MedWorm: Microbiology

Influence of subtilisin on the adhesion of a marine bacterium which produces mainly proteins as extracellular polymers

Journal of Applied Microbiology — Fri, 16 May 2008 18:26:10 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: The nature of exopolymers involved in the adhesion of a marine biofilm-forming bacterium Pseudoalteromonas sp. D41 was investigated to evaluate and understand the antifouling potential of subtilisin.Methods and Results: The exopolymers of ... (Source: Journal of Applied Microbiology)

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Antibody action after phagocytosis promotes cryptococcus neoformans and cryptococcus gattii macrophage exocytosis with biofilm-like microcolony formation

Cellular Microbiology — Fri, 16 May 2008 18:12:41 +0100

Cellular Microbiology, Volume 0, Issue 0, Page ???, December 2004. Summary Antibody-mediated phagocytosis was discovered over a century ago but little is known about antibody effects in phagolysosomes. We explored the consequences of antibody-mediated phagocytosis for two closely related human pathogenic fungal species, ... (Source: Cellular Microbiology)

In the news

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

In the News Nature Reviews Microbiology 6, 416 (2008). doi:10.1038/nrmicro1926 New fungicide foundInsects such as Drosophila spp. produce a range of antimicrobial peptides to protect against infection. One of the antimicrobial peptides that is produced by Drosophila spp. is drosomycin, which has been shown to be highly active against filamentous fungi and (Source: Nature Reviews Microbiology)

In this issue

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

In this issue Nature Reviews Microbiology 6, 409 (2008). doi:10.1038/nrmicro1925 Bacteria and archaea are able to move both in liquids and on solid surfaces, and the mechanisms that they use to do so have long been a fascination of many microbiologists. On page 466, Ken Jarrell and Mark McBride describe the many different methods (Source: Nature Reviews Microbiology)

Cellular microbiology: all aboard the cell-wall shuttle

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Cellular microbiology: All aboard the cell-wall shuttle Nature Reviews Microbiology 6, 414 (2008). doi:10.1038/nrmicro1924 Author: Sheilagh Molloy The coordination of bacterial cell-wall synthesis has been hotly debated for almost 40 years. A recent paper in Molecular Microbiology now sheds new light on this topic by revealing how the cell elongation–division cycle is controlled in Bacillus subtilis.In rod-shaped bacteria, such (Source: Nature Reviews Microbiology)

Cellular microbiology: virus plays dead

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Cellular microbiology: Virus plays dead Nature Reviews Microbiology 6, 411 (2008). doi:10.1038/nrmicro1923 Author: Arianne Heinrichs Vaccinia virus is a large, complex, enveloped DNA virus that belongs to the Poxviridae family of viruses, which includes variola, the causative agent of smallpox. The infectious mature virus (MV) form of vaccinia has been shown to bind to actin-containing finger-like protrusions (filopodia) of the (Source: Nature Reviews Microbiology)

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Virtual networking for microbiologists

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Virtual networking for microbiologists Nature Reviews Microbiology 6, 410 (2008). doi:10.1038/nrmicro1922 The advent of Web 2.0 applications, which enable information sharing and virtual networking, could revolutionize science. But are microbiologists taking advantage? (Source: Nature Reviews Microbiology)

Immune evasion: overcoming defensins

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Immune evasion: Overcoming defensins Nature Reviews Microbiology 6, 415 (2008). doi:10.1038/nrmicro1921 Author: Asher Mullard Human cells rely on various antimicrobial peptides, including defensins, to prevent the spread of pathogenic bacteria. For example, defensins can induce chemotaxis of dendritic cells, and expression of defensins correlates with inhibition of bacterial RNA, DNA and protein synthesis, as well as with reduced bacterial (Source: Nature Reviews Microbiology)

Techniques and applications: a model infection

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Techniques and applications: A model infection Nature Reviews Microbiology 6, 413 (2008). doi:10.1038/nrmicro1920 Author: Sheilagh Molloy Reporting in a recent issue of PLoS Biology, Andrew Grant and colleagues describe a new method of modelling the within-host spatiotemporal dynamics of an infection with an intracellular bacterial pathogen.Grant et al. chose to study Salmonella enterica serovar Typhimurium (S. (Source: Nature Reviews Microbiology)

In brief

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

In brief Nature Reviews Microbiology 6, 412 (2008). doi:10.1038/nrmicro1915 SymbiosisFree-living tubeworm endosymbionts found at deep-sea ventsHarmer, T. L.et al. Appl. Environ. Microbiol.11 Apr 2008 (doi: 10.1128/AEM.02470-07)Bacterial symbionts can be transmitted by vertical (parent to offspring), horizontal (between individuals in the same niche) or environmental (acquisition (Source: Nature Reviews Microbiology)

Coordinating assembly of a bacterial macromolecular machine

Nature Reviews Microbiology — Fri, 16 May 2008 14:47:42 +0100

Coordinating assembly of a bacterial macromolecular machine Nature Reviews Microbiology 6, 455 (2008). doi:10.1038/nrmicro1887 Authors: Fabienne F. V. Chevance & Kelly T. Hughes The assembly of large and complex organelles, such as the bacterial flagellum, poses the formidable problem of coupling temporal gene expression to specific stages of the organelle-assembly process. The discovery that levels of the bacterial flagellar regulatory protein FlgM are controlled by its secretion from (Source: Nature Reviews Microbiology)

