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. Thu, 09 Feb 2012 21:34:53 +0100 http://www.medworm.com/index.php?rid=5619714&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%3D22252797%26dopt%3DAbstract Authors: Nordmann P, Boulanger AE, Poirel L Abstract A clinical Escherichia coli isolate resistant to all β-lactams including carbapenems expressed a novel metallo-β-lactamase (MBL) NDM-4 differing from NDM-1 by a single amino acid substitution (Met154Leu). NDM-4 possessed increased hydrolytic activity toward carbapenems and several cephalosporins as compared to NDM-1. This amino-acid substitution was not located into the known active sites of NDM-1 indicating that remote amino-acid subtitutions might also play a role in the extended activity of this MBL. PMID: 22252797 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619714 Tue, 17 Jan 2012 05:00:00 +0100 5619714 http://www.medworm.com/index.php?rid=5619713&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%3D22252798%26dopt%3DAbstract Authors: Samara E, Shaw JP, Barriere SL, Wong SL, Worboys P Abstract A population pharmacokinetic model of telavancin, a lipoglycopeptide antibiotic, was developed and used to identify sources of inter-individual variability. Data were obtained from healthy subjects (seven phase 1 studies), patients with complicated skin and skin-structure infections (cSSSI; two phase 2 and two phase 3 studies), and patients with hospital-acquired pneumonia (HAP; two phase 3 studies). A two-compartment open model with zero order input best fit the telavancin data from healthy individuals and patients with cSSSI or HAP. Telavancin clearance was highly correlated with renal function and, to a lesser extent, to body weight. Other covariates were related to at least one parameter in cSSSI (gender, bact... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619713 Tue, 17 Jan 2012 05:00:00 +0100 5619713 http://www.medworm.com/index.php?rid=5619712&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%3D22252799%26dopt%3DAbstract This study characterized the pharmacokinetic/pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved telavancin renal dose adjustment schemes. A previously published two compartment open model with first-order elimination and a combined additive and proportional residual error model derived from 749 adult subjects in 11 clinical trials was used to simulate the individual concentration-time profiles for 10,260 subjects (NONMEM). The dosing regimens simulated were: 10 mg/kg once-daily for individuals with CL(CR) > 50 mL/min, 7.5 mg/kg once-daily for individuals with CL(CR) between 30 and 50 mL/min, and 10 mg/kg every two days for those with CL(CR) < 30 mL/min. The AUC under one dosing interval (AUC(τ)) was computed as dose/CL. The probability of achieving an AUC(τ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619712 Tue, 17 Jan 2012 05:00:00 +0100 5619712 http://www.medworm.com/index.php?rid=5619711&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%3D22252800%26dopt%3DAbstract Authors: Betuela I, Bassat Q, Kiniboro B, Robinson LJ, Rosanas-Urgell A, Stanisic D, Siba PM, Alonso PL, Mueller I Abstract Primaquine is currently the only drug available for radical cure of P. vivax and P. ovale liver stages, but limited safety data exists in children <10yrs. Detailed daily assessments of side effects in G6PD-normal children treated with 14 days(d) of 0.5mg/kg primaquine plus chloroquine (3d, n=252) or artesunate (7d, n=141) showed that both treatments are well tolerated, do not lead to reductions in hemoglobin levels and can thus safely be used in children 1-10yrs. PMID: 22252800 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619711 Tue, 17 Jan 2012 05:00:00 +0100 5619711 http://www.medworm.com/index.php?rid=5619710&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%3D22252801%26dopt%3DAbstract In this study, nagZ of S. maltophilia was characterized, with its role in basal-level β-lactamase derepression, induced β-lactamase activities, and β-lactam resistance of KJΔDI, KJΔmrcA, and KJΔDIΔmrcA evaluated. Expression of the nagZ gene was constitutive and not regulated by AmpR, AmpD(I), AmpN, AmpG, PBP1a, and NagZ. Introduction of ΔnagZ into KJΔDI nearly abolished basal-level derepressed β-lactamase activity; conversely, introduction of ΔnagZ into KJΔmrcA did not affect it. At least two activator ligands (ALs) are thus considered responsible for β-lactamase expression in S. maltophilia system, specifically the NagZ-dependent (AL1) and NagZ-independent one (AL2) responsible for the basal-level derepressed β-lactamase activities of KJΔDI and KJΔmrcA, respectively. Contr... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619710 Tue, 17 Jan 2012 05:00:00 +0100 5619710 http://www.medworm.com/index.php?rid=5619709&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%3D22252802%26dopt%3DAbstract Authors: Warrilow AG, Mullins JG, Hull CM, Parker JE, Lamb DC, Kelly DE, Kelly SL Abstract The effects of S279F and S279Y point mutations in Candida albicans CYP51 (CaCYP51) on activity and on substrate (lanosterol) and azole antifungal binding were investigated. Both S279F and S279Y bound lanosterol with two-fold increased affinities (K(s) 7.1 and 8.0 μM) compared to the wild-type CaCYP51 protein (K(s) 13.5 μM). S279F, S279Y and wild-type CaCYP51 proteins bound fluconazole, voriconazole and itraconazole tightly, producing typical type II binding spectra. However, S279F and S279Y had 4- to 5-fold lower affinities for fluconazole, 3.5-fold lower affinities for voriconazole and 3.5- to 4-fold lower affinities for itraconazole than the wild-type CaCYP51 protein. S279F and S279Y gave... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619709 Tue, 17 Jan 2012 05:00:00 +0100 5619709 http://www.medworm.com/index.php?rid=5619708&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%3D22252803%26dopt%3DAbstract Authors: Sutyak Noll K, Prichard MN, Khaykin A, Sinko PJ, Chikindas ML Abstract Subtilosin is a cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens that has antimicrobial activity against the bacterial vaginosis-associated human pathogen Gardnerella vaginalis. The ability of subtilosin to inhibit G. vaginalis alone and in combination with the natural antimicrobials glycerol monolaurate (Lauricidin®), lauric arginate and ε-poly-L-lysine was tested using a checkerboard approach. Subtilosin was found to synergize with all of the chosen antimicrobials. These promising results indicate that lower concentrations of subtilosin in combination with other compounds could effectively be used to inhibit growth of the pathogen, thereby decreasing the risk of developed antimi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619708 Tue, 17 Jan 2012 05:00:00 +0100 5619708 http://www.medworm.com/index.php?rid=5619707&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%3D22252804%26dopt%3DAbstract Authors: Lwin KM, Phyo AP, Tarning J, Hanpithakpong W, Ashley EA, Lee SJ, Cheah P, Singhasivanon P, White NJ, Lindegårdh N, Nosten F Abstract Background: Intermittent Preventive Treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used.Methods: Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day treatment dose of dihydroartemisinin-piperaquine monthly (DPm), every two months (DPalt), or an identical placebo with or without fat (6.4g/dose) over a 9 month period. All were followed weekly.Findings: 1000 adults were recruite... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619707 Tue, 17 Jan 2012 05:00:00 +0100 5619707 http://www.medworm.com/index.php?rid=5619706&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%3D22252805%26dopt%3DAbstract Authors: Stoddart CA, Nault G, Galkina SA, Bousquet-Gagnon N, Bridon D, Quraishi O Abstract PC-1505 is a C34 peptide derived from the heptad repeat 2 region of HIV-1 gp41 conjugated to human serum albumin for sustained in vivo activity. One single preexposure dose of PC-1505 reduced viral RNA in HIV-1-infected SCID-hu Thy/Liv mice by 3.3 log(10) and protected T cells from virus-mediated depletion. In contrast, a single preexposure dose of Truvada reduced viral RNA by only 0.8 log(10) and was substantially less effective in preventing T-cell depletion. PMID: 22252805 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619706 Tue, 17 Jan 2012 05:00:00 +0100 5619706 http://www.medworm.com/index.php?rid=5619705&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%3D22252806%26dopt%3DAbstract Authors: Furustrand Tafin U, Corvec S, Betrisey B, Zimmerli W, Trampuz A Abstract Propionibacterium acnes is an important cause of orthopedic implant-associated infections, for which the optimal treatment has not yet been determined. We investigated the activity of rifampin, alone and in combination, against planktonic and biofilm P. acnes in vitro and in a foreign-body infection model. The MIC and the minimal bactericidal concentration (MBC) were 0.007 and 4 μg/ml for rifampin, 1 and 4 μg/ml for daptomycin, 1 and 8 μg/ml for vancomycin, 1 and 2 μg/ml for levofloxacin, 0.03 and 16 μg/ml for penicillin G, 0.125 and 512 μg/ml for clindamycin, and 0.25 and 32 μg/ml for ceftriaxone, respectively. The P. acnes minimal biofilm eradication concentration (MBEC) was 16 μg/ml for rif... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619705 Tue, 17 Jan 2012 05:00:00 +0100 5619705 http://www.medworm.com/index.php?rid=5619704&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%3D22252807%26dopt%3DAbstract Authors: Vale-Silva LA, Coste AT, Ischer F, Parker JE, Kelly SL, Pinto E, Sanglard D Abstract The inactivation of ERG3, a gene encoding sterol Δ(5,6)-desaturase (essential for ergosterol biosynthesis), is a known mechanism of in vitro resistance to azole antifungal drugs in the human pathogen Candida albicans. ERG3 inactivation typically results in loss of filamentation and attenuated virulence in animal models of disseminated candidiasis. In this work, we identified a C. albicans clinical isolate (VSY2) with high level resistance to azole drugs in vitro and absence of ergosterol but normal filamentation. Sequencing of ERG3 in VSY2 revealed a double base deletion leading to a premature stop codon and thus a non-functional enzyme. The reversion of the double base deletion in the mu... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619704 Tue, 17 Jan 2012 05:00:00 +0100 5619704 http://www.medworm.com/index.php?rid=5619703&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%3D22252808%26dopt%3DAbstract Authors: Kelesidis T, Chow AL, Humphries R, Uslan DZ, Pegues D Abstract Understanding factors associated with de novo Daptomycin non-susceptible Enterococcus (DNSE) infections will aid in better understanding of the mechanisms of daptomycin non-susceptibility. We conducted a case-control study to compare patients with DNSE infections that were daptomycin treatment naïve (n=9) and those who had exposure to daptomycin (n=13). Less frequent exposure to antimicrobials, increased susceptibility to nitrofurantoin and gentamicin and shorter duration of hospitalization were associated with de novo DNSE infection, suggesting a potential community reservoir. PMID: 22252808 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619703 Tue, 17 Jan 2012 05:00:00 +0100 5619703 http://www.medworm.com/index.php?rid=5619702&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%3D22252809%26dopt%3DAbstract In conclusion, T-2307 exhibited in vitro and in vivo antimalarial activity. PMID: 22252809 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619702 Tue, 17 Jan 2012 05:00:00 +0100 5619702 http://www.medworm.com/index.php?rid=5619701&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%3D22252810%26dopt%3DAbstract In this study we describe high-level mupirocin resistance mediated by a novel locus, mupB. The mupB gene (3,102 bp) shared 65.5% sequence identity with mupA but only 45.5% identity with ileS. The deduced MupB protein shared 58.1% identity (72.3 % similarity) and 25.4% identity (41.8 % similarity) with MupA and IleS, respectively. Despite this limited homology, MupB contained conserved motifs found in class I tRNA synthetases. Attempts to transfer high-level mupirocin resistance via conjugation or transformation (using plasmid extracts from a mupB containing strain) were unsuccessful. However, by cloning mupB gene into a shuttle vector, it was possible to transfer the resistant phenotype to susceptible S. aureus by electroporation, proving that mupB was responsible for the high-level mupiro... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619701 Tue, 17 Jan 2012 05:00:00 +0100 5619701 http://www.medworm.com/index.php?rid=5619700&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%3D22252811%26dopt%3DAbstract Authors: Partridge SR, Paulsen IT, Iredell JR Abstract Complete sequencing of pJIE137 revealed a backbone closely related to p271A, encoding a novel RepA protein but with similar organization and up to ∼70% nucleotide identity to IncN plasmids. A region in pJIE137 resembling the IncN CUP regulon is mostly missing from p271A, presumably due to recombination. The class 1 In/Tn and ISEcp1-bla(CTX-M-62) transposition unit in pJIE137 and a putative transposon carrying bla(NDM-1) in p271A are inserted in different locations in the plasmid backbone. PMID: 22252811 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619700 Tue, 17 Jan 2012 05:00:00 +0100 5619700 http://www.medworm.com/index.php?rid=5619699&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%3D22252812%26dopt%3DAbstract Authors: Kirby KA, Marchand B, Ong YT, Ndongwe TP, Hachiya A, Michailidis E, Leslie MD, Sietsema DV, Fetterly TL, Dorst CA, Singh K, Wang Z, Parniak MA, Sarafianos SG Abstract Ribonuclease H (RNase H) inhibitors (RNHIs) have gained attention as potential HIV-1 therapeutics. Although several RNHIs have been studied in the context of HIV-1 Reverse Transcriptase (RT) RNase H, there is no information on inhibitors that might affect the RNase H activity of other RTs. We performed biochemical, virological, crystallographic, and molecular modeling studies to compare the RNase H function and inhibition profiles of the gammaretroviral Xenotropic Murine Leukemia Virus-Related Virus (XMRV) and Moloney Murine Leukemia Virus (MoMLV) RTs to HIV-1 RT. The RNase H activity of XMRV RT is significan... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619699 Tue, 17 Jan 2012 05:00:00 +0100 5619699 http://www.medworm.com/index.php?rid=5619698&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%3D22252813%26dopt%3DAbstract This study examines in-vitro antimicrobial resistance data from E. coli urine isolates from U.S. outpatients between 2000 and 2010 using The Surveillance Network (TSN). Antimicrobial susceptibility results (n=12,253,679) showed the greatest increases in E. coli resistance from 2000 to 2010 for ciprofloxacin (3% to 17.1%) and TMP/SMX (17.9% to 24.2%), whereas nitrofurantoin (0.8% to 1.6%) and ceftriaxone (0.2% to 2.3%) showed minimal change. From 2000 to 2010, outpatient urinary E. coli antimicrobial resistance to ciprofloxacin and TMP/SMX increased substantially. PMID: 22252813 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619698 Tue, 17 Jan 2012 05:00:00 +0100 5619698 http://www.medworm.com/index.php?rid=5619697&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%3D22252814%26dopt%3DAbstract Authors: Woods KL, Johnson JR, Padkowsky S, Mariano N, Colon-Urban R, Hassanein M, Wehbeh W, Johnston BD, Clabots C, Zahid S, Urban C Abstract Escherichia coli harboring CTX-M-β-lactamases have rarely been isolated from children in the United States.