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Biomedical subjects

Anton Y Peleg

Publications and source records attributed to Anton Y Peleg.

14 recordsLinked to original sources

Hospital Enterococcus faecium demonstrates distinct environmental and patient reservoirs: a genomic point prevalence survey.

We assessed the hospital environment as a reservoir of vancomycin-resistant E. faecium (VRE) and compared environmental VRE isolates to bloodstream infection E. faecium isolates. We identified distinct environmental and patient reservoirs, with the environment dominated by vanB VRE. Environment-clinical reservoir spillover accounted for 292/895 (33%) of putative transmission links.

Enterococcus faecium↗

Common infections in diabetes: pathogenesis, management and relationship to glycaemic control.

Specific defects in innate and adaptive immune function have been identified in diabetic patients in a range of in vitro studies. However, the relevance of these findings to the integrated response to infection in vivo remains unclear, especially in patients with good glycaemic control. Vaccine efficacy seems adequate in most diabetic patients, but those with type 1 diabetes and high glycosylated haemoglobin levels are most likely to exhibit hypo-responsiveness. While particular infections are closely associated with diabetes, this is usually in the context of extreme metabolic disturbances such as ketoacidosis. The link between glycaemic control and the risk of common community-acquired infections is less well established but could be clarified if infection data from large community-based observational or intervention studies were available. The relationship between hospital-acquired infections and diabetes is well recognized, particularly among post-operative cardiac and critically ill surgical patients in whom intensive insulin therapy improves clinical outcome independent of glycaemia. Nevertheless, further research is needed to improve our understanding of the role of diabetes and glycaemic control in the pathogenesis and management of community- and hospital-acquired infections.

Blood Glucose↗

Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody.

BACKGROUND: Alemtuzumab is being increasingly used for the prevention and/or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab. METHODS: All patients who received alemtuzumab from September 2002 through March 2004, either as induction therapy at the time of transplantation or for the treatment of rejection, were evaluated for the development of an opportunistic infection (OI) until death or for 12 months after receipt of the last dose of alemtuzumab. RESULTS: A total of 547 recipients were included, 65% of whom received alemtuzumab for induction therapy only. Overall, 56 recipients (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus infection (n=12), posttransplantation lymphoproliferative disease (n=5), human herpesvirus 6 infection (n=1), parvovirus infection (n=1), esophageal candidiasis (n=12), cryptococcosis (n=2), invasive mold infection (n=4), Nocardia infection (n=4), mycobacterial infection (n=3), Balamuthia mandrillaris infection (n=1), and toxoplasmosis (n=1). Patients who received alemtuzumab for induction therapy were significantly less likely to develop an OI, compared with patients who received alemtuzumab for rejection therapy (4.5% vs. 21%; P<.001). Independent predictors of the development of an OI were administration of alemtuzumab for rejection therapy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8; P<.001), allograft failure (OR, 2.1; 95% CI, 1.1-4.4; P=.04), and receipt of a lung transplant (OR, 3.7; 95% CI, 1.7-8.0; P=.001) or an intestinal transplant (OR, 8.3; 95% CI, 3.5-19.5; P<.001). CONCLUSIONS: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received alemtuzumab for induction therapy only. Such data have implications for new antimicrobial prophylactic strategies.

Adolescent↗

Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.

OBJECTIVES: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. METHODS: The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor. RESULTS: Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively. CONCLUSIONS: To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.

Acinetobacter baumannii↗

Emergence of carbapenem resistance in Acinetobacter baumannii recovered from blood cultures in Australia.

We describe the first emergence of carbapenem-resistant Acinetobacter baumannii in Australia. Ninety A. baumannii isolates recovered from cultures of blood specimens from 69 patients were analyzed. Overall, 58 isolates (64%) were resistant to meropenem. The chi 2 test for linear trend revealed that emergence of carbapenem resistance was statistically significant during the 32-month study period. Selected isolates were of the same clonal type, and no genes encoding carbapenemases were identified.

Acinetobacter baumannii↗

Epidemiological profile of linezolid-resistant coagulase-negative staphylococci.

BACKGROUND: Surveillance studies have shown that <0.1% of coagulase-negative staphylococci are linezolid resistant; however, at our institution, 4% of such organisms were found to be resistant. We investigated the risk factors for and the epidemiological profile of linezolid-resistant coagulase-negative staphylococci. METHODS: Susceptibility testing and pulsed-field gel electrophoresis were performed to analyze the genetic relatedness of both linezolid-resistant and linezolid-susceptible isolates. Clinical data were retrieved from medical records, and a case-case-control study was performed to identify unique risk factors for linezolid resistance. RESULTS: Isolates recovered from 25 patients with linezolid-resistant coagulase-negative staphylococci were examined; all but 1 of the isolates were identified as Staphylococcus epidermidis, and all but 1 had a minimum inhibitory concentration of linezolid of >256 microg/mL. Pulsed-field gel electrophoresis showed that 21 (84%) of 25 linezolid-resistant isolates exhibited genetic relatedness, whereas linezolid-susceptible isolates were of diverse clones. Unique, independent predictors of linezolid resistance included receipt of linezolid in the 3 months preceding isolation of the coagulase-negative staphylococci (odds ratio, 20.6; 95% confidence interval, 5.8-73.0). CONCLUSION: Linezolid-resistant coagulase-negative staphylococci have emerged at our institution and are predominately of a single clone. We believe that the most likely scenario to explain this emergence is that person-to-person spread of linezolid-resistant coagulase-negative staphylococci led to establishment of skin colonization with the strain. Subsequent use of linezolid was followed by selection of the linezolid-resistant strain, which then became the dominant skin flora. The potential for a parallel scenario involving clonal dissemination followed by selection of linezolid-resistant methicillin-resistant Staphylococcus aureus is a real possibility.