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Organic nitrogen of tomato waste hydrolysate enhances glucose uptake and lipid accumulation in cunninghamella echinulata

Journal of Applied Microbiology — Fri, 16 May 2008 14:02:41 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: To investigate the effect of organic nitrogen on lipogenesis during growth of Cunninghamella echinulata on tomato waste hydrolysate (TWH) media.Methods and Results: Cunninghamella echinulata grown on a TWH medium rapidly took up glucose and ... (Source: Journal of Applied Microbiology)

The copper-resistant bacterium acu isolated from the rhizosphere of eichhornia crassipes (mart.) increased the endurance of potamogeton crispus l. to copper toxicity

Journal of Applied Microbiology — Fri, 16 May 2008 14:02:40 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: This study aimed to develop endurance to copper stress in Potamogeton crispus L. by inoculation with the anti-copper strain ACU – a novel Enterobacteriaceae bacterium isolated from the rhizosphere of Eichhornia crassipes with high copper-... (Source: Journal of Applied Microbiology)

The use of a quantitative real-time polymerase chain reaction assay for identification and enumeration of lactobacillus buchneri in silage

Journal of Applied Microbiology — Fri, 16 May 2008 14:02:29 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: To detect and quantify Lactobacillus buchneri in plant samples with the aid of polymerase chain reaction (PCR) methods.Methods and Results: DNA from silage samples spiked with different amounts of L. buchneri cells was isolated using a ... (Source: Journal of Applied Microbiology)

Specific detection of escherichia coli isolated from water samples using polymerase chain reaction targeting four genes: cytochrome bd complex, lactose permease, β-d-glucuronidase, and β-d-galactosidase

Journal of Applied Microbiology — Fri, 16 May 2008 14:02:28 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: To develop a PCR-based method for reliable detection of Escherichia coli that enables its differentiation from biochemically and phylogenetically related bacteria.Methods and Results: Using multiplex PCR targeting four genes (cytochrome bd ... (Source: Journal of Applied Microbiology)

Towards a one-step enterobacter sakazakii enrichment

Journal of Applied Microbiology — Fri, 16 May 2008 14:02:24 +0100

Journal of Applied Microbiology, Volume 0, Issue 0, Page ???, September 2003. AbstractAims: The current international standard method for detection of Enterobacter sakazakii from milk products is by the International Organization for Standardization and the International Dairy Federation documented method, a procedure involving two-... (Source: Journal of Applied Microbiology)

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Focal adhesion kinase mediates the interferon-γ-inducible gtpase-induced phosphatidylinositol 3-kinase/akt survival pathway and further initiates a positive feedback loop of nf-κb activation

Cellular Microbiology — Fri, 16 May 2008 08:26:16 +0100

Cellular Microbiology, Volume 0, Issue 0, Page ???, December 2004. Summary Interferon-γ-inducible GTPase (IGTP) expression is upregulated in coxsackievirus B3 (CVB3)-infected murine heart and inhibits CVB3-induced apoptosis through activation of the PI3 kinase/Akt pathway. However, the mechanism of this pathway ... (Source: Cellular Microbiology)

Disseminated cutaneous and pulmonary abscesses in an injecting drug user caused by a panton-valentine leucocidin-positive, methicillin-susceptible staphylococcus aureus strain

European Journal of Clinical Microbiology & Infectious Diseases — Thu, 15 May 2008 06:38:08 +0100

Abstract Staphylococcus aureus is an important pathogen in injecting drug users. We illustrate this with a case of a young female patient who was admitted with multiple cutaneous and pulmonary abscesses. The causative strain was characterised using diagnostic microarrays. Genes encoding Panton-Valentine leucocidin (PVL) were detected, mecA was absent. The overall hybridisation profile allowed us to assign this isolate to ST152, being related to an epidemic community-acquired methicillin-resistant S. aureus (caMRSA) strain from south-eastern Europe. While PVL-positive MRSA has frequently been observed in injecting drug users, methicillin-susceptible isolates are usually not screened for the presence of PVL genes. The use of diagnostic microarrays contributes to patient care by the simultaneous detection of resistance and virulence markers. It also facilitates the study of phylogenetic relationships of epidemic strains. Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s10096-008-0533-3Authors A. Ditzen, University Hospital of Dresden Department of Medicine III Fetscherstrasse 74 01307 Dresden GermanyR. Ehricht, CLONDIAG GmbH Loebstedter Strasse, 103-105 07749 Jena GermanyS. Monecke, Technical University of Dresden Institute for Medical Microbiology and Hygiene, Faculty of Medicine “Carl Gustav Carus” Fetscherstrasse 74 01307 Dresden Germany Journal European Journal of Clinical Microbiology & Infectious DiseasesOnline ISSN 1435-4373Print ISSN 0934-9723 (Source: European Journal of Clinical Microbiology & Infectious Diseases)

Methicillin-resistant staphylococcus aureus in hospitals in tbilisi, the republic of georgia, are variants of the brazilian clone

European Journal of Clinical Microbiology & Infectious Diseases — Thu, 15 May 2008 06:38:05 +0100

