Archive for May 29, 2010

New directly acting antivirals for hepatitis C: potential for interaction with antiretrovirals

J. Antimicrob. Chemother. June 2010 V.65  N.6 p.1079-1085

Kay Seden1,*, David Back2 and Saye Khoo2

1 NIHR Biomedical Research Centre, Royal Liverpool & Broadgreen University Hospitals Trust, Liverpool, UK 2 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK

Recent advances in the development of agents that act specifically to inhibit hepatitis C virus (HCV) are set to fundamentally change the way that patients will be treated. New directly acting anti-HCV agents such as protease and polymerase inhibitors will initially be added to standard of care with pegylated interferon- and ribavirin. However, future therapy is likely to constitute combinations of agents which act at distinct stages of viral replication and have differing resistance profiles. While directly acting anti-HCV agents will undoubtedly improve treatment outcomes, the introduction of combination therapy may not be without complications in some patient groups. HIV-positive patients who are receiving antiretrovirals (ARVs) are relatively highly represented among those with HCV infection, and are at high risk of drug–drug interactions (DDIs). As combination anti-HCV treatment gradually evolves to resemble anti-HIV therapy, it is essential to consider the increased potential for DDIs in patients receiving combination anti-HCV therapy, and particularly in HCV/HIV-co-infected individuals. Therapeutic drug monitoring is likely to play a role in the clinical management of such interactions.



May 29, 2010 at 7:07 pm Leave a comment

Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection

J. Antimicrob. Chemother. June 2010 V.65  N.6 p.1119-1125


Elizabeth B. Hirsch1,2 and Vincent H. Tam1,2,*

1 University of Houston College of Pharmacy, Houston, TX, USA 2 St Luke’s Episcopal Hospital, Houston, TX, USA

Bacteria producing Klebsiella pneumoniae carbapenemases (KPCs) are rapidly emerging as a cause of multidrug-resistant infections worldwide. Bacterial isolates harbouring these enzymes are capable of hydrolysing a broad spectrum of β-lactams including the penicillins, cephalosporins, carbapenems and monobactam. Detection of isolates harbouring carbapenemases can be inconsistent using automated systems, often requiring subsequent confirmatory tests. Phenotypic methods utilizing boronic acid disc tests have demonstrated promising results and appear practical for use in clinical microbiology laboratories. Treatment of infection caused by KPC bacteria is particularly worrisome as the carbapenems are often agents of the last resort for resistant Gram-negative infections. The optimal treatment of infections caused by KPC bacteria is not well established and clinical outcome data remain sparse. We reviewed the current literature regarding clinical outcomes following KPC infections, with a specific effort to summarize the clinical data available for specific antimicrobial agents. A total of 15 papers involving 55 unique patient cases were reviewed. While the total number of patients is relatively small, some useful insights could still be gathered to guide clinicians in the management of KPC infections. Tigecycline and the aminoglycosides were associated with positive outcomes in the majority of cases. Clinical success rates were low when the polymyxins were used as monotherapy, but were much higher when they were used in combination. Studies examining combination therapy and well-controlled clinical trials are needed to ascertain the optimal treatment of infections caused by KPC bacteria.  


May 29, 2010 at 7:03 pm Leave a comment

Antibiotic use and impact on outcome from bacteraemic critical illness: the Bacteraemia Study in Intensive Care (BASIC)

J. Antimicrob. Chemother. June 2010 V.65  N.6 p.1276-1285

Alberto Corona1, Guido Bertolini2, Jeff Lipman3, A. Peter Wilson4 and Mervyn Singer1,*

1 Bloomsbury Institute of Intensive Care Medicine, Department of Medicine and Wolfson Institute of Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK 2 Laboratory of Clinical Epidemiology, GiViTI Coordinating Centre, Istituto di Ricerche Farmacologiche Mario Negri, Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Ranica (BG), Italy 3 Burns Trauma and Critical Care Research Centre, Royal Brisbane and Women’s Hospital and the University of Queensland, Brisbane, Australia 4 Department of Microbiology, University College London Hospitals NHS Foundation Trust, Windeyer Building, 46 Cleveland St, London W1, UK


The lack of prospective, randomized, controlled trial data to guide optimal antibiotic use in bacteraemic critically ill patients has led to a wide variety of strategies and major issues with drug resistance. We therefore prospectively investigated the epidemiology of bacteraemia and fungaemia in intensive care units (ICUs); and the impact of timing, type and appropriateness of antibiotic intervention.


We conducted a multinational, multicentre, prospective observational study in 132 ICUs from 26 countries with no interventions.


1702 patients [European (69.6%), Australasian (12.2%), South American (8.3%) and Asian (9.9%)] developed 1942 bacteraemic episodes over the study period. Mortality rates were similar for those receiving empirical (40.5%), semi-targeted (37.6%) or fully targeted (33.3%) antibiotic therapy (P = 0.40), and in those initially receiving broad- (39.3%) or restricted-spectrum (39.1%) therapy (P = 0.94). First-line therapy was effective in terms of the antibiogram (where available) in 70.4% of cases. This in vitro susceptibility ranged from 76.3% for broad-spectrum antibiotics to 46.3% for restricted-spectrum antibiotics (P < 0.0001). However, no antibiotic policy-associated variable, including in vitro susceptibility (odds ratio 0.89, 95% confidence interval 0.61–1.30), was a statistically significant predictor of mortality.


We could not show an impact of antibiotics on mortality in critically ill patients, despite in vitro activity and early commencement. Randomized, multicentre trials are urgently needed to establish the appropriate duration, timing and combinations of antibiotics that will both optimally treat infection and minimize development of resistance and other complications.


May 29, 2010 at 7:01 pm Leave a comment


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