Acetamides↗

Carriage of methicillin-resistant Staphylococcus aureus in a Queensland Indigenous community.

OBJECTIVE: To determine the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage and infection among children living in an Indigenous community in Queensland. DESIGN, SETTING AND PARTICIPANTS: Swabs for culture of S. aureus were collected from the nose, throat and skin wounds of primary school children. MAIN OUTCOME MEASURES: MRSA carriage, antibiotic sensitivity, genotype, and presence of the virulence factor Panton-Valentine leukocidin (PVL); and epidemiological risk factors for MRSA carriage. RESULTS: 92 (59%) of 157 eligible children were included in the study. Twenty-seven (29%) carried S. aureus; 14 of these (15% of total) carried MRSA. MRSA was isolated from 29% of wound swabs, 8% of nose swabs, and 1% of throat swabs. Fourteen of 15 MRSA isolates were sensitive to all non-beta-lactam antibiotics tested. Eight children (9%) carried CA-MRSA clonal types: six carried the Queensland clone (ST93), and two carried the South West Pacific clone (ST30). All these isolates carried the virulence factor PVL. The remaining six children carried a hospital-associated MRSA strain (ST5), negative for PVL. CONCLUSIONS: We have identified a high prevalence of CA-MRSA carriage in school children from a Queensland Indigenous community. In this setting, antibiotics with activity against CA-MRSA should be considered for empiric therapy of suspected staphylococcal infection. Larger community-based studies are needed to improve our understanding of the epidemiology of CA-MRSA, and to assist in the development of therapeutic guidelines for this important infection.

Adolescent↗

Phenotypic detection of carbapenem-susceptible metallo-beta-lactamase-producing gram-negative bacilli in the clinical laboratory.

Rapid detection of metallo-beta-lactamase (MBL)-producing gram-negative pathogens is critical to prevent their widespread dissemination. Thus far, no standardized phenotypic method is available, and previously reported techniques have poor sensitivity for detecting carbapenem-susceptible MBL-carrying isolates, an increasingly described phenomenon. We developed a phenotypic detection method using both a double-disk synergy test and a combined-disk test with imipenem and 292 microg EDTA on one agar plate. Genotypic confirmation was used for validation. Of the 134 clinical isolates, 84 were confirmed to carry an MBL. Of these, 51 (61%) were susceptible to at least one carbapenem, and 22 (26%) were isolated from blood. The phenotypic method correctly differentiated all MBL-producing isolates (sensitivity, 100%). Fifty-one of the 52 MBL-negative isolates were correctly differentiated (specificity, 98%). This study reports the validation of a simple and accurate MBL detection method that can be easily incorporated into the daily routine of a clinical laboratory. Early detection of MBL-carrying organisms, including those with susceptibility to carbapenems, is of paramount clinical importance, as it allows rapid initiation of strict infection control practices as well as therapeutic guidance for confirmed infection.

Acinetobacter↗

Dissemination of the metallo-beta-lactamase gene blaIMP-4 among gram-negative pathogens in a clinical setting in Australia.

BACKGROUND: The clinical utility of carbapenems is under threat because of the emergence of acquired metallo-beta-lactamase (MBL) genes. We describe the first outbreak in Australia of infection and/or colonization with gram-negative pathogens carrying the MBL gene blaIMP-4. METHODS: MBL-producing organisms were identified using susceptibility data in conjunction with MBL screening methods. PCR and sequence analysis were performed to characterize the resistance gene and identify the presence of integrons. DNA profiles were determined by ribotyping. Clinical and epidemiological data were prospectively collected from January-July 2004. RESULTS: A total of 19 isolates were recovered from 16 patients: Serratia marcescens (10 isolates), Klebsiella pneumoniae (4 isolates), Pseudomonas aeruginosa (3 isolates), Escherichia coli (1 isolate), and Enterobacter cloacae (1 isolate). Isolates were resistant to most beta-lactams except aztreonam, and variable resistance to carbapenems was observed (MIC range, 2 to >8 mg/L). PCR and sequence analysis identified the blaIMP-4 gene and a class 1 integrase (IntI1) in all isolates. Of the 16 patients, 12 (75%) had infection; 5 had septicemia, 5 had ventilator-associated pneumonia, 1 had a urinary tract infection, and 1 had a superficial central venous line infection. Six (38%) of the 16 patients died, and 5 of those 6 (31% of the group of 16) had clinical infection with an MBL-producing organism. All except 2 patients had spatio-temporal epidemiological links in the intensive care unit. All K. pneumoniae isolates were of different ribogroups, whereas the S. marcescens and P. aeruginosa isolates were predominately of the same ribogroup. CONCLUSIONS: MBL-producing gram-negative organisms have now emerged in Australia. The resistance gene, blaIMP-4, appears highly mobile; this outbreak involved 5 different gram-negative genera from patients with close epidemiological links.

Adolescent↗