Abstract The purpose of this study was to characterise methicillin-resistant Staphylococcus aureus (MRSA) isolates from the Republic of Georgia, part of the former Soviet Union. Thirty-two non-duplicate MRSA isolates were collected in the period from May 2006 to February 2007. The patient data were analysed and the isolates were characterised by staphylococcal protein A (spa) typing, staphylococcal chromosome cassette mec (SCCmec) typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and the detection of Panton-Valentine leukocidin (PVL) genes. Only two closely related spa types were found; 29 isolates were of spa type 459 and three were t030. The spa types belonged to sequence type (ST) 239, clonal complex (CC) 8. All isolates were multiresistant, PVL-negative and harboured SCCmec type IIIA. Based on the molecular findings and PFGE, the isolates most closely resembled the pandemic Brazilian clone (ST239-IIIA). Content Type Journal ArticleCategory Brief ReportDOI 10.1007/s10096-008-0500-zAuthors M. D. Bartels, Hvidovre Hospital Department of Clinical Microbiology Kettegaard alle 30 2650 Hvidovre DenmarkA. Nanuashvili, Tbilisi State Medical University Tbilisi Republic of GeorgiaK. Boye, Hvidovre Hospital Department of Clinical Microbiology Kettegaard alle 30 2650 Hvidovre DenmarkS. M. Rohde, Hvidovre Hospital Department of Clinical Microbiology Kettegaard alle 30 2650 Hvidovre DenmarkN. Jashiashvili, Tbilisi State Medical University Tbilisi Republic of GeorgiaN. A. Faria, Universidade Nova de Lisboa (ITQB/UNL) Laboratório de Genética Molecular, Instituto de Tecnologia Química e Biológica Oeiras PortugalM. Kereselidze, Medical Center CITO Tbilisi Republic of GeorgiaS. Kharebava, Medical Center CITO Tbilisi Republic of GeorgiaH. Westh, Hvidovre Hospital Department of Clinical Microbiology Kettegaard alle 30 2650 Hvidovre Denmark Journal European Journal of Clinical Microbiology & Infectious DiseasesOnline ISSN 1435-4373Print ISSN 0934-9723 (Source: European Journal of Clinical Microbiology & Infectious Diseases)

Characterization of two heparan sulphate-binding sites in the mycobacterial adhesin hlp

BMC Microbiology - Latest articles — Thu, 15 May 2008 04:00:00 +0100

Background: The histone-like Hlp protein is emerging as a key component in mycobacterial pathogenesis, being involved in the initial events of host colonization by interacting with laminin and glycosaminoglycans (GAGs). In the present study, nuclear magnetic resonance (NMR) was used to map the binding site(s) of Hlp to heparan sulfate and identify the nature of the amino acid residues directly involved in this interaction. Results: The capacity of a panel of 30 mer synthetic peptides covering the full length of Hlp to bind to heparin/heparan sulfate was analyzed by solid phase assays, NMR, and affinity chromatography. An additional active region between the residues Gly46 and Ala60 was defined at the N-terminal domain of Hlp, expanding the previously defined heparin-binding site between Thr31 and Phe50. Additionally, the C-terminus, rich in Lys residues, was confirmed as another heparan sulfate binding region. The amino acids in Hlp identified as mediators in the interaction with heparan sulfate were Arg, Val, Ile, Lys, Phe, and Thr. Conclusions: Our data indicate that Hlp interacts with heparan sulfate through two distinct regions of the protein. Both heparan sulfate-binding regions here defined are preserved in all mycobacterial Hlp homologues that have been sequenced, suggesting important but possibly divergent roles for this surface-exposed protein in both pathogenic and saprophic species. (Source: BMC Microbiology - Latest articles)

Complete genome sequence of treponema pallidum ssp. pallidum strain ss14 determined with oligonucleotide arrays

BMC Microbiology - Latest articles — Thu, 15 May 2008 04:00:00 +0100

Background: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. Results: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. Conclusions: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism. (Source: BMC Microbiology - Latest articles)

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Resistance to methicillin and other antimicrobials among community-acquired and nosocomial staphylococcus aureus strains in a pediatric teaching hospital in salvador, northeast brazil

Microbial Drug Resistance — Thu, 15 May 2008 03:05:13 +0100

Microbial Drug Resistance , Vol. 0, No. 0. To report the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infection and to compare the antimicrobial resistance patterns between community-acquired (CA) and nosocomial (NI) strains stratified for resistance to methicillin, this ... (Source: Microbial Drug Resistance)

Macrolide-resistance mechanisms in streptococcus pneumoniae isolates from chinese children in association with genes of tetm and integrase of conjugative transposons 1545

Microbial Drug Resistance — Wed, 14 May 2008 21:09:55 +0100

Microbial Drug Resistance , Vol. 0, No. 0. This study investigated macrolide-resistant Streptococcus pneumoniae carried by Beijing children presenting with respiratory tract infections. Nasopharyngeal S. pneumoniae strains were tested for sensitivity with 15 antibiotics and further analyzed for ... (Source: Microbial Drug Resistance)

