clinical trials. PMID: 20086151 [PubMed - as supplied by publisher] (Source: Antimicrobial Agent... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194680 Tue, 19 Jan 2010 00:00:00 +0100 3194680 http://www.medworm.com/index.php?rid=3194679&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086152%26dopt%3DAbstract Authors: Steadman E, Raisch DW, Bennett CL, Esterly JS, Becker T, Postelnick M, McKoy JM, Trifilio S, Yarnold PR, Scheetz MH In April 2009 the FDA retracted a warning asserting that ceftriaxone and intravenous calcium products should not be co-administered in any patient to prevent precipitation events leading to end organ damage. Following this announcement, we sought to evaluate if the retraction was justified. A search of the FDA Adverse Event Reporting System was conducted to identify ceftriaxone/calcium interactions resulting serious adverse drug events. Ceftazidime/calcium was used as a comparator agent. One-hundred-four events with ceftriaxone/calcium and 99 events with ceftazidime/calcium were identified. Adverse drug events were recorded according to the listed description of ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194679 Tue, 19 Jan 2010 00:00:00 +0100 3194679 http://www.medworm.com/index.php?rid=3194678&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086153%26dopt%3DAbstract Authors: Daniel A, Euler C, Collin M, Chahales P, Gorelick K, Fischetti VA Staphylococcus aureus is the causative agent of several serious infectious diseases. Emergence of antibiotic-resistant S. aureus strains has resulted in significant treatment difficulties, intensifying the need for new antimicrobial agents. Toward this end, we have developed a novel chimeric bacteriophage (phage) lysin that is active against staphylococci including methicillin-resistant S. aureus (MRSA). The chimeric lysin (called ClyS) was obtained by fusing the N-terminal catalytic domain of the S. aureus Twort phage lysin with the C-terminal cell wall targeting domain from another S. aureus phage lysin (phiNM3), which displayed Staphylococcus-specific binding. ClyS was expressed in E. coli and the purified pr... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194678 Tue, 19 Jan 2010 00:00:00 +0100 3194678 http://www.medworm.com/index.php?rid=3194677&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086154%26dopt%3DAbstract The objective of the present study was to evaluate the effect of these PA-824 therapeutic aerosols on the extent of TB infection in the low inoculum aerosol infected guinea pig model. Four weeks after infection by the pulmonary route, animals received daily treatment for four weeks of either a high or a low dose of PA-824 dry powder aerosol. Animals received PA-824 cyclodextrin/lecithin suspensions orally as positive controls and those receiving placebo particles or no treatment were negative controls. The lungs and spleens of animals receiving the high dose of inhaled PA-824 particles exhibited a smaller degree of inflammation (indicated by wet tissue weights), bacterial burden and tissue damage (indicated by histopathology) than those of untreated or placebo animals. Treatment with oral ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194677 Tue, 19 Jan 2010 00:00:00 +0100 3194677 http://www.medworm.com/index.php?rid=3194676&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086155%26dopt%3DAbstract This study demonstrates for the first time that human NGAL does not only neutralize pathogen-derived virulence factors but that it can also effectively scavenge an iron-chelate complex abundant in the host. PMID: 20086155 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194676 Tue, 19 Jan 2010 00:00:00 +0100 3194676 http://www.medworm.com/index.php?rid=3194675&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086156%26dopt%3DAbstract Authors: Krakauer T, Buckley M, Issaq HJ, Fox SD Staphylococcal enterotoxins are potent activators for human T cells and cause lethal toxic shock. Rapamycin, an immunosuppressant, was tested for its ability to inhibit staphylococcal enterotoxin B (SEB)-induced activation of human peripheral blood mononuclear cells (PBMC) in vitro and toxin-mediated shock in mice. Stimulation of PMBC by SEB was effectively blocked by rapamycin as evidenced by the inhibition of TNFalpha, interleukin 1beta (IL-1beta), IL-6, IL-2, gamma interferon (IFNgamma), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and T-cell proliferation. In vivo, rapamycin protected 100% of mice from lethal shock, even when administered 24 h after intranasal SEB challen... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194675 Tue, 19 Jan 2010 00:00:00 +0100 3194675 http://www.medworm.com/index.php?rid=3194674&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086157%26dopt%3DAbstract Authors: Carrër A, Poirel L, Yilmaz M, Akan OA, Feriha C, Cuzon G, Matar G, Honderlick P, Nordmann P Eighteen carbapenem-resistant OXA-48-positive enterobacterial isolates recovered from Turkey, Lebanon, Egypt, France and Belgium were analyzed. In most isolates, a similar 70-kb plasmid carrying the carbapenemase gene blaOXA-48 was identified. That gene was either located within transposons Tn1999 or Tn1999.2, being themselves always inserted within the same gene. This work highlights the current plamid-mediated dissemination of the OXA-48 carbapenemase worldwide. PMID: 20086157 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194674 Tue, 19 Jan 2010 00:00:00 +0100 3194674 http://www.medworm.com/index.php?rid=3194673&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086158%26dopt%3DAbstract Authors: Moya B, Zamorano L, Juan C, Pérez JL, Ge Y, Oliver A CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. We evaluated the activity of CXA-101 against a highly challenging collection of beta-lactam-resistant P. aeruginosa mutants selected in vitro and after antipseudomonal treatment of Intensive Care Unit (ICU) patients. The in vitro mutants investigated included strains with multiple combinations of mutations leading to several degrees of AmpC overexpression [ampD, ampDh2, ampDh3, and dacB (PBP4)], and porin loss (oprD). CXA-101 remained active even against the AmpD-PBP4 double mutant (MIC= 2 mug/ml), that shows extremely high AmpC expression. Indeed, this mutant showed high-level resistance to all tested beta-lactams, except carbapenems, incl... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194673 Tue, 19 Jan 2010 00:00:00 +0100 3194673 http://www.medworm.com/index.php?rid=3194672&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086159%26dopt%3DAbstract Authors: Wang G, Watson KM, Peterkofsky A, Buckheit RW To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with EC50 concentrations < 10 muM and therapeutic indices (TI) up to 17. Furthermore, among the eight peptides (with identical amino acid composition but different sequences) generated by sequence shuffling of an aurein 1.2 analog, two had a TI twice that of the original sequence. Because antiviral peptides in the database have an arginine/lysine (R/K) ratio > 1, an increase in the Arg content in amphibian maximin H5, dermaseptin S9, and database-derived GLK-19 peptides improved their TIs. These examples demonstrate that the antimicrobial peptide database (AP... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194672 Tue, 19 Jan 2010 00:00:00 +0100 3194672 http://www.medworm.com/index.php?rid=3194671&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086160%26dopt%3DAbstract Authors: Brown EM, Fisman DN, Drews SJ, Dolman S, Rawte P, Brown S, Jamieson F Neisseria meningitidis has been relatively slow to acquire resistance to penicillin. We previously reported an increase in the incidence of invasive meningococcal disease (IMD) strains with decreased susceptibility to penicillin (DSP) in Ontario. Our objectives were to evaluate trends in IMD-DSP; to identify case-level predictors of IMD-DSP; and to evaluate the relationship between DSP, bacterial phenotype, and likelihood of fatal outcome. All IMD derived isolates received in Ontario between 2000 and 2006 were submitted to the Public Health Laboratory, Toronto for confirmation, serogroup determination, and susceptibility testing. Isolates were considered to be IMD-DSP if penicillin MIC was >/= 0.125 mug/m... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194671 Tue, 19 Jan 2010 00:00:00 +0100 3194671 http://www.medworm.com/index.php?rid=3194670&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086161%26dopt%3DAbstract We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The liposomal amphotericin B AUCpleural fluid to AUCserum ratio over 24 hours was 9.4% with pleural fluid concentrations of 2.12 to 4.91 mcg/ml. Given the relatively low intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema. PMID: 20086161 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194670 Tue, 19 Jan 2010 00:00:00 +0100 3194670 http://www.medworm.com/index.php?rid=3194669&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086162%26dopt%3DAbstract Authors: Karunajeewa HA, Salman S, Mueller I, Baiwog F, Gomorrai S, Law I, Page-Sharp M, Rogerson S, Siba P, Ilett KF, Davis TM In order to determine the pharmacokinetic disposition of chloroquine (CQ) and its active metabolite, desethylchloroquine (DECQ) when administered as intermittent presumptive treatment in pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched non-pregnant women were administered three daily doses of 450 mg CQ (8.5 mg/kg/day) in addition to a single dose of sulfadoxine-pyrimethamine. Blood was taken at baseline and 1, 2, 4, 6, 12, 18, 24, 30, 48 and 72 h, and at 7, 10, 14, 28 and 42 days post-treatment in all women. Plasma was subsequently assayed for CQ and DECQ by high performance liquid chroma... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194669 Tue, 19 Jan 2010 00:00:00 +0100 3194669 http://www.medworm.com/index.php?rid=3194668&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086163%26dopt%3DAbstract Authors: Kumagai T, Koyama Y, Oda K, Noda M, Matoba Y, Sugiyama M In the present study, we successfully cloned a 21-kb DNA fragment containing a D-cycloserine (DCS) biosynthetic gene cluster from a DCS-producing Streptomyces (S.) lavendulae, ATCC11924. The putative gene cluster consists of 10 open reading frames (ORFs), designated dcsA to dcsJ. This cluster includes two ORFs encoding D-alanyl-D-alanine ligase (dcsI) and a putative membrane protein (dcsJ) as the self-resistance determinants of the producer organism, which were indicated by our previous works. When the 10 orfs were introduced into DCS-non-producing S. lividans 66 as a heterologous host cell, the transformant acquired DCS productivity. This reveals that the introduced genes are responsible for the biosynthesis of DCS. As ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194668 Tue, 19 Jan 2010 00:00:00 +0100 3194668 http://www.medworm.com/index.php?rid=3194667&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086164%26dopt%3DAbstract This study aimed at elucidating the physiological basis of bacterial antibiotic tolerance. Using a combined phenotypic and gene knockout approach, exogenous nutrient composition was identified as a crucial environmental factor which could mediate progressive development of tolerance with markedly varied drug specificity and sustainability. Deprivation of amino acids was a prerequisite for tolerance formation, conferring condition-specific phenotypes against inhibitors of cell wall synthesis and DNA replication (ampicillin and ofloxacin respectively) according to the relative abundance of ammonium salts, phosphate, and nucleobases. Upon further depletion of glucose, this variable phase consistently evolved into a sustainable mode, along with enhanced capacity to withstand the effect of the ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194667 Tue, 19 Jan 2010 00:00:00 +0100 3194667 http://www.medworm.com/index.php?rid=3194666&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20086165%26dopt%3DAbstract We examined the prevalence, mechanism and susceptibility of MDR [resistant to >/= 3 classes of anti-pseudomonal agent (penicillins/cephalosporins, carbapenems, quinolones and aminoglycosides)] P. aeruginosa isolates obtained from a large, university-affiliated hospital. Among 235 non-repeat bloodstream isolates screened between 2005 and 2007, 33 isolates (from 20 unique patients) were found to be MDR (crude prevalence rate = 14%). All isolates were resistant to carbapenems and quinolones, 91% were resistant to penicillins/cephalosporins, and 21% were resistant to the aminoglycosides. Using the first available isolate for each bacteremia episode (n=18), 13 distinct clones were revealed by rep-PCR. Western blotting revealed 8 isolates (44%) to have MexB over-expression. Production of a ca... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3194666 Tue, 19 Jan 2010 00:00:00 +0100 3194666 http://www.medworm.com/index.php?rid=3172541&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065048%26dopt%3DAbstract Authors: Liu A, Tran L, Becket E, Lee K, Chinn L, Park E, Tran K, Miller JH We have defined a "sensitivity profile" for 22 antibiotics by extending previous work that tested the entire KEIO collection of close to 4,000 single gene knockouts in E. coli for increased susceptibility to one of fourteen different antibiotics (ciprofloxacin, CIP; rifampicin, RIF, vancomycin, VAN, ampicillin, AMP; sulfamethoxazole, SFX, gentamicin, GEN; metronidazole, MTR; streptomycin, STR; fusidic Acid, FUS; tetracycline, TET; chloramphenicol, CHL; nitrofurantoin, NIT; erythromycin, ERY; and triclosan, TRI). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display si... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172541 Mon, 11 Jan 2010 00:00:00 +0100 3172541 http://www.medworm.com/index.php?rid=3172540&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065049%26dopt%3DAbstract Authors: Niesters HG, Zoulim F, Pichoud C, Buti M, Shapiro F, D'Heuvaert N, Celis L, Doutreloigne J, Sablon E HBV antiviral drug resistance mutations prevent successful outcome of treatment and lead to worsening of liver disease. Detection of its emergence permits opportune treatment with alternative drugs. Unfortunately, the use of newly approved antivirals, including adefovir dipivoxil, emtricitabine, and telbivudine is also associated with the development of drug resistance, albeit to a lesser extent than lamivudine. To assess the performance characteristics (sensitivity, accuracy) of an updated drug-resistance test, the INNO-LiPA HBV DR v2, which includes mutations associated with lamivudine, adefovir, emtricitabine, and telbivudine resistance, and compare the results with consensu... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172540 Mon, 11 Jan 2010 00:00:00 +0100 3172540 http://www.medworm.com/index.php?rid=3172539&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065050%26dopt%3DAbstract Authors: Khlif M, Bogreau H, Michel-Nguyen A, Ayadi A, Ranque S Multilocus microsatellite polymorphisms in 27 clinical Candida albicans isolates were found to be clearly unrelated to in-vitro paradoxical growth or trailing effect with caspofungin. These findings suggest that such in vitro phenotypes are either gained or lost too rapidly to be predicted by more stable genomic markers. PMID: 20065050 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172539 Mon, 11 Jan 2010 00:00:00 +0100 3172539 http://www.medworm.com/index.php?rid=3172538&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065051%26dopt%3DAbstract Authors: Nsobya SL, Kiggundu M, Nanyunja S, Joloba M, Greenhouse B, Rosenthal PJ The control of malaria is challenged by resistance of Plasmodium falciparum to multiple drugs. New combination regimens are now advocated for the treatment of uncomplicated falciparum malaria, but the extent of resistance to newer agents is incompletely understood. We measured the in vitro sensitivity of P. falciparum parasites cultured from children enrolled in a drug efficacy trial in Kampala, Uganda from 2006-2008. Sensitivities were measured by comparing levels of histidine rich protein-2 in parasites incubated with different concentrations of drugs with those in untreated controls. The cultured parasites exhibited a wide range of sensitivities to chloroquine (CQ), monodesethylamodiaquine (MDAQ), the m... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172538 Mon, 11 Jan 2010 00:00:00 +0100 3172538 http://www.medworm.com/index.php?rid=3172537&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065052%26dopt%3DAbstract Authors: Binet R, Bowlin AK, Maurelli AT, Rank RG Azithromycin (AZM) is a major drug used in the treatment and prophylaxis of infections caused by Chlamydia, yet no significant clinical resistance has been reported for these obligate intracellular bacteria. Nevertheless, spontaneous AZM resistance (AZM(R)) arose in vitro at frequencies ranging from 3 x 10(-8) to 8 x 10(-10) for clonal isolates of C. caviae which is a natural pathogen of guinea pigs. Sequencing of the unique 23S rRNA gene copy in 44 independent AZM(R) isolates identified single mutations at positions A2058 or A2059 (Escherichia coli numbering system). While SP6AZ1 (A2058C) and SP6AZ2 (A2059C) AZM(R) mutants showed growth defects in cell culture and were less pathogenicin the guinea pig ocular infection model compared to... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172537 Mon, 11 Jan 2010 00:00:00 +0100 3172537 http://www.medworm.com/index.php?rid=3172536&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065053%26dopt%3DAbstract Authors: Cairns M, Cisse B, Sokhna C, Cames C, Simondon K, Ba EH, Trape JF, Gaye O, Greenwood BM, Milligan PJ Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body-weight and mild adverse events (AEs), and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age, the other by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increase... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172536 Mon, 11 Jan 2010 00:00:00 +0100 3172536 http://www.medworm.com/index.php?rid=3172535&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065054%26dopt%3DAbstract Authors: Wiederhold NP, Najvar LK, Bocanegra R, Graybill JR, Patterson TF Invasive fusariosis is a highly aggressive fungal infection associated with high mortality in heavily immunocompromised patients. Although posaconazole is efficacious as salvage therapy against infections caused by Fusarium species, concerns remain regarding this agent in the setting of reduced potency. To evaluate the efficacy of posaconazole as treatment or prophylaxis against invasive fusariosis caused by F. solani, we utilized a neutropenic murine model of disseminated disease. ICR mice were administered escalating doses of posaconazole (6.25, 12.5, 25, or 50 mg/kg BID) by oral gavage beginning 2 days prior to inoculation in the prophylaxis studies or beginning12 hours after inoculation as treatment. Therapy ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172535 Mon, 11 Jan 2010 00:00:00 +0100 3172535 http://www.medworm.com/index.php?rid=3172534&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065055%26dopt%3DAbstract In conclusion, our data demonstrated correlation between prescription of and gram-negative resistance to several but not all key antimicrobial agents in Singapore hospitals. In areas where gram-negative resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates. PMID: 20065055 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172534 Mon, 11 Jan 2010 00:00:00 +0100 3172534 http://www.medworm.com/index.php?rid=3172533&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065056%26dopt%3DAbstract Authors: Kotsakis SD, Papagiannitsis CC, Tzelepi E, Legakis NJ, Miriagou V, Tzouvelekis LS GES-13 beta-lactamase, a novel GES variant possessing Lys-104 and Asn-170, was identified in Pseudomonas aeruginosa. blaGES-13 was the single gene cassette of a class 1 integron probably located in the chromosome. GES-13 efficiently hydrolyzed broad-spectrum cephalosporins and aztreonam. Imipenem was a potent inhibitor of GES-13 but was not hydrolyzed at measurable rates. PMID: 20065056 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172533 Mon, 11 Jan 2010 00:00:00 +0100 3172533 http://www.medworm.com/index.php?rid=3172532&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065057%26dopt%3DAbstract Authors: Xu X, Cai L, Xiao M, Kong F, Oftadeh S, Zhou F, Gilbert GL Macrolide resistance in Streptococcus pneumoniae has emerged as an important clinical problem, worldwide, over the past decade. The aim of this study was to analyze the phenotypes (serotype, antibiotic susceptibility), genotypes (multilocus sequence type [MLST] and antibiotic resistance gene/transposon profiles) among the 31%, of invasive isolates (102/328) from children, in New South Wales Australia in 2005, which were resistant to erythromycin. Three serotypes - 19F (47; 46%), 14 (27; 26%), and 6B (12; 12%) - accounted for 86 (84%) of these 102 isolates. Seventy four (73%) isolates had the MLSB resistance phenotype and carried Tn916 transposons (most commonly Tn6002); of these, 73 (99%) contained the erythromycin rib... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172532 Mon, 11 Jan 2010 00:00:00 +0100 3172532 http://www.medworm.com/index.php?rid=3172531&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065058%26dopt%3DAbstract Authors: Lauderdale TL, Shiau YR, Lai JF, Chen HC, King CH The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, and Neisseria gonorrhoeae and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than moxifloxacin against these pathogens including ciprofloxacin-resistant methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae. PMID: 20065058 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemothera... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172531 Mon, 11 Jan 2010 00:00:00 +0100 3172531 http://www.medworm.com/index.php?rid=3172530&cid=s_37538_77_f&fid=37538&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20065059%26dopt%3DAbstract Authors: Bulitta JB, Landersdorfer CB, Hüttner SJ, Drusano GL, Kinzig M, Holzgrabe U, Stephan U, Sörgel F Despite promising activity against Pseudomonas aeruginosa and Burkholderia cepacia, the pharmacokinetics (PK) of ceftazidime has not yet been compared between cystic fibrosis (CF) patients and healthy volunteers in one study by population PK methodology. We assessed the population PK and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints of ceftazidime in CF-patients and healthy volunteers. Eight CF-patients (total body weight, WT = 42.9 +/- 18.4kg, average +/- SD) and seven healthy volunteers (WT = 66.2 +/- 4.9 kg) received 2g ceftazidime as 5-min intravenous infusion. HPLC was used for drug analysis and NONMEM (results reported), S-Adapt, and NPAG for parametric and no... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=3172530 Mon, 11 Jan 2010 00:00:00 +0100 3172530