… PMID: 22252814 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619697 Tue, 17 Jan 2012 05:00:00 +0100 5619697 http://www.medworm.com/index.php?rid=5619696&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%3D22252815%26dopt%3DAbstract Authors: García-Fernández A, Villa L, Carta C, Venditti C, Giordano A, Venditti M, Mancini C, Carattoli A Abstract A carbapenemase resistant Klebsiella pneumoniae strain, clone ST258 producing KPC-3 was fully characterized. The entire plasmid content was investigated, identifying plasmids of the IncFII(k) (two of them similar to pKPQIL and pKPN3, respectively), IncX and ColE types, encoding for a formidable set of resistance genes against toxic compounds, metals and antimicrobial drugs and a novel iron(III) uptake system. PMID: 22252815 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619696 Tue, 17 Jan 2012 05:00:00 +0100 5619696 http://www.medworm.com/index.php?rid=5619695&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%3D22252816%26dopt%3DAbstract Authors: Qureshi ZA, Paterson DL, Potoski BA, Kilayko MC, Sandovsky G, Sordillo E, Polsky B, Adams-Haduch JM, Doi Y Abstract Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenamase (KPC) has been associated with serious infections and high mortality. The optimal antimicrobial therapy for infection due to KPC-producing K. pneumoniae is not well established. We conducted a retrospective cohort study to evaluate the clinical outcome of patients with bacteremia caused by KPC-producing K. pneumoniae. A total of 41 unique patients with blood cultures growing KPC-producing K. pneumoniae were identified at two medical centers in the United States. Most of the infections were hospital-acquired (32; 78%), while the rest of cases were healthcare-associated (9; 22%). The overall 28... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619695 Tue, 17 Jan 2012 05:00:00 +0100 5619695 http://www.medworm.com/index.php?rid=5619694&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%3D22252817%26dopt%3DAbstract Authors: Fang Y, Hu L, Zhou X, Jaiseng W, Zhang B, Takami T, Kuno T Abstract We performed a genome-wide screening for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine that target ergosterol biosynthesis using a Schizosaccharomyces pombe gene deletion library consisting of 3004 nonessential haploid deletion mutants. We identified 109 hypersensitive and 11 resistant mutants to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories, including ergosterol biosynthesis, membrane trafficking, histone acetylation and deacetylation, ubiquitination, signal transduction, ribosome biosynthesis and assembly, regulation of transcription and translation, cell wall organization and bi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619694 Tue, 17 Jan 2012 05:00:00 +0100 5619694 http://www.medworm.com/index.php?rid=5619687&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%3D22252818%26dopt%3DAbstract Authors: Martini C, Hammerer-Lercher A, Zuck M, Jekle A, Debabov D, Anderson M, Nagl M Abstract The aim of this study was to determine the potential application of N-chlorotaurine (NCT), N,N-dichloro-2,2- dimethyltaurine (NVC-422) and N-chloro-2,2-dimethyltaurine (NVC-612) as catheter-lock solutions for the prevention of catheter blockage and catheter-related bloodstream infections by testing their anticoagulant and broad-spectrum antimicrobial activity in human blood.NCT, NVC-422 and NVC-612 and control compounds were serially diluted in fresh human blood to evaluate the effects on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and direct thrombin inhibition. Quantitative killing assays against pathogens including methicillin-resistant Staphylo... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619687 Tue, 17 Jan 2012 05:00:00 +0100 5619687 http://www.medworm.com/index.php?rid=5619684&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%3D22252819%26dopt%3DAbstract Authors: Cohen-Wolkowiez M, Ouellet D, Smith PB, James LP, Ross A, Sullivan JE, Walsh MC, Zadell A, Newman N, White NR, Kashuba AD, Benjamin DK Abstract Pharmacokinetic (PK) studies in preterm infants are rarely conducted due to the research challenges posed by this population. To overcome these challenges, minimal-risk methods such as scavenged sampling can be used to evaluate the PK of commonly used drugs in this population. We evaluated the population PK of metronidazole using targeted sparse sampling and scavenged samples from infants ≤32 weeks gestational age at birth and <120 postnatal days. A 5-center study was performed. A population PK model using nonlinear mixed effect modeling (NONMEM) was developed. Covariate effects were evaluated based on estimated precision and ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619684 Tue, 17 Jan 2012 05:00:00 +0100 5619684 http://www.medworm.com/index.php?rid=5619680&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%3D22252820%26dopt%3DAbstract Authors: Henrich TJ, Lewine NR, Lee SH, Rao SS, Berro R, Gulick RM, Moore JP, Tsibris AM, Kuritzkes DR Abstract How HIV-1 resistant to small molecule CCR5 antagonists uses the coreceptor for entry has been studied in a limited number of isolates. We characterized dependence on the N-terminus (NT) and the second extra-cellular loop (ECL2) of CCR5 of three vicriviroc (VCV)-resistant clinical isolates broadly cross-resistant to other CCR5 antagonists. Pseudoviruses were constructed to assess CCR5 use by VCV-sensitive and resistant envelopes of subtype B and C viruses. We determined the extent of entry inhibition by monoclonal antibodies (mAbs) directed against the NT and ECL2 in the presence and absence of VCV, and the capacity of these pseudoviruses to use CCR5 mutants that contained... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619680 Tue, 17 Jan 2012 05:00:00 +0100 5619680 http://www.medworm.com/index.php?rid=5619672&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%3D22252821%26dopt%3DAbstract Authors: McGillivray SM, Tran DN, Ramadoss NS, Alumasa JN, Okumura CY, Sakoulas G, Vaughn MM, Zhang DX, Keiler KC, Nizet V Abstract The ClpXP protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. Here we identified a pharmacological inhibitor of the ClpXP protease, F2, and evaluated its action in Bacillus anthracis and Staphylococcus aureus. We found that F2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane such as penicillin and daptomycin in B. anthracis and drug resistant strains of S. aureus. ClpXP inhibition represents a novel therapeutic strategy to simultaneously sensitize pathogenic bacteria to host defenses and phar... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619672 Tue, 17 Jan 2012 05:00:00 +0100 5619672 http://www.medworm.com/index.php?rid=5619662&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%3D22252822%26dopt%3DAbstract The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria. Twenty four pregnant and 24 matched non-pregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics was evaluated with nonlinear mixed-effects modelling. The main pharmacokinetic finding was an unaltered total exposure of piperaquine but a 38% lower total exposure of dihydroartemisinin in pregnant compared to non-pregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% h... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619662 Tue, 17 Jan 2012 05:00:00 +0100 5619662 http://www.medworm.com/index.php?rid=5619655&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%3D22252823%26dopt%3DAbstract Authors: Welsch C, Schweizer S, Shimakami T, Domingues FS, Kim S, Lemon SM, Antes I Abstract Drug resistant viral variants are a major issue in the use of direct-acting antiviral agents in chronic hepatitis C. Ketoamides are potent inhibitors of the NS3 protease with V55A identified as mutation associated with resistance to boceprevir. Underlying molecular mechanisms are only partially understood. We applied a comprehensive sequence analysis to characterize the natural variability at Val55 within dominant worldwide patient strains. A residue-interaction network and molecular dynamics simulation were applied to identify mechanisms for ketoamide resistance and viral fitness in Val55 variants. An infectious H77S.3 cell culture system was used for variant phenotype characterization. We... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619655 Tue, 17 Jan 2012 05:00:00 +0100 5619655 http://www.medworm.com/index.php?rid=5619645&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%3D22252824%26dopt%3DAbstract Authors: Morán-Barrio J, Lisa MN, Vila AJ Abstract Metallo-β-lactamases (MβLs) represent one of the main mechanisms of bacterial resistance against β-lactam antibiotics. Elucidation of their mechanism has been mostly limited by the structural diversity among their active sites. All MβLs structurally characterized so far present a Cys or a Ser residue in position 221, which is critical for catalysis. GOB lactamases stand as an exception within this picture, possessing a Met residue in this location. We studied different mutants in this position, and we show that Met221 is essential for protein stability, most likely due to its involvement in a hydrophobic core. In contrast to other known MβLs, residue 221 is not involved in metal binding or in catalysis in GOB enzymes, further... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619645 Tue, 17 Jan 2012 05:00:00 +0100 5619645 http://www.medworm.com/index.php?rid=5619643&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%3D22252825%26dopt%3DAbstract Authors: Ananworanich J, Gorowara M, Avihingsanon A, Kerr SJ, van Heesch N, Khongpetch C, Uanithirat A, Hill A, Ruxrungtham K, Burger DM, Abstract Because studies showed similar viral suppression with lower raltegravir doses and Asians usually have high antiretroviral concentrations, we explored low dose raltegravir in Thais. Nineteen adults on raltegravir 400 mg twice-daily (BID) with HIV-RNA < 50 copies/ml were randomized to 400mg once-daily (QD) or 800mg QD for 2 weeks followed by the other dosing for 2 weeks. Intensive pharmacokinetics were performed and HIV-RNA monitored. Two were excluded from the 400mg QD analysis due to inevaluable pharmacokinetic data. Mean weight was 58 kg. Mean values were AUC(0-12h) 15.6 mg/L.h and C(trough) 0.22 mg/L for raltegravir 400mg BID; AUC(... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619643 Tue, 17 Jan 2012 05:00:00 +0100 5619643 http://www.medworm.com/index.php?rid=5619642&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%3D22252826%26dopt%3DAbstract Authors: Piedade R, Schaeffeler E, Winter S, Asimus S, Schwab M, Ashton M, Burk O, Gil JP Abstract Artemisinins induce drug metabolism through the activation of pregnane x receptor (PXR) in vitro. Herein, we report the re-sequencing and genotyping of PXR variants in 75 Vietnamese individuals previously characterized for CYP3A enzyme activity after artemisinin exposure. A total of 31 PXR variants were identified, including five novel SNPs, and we identified significantly different allele frequencies relative to other ethnic groups. A trend of significance was observed between the level of CYP3A4 induction by artemisinin and two PXR variants, 8118 C>T (Y328Y) and 10719 A>G. PMID: 22252826 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619642 Tue, 17 Jan 2012 05:00:00 +0100 5619642 http://www.medworm.com/index.php?rid=5619636&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%3D22252827%26dopt%3DAbstract This study aimed to investigate rifampicin autoinduction using a semi-mechanistic pharmacokinetic-enzyme turn-over model. Four different structural basic models were explored to assess whether different scaling methods affected the final covariate selection procedure. Covariates were selected using a linearized approach. The final model included allometric scaling of oral clearance and volume of distribution. Although HIV infection was associated with a 30% increase in apparent volume of distribution, simulations demonstrated the effect of HIV on rifampicin exposure to be slight. Model-based simulations showed close to maximum induction achieved after 450 mg daily dosing since negligible increases in oral clearance were observed following the 600 mg/day regimen. Thus, dosing above 600 mg/d... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619636 Tue, 17 Jan 2012 05:00:00 +0100 5619636 http://www.medworm.com/index.php?rid=5619635&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%3D22252828%26dopt%3DAbstract Authors: Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V, Fischer E, Barnes SW, Walker JR, Alland D, Barry CE, Boshoff HI Abstract SQ109, a 1,2-diamine related to ethambutol, is currently in clinical trials for the treatment of tuberculosis, but its mode of action remains unclear. Here we demonstrate that SQ109 disrupts cell wall assembly as evidenced by macromolecular incorporation assays and ultrastructural analyses. SQ109 interferes with the assembly of mycolic acids into the cell wall core of Mycobacterium tuberculosis, as bacilli exposed to SQ109 show immediate inhibition of trehalose dimycolate (TDM) production and fail to attach mycolates to the cell wall arabinogalactan. These effects were not due to inhibition of mycolate synthesis, since total mycolate levels were unaf... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619635 Tue, 17 Jan 2012 05:00:00 +0100 5619635 http://www.medworm.com/index.php?rid=5619634&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%3D22252829%26dopt%3DAbstract This reporter could be used for High Throughput Screening of translation inhibitors. PMID: 22252829 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619634 Tue, 17 Jan 2012 05:00:00 +0100 5619634 http://www.medworm.com/index.php?rid=5619633&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%3D22252830%26dopt%3DAbstract ConclusionThis study generates the hypothesis that treatment with i.v. metronidazole is inferior to the oral alternatives metronidazole and vancomycin. PMID: 22252830 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619633 Tue, 17 Jan 2012 05:00:00 +0100 5619633 http://www.medworm.com/index.php?rid=5619632&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%3D22252831%26dopt%3DAbstract Authors: Nakata N, Kai M, Makino M Abstract Rifampicin is a major drug used to treat leprosy and tuberculosis. Rifampicin resistance of Mycobacterium leprae and Mycobacterium tuberculosis results from mutation in the rpoB encoding the β subunit of RNA polymerase. Molecular diagnosis for rifampicin resistance in these two mycobacteria would be clinically valuable, but the relation between the mutations and susceptibility to rifampicin must be clarified before its use. Analysis of responsible mutations for rifampicin resistance using clinical isolates presents some limitations. Each clinical isolate has its own genetic variations in some loci other than rpoB, which might affect rifampicin susceptibility. For this study, we constructed recombinant strains of Mycobacterium smegmatis, ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5619632 Tue, 17 Jan 2012 05:00:00 +0100 5619632 http://www.medworm.com/index.php?rid=5597519&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%3D22232273%26dopt%3DAbstract Authors: Ko KC, Tai PC, Derby CD Abstract The marine snail Aplysia californica produces in its defensive ink escapin, an (L)-amino acid oxidase. Escapin uses (L)-lysine to produce diverse products called escapin intermediates products of (L)-lysine (EIP-K), including α-amino-ε-caproic acid, Δ(1)-piperidine-2-carboxylic acid, and Δ(2)-piperidine-2-carboxylic acid. EIP-K and H(2)O(2) together, but neither alone, is a powerful bactericide. Here we report bactericidal mechanisms of escapin products on E. coli. We show that EIP-K and H(2)O(2) together cause rapid and long-lastingDNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect lasting at least 70 hr. We isolated two mutants resistant to EIP-K + H(2)O(2), bo... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597519 Mon, 09 Jan 2012 05:00:00 +0100 5597519 http://www.medworm.com/index.php?rid=5597518&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%3D22232274%26dopt%3DAbstract Authors: Novotna G, Hill C, Vincent K, Liu C, Hong HJ Abstract Bacterial resistance to the glycopeptide antibiotic teicoplanin shows some important differences compared to the closely related compound vancomycin. These are currently poorly understood, but may reflect significant differences in the mode of action of each antibiotic. Streptomyces coelicolor possesses a vanRSJKHAX gene cluster which when expressed confers resistance to both vancomycin and teicoplanin. The resistance to vancomycin is mediated by the enzymes encoded by vanKHAX but not by vanJ. vanHAX effect a reprogramming of peptidoglycan biosynthesis which is considered to be generic for conferring resistance to all glycopeptide antibiotics. Here we show that vanKHAX are not in fact required for teicoplanin resistance... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597518 Mon, 09 Jan 2012 05:00:00 +0100 5597518 http://www.medworm.com/index.php?rid=5597517&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%3D22232275%26dopt%3DAbstract Authors: Ramón-García S, Mick V, Dainese E, Martín C, Thompson CJ, De Rossi E, Manganelli R, Aínsa JA Abstract Efflux pumps extrude a wide variety of chemically unrelated compounds conferring multidrug resistance and participating in numerous physiological processes. Mycobacterium tuberculosis possesses many efflux pumps, and their roles in drug resistance and physiology are actively investigated. In this work we found that tap mutant cells showed changes in morphology and a progressive loss of viability upon sub-cultivation in liquid medium. Transcriptome analysis in Mycobacterium bovis BCG revealed that disruption of the Rv1258c gene, encoding the Tap efflux pump, led to an extensive change in gene expression patterns during stationary phase, with no changes during exponentia... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597517 Mon, 09 Jan 2012 05:00:00 +0100 5597517 http://www.medworm.com/index.php?rid=5597498&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%3D22232276%26dopt%3DAbstract Conclusion: Quinolones are commonly prescribed to outpatients with UTI. Non-clinical factors influence the choice of quinolones versus TMP/SMX, which may provide opportunities for interventions to improve prescribing patterns and control quinolone resistance. PMID: 22232276 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597498 Mon, 09 Jan 2012 05:00:00 +0100 5597498 http://www.medworm.com/index.php?rid=5597497&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%3D22232277%26dopt%3DAbstract Authors: Xiao Y, Gerth K, Müller R, Wall D Abstract Antibiotic TA is a macrocyclic secondary metabolite produced by myxobacteria that has broad-spectrum bactericidal activity. The structure of TA is unique and its molecular target is unknown. Here, we sought to elucidate TA's mode of action (MOA) through two parallel genetic approaches. First, chromosomal Escherichia coli resistant mutants were isolated. One mutant that showed specific resistance toward TA was mapped and resulted from an IS4 insertion in the gene lpp, which encodes an abundant outer membrane (Braun's) lipoprotein. In a second approach the comprehensive E. coli ASKA plasmid library was screened for overexpressing clones that conferred TA(r). This effort resulted in the isolation of the lspA gene, which encodes the ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597497 Mon, 09 Jan 2012 05:00:00 +0100 5597497 http://www.medworm.com/index.php?rid=5597489&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%3D22232278%26dopt%3DAbstract Authors: Fernandez J, Abbanat D, Shang W, He W, Amsler K, Hastings J, Queenan AM, Melton JL, Barron AM, Flamm RK, Lynch AS Abstract The therapeutic activity of ceftobiprole medocaril, the prodrug of ceftobiprole, was compared to vancomycin, daptomycin, and the combination of a sub-therapeutic dose of ceftobiprole and vancomycin in a rat model of infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA ATCC 43300) or glycopeptide-intermediate Staphylococcus aureus (GISA, NRS4, HIP 5836) strains. The minimum bactericidal concentrations of ceftobiprole, vancomycin, and daptomycin at bacterial cell densities similar to those encountered in the cardiac vegetation in the rat endocarditis model were 2, >64, and 8 μg/mL respectively for MRSA ATCC 43300 and 4, &gt... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597489 Mon, 09 Jan 2012 05:00:00 +0100 5597489 http://www.medworm.com/index.php?rid=5597479&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%3D22232279%26dopt%3DAbstract Authors: Singh R, Swick MC, Ledesma KR, Yang Z, Hu M, Zechiedrich L, Tam VH Abstract The emergence of resistance presents a debilitating change in the management of infectious diseases. Currently, the temporal relationship and interplay between various mechanisms of drug resistance are not well understood. A thorough understanding of the resistance development process is needed to facilitate rational design of countermeasure strategies. Using an in vitro hollow fiber infection model that simulates human drug treatment, we examined the appearance of efflux pump (acrAB) over-expression and target topoisomerase gene (gyrA and parC) mutations over time in the emergence of quinolone resistance in Escherichia coli. Drug-resistant isolates recovered early (24 h) had 2-8× elevation in min... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597479 Mon, 09 Jan 2012 05:00:00 +0100 5597479 http://www.medworm.com/index.php?rid=5597477&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%3D22232280%26dopt%3DAbstract Authors: Legrand E, Yrinesi J, Ekala MT, Péneau J, Volney B, Berger F, Bouchier C, Bertani S, Musset L, Meynard JB, Mercereau-Puijalon O Abstract Analysing the evolution of drug target genes under changing drug policy is needed to assist monitoring of Plasmodium falciparum drug resistance in the field. Here, we genotype Pfcrt and Pfdmr1 of 700 isolates collected in French Guiana from 2000 (five years after withdrawal of chloroquine) to 2008, i.e. the period when artemether-lumefantrine combination was progressively introduced and mefloquine abandoned. Gene sequencing showed fixation of the 7G8-type Pfcrt SMVNT resistance haplotype and near-fixation of the NYCDY Pfdmr1 haplotype. Pfdmr1 gene copy number correlated with IC(50) for mefloquine and halofantrine (r= 0.64 and 0.47, respe... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597477 Mon, 09 Jan 2012 05:00:00 +0100 5597477 http://www.medworm.com/index.php?rid=5597466&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%3D22232281%26dopt%3DAbstract This study shows that the Y-X-N loop is a novel hot spot for mutations accounting for hydrolysis spectrum extension in CMY-2-type enzymes. PMID: 22232281 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597466 Mon, 09 Jan 2012 05:00:00 +0100 5597466 http://www.medworm.com/index.php?rid=5597460&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%3D22232282%26dopt%3DAbstract Authors: Fernández-Canigia L, Litterio M, Legaria MC, Castello L, Predari SC, Di Martino A, Rossetti A, Rollet R, Carloni G, Bianchini H, Cejas D, Radice M, Gutkind G, Abstract The susceptibility rates of 363 clinical Bacteroides fragilis group isolates collected from 17 centers in Argentina during the period 2006-2009 were as follows: piperacillin-tazobactam 99 %, ampicillin-sulbactam 92 %, cefoxitin 72 %, tigecycline 100 %, moxifloxacin 91 %, clindamycin 52 %, and no metronidazole resistance was detected. Resistance to imipenem, doripenem and ertapenem was observed in 1.1 %, 1.6 % and 2.3 % of B. fragilis group strains, respectively. B. fragilis species showed a resistance profile of 1.5 % to imipenem, 1.9 % to doripenem and 2.4 % to ertapenem, being the first report of carbape... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597460 Mon, 09 Jan 2012 05:00:00 +0100 5597460 http://www.medworm.com/index.php?rid=5597457&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%3D22232283%26dopt%3DAbstract Authors: Schlusselhuber M, Jung S, Bruhn O, Goux D, Leippe M, Leclercq R, Laugier C, Grötzinger J, Cauchard J Abstract Rhodococcus equi, the causal agent of rhodococcosis, is a severe pathogen of foals but also of immunodeficient humans causing bronchopneumonia. The pathogen is often found together with Klebsiella pneumoniae or Streptococcus zooepidemicus in foals. Of great concern is the fact that some R. equi strains are already resistant to commonly used antibiotics. In the present study, we evaluated the in vitro potential of two equine antimicrobial peptides (AMPs), eCATH1 and DEFA1, as new drugs against R. equi and its associated pathogens. The peptides led to growth inhibition and death of R. equi and S. zooepidemicus at low micromolar concentrations. Moreover, eCATH1 was a... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597457 Mon, 09 Jan 2012 05:00:00 +0100 5597457 http://www.medworm.com/index.php?rid=5597456&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%3D22232284%26dopt%3DAbstract Authors: Macleod DL, Velayudhan J, Kenney TF, Therrien JH, Sutherland JL, Barker LM, Baker WR Abstract Elevated levels of mucins present in bronchiectatic airways predispose patients to bacterial infections and reduce the effectiveness of antibiotic therapies by directly inactivating antibiotics. Consequently, new antibiotics that are not inhibited by mucins are needed to treat chronic respiratory infections caused by Pseudomonas aeruginosa and Staphylococcus aureus. In these studies, we demonstrate that fosfomycin synergistically enhances the activity of tobramycin in the presence of mucin. The bactericidal killing of a novel 4:1 (wt/wt) combination of fosfomycin:tobramycin (FTI) is superior (>9-log(10) CFU/mL) relative to its individual components fosfomycin and tobramycin. Ad... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597456 Mon, 09 Jan 2012 05:00:00 +0100 5597456 http://www.medworm.com/index.php?rid=5597455&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%3D22232285%26dopt%3DAbstract Authors: Kim SH, Song JH, Chung DR, Thamlikitkul V, Yang Y, Wang H, Lu M, So TM, Hsueh PR, Yasin RM, Carlos CC, Pham HV, Lalitha MK, Shimono N, Perera J, Shibl AM, Baek JY, Kang CI, Ko KS, Peck KR, Abstract Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among non-meningeal isolates, prevalence rate of penicillin non-susceptible pneumococci (MIC ≥ 4 μg/ml) was 4.6% and penicill... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597455 Mon, 09 Jan 2012 05:00:00 +0100 5597455 http://www.medworm.com/index.php?rid=5597454&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%3D22232286%26dopt%3DAbstract Authors: Kim CJ, Song KH, Park WB, Kim ES, Park SW, Kim HB, Oh MD, Kim NJ Abstract We retrospectively reviewed medical records to identify the factors that affect the results of culture in patients with pyogenic vertebral osteomyelitis. In multivariate analysis, presence of paravertebral abscess was associated with positive results of microbiologic culture. Prior antibiotic exposures, especially of longer duration, was strongly associated with negative results. PMID: 22232286 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597454 Mon, 09 Jan 2012 05:00:00 +0100 5597454 http://www.medworm.com/index.php?rid=5597453&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%3D22232287%26dopt%3DAbstract In conclusion, our results show that by facilitating its uptake and accumulation in OR6 cells, ENT1 plays a pivotal role in the antiviral effectiveness of ribavirin and therefore provides an important insight into understanding the efficacy of the drug in anti-HCV therapy. PMID: 22232287 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597453 Mon, 09 Jan 2012 05:00:00 +0100 5597453 http://www.medworm.com/index.php?rid=5597452&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%3D22232288%26dopt%3DAbstract Authors: van de Kassteele J, van Santen-Verheuvel MG, Koedijk FD, van Dam AP, van der Sande MA, de Neeling AJ Abstract Seventeen laboratories participated in a cooperative study to validate the regional susceptibility testing of Neisseria gonorrhoeae in The Netherlands. International reference strains were distributed. Each laboratory determined the MIC of ciprofloxacin, penicillin and tetracycline, for each strain by E-test. To explore a more transparent assessment of quality and comparability, a statistical regression model was fitted to the data that accounted for the censoring of the MICs. The mean MIC as found by all laboratories except three were closer than one two-fold dilution step to the overall mean and the mean MICs of each antimicrobial agent were close to the MICs of ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597452 Mon, 09 Jan 2012 05:00:00 +0100 5597452 http://www.medworm.com/index.php?rid=5597451&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%3D22232289%26dopt%3DAbstract Authors: Sader HS, Biedenbach DJ, Paukner S, Ivezic-Schoenfeld Z, Jones RN Abstract BC-3781 is a novel semi-synthetic pleuromutilin antimicrobial agent which is developed as an intravenous and oral therapy for acute bacterial skin and skin structure infections (ABSSSI) and respiratory tract infections (RTI). BC-3781 and comparator agents were tested against 1,893 clinical Gram-positive organisms predominantly causing ABSSSI by broth microdilution method. BC-3781 exhibited potent activity against methicillin-resistant Staphylococcus aureus (MIC(50/90), 0.12/0.25 μg/ml), coagulase-negative staphylococci (MIC(50/90), 0.06/0.12 μg/ml), β-haemolytic streptococci (MIC(50/90), 0.03/0.06 μg/ml), viridans group streptococci (MIC(50/90), 0.12/0.5 μg/ml) and Enterococcus faecium (includi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597451 Mon, 09 Jan 2012 05:00:00 +0100 5597451 http://www.medworm.com/index.php?rid=5597450&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%3D22232290%26dopt%3DAbstract Authors: Hou J, Huang X, Deng Y, He L, Yang T, Zeng Z, Chen Z, Liu JH Abstract The presence and characterization of plasmid-mediated fosfomycin resistance determinants among Escherichia coli isolates collected from pets in China between 2006 and 2010 were investigated. Twenty-nine isolates (9.0%) were positive for fosA3 and all of them were CTX-M producers. The fosA3 genes were flanked by IS26 and were localized on F2:A-:B- plasmids or on very similar F33:A-:B- plasmids carrying both bla(CTX-M-65) and rmtB. Current findings indicate that the fosA3 gene may be co-selected by other antimicrobials. PMID: 22232290 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597450 Mon, 09 Jan 2012 05:00:00 +0100 5597450 http://www.medworm.com/index.php?rid=5597449&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%3D22232291%26dopt%3DAbstract This study informs empirical treatment of suspected IPD in patients with a history of TMP-SMX use. PMID: 22232291 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597449 Mon, 09 Jan 2012 05:00:00 +0100 5597449 http://www.medworm.com/index.php?rid=5597443&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%3D22232292%26dopt%3DAbstract Authors: Kvam E, Davis B, Mondello F, Garner AL Abstract Plasma, a unique state of matter with properties similar to ionized gas, is an effective biological disinfectant. However, the mechanism through which non-thermal or "cold" plasma inactivates microbes on surfaces is poorly understood due, in part, to challenges associated with processing and analyzing live cells on surfaces rather than in aqueous solution. Here, we employ membrane-adsorption techniques to visualize the cellular effects of plasma on representative clinical isolates of drug-resistant microbes. Through direct fluorescent imaging, we demonstrate that plasma rapidly inactivates planktonic cultures, with >5-log(10) kill in 30 seconds, by damaging the cell surface in a time-dependent manner, resulting in a loss o... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597443 Mon, 09 Jan 2012 05:00:00 +0100 5597443 http://www.medworm.com/index.php?rid=5597442&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%3D22232293%26dopt%3DAbstract Authors: Danby CS, Boikov D, Rautemaa R, Sobel JD Abstract The treatment of vulvovaginal candidiasis (VVC) due to Candida glabrata is challenging with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite of in vitro susceptibility. Given that vaginal pH of patients with VVC is unchanged at 4 - 4.5, we studied the effect of pH on the in vitro activity of eleven antifungal agents against 40 C. glabrata isolates and compared activity against 15 fluconazole sensitive, and 10 fluconazole reduced-susceptibility C. albicans strains. In vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopiroxolamine, amphoteri... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5597442 Mon, 09 Jan 2012 05:00:00 +0100 5597442 http://www.medworm.com/index.php?rid=5577585&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%3D22214774%26dopt%3DAbstract In conclusion, FOX appears as an effective therapeutic alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli. PMID: 22214774 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577585 Tue, 03 Jan 2012 05:00:00 +0100 5577585 http://www.medworm.com/index.php?rid=5577584&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%3D22214775%26dopt%3DAbstract Authors: Mercante AD, Jackson L, Johnson PJ, Stringer VA, Dyer DW, Shafer WM Abstract Previous studies have shown that the MpeR transcriptional regulator produced by Neisseria gonorrhoeae represses expression of mtrF, which encodes a putative inner membrane protein (MtrF). MtrF works as an accessory protein with the Mtr efflux pump helping gonococci to resist high levels of diverse hydrophobic antimicrobials. Regulation of mpeR has been reported to occur by an iron-dependent mechanism involving Fur (Ferric uptake regulator). Collectively, these observations suggest the presence of an interconnected regulatory system in gonococci that modulates expression of efflux pump protein-encoding genes in an iron-responsive manner. Herein, we describe this connection and report that levels of... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577584 Tue, 03 Jan 2012 05:00:00 +0100 5577584 http://www.medworm.com/index.php?rid=5577583&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%3D22214776%26dopt%3DAbstract Authors: Ruiz de Gopegui E, Juan C, Zamorano L, Pérez JL, Oliver A Abstract A multidrug resistance (MDR) conjugative plasmid of ca. 50 kb (designated pERGB) was detected in a linezolid and methicillin-resistant Staphylococcus aureus strain with sequence type 125 (ST125-MRSA-IVc). This strain was detected in two patients with chronic obstructive pulmonary disease, previously treated with multiple antimicrobials, including linezolid. pERGB was transferable by conjugation, and carried the resistance genes cfr (oxazolidinones, phenicols, lincosamides, pleuromutilins, and streptogramin A), ant(4' )-Ia (tobramycin), tet(L) (tetracycline), and dfrK (trimethoprim). A novel genetic structure, linking for the first time all these resistance genes, was elucidated through sequencing of a 15,2... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577583 Tue, 03 Jan 2012 05:00:00 +0100 5577583 http://www.medworm.com/index.php?rid=5577582&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%3D22214777%26dopt%3DAbstract Authors: Wang C, Huang H, Valera L, Sun JH, O'Boyle DR, Nower PT, Jia L, Qiu D, Huang X, Altaf A, Gao M, Fridell RA Abstract BMS-790052, a first-in-class Hepatitis C Virus (HCV) replication complex inhibitor, targeting nonstructural protein 5A (NS5A), displays picomolar to nanomolar potency against genotypes 1-5. This exceptional potency translated into robust anti-HCV activity in clinical studies with HCV genotype 1-infected subjects. To date, all BMS-790052-associated resistance mutations have mapped to the N-terminal region of NS5A. To further characterize the antiviral activity of BMS-790052, HCV replicon elimination and colony formation assays were performed. Replicon was cleared from genotype 1a and 1b replicon cells in time and dose dependent manners. Longer treatment durati... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577582 Tue, 03 Jan 2012 05:00:00 +0100 5577582 http://www.medworm.com/index.php?rid=5577581&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%3D22214778%26dopt%3DAbstract Authors: Levasseur P, Girard AM, Claudon M, Goossens H, Black MT, Coleman K, Miossec C Abstract The β-lactamase inhibitor avibactam (NXL104) displays potent inhibition of both class A and C enzymes. The in vitro antibacterial activity of the combination ceftazidime-avibactam was evaluated against a clinical panel of Pseudomonas aeruginosa isolates. Avibactam offered efficient protection from hydrolysis since 94% of isolates were susceptible to ceftazidime when combined with 4 μg/mL avibactam, as compared with 65% to ceftazidime alone. Ceftazidime-avibactam also demonstrated better antipseudomonal activity than imipenem (82% susceptibility), a common reference treatment. PMID: 22214778 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577581 Tue, 03 Jan 2012 05:00:00 +0100 5577581 http://www.medworm.com/index.php?rid=5577580&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%3D22214779%26dopt%3DAbstract Authors: Heymans R, Bruisten SM, Golparian D, Unemo M, de Vries HJ, van Dam AP Abstract From 2006 to 2008, Neisseria gonorrhoeae (NG) isolates were identified with decreased susceptibility to the extended-spectrum cephalosporin (ESC) cefotaxime among visitors of the Amsterdam STI clinic, the Netherlands. Spread, clonality, and characteristics of 202 isolates were examined using antibiograms, conventional penA mosaic gene PCR, and NG multiple-locus variable-number tandem repeat analysis (NG-MLVA). A strictly defined subset was further characterized by NG multilocus sequence typing (NG-MAST) and sequencing of ESC resistance determinants (penA, mtrR, and porB1b). Seventy-four NG isolates with a cefotaxime MIC of >0.125 μg/ml (group A), 54 with a cefotaxime MIC of 0.125 μg/ml (gro... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577580 Tue, 03 Jan 2012 05:00:00 +0100 5577580 http://www.medworm.com/index.php?rid=5577579&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%3D22214780%26dopt%3DAbstract In this study bovine milk LF displayed proteinase inhibitory activity against P. gingivalis whole cells significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner with a first-order inactivation rate constant (k(inact)) of 0.023 min(-1) and an inhibitor affinity constant (K(I)) of 5.02 μM. LF inhibited P. gingivalis biofilm formation by >80% at concentrations above 0.625 μM. LF was relatively resistant to hydrolysis by P. gingivalis cells but was cleaved into two major polypeptides (53 and 33 kDa) at R(284)-S(285) as determined by In Source Decay Mass Spectrometry, however the... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5577579 Tue, 03 Jan 2012 05:00:00 +0100 5577579 http://www.medworm.com/index.php?rid=5559034&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%3D22203585%26dopt%3DAbstract Authors: Blais J, Lewis SR, Krause KM, Benton BM Abstract TD-1792 is a new multivalent glycopeptide-cephalosporin antibiotic with potent activity against gram-positive bacteria. The in vitro activity of TD-1792 was tested against 527 Staphylococcus aureus, including multidrug-resistant isolates. TD-1792 was highly active against methicillin-susceptible S. aureus (MIC(90), 0.015 μg/mL), methicillin-resistant S. aureus and heterogeneous vancomycin-intermediate S. aureus (MIC(90), 0.03 μg/mL). Time kill studies demonstrated the potent bactericidal activity of TD-1792 at concentrations ≤0.12 μg/mL. A postantibiotic effect >2 h was observed after exposure to TD-1792. PMID: 22203585 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559034 Tue, 27 Dec 2011 05:00:00 +0100 5559034 http://www.medworm.com/index.php?rid=5559033&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%3D22203586%26dopt%3DAbstract Authors: Trancart S, Charreau I, Marchou B, Bocquentin M, Molina JM, Izopet J, Tangre P, Aboulker JP, Taburet AM, Abstract Efavirenz concentrations were measured in 21 patients during an interruption cycle of the ANRS 106 WINDOW trial. Median concentrations at 12h, 3 days, and 7 days after efavirenz discontinuation, were 1962 ng/mL, 416 ng/mL and 112 ng/mL respectively. Half-life ranged from 27 to 136 hours. No relationship between efavirenz exposure and detection of NNRTI mutations were demonstrated. Patients who were treated by a lamivudine or emtricitabine-based regimen had a lesser risk of NNRTI mutation selection. PMID: 22203586 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559033 Tue, 27 Dec 2011 05:00:00 +0100 5559033 http://www.medworm.com/index.php?rid=5559032&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%3D22203587%26dopt%3DAbstract Authors: Werngren J, Sturegård E, Juréen P, Angeby K, Hoffner S, Schön T Abstract Pyrazinamide (PZA) is a potent first line agent for the treatment of tuberculosis (TB) with activity also against a significant part of drug resistant TB strains. Since PZA is active only at acid pH, susceptibility testing to PZA is difficult and insufficiently reproducible. The recommended critical concentration for PZA susceptibility (100 mg/L) used in the BACTEC systems (460 and MGIT 960) has not been critically evaluated against wild-type minimal inhibitory concentration (MIC) distributions in clinical isolates of Mycobacterium tuberculosis.Using the BACTEC MGIT 960 we determined the PZA MIC for 46 clinical M. tuberculosis isolates and compared the results to >pncA sequencing and previously ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559032 Tue, 27 Dec 2011 05:00:00 +0100 5559032 http://www.medworm.com/index.php?rid=5559031&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%3D22203588%26dopt%3DAbstract Authors: Poirel L, Barbosa-Vasconcelos A, Simões RR, Martins Da Costa P, Liu W, Nordmann P Abstract Carbapenemase-producing Enterobacteriaceae isolates are reported increasingly worldwide (9).… PMID: 22203588 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559031 Tue, 27 Dec 2011 05:00:00 +0100 5559031 http://www.medworm.com/index.php?rid=5559030&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%3D22203589%26dopt%3DAbstract In conclusion, amino acid changes at residue I223 may alter the NAI susceptibilities of pH1N1 variants without compromising fitness. Consequently, I223R/V mutations, alone or with H275Y, need to be thoroughly monitored. PMID: 22203589 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559030 Tue, 27 Dec 2011 05:00:00 +0100 5559030 http://www.medworm.com/index.php?rid=5559029&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%3D22203590%26dopt%3DAbstract Authors: Berdugo M, Larsen IV, Abadie C, Deloche C, Kowalczuk L, Touchard E, Dubielzig R, Brandt CR, Behar-Cohen F, Combette JM Abstract Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of an anti-HSV humanized IgG FAb fragment (AC-8, 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, sub-epithelial stromal cells and retinal glial cells, with a preferential entry through ocular limbus. AC-8 was active against 13 different strains of HSV-1 with MEC(50) and MEC(90) values ranged from 0.03 to 0.13 μg/mL indicating broad-spectrum activity. The in vivo... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559029 Tue, 27 Dec 2011 05:00:00 +0100 5559029 http://www.medworm.com/index.php?rid=5559028&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%3D22203591%26dopt%3DAbstract Authors: Firsov AA, Gilbert D, Greer K, Portnoy YA, Zinner SH Abstract To compare the anti-pseudomonal efficacy of doripenem and imipenem as well as their abilities to restrict the enrichment of resistant P. aeruginosa, multiple dosing regimens of each drug were simulated at comparable times above the MIC (T(>MIC)) and ratios of the 24-hour area under the curve (AUC(24)) to the MIC. Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem 1 μg/ml, MIC of imipenem 1, 2 and 2 μg/ml) were exposed to thrice-daily doripenem or imipenem for three days at AUC(24)/MIC ratios from 50 to 170 h (doripenem) and from 30 to 140 h (imipenem). The antimicrobial effects for susceptible and resistant subpopulations of bacteria were expressed by the areas between contro... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559028 Tue, 27 Dec 2011 05:00:00 +0100 5559028 http://www.medworm.com/index.php?rid=5559027&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%3D22203592%26dopt%3DAbstract We describe the activity of RX-P763, RX-P766, RX-P770, RX-P792, RX-P793, and RX-P808 against strains of resistant Pseudomonas aeruginosa. These compounds target the large subunit of the bacterial ribosome and have broad-spectrum activity against multi-drug resistant pathogens. All compounds demonstrated in vitro activity against P.aeruginosa with MIC(90) (range, μg/mL) values of 4-8μg/mL (0.5-64). These novel compounds had narrow MIC distributions and maintained activity despite resistant phenotypes to other commonly utilized agents. PMID: 22203592 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559027 Tue, 27 Dec 2011 05:00:00 +0100 5559027 http://www.medworm.com/index.php?rid=5559026&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%3D22203593%26dopt%3DAbstract This study highlights that the region surrounding bla(KPC) is undergoing recombination, and that Tn4401 itself is heterogeneous and highly plastic. PMID: 22203593 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559026 Tue, 27 Dec 2011 05:00:00 +0100 5559026 http://www.medworm.com/index.php?rid=5559025&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%3D22203594%26dopt%3DAbstract Authors: Karlowsky JA, Walkty AJ, Adam HJ, Baxter MR, Hoban DJ, Zhanel GG Abstract Clinical isolates of Bacteroides fragilis group (n = 387) were collected from patients attending nine Canadian hospitals in 2010-2011 and tested for susceptibility to 10 antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. B. fragilis (59.9%), Bacteroides ovatus (16.3%), and Bacteroides thetaiotamicron (12.7%) accounted for ∼90% of isolates collected. Overall rates of percent susceptibility were: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2% imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cef... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559025 Tue, 27 Dec 2011 05:00:00 +0100 5559025 http://www.medworm.com/index.php?rid=5559024&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%3D22203595%26dopt%3DAbstract Authors: Wang C, Jia L, Huang H, Qiu D, Valera L, Huang X, Sun JH, Nower PT, O'Boyle DR, Gao M, Fridell RA Abstract The antiviral profile of BMS-790052, a potent hepatitis C virus (HCV) replication complex inhibitor targeting nonstructural protein NS5A, is well-characterized for HCV genotype-1. Here, we report that BMS-790052 inhibits hybrid replicons containing HCV genotype-4 NS5A genes with EC(50)s ranging from 7-13 pM. NS5A residue 30 was an important site for BMS-790052-selected resistance in the hybrid replicons. Our results support the potential of BMS-790052 as a valuable component of combination therapy for HCV genotype-4 chronic infection. PMID: 22203595 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559024 Tue, 27 Dec 2011 05:00:00 +0100 5559024 http://www.medworm.com/index.php?rid=5559023&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%3D22203596%26dopt%3DAbstract This study examined differences in antibiotic resistant soil bacteria and the presence and quantity of resistance genes in soils with a range of management histories. We analyzed four soils from agricultural systems that were amended with manure from animals treated with erythromycin, exposed to streptomycin and/or oxytetracycline,, and non-manure amended compost and forest soil. Low concentrations of certain antibiotic resistance genes were detected using multiplex quantitative real-time PCR (qPCR), with tet(B), aad(A), and str(A) each present in only one soil, and tet(M) and tet(W) detected in all soils. The most frequently detected resistance genes for tetracycline, streptomycin and erythromycin resistance were tet(B), tet(D), tet(O), tet(T), tet(W), and str(A), str(B), aac, and erm(C),... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559023 Tue, 27 Dec 2011 05:00:00 +0100 5559023 http://www.medworm.com/index.php?rid=5559022&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%3D22203597%26dopt%3DAbstract Authors: Liu Y, Wang Y, Wu C, Shen Z, Schwarz S, Du X, Dai L, Zhang W, Zhang Q, Shen J Abstract The multi-resistance gene cfr was identified for the first time in an Enterococcus faecalis isolate of animal origin. The 32,388-bp plasmid pEF-01, which carried the cfr gene, was sequenced completely. Three copies of the insertion sequence IS1216 were identified in pEF-01 and the detection of a cfr- and IS1216-containing amplicon by inverse PCR suggests that IS1216 may play a role in the dissemination of cfr by a recombination process. PMID: 22203597 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559022 Tue, 27 Dec 2011 05:00:00 +0100 5559022 http://www.medworm.com/index.php?rid=5559021&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%3D22203598%26dopt%3DAbstract Authors: Chen YH, Lu PL, Huang CH, Liao CH, Lu CT, Chuang YC, Tsao SM, Chen YS, Liu YC, Chen WY, Jang TN, Lin HC, Chen CM, Shi ZY, Pan SC, Yang CL, Kung HC, Liu CE, Cheng YJ, Liu JW, Sun W, Wang LS, Ko WC, Yu KW, Chiang PC, Lee MH, Lee CM, Hsu GJ, Hsueh PR Abstract The Tigecycline In-vitro Surveillance in Taiwan (TIST), a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n=1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n=423), vancomycin-resistant enterococci (VRE) (n=219), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n=1,141), ESBL-producing Klebsiella pneumoniae (n=1,330), Acinetobacter baumannii (n=1,645), and Stenotrophomonas ma... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559021 Tue, 27 Dec 2011 05:00:00 +0100 5559021 http://www.medworm.com/index.php?rid=5559020&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%3D22203599%26dopt%3DAbstract Authors: Naas T, Cattoen C, Bernusset S, Cuzon G, Nordmann P Abstract Carbapenem resistance in Enterobacteriaceae is a growing concern worldwide (13).… PMID: 22203599 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559020 Tue, 27 Dec 2011 05:00:00 +0100 5559020 http://www.medworm.com/index.php?rid=5559019&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%3D22203600%26dopt%3DAbstract Authors: Dvoskin S, Xu WC, Brown NC, Yanachkov IB, Yanachkova M, Wright GE Abstract N(2)-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase of Clostridium difficile (CD). MorE-DCBG and analogs strongly inhibited the growth of a wide variety of CD strains. When administered orally in a hamster model of CD-specific colitis, 362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease. PMID: 22203600 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559019 Tue, 27 Dec 2011 05:00:00 +0100 5559019 http://www.medworm.com/index.php?rid=5559018&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%3D22203601%26dopt%3DAbstract Authors: Matsuzaki J, Suzuki H, Nishizawa T, Hirata K, Tsugawa H, Saito Y, Okada S, Fukuhara S, Hibi T Abstract Sitafloxacin-based triple therapy achieved 83.6% (per-protocol) and 78.2% (intention-to-treat) success in eradicating Helicobacter pylori among 78 Japanese patients after clarithromycin-based first-line and metronidazole-based second-line triple therapies failed. Eradication succeeded in 32 out of 43 patients even with gyrA mutation-positive Helicobacter pylori (per-protocol). The position of the gyrA mutation (N87 or D91) was determined to be a better marker than minimum inhibitory concentration levels for predicting outcomes of sitafloxacin-based treatment. PMID: 22203601 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559018 Tue, 27 Dec 2011 05:00:00 +0100 5559018 http://www.medworm.com/index.php?rid=5559017&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%3D22203602%26dopt%3DAbstract In conclusion, N-(morpholine-4-carbonyloxy) amidine and other related morpholine compounds specifically suppressed HCV replication, and may have potential as novel chemotherapeutic agents. PMID: 22203602 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559017 Tue, 27 Dec 2011 05:00:00 +0100 5559017 http://www.medworm.com/index.php?rid=5559016&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%3D22203603%26dopt%3DAbstract Authors: Verwer PE, van Duijn ML, Tavakol M, Bakker-Woudenberg IA, van de Sande WW Abstract Chitin and β-glucan are major cell wall components of Aspergillus spp. We investigated the antifungal activity of chitin synthesis inhibitors nikkomycin Z, polyoxin D, flufenoxuron, lufenuron and teflubenzuron, alone and combined with β-glucan synthesis inhibitor caspofungin. Only nikkomycin Z and caspofungin were found to act synergistically. The nikkomycin Z-induced chitin decrease corresponded with a β-glucan increase, while with the caspofungin-induced β-glucan decrease, an increase in chitin was found. This could explain the synergistic activity of this combination of drugs. PMID: 22203603 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559016 Tue, 27 Dec 2011 05:00:00 +0100 5559016 http://www.medworm.com/index.php?rid=5559015&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%3D22203604%26dopt%3DAbstract Authors: Spreghini E, Orlando F, Sanguinetti M, Posteraro B, Giannini D, Manso E, Barchiesi F Abstract The aim of this study was to compare the in vitro and in vivo activities of micafungin, caspofungin and anidulafungin against Candida glabrata. Minimum inhibitory concentrations against 28 clinical isolates showed that the overall susceptibilities to caspofungin and to micafungin were not statistically different in absence of human serum, whereas the isolates were less susceptible to micafungin than caspofungin in its presence. Minimum fungicidal concentrations as well time-kill experiments showed that caspofungin was more active than anidulafungin, while micafungin was superior either to caspofungin or to anidulafungin without serum; its addition rendered caspofungin and micafung... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559015 Tue, 27 Dec 2011 05:00:00 +0100 5559015 http://www.medworm.com/index.php?rid=5559014&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%3D22203605%26dopt%3DAbstract Authors: Troke PJ, Lewis M, Simpson P, Gore K, Hammond J, Craig C, Westby M Abstract Filibuvir (PF-00868554) is an investigational non-nucleoside inhibitor of the hepatitis C virus (HCV) non-structural 5B (NS5B) RNA-dependent RNA polymerase, currently in development for treating chronic HCV infection. The aim of this study was to characterize the selection of filibuvir-resistant variants in HCV-infected individuals receiving filibuvir as short (3-10 days) monotherapy. We identified amino acid M423 as the primary site of mutation arising upon filibuvir dosing. Through bulk cloning of clinical NS5B sequences into a transient replicon system, and supported by site-directed mutagenesis of the Con1 replicon, we confirmed that mutations M423I/T/V mediate phenotypic resistance. Selection ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559014 Tue, 27 Dec 2011 05:00:00 +0100 5559014 http://www.medworm.com/index.php?rid=5559013&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%3D22203606%26dopt%3DAbstract Authors: Lavender H, Brady K, Burden F, Delpuech-Adams O, Denise H, Palmer A, Perkins H, Savic B, Scott S, Smith-Burchnell C, Troke P, Wright JF, Suhy D, Corbau R Abstract PF-05095808 is a novel biological agent for chronic Hepatitis C Virus (HCV) therapy. It comprises a recombinant Adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of 3 short hairpin (sh) RNAs targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence specific cleavage of target regions. For small molecule inhibitors the key screens needed to assess in vitro activity are well defined, we developed new assays to assess this RNA interference agent and so understand its t... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559013 Tue, 27 Dec 2011 05:00:00 +0100 5559013 http://www.medworm.com/index.php?rid=5559012&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%3D22203607%26dopt%3DAbstract Authors: Holmes AR, Keniya MV, Ivnitski-Steele I, Monk BC, Lamping E, Sklar LA, Cannon RD Abstract Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to over-expression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant Saccharomyces cerevisiae strains hyper-expressing individual transporters from the opportunistic fungal pathogen Candida albicans. The recombinant strains possess greater resistance to azoles and other pump substrates than the parental host strain. A flow cytometry-based HTS, which measured increased ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5559012 Tue, 27 Dec 2011 05:00:00 +0100 5559012 http://www.medworm.com/index.php?rid=5531033&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%3D22183166%26dopt%3DAbstract Authors: Citron DM, Tyrrel KL, Merriam CV, Goldstein EJ Abstract MICs for CB-183,315, a novel lipopeptide antibiotic, vancomycin and metronidazole were determined for intestinal anaerobes and Enterobacteriaceae. The MIC(90) for gram-negative anaerobes was >8192, 8192 and 4 μg/ml for CB-183,315, vancomycin and metronidazole, respectively. Against Enterobacteriaceae, MIC(90)s were >8192 μg/ml, 1024 μg/ml and1024 μg/ml, respectively. CB-183,315 MIC(90) for C. difficile was 0.5 μg/ml. Its lack of activity against normal fecal organisms makes it a promising new agent for treating C. difficile. PMID: 22183166 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531033 Mon, 19 Dec 2011 05:00:00 +0100 5531033 http://www.medworm.com/index.php?rid=5531032&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%3D22183167%26dopt%3DAbstract Authors: Eakin AE, Green O, Hales N, Walkup GK, Bist S, Singh A, Mullen G, Bryant J, Embrey K, Gao N, Breeze A, Timms D, Andrews B, Uria-Nickelsen M, Demeritt J, Loch JT, Hull K, Blodgett A, Illingworth RN, Prince B, Boriack-Sjodin PA, Hauck S, Macpherson LJ, Ni H, Sherer B Abstract DNA gyrase is an essential enzyme in bacteria and its inhibition results in the disruption of DNA synthesis and subsequently cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified from a fragment-based lead generation (FBLG) approach using NMR screening to identify low molecular weight compounds that bind to the ATP pocket of DNA gyrase. A pyrrole hit with a binding constant of 1 mM formed the basis of the design and synthesis of a fo... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531032 Mon, 19 Dec 2011 05:00:00 +0100 5531032 http://www.medworm.com/index.php?rid=5531031&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%3D22183168%26dopt%3DAbstract Authors: Wang Y, Zhang W, Wang J, Wu C, Shen Z, Fu X, Yan Y, Zhang Q, Schwarz S, Shen J Abstract A total of 149 porcine Staphylococcus isolates with florfenicol MICs of ≥16 μg/ml were screened for the presence of the multiresistance gene cfr, its location on plasmids and its genetic environment. In total, 125 isolates carried either cfr (16 isolates), fexA (92 isolates) or both genes (17 isolates). The 33 cfr-carrying staphylococci, which included isolates of the species S. cohnii, S. arlettae, and S. saprophyticus in which the cfr gene has not been described before, exhibited a wide variety of SmaI pulsed-field gel electrophoresis patterns. In 18 cases, the cfr gene was located on plasmids. Four different types of cfr-carrying plasmids, pSS-01 (n=2; 40 kb), pSS-02 (n=3; 35.4 kb... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531031 Mon, 19 Dec 2011 05:00:00 +0100 5531031 http://www.medworm.com/index.php?rid=5531030&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%3D22183169%26dopt%3DAbstract Authors: Mendes RE, Woosley LN, Farrell DJ, Sader HS, Jones RN Abstract Oritavancin exhibited potent activity when tested against vancomycin-susceptible (MIC(50/90), 0.015/0.03 μg/ml) and vanB-carrying E. faecalis isolates (MIC(50/90), 0.015/0.015 μg/ml). Higher (16- to 32-fold) MIC(50/90) results were noted against vanA-harboring E. faecalis (MIC(50/90), 0.25/0.5 μg/ml), although oritavancin inhibited all strains at ≤0.5 μg/ml. Vancomycin-susceptible and vanB-carrying E. faecium strains (MIC(50/90), ≤0.008/≤0.008 μg/ml for both) were very susceptible to oritavancin, as were VanA-producing isolates (MIC(50/90), 0.03/0.06 μg/ml). Oritavancin exhibited good in vitro potency against this collection of organisms, including vancomycin-resistant enterococci. PMID: 2218316... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531030 Mon, 19 Dec 2011 05:00:00 +0100 5531030 http://www.medworm.com/index.php?rid=5531029&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%3D22183170%26dopt%3DAbstract In this study we conducted pairwise competitions and co-mingling experiments in chickens using clonally related and isogenic C. jejuni strains, which are either susceptible or resistant to erythromycin (Ery). In every competition pair, Ery-resistant (Ery(r)) Campylobacter was consistently outcompeted by the Ery-susceptible (Ery(s)) strain. In the co-mingling experiments, Ery(r) Campylobacter failed to transmit to chickens pre-colonized by Ery(s) Campylobacter, while isogenic Ery(s) Campylobacter was able to transmit to and establish dominance in chickens pre-colonized by Ery(r) Campylobacter. The fitness disadvantage was linked to the resistance-conferring mutations in the 23S rRNA. These findings clearly indicate that acquisition of macrolide resistance impairs the fitness and transmissio... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531029 Mon, 19 Dec 2011 05:00:00 +0100 5531029 http://www.medworm.com/index.php?rid=5531028&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%3D22183171%26dopt%3DAbstract Authors: Qian CD, Wu XC, Teng Y, Zhao WP, Li O, Fang SG, Huang ZH, Gao HC Abstract Hospital-acquired infections caused by drug-resistant bacteria are a significant challenge to patient safety. Numerous clinical isolates resistant to almost all commercially available antibiotics have emerged. Thus, novel antimicrobial agents, specifically those for multidrug-resistant Gram-negative bacteria, are urgently needed. In the current study, we report the isolation, structure elucidation, and preliminary biological characterization of a new cationic lipopeptide antibiotic, battacin or octapeptin B5, produced from a Paenibacillus tianmuensis soil isolate. Battacin kills bacteria in vitro and has potent activity against Gram-negative bacteria, including multidrug-resistant and extremely drug-... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531028 Mon, 19 Dec 2011 05:00:00 +0100 5531028 http://www.medworm.com/index.php?rid=5531027&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%3D22183172%26dopt%3DAbstract Conclusions: 3TC at 150 mg is not bioequivalent to the standard regimen of 300 mg, indicating that saturation of cytosine phosphorylation pathways is not achieved at a dose of 150 mg. PMID: 22183172 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531027 Mon, 19 Dec 2011 05:00:00 +0100 5531027 http://www.medworm.com/index.php?rid=5531026&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%3D22183173%26dopt%3DAbstract Authors: Song I, Borland J, Chen S, Patel P, Wajima T, Peppercorn A, Piscitelli SC Abstract Healthy subjects received dolutegravir 50 mg in a single-dose crossover study while they were in the fasted state and with low-, moderate-, and high-fat meals. Food increased dolutegravir exposures and reduced the rate of absorption. AUC(0-∞) increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting. This increase in dolutegravir exposure is not anticipated to impact clinical efficacy and therefore dolutegravir can be taken with or without food and without regard to fat content. PMID: 22183173 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531026 Mon, 19 Dec 2011 05:00:00 +0100 5531026 http://www.medworm.com/index.php?rid=5531025&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%3D22183174%26dopt%3DAbstract In this report we show that pyocin S2 displays potent activity against P. aeruginosa biofilms, thus representing a potentially improved therapeutic option. Using an invertebrate model of P. aeruginosa infection we also show that pyocin S2 is highly active in vivo. PMID: 22183174 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531025 Mon, 19 Dec 2011 05:00:00 +0100 5531025 http://www.medworm.com/index.php?rid=5531087&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%3D22155815%26dopt%3DAbstract Authors: Rouan MC, Lounis N, Gevers T, Dillen L, Gilissen R, Raoof A, Andries K Abstract TMC207 is a first in class diarylquinoline with a new mode of action against mycobacteria targeting the ATP synthase. It is metabolized to an active derivative, N-desmethyl TMC207, and both compounds are eliminated with long terminal half-lives (50-60 hours in mice) reflecting slow release from tissues such as lung and spleen. In vitro, TMC207 is 5-fold more potent against Mycobacterium tuberculosis than N-desmethyl TMC207, and the effects of the two compounds are additive. The pharmacokinetic-pharmacodynamic (PK-PD) response was investigated in the murine model of tuberculosis infection following oral administration of different doses of TMC207 or N-desmethyl TMC207 5 days per week for 4 weeks... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531087 Mon, 12 Dec 2011 05:00:00 +0100 5531087 http://www.medworm.com/index.php?rid=5531086&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%3D22155816%26dopt%3DAbstract In this study we also show the structural gene alone can be cloned into E. coli strain BL21 (DE3) and expression yields active peptide. PMID: 22155816 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531086 Mon, 12 Dec 2011 05:00:00 +0100 5531086 http://www.medworm.com/index.php?rid=5531085&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%3D22155817%26dopt%3DAbstract Authors: Hall RG, Swancutt MA, Meek C, Leff R, Gumbo T Abstract We conducted a prospective study of 18 adult volunteers (male-to-female ratio=1) whose body mass index fell into categories of <25, 25-40, >40 kg/m(2), who received a single oral dose of 1600 mg ethambutol. Only individuals with normal renal function were recruited. The minimum body mass (M) was 45.6 kg, the median 90.8 kg, and the maximum weight 160.4 kg. Ethambutol pharmacokinetics were best described by a two-compartment model. Inclusion of weight as covariate dramatically improved the model, with a relative likelihood approaching infinity. The typical clearance was 42.6 L/hr. Ethambutol systemic clearance was proportional to (M/45.6)(3/4), and thus obeyed fractal geometry based laws. This means that area unde... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531085 Mon, 12 Dec 2011 05:00:00 +0100 5531085 http://www.medworm.com/index.php?rid=5531084&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%3D22155818%26dopt%3DAbstract Authors: Tenover FC, Tickler IA, Goering RV, Kreiswirth BN, Mediavilla JR, Persing DH, Abstract A total of 299 nares and 194 blood isolates of methicillin-resistant Staphylococcus aureus (MRSA), each recovered from a unique patient, were collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates underwent spa and SCCmec typing and antimicrobial susceptibility testing; a subset of 84 isolates was typed by pulsed-field gel electrophoresis using SmaI. Seventy-six spa types were observed among the isolates. Overall, for nasal isolates, spa type t002/SCCmec type II (USA100) was the most common strain type (37% of isolates), while among blood isolates, spa type t008/SCCmec type IV (USA300) was the most common (39%). However, the proportion of all USA100 and USA300 isolat... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531084 Mon, 12 Dec 2011 05:00:00 +0100 5531084 http://www.medworm.com/index.php?rid=5531083&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%3D22155819%26dopt%3DAbstract This study compared the in-vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA, n=759), vancomycin-resistant Enterococcus faecium (VRE, n=191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n=602), ESBL-producing Klebsiella pneumoniae (n=736), and Acinetobacter baumannii (n=726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. Minimum inhibitory concentrations (MICs) and inhibition zone diameters were interpreted according to the currently recommended US Food and Drug Administration (US FDA) criteria and the European Committee on Antimic... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531083 Mon, 12 Dec 2011 05:00:00 +0100 5531083 http://www.medworm.com/index.php?rid=5531082&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%3D22155820%26dopt%3DAbstract Authors: Johnson TJ, Srinivasan P, Albright TH, Watson-Buckheit K, Rabe L, Martin A, Pau CP, Hendry RM, Otten R, McNicholl J, Buckheit R, Smith J, Kiser PF Abstract The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) or IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the IVR delivery system, four pyrimidinedione IVR formulations (PYD1(0.5wt%), PYD1(1wt%), PYD2(4wt%), and PYD2(14wt%)) were evaluated in pigtailed macaques over 28 days for safety and pyrimidinedione vaginal biodistribution. Kinetic analysis of vaginal proinflammatory cytokines, native microflora, and drug levels... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531082 Mon, 12 Dec 2011 05:00:00 +0100 5531082 http://www.medworm.com/index.php?rid=5531081&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%3D22155821%26dopt%3DAbstract Conclusions: Spores have a profound impact on the rate and extent of kill of BA. Against spore-forming BA, the five antibiotics killed the total (spore and vegetative) bacterial population at similar rates (within 1 log(10)CFU/mL of each other). However, bactericidal antibiotics killed vegetative BA faster than bacteriostatic drugs. Since only vegetative-phase BA produce the toxins that may kill the infected host, the rate and mechanism of kill of an antibiotic may determine its overall in vivo efficacy. Further studies are needed to examine this important observation. PMID: 22155821 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531081 Mon, 12 Dec 2011 05:00:00 +0100 5531081 http://www.medworm.com/index.php?rid=5531080&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%3D22155822%26dopt%3DAbstract THE EFFICACY AND TOLERABILITY OF ANTIBIOTIC COMBINATIONS IN NEUROBRUCELLOSIS: RESULTS OF THE ISTANBUL STUDY. Antimicrob Agents Chemother. 2011 Dec 12; Authors: Erdem H, Ulu A, Kilic S, Karahocagil M, Sheeta G, Eren-Tulek N, Yetkin F, Celen MK, Ceran N, Gul HC, Mert G, Tekin-Koruk S, Dizbay M, Inal AS, Nayman-Alpat S, Bosilkovski M, Inan D, Saltoglu N, Abdel-Baky L, Adeva-Bartolome MT, Ceylan B, Sacar S, Turhan V, Yilmaz E, Elaldi N, Kocak-Tufan Z, Ugurlu K, Dokuzoguz B, Yilmaz H, Gundes S, Guner R, Ozgunes N, Ulcay A, Unal S, Dayan S, Gorenek L, Karakas A, Tasova Y, Usluer G, Bayindir Y, Kurtaran B, Sipahi OR, Leblebicioglu H Abstract No datum exists in the literature whether Brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or should an intra... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531080 Mon, 12 Dec 2011 05:00:00 +0100 5531080 http://www.medworm.com/index.php?rid=5531079&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%3D22155823%26dopt%3DAbstract Authors: Sohl CD, Singh K, Kasiviswanathan R, Copeland WC, Mitsuya H, Sarafianos SG, Anderson KS Abstract The potent 4' -ethynyl-2-fluoro-2' -deoxyadenosine (EFdA) is a promising experimental agent for treating HIV infection. Pre-steady-state kinetics were used to characterize the interaction of EFdA-triphosphate (EFdA-TP) with human mitochondrial DNA polymerase γ (Pol γ) to assess the potential for toxicity. Pol γ incorporated EFdA-TP 4,300-fold less efficiently than dATP, with an excision rate similar to ddATP. This strongly indicates EFdA is a poor Pol γ substrate suggesting minimal Pol γ-mediated toxicity, although this should be examined under clinical settings. PMID: 22155823 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531079 Mon, 12 Dec 2011 05:00:00 +0100 5531079 http://www.medworm.com/index.php?rid=5531078&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%3D22155824%26dopt%3DAbstract Authors: Uçkay I, Bernard L, Buzzi M, Harbarth S, François P, Huggler E, Ferry T, Schrenzel J, Renzoni A, Vaudaux P, Lew DP Abstract Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates is considered a risk factor for failure of glycopeptide therapy. We compared the prevalence of MRSA isolates with reduced glycopeptide susceptibility in patients with versus without persistent or recurrent MRSA bloodstream infections. A retrospective, cohort study at the University Hospital of Geneva identified 27 patients with persistent or recurrent, clonally-related MRSA bacteremic episodes over an 8-year period that included 208 consecutive, nosocomial MRSA bacteremic episodes. Vancomycin and teicoplanin MICs were determined by a modif... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531078 Mon, 12 Dec 2011 05:00:00 +0100 5531078 http://www.medworm.com/index.php?rid=5531077&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%3D22155825%26dopt%3DAbstract Authors: Arpin C, Thabet L, Yassine H, Messadi A, Boukadida J, Dubois V, Coulange-Mayonnove L, Andre C, Quentin C Abstract During a 2-year period in 2005-2006, 64 multidrug-resistant Providencia stuartii including 58 isolates from 58 patients and six strains obtained from the same tracheal aspirator were collected in a burn unit of a Tunisian Hospital. They divided in four antibiotypes (ATB) and three SmaI-pulsotypes, including 49 strains belonging to clone PsA (48 of ATB1 and, 1 of ATB4), 11 strains to clone PsB (7 of ATB2 and, 4 of ATB3), and 4 strains to clone PsC (ATB3). All strains, except for the PsA/ATB4 isolate, were highly resistant to broad-spectrum cephalosporins due to the production of the plasmid-mediated CMY-16 ß-lactamase. In addition, the 15 strains of ATB2 and AT... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531077 Mon, 12 Dec 2011 05:00:00 +0100 5531077 http://www.medworm.com/index.php?rid=5531076&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%3D22155826%26dopt%3DAbstract Authors: Wivagg CN, Hung DT Abstract Mycobacterial resuscitation-promoting factors (RPFs) have been of great interest since the discovery that they promote the growth of non-culturable Mycobacterium tuberculosis cells. Yet, their precise role in mycobacterial survival and infection has remained elusive. We performed a chemical screen to identify molecules that show preferential killing of a Mycobacterium tuberculosis mutant lacking RPFs over wild-type bacilli and found that the mutant has enhanced sensitivity to the β-lactam class of antibiotics. By monitoring β-lactam diffusion across the mycobacterial outer membrane, we found that the RPFs are required to maintain the outer membrane integrity, as their deletion results in an increase in outer membrane permeability. PMID: 22... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531076 Mon, 12 Dec 2011 05:00:00 +0100 5531076 http://www.medworm.com/index.php?rid=5531075&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%3D22155827%26dopt%3DAbstract Authors: Belser JA, Sleeman K, Pearce MB, Katz JM, Gubareva LV, Tumpey TM Abstract The majority of human infections associated with H7 influenza viruses have resulted in ocular and not respiratory disease. While oseltamivir has been prescribed to individuals presenting with conjunctivitis following H7 virus exposure, it is unknown if oseltamivir inhibits virus replication in ocular tissue. We demonstrate that H7 viruses possess sensitivity to neuraminidase inhibitors, and that administration of oseltamivir before ocular virus challenge in mice inhibits H7N7 and H7N3 virus replication in ocular and respiratory tissues. PMID: 22155827 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531075 Mon, 12 Dec 2011 05:00:00 +0100 5531075 http://www.medworm.com/index.php?rid=5531074&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%3D22155828%26dopt%3DAbstract This study paves the way for the potential use of CO-RMs, such as ALF492, as adjunctive/adjuvant treatment in severe forms of malaria infection. PMID: 22155828 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531074 Mon, 12 Dec 2011 05:00:00 +0100 5531074 http://www.medworm.com/index.php?rid=5531073&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%3D22155829%26dopt%3DAbstract This study shows the importance in Y145F alteration of Erg11 in C. neoformans for manifestation of differential susceptibility towards different triazoles. It underscores the necessity of in vitro susceptibility testing for each FLC resistant C. neoformans clinical isolate against different groups of azoles in order to assist patient management. PMID: 22155829 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531073 Mon, 12 Dec 2011 05:00:00 +0100 5531073 http://www.medworm.com/index.php?rid=5531072&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%3D22155830%26dopt%3DAbstract Authors: Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P Abstract Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the extended-spectrum cephalosporins (ESC) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhoea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance, which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, pe... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531072 Mon, 12 Dec 2011 05:00:00 +0100 5531072 http://www.medworm.com/index.php?rid=5531071&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%3D22155831%26dopt%3DAbstract Authors: Dodds S, Smith TJ, Akid R, Stephenson J, Nichol T, Banerjee RD, Stockley I, Townsend R Abstract The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account has been taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used ant... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531071 Mon, 12 Dec 2011 05:00:00 +0100 5531071 http://www.medworm.com/index.php?rid=5531041&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%3D22155832%26dopt%3DAbstract This study clarifies the relationship between carbapenem resistance and mortality of patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may be not as great during the first days of the bacteremia or in the presence of comorbidities. PMID: 22155832 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531041 Mon, 12 Dec 2011 05:00:00 +0100 5531041 http://www.medworm.com/index.php?rid=5531040&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%3D22155833%26dopt%3DAbstract Authors: Fischer CL, Drake D, Dawson DV, Blanchette DR, Brogden KA, Wertz PW Abstract There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address mechanisms of antibacterial activity, we determined minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of lipids common to the skin and oral cavity: sphingoid bases D-sphingosine, phytosphingosine, and dihydrosphingosine, and fatty acids sapienic acid and lauric acid, against four gram-negative bacteria and seven gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (p = <... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531040 Mon, 12 Dec 2011 05:00:00 +0100 5531040 http://www.medworm.com/index.php?rid=5531039&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%3D22155834%26dopt%3DAbstract Conclusions.These results demonstrate the utility of frequentist and Bayesian pharmacometric-based analyses for the determination of treatment effect using contemporary trial endpoints. Additionally, as demonstrated using pharmacokinetic-pharmacodynamic data, the magnitude of treatment effect for patients with HAP is large. PMID: 22155834 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531039 Mon, 12 Dec 2011 05:00:00 +0100 5531039 http://www.medworm.com/index.php?rid=5531038&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%3D22155835%26dopt%3DAbstract Authors: Hegde SS, Okusanya OO, Skinner R, Shaw JP, Obedencio G, Ambrose PG, Blais J, Bhavnani SM Abstract TD-1792 is a novel glycopeptide-cephalosporin heterodimer investigational antibiotic that displays potent bactericidal effects against clinically relevant Gram-positive organisms in vitro. The present studies evaluated the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of TD-1792 in the neutropenic murine thigh infection animal model. TD-1792, dosed subcutaneously (SC), produced dose-dependent reduction in the thigh bacterial burden of several organisms including methicillin susceptible and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis (MSSA, MRSA, MSSE, MRSE, respectively), penicillin susceptible strains of Streptococcus pneumoniae (PSSP),... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531038 Mon, 12 Dec 2011 05:00:00 +0100 5531038 http://www.medworm.com/index.php?rid=5531037&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%3D22155836%26dopt%3DAbstract In this study fecal samples of 586 healthy humans were investigated to determine the occurrence of ESBL producing Enterobacteriaceae in Swiss people. A total of 5.8% of the human fecal samples yielded ESBL producers and all of the 34 isolated strains were Escherichia coli. PCR analysis revealed that 14 strains produced CTX-M-15, ten produced CTX-M-1, seven strains produced CTX-M-14 while two strains produced CTX-M-2 ESBLs. One strain produced SHV-12 ESBL. Fifteen of the 34 isolates produced additional TEM-1 broad-spectrum β-lactamase. By serotyping, a high diversity among the strains was found. PMID: 22155836 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531037 Mon, 12 Dec 2011 05:00:00 +0100 5531037 http://www.medworm.com/index.php?rid=5531036&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%3D22155837%26dopt%3DAbstract Authors: Brown AN, McSharry JJ, Adams JR, Kulawy R, Barnard RJ, Newhard W, Corbin A, Hazuda DJ, Louie A, Drusano GL Abstract The development of new antiviral compounds active against HCV has surged in recent years. In order for these new compounds to be efficacious in man, optimal dosage regimens for each compound must be elucidated. We have developed a novel in vitro PK/PD system, the BelloCell system, to identify optimal dosage regimens for anti-HCV compounds. In these experiments, genotype 1b HCV replicon-bearing cells (2209-23 cells) were inoculated on to carrier flakes in BelloCell bottles and treated with MK-4519, a serine protease inhibitor. Our dose ranging studies illustrated that MK-4519 inhibited replicon replication in a dose dependant manner, yielding an EC(50) of 1.8 ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531036 Mon, 12 Dec 2011 05:00:00 +0100 5531036 http://www.medworm.com/index.php?rid=5531035&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%3D22155838%26dopt%3DAbstract Authors: Matos J, P da Cruz F, Cabrita E, Gut J, Nogueira F, do Rosário VE, Moreira R, Rosenthal PJ, Prudêncio M, Gomes P Abstract Novel conjugates of the antimalarial drug primaquine (1) with ferrocene, named primacenes, have been synthesized and screened for their activity against blood- and liver-stage malaria in vitro and host-vector transmission in vivo. Both transmission-blocking and blood-schizontocidal activities of the parent drug were only conserved in primacenes bearing a basic aliphatic amine group. Liver-stage activity did not require this structural feature, and all metallocenes tested were comparable to or better than primaquine in this regard. Remarkably, replacing primaquine's aliphatic chain by hexylferrocene, as in 7, led to ∼45-fold greater activity against ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531035 Mon, 12 Dec 2011 05:00:00 +0100 5531035 http://www.medworm.com/index.php?rid=5531034&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%3D22155839%26dopt%3DAbstract Authors: Papaevangelou V, Rousounides A, Hadjipanagis A, Katsioulis A, Theodoridou M, Hadjichristodoulou C Abstract To assess the impact of intervention on antibiotic misuse in children, parental and pediatricians' Knowledge (K), Attitude (A) and Practices (P) concerning antibiotic use, were evaluated pre- and post-intervention in Larnaca and Limassol. Concurrently, pediatricians documented URTI visits and pharmacists provided antibiotic consumption data. Intervention was implemented on parents and pediatricians residing in Larnaca. The consumption/URTI-incidence index was significantly reduced in Larnaca but not Limassol. Parental responses remained unchanged therefore antibiotic consumption reduction is attributable to pediatricians' education. PMID: 22155839 [PubMed - as sup... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5531034 Mon, 12 Dec 2011 05:00:00 +0100 5531034 http://www.medworm.com/index.php?rid=5492523&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%3D22143517%26dopt%3DAbstract In conclusion, the specific identity of M. tuberculosis strain used was found to be an important variable that can change the apparent outcome of in vivo efficacy studies in mice. We highly recommend confirmation of efficacy results in late preclinical testing against a different M. tuberculosis strain than the one used in the initial mouse efficacy study thereby, increasing confidence to advance potent drug regimens forward into clinical trials. PMID: 22143517 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492523 Mon, 05 Dec 2011 05:00:00 +0100 5492523 http://www.medworm.com/index.php?rid=5492522&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%3D22143518%26dopt%3DAbstract Authors: Ruf MT, Schütte D, Chauffour A, Jarlier V, Ji B, Pluschke G Abstract Combination chemotherapy with rifampicin and streptomycin (RIF-STR) for eight weeks is currently recommended by WHO as first line treatment in Mycobacterium ulcerans infection (Buruli ulcer). To gain better insight into the mode of action of these antibiotics against established M. ulcerans infection foci and to characterize recovery of local immune responses during chemotherapy, we conducted a detailed histopathological study in M. ulcerans infected and RIF-STR treated mice. Mice were inoculated with M. ulcerans in the footpad and eleven weeks later treated with RIF-STR. Development of lesions during the first eleven weeks after infection and subsequent differences in disease progression between RIF-STR... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492522 Mon, 05 Dec 2011 05:00:00 +0100 5492522 http://www.medworm.com/index.php?rid=5492521&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%3D22143519%26dopt%3DAbstract Authors: Fernández M, Conde S, de la Torre J, Molina-Santiago C, Ramos JL, Duque E Abstract Pseudomonas putida KT2440 is a chloramphenicol resistant bacterium that is able to grow in the presence of this antibiotic at a concentration of up to 25 μg/mL. Transcriptomic analyses revealed that the expression profile of 102 genes changed in response to this concentration of chloramphenicol in the culture medium. The genes that showed altered expression include those involved in general metabolism, cellular stress response, gene regulation, efflux pump transporters and protein biosynthesis. Analysis of a genome-wide collection of mutants showed that survival of a knock-out mutant in the TtgABC RND efflux pump and mutants in the biosynthesis of pyrrolquinoline (PQQ) were compromised in ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492521 Mon, 05 Dec 2011 05:00:00 +0100 5492521 http://www.medworm.com/index.php?rid=5492520&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%3D22143520%26dopt%3DAbstract Authors: Yi G, Deval J, Fan B, Cai H, Soulard C, Ranjith-Kumar CT, Smith DB, Blatt L, Beigelman L, Kao CC Abstract Filibuvir and VX-222 are non-nucleoside inhibitors (NNIs) that bind to the thumb II allosteric pocket of the hepatitis C virus (HCV) RNA-dependent RNA polymerase. Both compounds have shown significant promise in clinical trials and, therefore, it is relevant to better understand their mechanisms of inhibition. In our study, Filibuvir and VX-222 inhibited the 1b/Con1 HCV subgenomic replicon with an EC(50) of 70 nM and 5 nM, respectively. Using several RNA templates in biochemical assays, we show that both compounds preferentially inhibited primer-dependent RNA synthesis, but had either no or only modest effects on de novo initiated RNA synthesis. Filibuvir and VX-222 bi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492520 Mon, 05 Dec 2011 05:00:00 +0100 5492520 http://www.medworm.com/index.php?rid=5492519&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%3D22143521%26dopt%3DAbstract Authors: Roy CJ, Sivasubramani SK, Dutta NK, Mehra S, Golden NA, Killeen S, Talton JD, Hammoud BE, Didier PJ, Kaushal D Abstract Tuberculosis (TB) is a major infectious disease problem. 1.8 million people annually die due to TB. Emergence of drug-resistant Mycobacterium tuberculosis (Mtb) and the lack of new antibiotics have exacerbated the situation. There is an urgent need to develop or repurpose drugs against TB. We evaluated inhaled gentamicin as direct respiratory-targeted therapy in a murine model of TB. Aerosolized gentamicin treated mice showed significantly reduced lung Mtb loads and fewer granulomas relative to untreated controls. These results suggest that direct delivery of antibiotics to the respiratory system may provide therapeutic benefit to conventional treatment r... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492519 Mon, 05 Dec 2011 05:00:00 +0100 5492519 http://www.medworm.com/index.php?rid=5492518&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%3D22143522%26dopt%3DAbstract Authors: Ho KK, Cole N, Chen R, Willcox MD, Rice SA, Kumar N Abstract Antibiotic resistant Staphylococcus aureus is of great concern as it causes a wide range of life-threatening infections. The current study demonstrates that dihydropyrrolone (DHP)-coated polyacrylamide substrates are effective in reducing the number of culturable clinical isolate of S. aureus in vitro in a dose dependent manner, and are able to reduce the pathogenic potential of Staphylococcal infection in a subcutaneous infection model. Covalently bound DHPs therefore show great potential for use as an antimicrobial strategy in device-related applications. PMID: 22143522 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492518 Mon, 05 Dec 2011 05:00:00 +0100 5492518 http://www.medworm.com/index.php?rid=5492517&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%3D22143523%26dopt%3DAbstract Authors: Zhu X, Pandharkar T, Werbovetz K Abstract A previous screen of ∼200,000 compounds from the PubChem database identified seventy compounds possessing EC(50) values below 1 μM against L. major promastigotes that were not toxic to mammalian epithelial cancer cells at this concentration (Sharlow, E., D. Close, T. Shun, S. Leimgruber, R. Reed, G. Mustata, P. Wipf, J. Johnson, M. O'Neil, M. Grögl, A. Magill, and J. Lazo. 2009. PLoS Negl. Trop. Dis. 3:e540). Based on availability and chemical exclusion criteria, thirty-one of these compounds were purchased from commercial suppliers and evaluated for in vitro activity against intracellular L. donovani and L. amazonensis parasites. Benzothiazole cyanine compounds (PubChem 16196319 and 16196223) displayed potent activity against ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492517 Mon, 05 Dec 2011 05:00:00 +0100 5492517 http://www.medworm.com/index.php?rid=5492516&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%3D22143524%26dopt%3DAbstract Authors: Bhavnani SM, Rubino CM, Hammel JP, Forrest A, Dartois N, Cooper CA, Korth-Bradley J, Ambrose PG Abstract Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) enrolled in a Phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological response using data from 61 evaluable HAP patients who received tigecycline intravenously as a 100 mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and who had adequate clinical, pharmacokinetic and response data. The final multivariable logistic regression model for clinical response cont... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492516 Mon, 05 Dec 2011 05:00:00 +0100 5492516 http://www.medworm.com/index.php?rid=5492515&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%3D22143525%26dopt%3DAbstract Authors: Long KS, Vester B Abstract Linezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the ribosomal 50S subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away fr... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492515 Mon, 05 Dec 2011 05:00:00 +0100 5492515 http://www.medworm.com/index.php?rid=5492514&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%3D22143526%26dopt%3DAbstract Authors: Poirel L, Bonnin RA, Boulanger A, Schrenzel J, Kaase M, Nordmann P Abstract A multidrug-resistant Acinetobacter baumannii isolate recovered from a patient hospitalized in Switzerland after a transfer from Serbia produced the NDM-1 carbapenemase. The bla(NDM-1) gene was part of a chromosomally-located Tn125 composite transposon bracketed by two copies of the same insertion sequence ISAba125. This transposon was also associated to the acquisition and the expression of the bla(NDM-2) gene in an A. baumannii isolate in Germany. Tn125 appears to be the main vehicle for dissemination of bla(NDM) genes in that species. PMID: 22143526 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492514 Mon, 05 Dec 2011 05:00:00 +0100 5492514 http://www.medworm.com/index.php?rid=5492513&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%3D22143527%26dopt%3DAbstract Authors: Hyytiäinen H, Hänninen ML Abstract Campylobacter jejuni ATCC 33560 (CCM 6214) is the quality-control (QC) strain for the antimicrobial susceptibility testing of Campylobacter spp. (1, 6).