An endocytic mechanism for haemoglobin-iron acquisition in candida albicans

Molecular Microbiology — Wed, 14 May 2008 18:37:59 +0100

Molecular Microbiology, Volume 0, Issue 0, Page ???, December 2004. Summary The fungal pathogen Candida albicans is able to utilize haemin and haemoglobin as iron sources. Haem-iron utilization is facilitated by Rbt5, an extracellular, glycosylphophatidylinositol (GPI)-anchored, haemin- and haemoglobin-binding protein. ... (Source: Molecular Microbiology)

Looking inside the box: bacterial transistor arrays

Molecular Microbiology — Wed, 14 May 2008 13:03:35 +0100

Molecular Microbiology, Volume 0, Issue 0, Page ???, December 2004. Summary One often compares cells to computers, and signalling proteins to transistors. Location and wiring of those molecular transistors is paramount in defining the function of the subcellular chips. The bacterial chemotactic sensing apparatus is a ... (Source: Molecular Microbiology)

Ehmlbp is an essential constituent of the entamoeba histolytica epigenetic machinery and a potential drug target

Molecular Microbiology — Wed, 14 May 2008 13:03:34 +0100

Molecular Microbiology, Volume 0, Issue 0, Page ???, December 2004. Summary EhMLBP has been identified as a protein that specifically binds to methylated long interspersed element (LINE) retrotransposons and rDNA in Entamoeba histolytica. EhMLBP is unique to Entamoeba parasites, which makes this protein a possible drug ... (Source: Molecular Microbiology)

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Diversity of vibrios associated with reared clams in galicia (nw spain).

Systematic and Applied Microbiology — Wed, 14 May 2008 04:00:00 +0100

Diversity of Vibrios associated with reared clams in Galicia (NW Spain).

Syst Appl Microbiol. 2008 May 14;

Authors: Beaz Hidalgo R, Cleenwerck I, Balboa S, De Wachter M, Thompson FL, Swings J, De Vos P, Romalde JL

The aim of the present study was to characterize and identify vibrios isolated from cultured clams in Galicia (NW Spain). A total of 759 isolates were obtained, phenotypically characterized, grouped and assigned to the genus Vibrio. Subsequently, the genomic diversity of 145 representative strains was analyzed by means of amplified fragment length polymorphism (AFLP), which revealed a high genetic diversity amongst these isolates. Only 57 out of 145 strains could be identified to the species level, and they were distributed in 13 AFLP clusters. V. cyclitrophicus, V. splendidus and V. alginolyticus were the most abundantly represented species. Eighty-eight isolates remained unidentified, 59 were distributed over 16 clusters, while 29 were unclustered. Sequencing of the 16S rRNA and two house-keeping genes (rpoA and recA) from representative strains belonging to eight unidentified clusters with the highest number of isolates confirmed their assignation to the Vibrionaceae family, and some of these probably represent new species within the genus. The present study confirmed that the phenotypic characterization of vibrios is not sufficient to identify them at the species level. A wide diversity of vibrios was found in cultured clams from all four geographic locations analyzed. In total, more than 12 Vibrio species and at least three potential new species in this genus were identified.

PMID: 18482814 [PubMed - as supplied by publisher]

(Source: Systematic and Applied Microbiology)

Comment on: unexpected antimicrobial effect of statins

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

A review of vancomycin therapeutic drug monitoring recommendations in scotland

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Severe hypokalaemia caused by flucloxacillin

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Daptomycin resistance in enterococcus faecalis prosthetic valve endocarditis

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

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High prevalence of ctx-m-15-producing klebsiella pneumoniae among inpatients and outpatients with urinary tract infection in southern india

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Multidrug-resistant providencia stuartii expressing extended-spectrum {beta}-lactamase per-1, originating in kosovo

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Reduced susceptibility to tetracyclines is associated in vitro with the presence of 16s rrna mutations in mycoplasma hominis and mycoplasma pneumoniae

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Evidence for chromosomal and plasmid location of cmy-2 cephalosporinase gene in salmonella serotype typhimurium

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

(Source: Journal of Antimicrobial Chemotherapy)

Design of a 'day 3 bundle' to improve the reassessment of inpatient empirical antibiotic prescriptions

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives To develop and test a set of process measures of quality of care in the reassessment of inpatient empirical antibiotic prescriptions, to determine the inter-rater reliability of medical notes’ review in assessment of these measures and to test these measures on one ward. Methods Measures of process of care were identified from a literature review. Forty sets of medical notes were reviewed by two independent doctors and the inter-rater reliability determined using observed percentage agreement and the kappa statistic. These measures were collected weekly and fed back to doctors in order to stimulate improvement. Results Four process measures were identified and were grouped together to create a ‘day 3 bundle’: antibiotic plan, review of the diagnosis, adaptation to microbiology and intravenous–oral switch. The inter-rater agreement was ≥80% for all measures. Data collection was feasible and was easily sustained over several weeks. The reassessment of antibiotic prescriptions around day 3 was better documented using real-time feedback of the measures to the medical team. Conclusions Our measures of care are suitable for the reassessment of empirical inpatient antibiotic prescriptions, with good inter-rater reliability. This quality intervention should be part of a more comprehensive and multifaceted plan to improve antibiotic use in hospitals. (Source: Journal of Antimicrobial Chemotherapy)

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Gram-negative bacteraemia in non-icu patients: factors associated with inadequate antibiotic therapy and impact on outcomes

