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Van Hal S.J.,Sydney South West Pathology Service Liverpool | Van Hal S.J.,University of Western Sydney | Paterson D.L.,University of Western Sydney
Current Opinion in Infectious Diseases | Year: 2011

PURPOSE OF REVIEW: Despite concerns about vancomycin use in the treatment of multidrug-resistant Gram positives, evidence for better therapeutic outcomes with alternative antibiotics is lacking. This review focuses on recent advances. RECENT FINDINGS: Combination therapy with vancomycin-rifampin, although associated with better cure rates, resulted in the emergence of high rates of rifampin resistance. Of the newer anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics, ceftopibrole, ortivancin and dalbavancin require further development prior to a further assessment by the United States Food and Drug Administration. Ceftaroline, telavancin and daptomycin were associated with comparable clinical cure rates compared with vancomycin in the treatment of complicated MRSA skin and soft tissue infections. In the treatment of hospital-acquired pneumonia, both telavancin and linezolid resulted in significantly greater clinical cure rates compared with vancomycin. Despite greater clinical cure rates, no difference in overall or infection-related mortality was detected. Of concern is the appearance of daptomycin and linezolid resistance following increased use. Toxicity profiles (especially of linezolid) are comparable to vancomycin provided short-duration therapy is prescribed. The first reports of daptomycin-induced acute eosinophillic pneumonia were described in 2010. SUMMARY: Based on current evidence, greater microbiological and clinical cure rates are achieved with alternative agents. However, these differences do not translate into mortality benefits compared with vancomycin for the treatment of S. aureus infections. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Van Hal S.J.,Sydney South West Pathology Service Liverpool | Paterson D.L.,University of Queensland | Gosbell I.B.,Sydney South West Pathology Service Liverpool | Gosbell I.B.,University of Western Sydney
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2011

A patient developed a daptomycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) infection, despite being daptomycin-naïve, in the setting of persistent bacteraemia secondary to vertebral osteomyelitis. Modified population analysis profiling of sequential MRSA blood culture isolates revealed transition from a vancomycin-susceptible phenotype to a vancomycin-intermediate S. aureus (VISA) phenotype through a vancomycin-heteroresistant S. aureus (hVISA) intermediary. Increased cell wall thickening, determined by transmission electron microscopy, correlated with the emergence of daptomycin resistance. This case supports the current hypothesis that MRSA with reduced glycopeptide susceptibility are less susceptible to daptomycin because of a thickened cell wall. This may have significance for the use of daptomycin in salvage therapy. Other predictors of daptomycin resistance include bacteraemic persistence and the presence of high inoculum infections. As resistance may appear de novo and be unstable in vivo, all isolates should have daptomycin susceptibility testing performed. The optimal antibiotic option for salvage therapy of these daptomycin-resistant infections is unknown. However, these findings emphasise the importance of optimising management, including the consideration of early surgical intervention to avoid the emergence of daptomycin resistance, especially in high inoculum infections. © 2010 Springer-Verlag.


Ginn A.N.,University of Sydney | Ginn A.N.,Westmead Millennium Institute | Zong Z.,University of Sydney | Zong Z.,University of Sichuan | And 13 more authors.
International Journal of Antimicrobial Agents | Year: 2013

Early appropriate antibiotic treatment reduces mortality in severe sepsis, but current methods to identify antibiotic resistance still generally rely on bacterial culture. Modern diagnostics promise rapid gene detection, but the apparent diversity of relevant resistance genes in Enterobacteriaceae is a problem. Local surveys and analysis of publicly available data sets suggested that the resistance gene pool is dominated by a relatively small subset of genes, with a very high positive predictive value for phenotype. In this study, 152 Escherichia coli and 115 Klebsiella pneumoniae consecutive isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration (MIC) of ≥2 μg/mL were collected from seven major hospitals in Sydney (Australia) in 2008-2009. Nearly all of those with a MIC in excess of European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoints contained one or more representatives of only seven gene types capable of explaining this phenotype, and this included 96% of those with a MIC ≥ 2 μg/mL to any one of these drugs. Similarly, 97% of associated gentamicin-non-susceptibility (MIC ≥ 8 μg/mL) could be explained by three gene types. In a country like Australia, with a background prevalence of resistance to third-generation cephalosporins of 5-10%, this equates to a negative predictive value of >99.5% for non-susceptibility and is therefore suitable for diagnostic application. This is an important proof-of-principle that should be tested in other geographic locations. © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.


van Hal S.J.,Sydney South West Pathology Service Liverpool | van Hal S.J.,University of Western Sydney | Jensen S.O.,University of Western Sydney | Jensen S.O.,Ingham Institute of Applied Medical Research | And 7 more authors.
Clinical Microbiology Reviews | Year: 2012

Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes. © 2012, American Society for Microbiology. All Rights Reserved.


Gray M.C.,Sydney South West Pathology Service Liverpool | Su W.-Y.,Sydney South West Pathology Service Liverpool | Van Hal S.J.,Sydney South West Pathology Service Liverpool
Expert Opinion on Medical Diagnostics | Year: 2012

Influenza virus infections cause significant morbidity, and the unique ability of these viruses to undergo antigenic drift and shift means that it is critical for current laboratory assays to keep pace with these changes for accurate diagnosis. New subtypes have the potential to evolve into pandemics hence accurate virus subtyping is also essential. Areas covered: In this article, the authors review the current techniques available to detect influenza virus. Expert opinion: The biggest gains in improving on influenza diagnostics may lie in reappraising our current approach and optimizing all existing steps in influenza detection: pre-analytical, analytical, post-analytical. In addition, we must foster close collaboration between governments, surveillance networks and frontline diagnostic laboratories, and utilize advances in information technology to facilitate these interactions and to disseminate crucial information. © 2012 Informa UK, Ltd.

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