… PMID: 22143527 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492513 Mon, 05 Dec 2011 05:00:00 +0100 5492513 http://www.medworm.com/index.php?rid=5492512&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%3D22143528%26dopt%3DAbstract Authors: Reisfeld B, Metzler CP, Lyons MA, Mayeno AN, Brooks EJ, Degroote MA Abstract The emergence of multidrug-resistant tuberculosis (MDR-TB) has led to a renewed interest in the use of second-line antibiotic agents. Unfortunately, there is currently a dearth of information, data, and computational models that can be used to help design rational regimens for administration of these drugs. To help fill this knowledge gap, an exploratory physiologically-based pharmacokinetic (PBPK) model, supported by targeted experimental data, was developed to predict the absorption, distribution, metabolism, and excretion (ADME) of the second-line agent capreomycin, a cyclic peptide antibiotic often grouped with the aminoglycoside antibiotics. To account for inter-individual variability, Bayesi... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492512 Mon, 05 Dec 2011 05:00:00 +0100 5492512 http://www.medworm.com/index.php?rid=5492511&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%3D22143529%26dopt%3DAbstract CONCLUSION:Rates of GBS resistance to clindamycin and erythromycin are much higher than reported in earlier US studies, suggesting both increasing resistance as well as regional variation in resistance. These findings lend strong support to the CDC and ACOG recommendations that clindamycin use for intrapartum antibiotic prophylaxis be restricted to penicillin allergic women at high risk of anaphylaxis and that GBS isolates be tested for antibiotic resistance prior to the use of clindamycin in these women. PMID: 22143529 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492511 Mon, 05 Dec 2011 05:00:00 +0100 5492511 http://www.medworm.com/index.php?rid=5492510&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%3D22143530%26dopt%3DAbstract In this study, we assessed the selectivity of the inhibitory activity of E1210 against Candida albicans GWT1 (Orf19.6884) protein, Aspergillus fumigatus GWT1 (AFUA_1G14870) protein, and human PIG-W proteins that could catalyze the inositol acylation of GPI early in the GPI biosynthesis pathway, and then assessed the effects of E1210 on key C. albicans virulence factors. E1210 inhibited the inositol acylation activity of C. albicans Gwt1p and A. fumigatus Gwt1p with IC(50)s of 0.3 to 0.6 μM, but had no inhibitory activity on human Pig-Wp even at concentrations as high as 100 μM. To confirm the inhibition of fungal GPI biosynthesis, expression of ALS1 protein, a GPI-anchored protein, on the cell surface of C. albicans treated with E1210 was studied and shown to be significantly lower than ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492510 Mon, 05 Dec 2011 05:00:00 +0100 5492510 http://www.medworm.com/index.php?rid=5492509&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%3D22143531%26dopt%3DAbstract Authors: Schaeffer M, Schroeder J, Heckeroth AR, Noack S, Gassel M, Mottram JC, Selzer PM, Coombs GH Abstract Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria. We have identified a single copy cathepsin B-like cysteine peptidase (EtCatB) gene in the genome database of Eimeria tenella. Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris. Biochemical characterisation of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone and an oxazolon) that c... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492509 Mon, 05 Dec 2011 05:00:00 +0100 5492509 http://www.medworm.com/index.php?rid=5492508&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%3D22143532%26dopt%3DAbstract This study identified a bla(TEM) variant (bla(TEM-135)) that is a possible intermediate precursor for an ESBL, which warrants international awareness. PMID: 22143532 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492508 Mon, 05 Dec 2011 05:00:00 +0100 5492508 http://www.medworm.com/index.php?rid=5492507&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%3D22143533%26dopt%3DAbstract Authors: Gonzalez-Serna A, McGovern RA, Harrigan PR, Vidal F, Poon AF, Ferrando-Martinez S, Abad MA, Genebat M, Leal M, Ruiz-Mateos E Abstract Genotypic tropism methods are emerging as the first treatment option before prescription of the CCR5 antagonist Maraviroc (MVC) to HIV-infected patients in Europe. Studies validating the genotypic tests have included other active drugs that could have potentially convoluted the effects of MVC. The Maraviroc Clinical Test (MCT) is an in vivo drug sensitivity test based on the virological response to a short-term exposure to MVC monotherapy. Thus, our aim was to compare genotypic tropism methods with the short-term virological response to MVC monotherapy. A virological response in the MCT was defined as a ≥1 log(10) decrease in HIV-RNA or un... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5492507 Mon, 05 Dec 2011 05:00:00 +0100 5492507 http://www.medworm.com/index.php?rid=5417821&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%3D22081724%26dopt%3DAbstract Authors: Rice LB PMID: 22081724 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417821 Fri, 18 Nov 2011 02:22:16 +0100 5417821 http://www.medworm.com/index.php?rid=5417820&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%3D22081725%26dopt%3DAbstract Authors: Kees MG, Lodise TP, Drusano GL PMID: 22081725 [PubMed - in process] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417820 Fri, 18 Nov 2011 02:22:07 +0100 5417820 http://www.medworm.com/index.php?rid=5417819&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%3D22083465%26dopt%3DAbstract Authors: Poirel L, Bonnin RA, Nordmann P Abstract Complete sequencing of plasmid pOXA-48a carrying the bla(OXA-48) gene from a Klebsiella pneumoniae isolate was performed. Its backbone corresponded to that of an IncL/M-type plasmid, on which the bla(OXA-48) gene had been integrated through the acquisition of the Tn1999 composite transposon, without any other antibiotic resistance gene. Molecular epidemiology using a collection of international OXA-48 producers revealed the wide diffusion of pOXA-48a or closely related plasmids. PMID: 22083465 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417819 Mon, 14 Nov 2011 05:00:00 +0100 5417819 http://www.medworm.com/index.php?rid=5417818&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%3D22083466%26dopt%3DAbstract Conclusions: Doripenem penetrates well into interstitial space fluid of skeletal muscle and adipose tissue suggesting good antimicrobial activity in infected soft tissues, whereas it is detectable in relatively low concentrations in saliva. PMID: 22083466 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417818 Mon, 14 Nov 2011 05:00:00 +0100 5417818 http://www.medworm.com/index.php?rid=5417817&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%3D22083467%26dopt%3DAbstract Authors: Tucker MS, Mutka T, Sparks K, Patel J, Kyle DE Abstract Emergence of artemisinin resistance in Cambodia highlights the importance of characterizing resistance to this class of drugs. Previously, intermediate levels of resistance in Plasmodium falciparum were generated in vitro for artelinic acid (AL) and artemisinin (QHS). Here we expand on earlier selection efforts to produce levels of clinically relevant concentrations and the resulting lines were characterized genotypically and phenotypically. Recrudescence assays determined the ability of resistant and parent lines to recover following exposure to clinically relevant levels of drugs. Interestingly, the parent clone (D6) tolerated up to 1500 ng/ml QHS, but the resistant parasite, D6.QHS340x3, recovered following exposur... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417817 Mon, 14 Nov 2011 05:00:00 +0100 5417817 http://www.medworm.com/index.php?rid=5417816&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%3D22083468%26dopt%3DAbstract We describe a virucidal small molecule, PD 404,182, effective against hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The median IC(50) values for the antiviral effect of PD 404,182 against HCV and HIV in cell culture are 11 μM and 1 μM, respectively. The antiviral activity of PD 404,182 is due to physical disruption of virions that is accompanied to varying degrees (depending on the virus and exposure temperature/time) by release of viral nucleic acids into the surrounding medium. PD 404,182 does not directly lyse liposomal membranes even after extended exposure and shows no attenuation in antiviral activity when pre-incubated with liposomes of various lipid compositions, suggesting that the compound inactivates viruses through interaction with a non-lipid structural com... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417816 Mon, 14 Nov 2011 05:00:00 +0100 5417816 http://www.medworm.com/index.php?rid=5417815&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%3D22083469%26dopt%3DAbstract In conclusion, E1210 exhibited very potent and broad-spectrum antifungal activity against azole- and amphotericin B -resistant strains of Fusarium spp. and Scedosporium spp. Furthermore, in vitro susceptibility testing of E1210 against isolates of Fusarium and Scedosporium may be accomplished using either CLSI or EUCAST BMD methods, each producing very similar results. PMID: 22083469 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417815 Mon, 14 Nov 2011 05:00:00 +0100 5417815 http://www.medworm.com/index.php?rid=5417814&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%3D22083470%26dopt%3DAbstract Authors: Matsumoto T, Nagata M, Ishimine N, Kawasaki K, Yamauchi K, Hidaka E, Kasuga E, Horiuchi K, Oana K, Kawakami Y, Honda T Abstract An Ambler class A β-lactamase gene, bla(CIA-1), was cloned from the reference strain Chryseobacterium indologenes ATCC 29897 and expressed in Escherichia coli BL21. The bla(CIA-1) gene encodes a novel extended-spectrum β-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 β-lactamases, respectively. bla(CIA-1)-like genes were detected from clinical isolates. In addition to the metallo-β-lactamase IND of Ambler class B, C. indologenes has a class A ESBL gene, bla(CIA-1), located on the chromosome. PMID: 22083470 [PubMed - as supplied by publisher] (Source: Antimicrobial Agents and Chemotherapy) Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417814 Mon, 14 Nov 2011 05:00:00 +0100 5417814 http://www.medworm.com/index.php?rid=5417813&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%3D22083471%26dopt%3DAbstract Authors: Würthwein G, Young C, Lanvers-Kaminsky C, Hempel G, Trame MN, Schwerdtfeger R, Ostermann H, Heinz WJ, Cornely OA, Kolve H, Boos J, Silling G, Groll AH Abstract Liposomal amphotericin B (LAMB) and caspofungin (CAS) are important antifungal agents in allogeneic hematopoietic stem cell transplant (aHSCT) recipients. Little is known, however, about the pharmacokinetics (PK) of both agents and their combination in this population.The PK of LAMB and CAS and the potential for PK interactions between both agents were investigated within a risk-stratified, randomized phase II clinical trial in 53 adult aHSCT recipients with granulocytopenia and refractory fever. Patients received either LAMB (n=17; 3 mg/kg once a day (QD), CAS (n=19; 50 mg QD; day 1: 70 mg) or the combination of b... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417813 Mon, 14 Nov 2011 05:00:00 +0100 5417813 http://www.medworm.com/index.php?rid=5417812&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%3D22083472%26dopt%3DAbstract IN VITRO ACTIVITY OF CANDIDATE MICROBICIDES AGAINST CELL-ASSOCIATED HIV. Antimicrob Agents Chemother. 2011 Nov 14; Authors: Selhorst P, Grupping K, Bourlet T, Delézay O, Ariën KK, Vanham G Abstract Most research on HIV transmission and microbicides focuses on the inhibition of cell-free virus (CFV) present in genital secretions. However, an effective microbicide should also block the transmission of cell-associated virus (CAV) originating from seminal T-cells and macrophages. Because inhibition of CAV remains controversial, especially for viral entry inhibitors, we developed a novel in vitro assay to evaluate the activity of different classes of candidate microbicides against cell-free HIV and HIV-infected leucocytes (i.e, resting PBMC, activated PBMC and monocyte-derived... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417812 Mon, 14 Nov 2011 05:00:00 +0100 5417812 http://www.medworm.com/index.php?rid=5417811&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%3D22083473%26dopt%3DAbstract Authors: Cardone KE, Grabe DW, Kulawy RW, Daoui R, Roglieri J, Meola S, Drusano GL, Lodise TP Abstract Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to: characterize the PK profile of ertapenem during CAPD; determine extent of ertapenem penetration into the peritoneal cavity; and quantify the probability of target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined probability that ertapenem 500 mg IV Q24 hours would achieve concentrations in excess of the minimum inhibitory concentration (MIC) for 40% of the dosing interval (40% T>MIC) in t... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417811 Mon, 14 Nov 2011 05:00:00 +0100 5417811 http://www.medworm.com/index.php?rid=5417810&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%3D22083474%26dopt%3DAbstract INACTIVATION OF THE LIPOPEPTIDE ANTIBIOTIC DAPTOMYCIN BY HYDROLYTIC MECHANISMS. Antimicrob Agents Chemother. 2011 Nov 14; Authors: D'Costa VM, Mukhtar TA, Patel T, Koteva K, Waglechner N, Hughes DW, Wright GD, De Pascale G Abstract The lipopeptide daptomycin is a member of the newest FDA-approved antimicrobial class, exhibiting potency against a broad range of Gram-positive pathogens, with only rare incidences of clinical resistance. Environmental bacteria harbor an abundance of resistance determinants orthologous to those in pathogens, and thus may serve as an early warning system for future clinical emergence. A collection of morphologically diverse environmental actinomycetes, demonstrating unprecedented frequencies of daptomycin resistance and high levels of resistance ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417810 Mon, 14 Nov 2011 05:00:00 +0100 5417810 http://www.medworm.com/index.php?rid=5417809&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%3D22083475%26dopt%3DAbstract Authors: Wittlin S, Ekland E, Craft JC, Lotharius J, Bathurst I, Fidock DA, Fernandes P Abstract With the emergence of Plasmodium falciparum infections exhibiting increased parasite clearance times in response to treatment with artemisinin-based combination therapies, the need for new therapeutic agents is urgent. Solithromycin, a potent new fluoroketolide currently in development, has been shown to be an effective, broad-spectrum antimicrobial agent. Malarial parasites possess an unusual organelle, termed the apicoplast, which carries a cryptic genome of prokaryotic origin that encodes its own translation and transcription machinery. Given the similarity of apicoplast and bacterial ribosomes, we have examined solithromycin for antimalarial activity. Other antibiotics known to targ... Antimicrobial Agents and Chemotherapy journals http://www.medworm.com/rss/comments.php?id=5417809 Mon, 14 Nov 2011 05:00:00 +0100 5417809