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background A considerable number of Gram-negative bacteraemias occur outside intensive care units (ICUs). Inadequate antibiotic therapy in ICUs has been associated with adverse outcomes; however, there are no prospective studies in non-ICU patients. Methods A 6 month (1 August 2006–31 January 2007), prospective cohort study of non-ICU patients with Gram-negative bacteraemia in a tertiary-care hospital was performed. Inadequate empirical antibiotic therapy was defined as no antibiotic or starting a non-susceptible antibiotic within 24 h after the initial positive blood culture. Results Two hundred and fifty non-ICU patients had Gram-negative bacteraemia. The mean age was 56.4 (±16.1) years. The predominant bacteria in monomicrobial infections were Escherichia coli (24%), Klebsiella pneumoniae (18%) and Pseudomonas aeruginosa (8%). Sixty-one (24%) patients had polymicrobial bacteraemia. Seventy patients (28%) required ICU transfer and 35 (14%) died. Seventy-nine (31.6%) received inadequate empirical antibiotic therapy. These patients were more likely to have a hospital-acquired infection [odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.11–3.56, P = 0.02] and less likely to have E. coli monomicrobial bacteraemia [OR 0.40 (95% CI 0.19–0.86), P = 0.02]. There were no differences in occurrence of sepsis [72 (91.1%) patients with inadequate versus 159 (93.0%) with adequate therapy; P = 0.6], ICU transfer [20 (25.3%) versus 50 (29.2%); P = 0.5], post-bacteraemia length of stay (median = 6.8 versus 6.1 days; P = 0.09) or death [11 (13.9%) versus 24 (14.0%); P = 1.0]. Conclusions Nearly one-third of the non-ICU patients with Gram-negative bacteraemia received inadequate empirical antibiotic therapy. There was no difference in adverse outcomes between patients receiving inadequate or adequate therapy in this study. (Source: Journal of Antimicrobial Chemotherapy)

Ampicillin/sulbactam compared with polymyxins for the treatment of infections caused by carbapenem-resistant acinetobacter spp.

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background There has been an increase in worldwide infections caused by carbapenem-resistant Acinetobacter. This poses a therapeutic challenge as few treatment options are available. Objectives The aim of this study was to evaluate the efficacy and safety of polymyxins and ampicillin/sulbactam for treating infections caused by carbapenem-resistant Acinetobacter spp. and to evaluate prognostic factors. Methods This was a retrospective review of patients from two teaching hospitals who had nosocomial infections caused by carbapenem-resistant Acinetobacter spp. from 1996 to 2004. Diagnosis of infection was based on CDC criteria plus the isolation of Acinetobacter from a usually sterile site or from bronchoalveolar lavage. Urinary tract infections were not included. Data on demographic and clinical features and treatment were collected from medical records. Prognostic factors associated with two outcomes (mortality during treatment and in-hospital mortality) were evaluated. Results Eighty-two patients received polymyxins and 85 were treated with ampicillin/sulbactam. Multiple logistic regression analysis revealed that independent predictors of mortality during treatment were treatment with polymyxins, higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score, septic shock, delay in starting treatment and renal failure. On multivariate analysis, prognostic factors for in-hospital mortality were older age, septic shock and higher APACHE II score. Conclusions This is the first study comparing current therapeutic options for infections due to carbapenem-resistant Acinetobacter. The most important finding of the present study is that ampicillin/sulbactam appears to be more efficacious than polymyxins, which was an independent factor associated with mortality during treatment. (Source: Journal of Antimicrobial Chemotherapy)

Clinically validated mutation scores for hiv-1 resistance to fosamprenavir/ritonavir

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background We developed clinically relevant genotypic scores for resistance to fosamprenavir/ritonavir in HIV-1 protease inhibitor (PI)-experienced patients. Methods PI-experienced patients with virological failure receiving fosamprenavir/ritonavir as the sole PI for at least 3 months and with detectable fosamprenavir plasma levels were included. The impact of baseline protease mutations on virological response (VR, i.e. decrease in plasma HIV-1 RNA between baseline and month 3) was analysed using the Mann–Whitney test. Mutations with prevalence >10% and P value <0.10 were retained. The Jonckheere–Terpstra test was used to select the combination of mutations most strongly associated with VR. The association between score and VR was assessed by multivariate backward regression. Results In the 73 patients included, the median baseline HIV-1 RNA was 4.6 log10 copies/mL (range: 2.7–6.9) and the mean decrease at month 3 was –1.07 ± 1.40 log10 copies/mL. Ninety per cent of the patients were infected by HIV-1 subtype B variants. Two fosamprenavir/ritonavir mutation scores were constructed: score A (L10F/I/V + L33F + M36I + I54L/M/V/A/T/S + I62V + V82A/F/C/G + I84V + L90M) was based only on mutations associated with a worse VR, whereas score B (L10FIV + L33F + M36I + I54L/M/V/A/T/S + A71V – V77I – N88S + L90M) also took into account favourable mutations. Both scores were independent predictors of VR, however, co-administration of tenofovir was associated with a worse VR and the presence of the N88S protease mutation and co-administration of enfuvirtide with a better VR. Conclusions These clinically validated mutation scores should be of interest for the clinical management of PI-experienced patients. The fosamprenavir/ritonavir score A was introduced in the 2006 ANRS algorithm along with isolated mutations I50V and V32I + I47V. (Source: Journal of Antimicrobial Chemotherapy)

