Effectiveness and safety of colistin: prospective comparative cohort study

Journal of Antimicrobial and Chemotherapy May 2010 V.65 N.5 P.1019-1027

Mical Paul1,2,*, Jihad Bishara1,2, Ariela Levcovich1,2, Michal Chowers2,3, Elad Goldberg1,2, Pierre Singer2,4, Shaul Lev2,4, Perla Leon5, Maria Raskin1,2, Dafna Yahav2,6 and Leonard Leibovici2,6

1Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

2Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

3Unit of Infectious Diseases, Meir Medical Center, Kfar Saba, Israel

4Intensive Care Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

5Department of Anesthesiology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

6Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

Background

Colistin has re-entered clinical use by necessity. We aimed to assess its effectiveness and safety compared with newer antibiotics.

Methods

This was a single-centre, prospective cohort study. Inclusion criteria were microbiologically documented pneumonia, urinary tract infection, surgical site infection, meningitis or bacteraemia treated appropriately with colistin versus imipenem, meropenem or ampicillin/sulbactam (comparators). All consecutive patients were included, only once, between May 2006 and July 2009. The primary outcome was 30 day mortality. Multivariable and Cox regression survival analyses were used to adjust comparisons between groups. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals are reported.

Results

Two hundred patients treated with colistin and 295 patients treated with comparators were included. Treatment with colistin was associated with older age, admission from healthcare facilities, mechanical ventilation and lower rate of early appropriate antibiotic treatment. The 30 day mortality was 39% (78/200) for colistin versus 28.8% (85/295) for comparators; unadjusted OR 1.58 (1.08–2.31). In the adjusted analysis the OR was 1.44 (0.91–2.26) overall and 1.99 (1.06–3.77) for bacteraemic patients (n = 220). At the end of follow-up, treatment with colistin was significantly associated with cumulative mortality; adjusted HR 1.27 (1.01–1.60) overall and 1.65 (1.18–2.31) among patients with bacteraemia. Nephrotoxicity at the end of treatment was more frequent with colistin; OR adjusted for other risk factors for nephrotoxicity 3.31 (1.54–7.08). Treatment with colistin was followed by increased incidence of Proteus spp. infections during a 3 month follow-up.

Conclusions

The need for colistin treatment is associated with poorer survival. Adjusted analyses suggest that colistin is less effective and more toxic than β-lactam antibiotics.

abstract

http://jac.oxfordjournals.org/content/65/5/1019.abstract

PDF

http://jac.oxfordjournals.org/content/65/5/1019.full.pdf+html

http://jac.oxfordjournals.org/content/early/2010/03/18/jac.dkq069.full.pdf+html

Hepatitis E virus: a zoonosis adapting to humans

Journal of Antimicrobial and Chemotherapy May 2010 V.65 N.5 P.817-821

Florian Bihl* and Francesco Negro

Department of Gastroenterology and Hepatology, University Hospital Geneva, Geneva, Switzerland

Hepatitis E virus (HEV) infection is gaining global attention, not only because of the increasing burden of the disease in low endemicity countries, in terms of morbidity and mortality rates, but also due to recent advances in the molecular virology and epidemiology of this emerging pathogen. HEV infection spread can be described as the evolution of a zoonosis towards an established human infection. As known from other viruses, such as the human immunodeficiency virus or the influenza viruses, crossing the species barriers from animals to humans is a recurrent phenomenon. Albeit slow at the beginning, once the virus has adapted to humans, the person-to-person spread can proceed very quickly. Although an optimal cell culture system for HEV is not yet available, outstanding progress has been made with the in vitro expression of HEV-like particles. These new tools have fostered new research to understand the molecular, structural and immunological aspects of human HEV infection. Although some promising data from Phase II vaccine trials are available, recent discoveries will certainly open new avenues for HEV-specific prophylaxis and therapy.

abstract

http://jac.oxfordjournals.org/content/65/5/817.abstract

PDF

http://jac.oxfordjournals.org/content/65/5/817.full.pdf+html