Long-term (4 years) efficacy of lopinavir/ritonavir monotherapy for maintenance of hiv suppression

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives Data are scarce on the long-term efficacy of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression. Four years of results of patients randomized to monotherapy in the Only Kaletra (OK) pilot clinical trial are presented. Patients and methods Twenty-one HIV-infected patients with suppressed HIV replication (<50 copies/mL) for at least 6 months and without previous failure while receiving a protease inhibitor-based regimen started lopinavir/ritonavir monotherapy. Follow-up was performed within the OK pilot clinical trial during the first 2 years and according to routine clinical practice during the 3rd and 4th years. Results Fourteen patients (67%) remain on monotherapy and with RNA <50 copies/mL (intention-to-treat analysis, with missing patients scored as failures). Five patients (24%) had virological rebound and all of them were successfully re-suppressed by adding two nucleosides. No major protease inhibitor mutations were found. Conclusions Our data support the long-term efficacy and safety of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression, a finding that must be confirmed in larger studies. (Source: Journal of Antimicrobial Chemotherapy)

First-line antiretroviral therapy with efavirenz or lopinavir/ritonavir plus two nucleoside analogues: the suska study, a non-randomized comparison from the vach cohort

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background Efavirenz and lopinavir/ritonavir are both recommended antiretroviral agents for combination first-line therapy, although information on direct comparisons between them is scarce. A retrospective longitudinal study from the VACH cohort comparing both regimens was performed. Methods Efficacy was examined comparing time to virological failure, CD4 recovery and clinical progression. Tolerability was examined comparing time to treatment discontinuation for any reason and for toxicity. Survival analysis was conducted using the Kaplan–Meier method, and standard and weighted Cox regression models. Results A total of 1550 antiretroviral-naive patients starting a two-nucleoside reverse transcriptase inhibitor regimen plus either efavirenz (n = 1159) or lopinavir/ritonavir (n = 391) were included in the study. At baseline, patients starting lopinavir/ritonavir had higher HIV-1 RNA and lower CD4+ cell counts. There was no difference in the adjusted hazards of virological failure [efavirenz versus lopinavir/ritonavir hazard ratio (HR) = 0.93, 95% confidence interval (CI): 0.77–1.12, P = 0.43], CD4 recovery (HR = 1.11, 95% CI: 0.95–1.30, P = 0.19) and clinical progression (HR = 0.71, 95% CI: 0.39–1.31, P = 0.27). There was an increased risk of discontinuation for any reason or for toxicity for lopinavir/ritonavir (HR = 2.10, 95% CI: 1.40–3.15, P = 0.0003). CD4 recovery with both drugs was also similar in the lowest CD4 strata. A higher risk of early hypertriglyceridaemia was associated with lopinavir/ritonavir-based regimens. Conclusions Our study suggests similar virological efficacy for efavirenz- or lopinavir/ritonavir-based first-line antiretroviral regimens, but an increased risk of discontinuation because of toxicity in case of lopinavir/ritonavir-based therapy. Immunological outcome appeared similar with both regimens. (Source: Journal of Antimicrobial Chemotherapy)

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Absence of hiv-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background New strategies such as boosted-protease inhibitor (PI) monotherapy are being investigated. However, a concern remains regarding the efficacy of this strategy in viral sanctuaries such as the male genital tract. More than 80% of untreated HIV-infected men have detectable HIV-RNA in semen and such a strategy could favour local selection of resistant variants, given the poor penetration of most PIs in semen. Objectives To evaluate the impact of a first-line lopinavir/ritonavir alone or standard triple combination on HIV-1 shedding in the genital tract. Methods HIV-1-infected men enrolled in the Monark randomized trial were eligible for the present study after 48 weeks of a first-line lopinavir/ritonavir alone or in combination with zidovudine and lamivudine. Single-paired samples of blood and semen were collected at week 48. Blood plasma HIV-RNA and seminal plasma HIV-RNA were measured at week 48. Lopinavir and ritonavir concentrations were measured in blood and in semen at week 48 by high-performance liquid chromatography. Results Ten patients were included: five of them received lopinavir/ritonavir monotherapy and five received a triple combination. At week 48, all patients had blood plasma HIV-RNA <1.7 log10 copies/mL. Median lopinavir and ritonavir concentrations were within the expected therapeutic target range in blood plasma (4896 and 130.5 ng/mL, respectively), whereas both lopinavir and ritonavir were undetectable in all seminal plasma samples (<30 ng/mL). All 10 patients had undetectable seminal plasma HIV-RNA at week 48 (<2.3 log10 copies/mL). Conclusions No local viral production was evident in semen, despite the local absence of therapeutic antiretroviral drug concentrations in the five patients receiving lopinavir/ritonavir alone. (Source: Journal of Antimicrobial Chemotherapy)

Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a staccato trial substudy

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives Stavudine is widely used in Thailand and is associated with mitochondrial toxicity. Here, we evaluated the effect of switching from stavudine/didanosine to tenofovir/lamivudine on measures of metabolic and mitochondrial toxicity in Thai patients. Methods Thirty-five Thai patients with full HIV RNA suppression were switched from stavudine/didanosine to tenofovir/lamivudine while receiving saquinavir/ritonavir 1600/100 mg once daily. Patients were assessed at the time of switch and 24 and 48 weeks after for lipids, liver enzymes, lactate, mitochondrial DNA content and limb/total fat mass by dual energy X-ray absorptiometry (DEXA) scanning. Results Forty-eight weeks after the switch, there were significant reductions in lipids and lactate, but no change in liver enzymes. There was reversal of lipoatrophy, as shown by rises in limb fat mass (+0.38 kg, P = 0.006) and total fat mass (+0.69 kg, P = 0.02) on DEXA scan. Patients perceived weight improvement, but did not report reversal of lipoatrophy of individual body parts. The mitochondrial DNA/nuclear DNA ratio rose (+1.06, P < 0.0001). Conclusions After the nucleoside reverse transcriptase inhibitor switch, reversal of mitochondrial toxicity was consistent with switch studies of mainly Caucasian patients, although the peripheral mononuclear cell mitochondrial DNA rise exceeded previous reports. (Source: Journal of Antimicrobial Chemotherapy)

Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of hiv-infected children

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives To obtain data on the pharmacokinetics of efavirenz in children in clinical practice. Methods HIV-1-infected children received efavirenz capsules or tablets in accordance with manufacturer's dosing recommendations. Plasma was collected at regular visits and analysed by HPLC. The therapeutic range of efavirenz was defined as 1.0–4.0 mg/L. Results Thirty-three children were included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1–16.7) years, 24 (12–62) kg, 300 (200–800) mg and 13.3 (9.7–22.5) mg/kg, respectively. Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13–11.6) mg/L. Plasma concentrations were not dependent on age (P = 0.97) or dose/kg (P = 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty-five samples (14.7%) contained >4.0 mg/L, and 27 samples (8.8%) contained <1.0 mg/L. Eight children (24%) reported persistent adverse events probably caused by efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1) and seizure (1)]; six discontinued efavirenz for this reason. A non-significant trend existed towards a higher proportion of toxic efavirenz plasma concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events: 25.9% versus 12.8% (P = 0.23; t-test). Viral load was <50 copies/mL in all 27 subjects who continued efavirenz, despite occasional subtherapeutic efavirenz plasma concentrations in 12 children. The occasional subtherapeutic levels suggest that temporal non-adherence was present. Conclusions Efavirenz as part of highly active antiretroviral therapy was highly effective in children able to tolerate the drug. Therapeutic drug monitoring (TDM) as part of toxicity management may prevent discontinuation in a subset of patients. Temporal non-adherence occurs frequently. TDM may allow initiation of adherence interventions before viral load becomes detectable. (Source: Journal of Antimicrobial Chemotherapy)

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). Patients and methods Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. Results Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. Conclusions A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure. (Source: Journal of Antimicrobial Chemotherapy)

Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives To evaluate the ability of moxifloxacin to penetrate healthy brain barriers. Methods Fifty patients received a single oral dose of 400 mg as an antimicrobial prophylaxis regimen for a short urological procedure under spinal anaesthesia. Serum and cerebrospinal fluid (CSF) were sampled at different time intervals post-drug intake and patients were divided into five groups, as follows: group I: 0.5–1 h; group II: 1–2 h; group III: 2–4 h; group IV: 4–6 h; and group V: 6–8 h. Concentrations of moxifloxacin were estimated after analysis by an HPLC system. Bactericidal activity of CSF samples of groups III and IV was assessed by a microdilution technique against two penicillin-resistant isolates of Streptococcus pneumoniae with MICs of moxifloxacin of 0.19 and 0.125 mg/L, respectively. Results Mean CSF concentrations of moxifloxacin of groups I, II, III, IV and V were 0.19, 0.87, 3.00, 4.07 and 1.82 mg/L, respectively. The mean bactericidal activity of CSF of group III was 8 and that of group IV was 4. Conclusions Single oral intake of 400 mg moxifloxacin is accompanied by good penetration through healthy meninges within 2–6 h post-dose and reached adequately high levels in human CSF exerting satisfactory bactericidal activity against penicillin-resistant S. pneumoniae. These results render novel perspectives for a role of moxifloxacin in CNS infections. (Source: Journal of Antimicrobial Chemotherapy)

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Persistence of pcr-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with trypanosoma cruzi stocks from different genotypes

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives To assess different methodologies to better define an early post-therapeutic cure criterion after benznidazole treatment in BALB/c mice following mixed infection with dual Trypanosoma cruzi genotypes. Methods According to the classical cure criteria, animals were classified as treated not cured (TNC = 76.4%), treated cured (TC = 12.5%) and dissociated (DIS = 11.1%) using parasitological [fresh blood examination (FBE), blood culture (BC) and blood PCR] and serological methods [conventional serology (CS-ELISA) and non-conventional serology (NCS-FC-ALTA)]. Tissues were also evaluated by PCR. Results FBE was able to detect patent parasitaemia in only 18.1% of TNC and therapeutic failure was detected in 79.1% and 97.2% of TNC by BC and blood PCR, respectively. CS-ELISA should not be used before 3 months after treatment since it may lead to false-negative results. At 3 months after treatment with benznidazole, NCS-FC-ALTA was more efficient for categorizing the groups of treated mice. In the TNC group, although a decreased frequency of PCR-positive tissue was observed in several host tissues, increased positivity was also observed, despite the T. cruzi genotype combination. All TC animals presented at least two positive tissue-PCR results. Conclusions Our results confirm that NSC-FC-ALTA and blood PCR are the most suitable methods to early detect therapeutic failure in acute murine T. cruzi infection. Additionally, our data show that BC positivity is highly dependent upon the T. cruzi genotype combination. Moreover, our findings demonstrated that PCR tests performed on tissues from animals considered cured after benznidazole treatment still detected T. cruzi DNA, most probably indicating residual infection. (Source: Journal of Antimicrobial Chemotherapy)

High rate of resistance to locally used antibiotics among enteric bacteria from children in northern ghana

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives Information on antimicrobial susceptibility of bacterial pathogens is scarce in resource-poor settings. We determined the susceptibility of bacterial enteric pathogens and faecal Escherichia coli isolates obtained from children in urban Tamale, Northern Ghana, to antibiotics widely used in the that area [ampicillin or amoxicillin, trimethoprim/sulfamethoxazole (SXT) and chloramphenicol] and to alternative drugs. Methods Five Shigella spp., 6 Salmonella spp. and 318 E. coli were isolated from stool specimens obtained from 367 children with or without acute diarrhoea. Isolates were differentiated using standard laboratory procedures and tested using a breakpoint microbroth dilution method for their susceptibility to 18 antimicrobials and by disc diffusion for their susceptibility to chloramphenicol. Results Although the salmonellae showed an acceptable resistance pattern, E. coli isolates and the closely related shigellae were highly resistant. About 91% and 81% of E. coli isolates from patients or controls, respectively, were resistant to ampicillin (MICs ≥ 8 mg/L), 88% and 76% to trimethoprim/sulfamethoxazole (MICs ≥ 80/4 mg/L) and 46% and 41% to chloramphenicol (inhibition zones ≤ 12 mm). Resistance to β-lactam antibiotics or chloramphenicol was observed more frequently among isolates obtained from infants when compared with older children (1–4 years of age). Conclusions Enteric bacteria from children in urban Northern Ghana are highly resistant to antibiotics used in that area. Therefore, new antibiotics should be introduced for the treatment of infections caused by these bacteria. Additionally, the establishment of a surveillance of the prevalence of the main bacterial infectious agents and their antimicrobial resistance is desirable. (Source: Journal of Antimicrobial Chemotherapy)

In vitro activity of conventional antifungal drugs and natural essences against the yeast-like alga prototheca

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Background Two outbreaks of mastitis due to the yeast-like alga Prototheca zopfii recently occurred in dairy herds in Lombardia (Italy) involving 180 and 150 lactating cows, respectively. Objectives To determine the in vitro susceptibility of Prototheca isolates to conventional antifungal agents and to essential oils. Methods Twenty P. zopfii isolated from milk during these outbreaks, six P. zopfii isolated from fresh water and two Prototheca sp. reference strains were submitted to antifungal susceptibility testing by broth microdilution assay following the CLSI guidelines for yeasts. Results The tested isolates were shown to be resistant to fluconazole and caspofungin. A wide range of voriconazole MICs was observed. In contrast, amphotericin B, itraconazole and posaconazole appeared active with MICs ≤ 1 mg/L. Bergamot and tea tree oils seemed to exert an interesting activity against this yeast-like alga. Conclusions Difficulties in treating animals with conventional drugs and the potent in vitro activity of essential oils demonstrated here raise the interest in further investigations on the therapeutic use of these non-conventional natural products. (Source: Journal of Antimicrobial Chemotherapy)

Post-antifungal effect of amphotericin b and voriconazole against germinated aspergillus fumigatus conidia

Journal of Antimicrobial Chemotherapy — Wed, 14 May 2008 04:00:00 +0100

Objectives The post-antifungal effect (PAFE) of amphotericin B and voriconazole on germinated Aspergillus fumigatus conidia was studied using the BacT/Alert detection system based on fungal CO2 production. Methods Germinated conidia of A. fumigatus were exposed to 1–10x MIC of amphotericin B for 1 and 4 h and to 2.5–40x MIC of voriconazole for 4 and 24 h. After removal of the drug by washing, similar numbers of exposed and control germlings were inoculated into Pedi-BacT culture bottles. CO2 production was automatically monitored until the bottles signalled positive. The difference in time for positive signals in drug-exposed and control bottles was used to calculate the PAFE. Results The killing rate of amphotericin B against germlings was both concentration- and time-dependent, as has been previously found for actively growing hyphae. Similarly, voriconazole showed fungicidal effect after 24 h of exposure, but not after 4 h. Amphotericin B induced a long concentration- and time-dependent PAFE, whereas voriconazole resulted in a short and dose-independent PAFE that was significantly longer after 24 h than after 4 h of exposure. Conclusions An automated method is presented for the determination of PAFE on filamentous fungi using quantifiable numbers of germinated conidia. In contrast to previous results obtained from conidia, this method could demonstrate a PAFE of amphotericin B on Aspergillus that shared characteristics similar to that on Candida spp. (Source: Journal of Antimicrobial Chemotherapy)