Archive for January, 2012

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


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


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.


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.


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.



January 27, 2012 at 3:29 pm Leave a comment

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.



January 27, 2012 at 3:27 pm Leave a comment

Complicated skin and soft tissue infection

JAC  NOV 2010 V.65 suppl 3

Matthew S. Dryden*

Department of Microbiology, Royal Hampshire County Hospital, Romsey Road, Winchester SO22 5DG, UK

*Corresponding author. Tel: +44-196-282-4451; Fax: +44-196-282-5431; E-mail:


Skin and soft tissue infections (SSTIs) are common, and complicated SSTIs (cSSTIs) are the more extreme end of this clinical spectrum, encompassing a range of clinical presentations such as deep-seated infection, a requirement for surgical intervention, the presence of systemic signs of sepsis, the presence of complicating co-morbidities, accompanying neutropenia, accompanying ischaemia, tissue necrosis, burns and bites. Staphylococcus aureus is the commonest cause of SSTI across all continents, although its epidemiology in terms of causative strains and antibiotic susceptibility can no longer be predicted with accuracy. The epidemiology of community-acquired and healthcare-acquired strains is constantly shifting and this presents challenges in the choice of empirical antibiotic therapy. Toxin production, particularly with Panton–Valentine leucocidin, may complicate the presentation still further. Polymicrobial infection with Gram-positive and Gram-negative organisms and anaerobes may occur in infections approximating the rectum or genital tract and in diabetic foot infections and burns.

Successful management of cSSTI involves prompt recognition, timely surgical debridement or drainage, resuscitation if required and appropriate antibiotic therapy. The mainstays of treatment are the penicillins, cephalosporins, clindamycin and co-trimoxazole. β-Lactam/β-lactamase inhibitor combinations are indicated for polymicrobial infection. A range of new agents for the treatment of methicillin-resistant S. aureus infections have compared favourably with the glycopeptides and some have distinct pharmacokinetic advantages. These include linezolid, daptomycin and tigecycline. The latter and fluoroquinolones with enhanced anti-Gram-positive activity such as moxifloxacin are better suited for polymicrobial infection.


January 26, 2012 at 7:47 pm Leave a comment

The diagnosis and management of prosthetic joint infections

JAC  NOV 2010 V.65 suppl 3

E. Moran1,2,*, I. Byren1,2 and B. L. Atkins1,2

1Department of Microbiology and Infectious Disease, John Radcliffe Hospital, Oxford OX3 9DU, UK

2Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK

*Corresponding author. Tel: +44-1865-220886; E-mail:


A host of technical and operative improvements have seen the rates of infection associated with joint replacement reach historic lows. However, the increasing number of operations being performed means that the absolute number of such infections remains significant. Diagnosis may be challenging and delaying appropriate treatment can lead to reduced joint function and the need for more complex, perhaps multiple, procedures. Individual centres tend to see small numbers of such cases, and in the absence of large clinical trials management varies. Early diagnosis, selection of an appropriate surgical strategy, accurate identification of the responsible microorganisms and construction of an appropriate antibiotic regimen are essential elements of any management strategy. Such packages of care are best delivered by a multidisciplinary team composed of orthopaedic and plastic surgeons, microbiologists, infectious disease physicians, specialist nurses, physiotherapists and occupational therapists. Each treatment plan must be developed in consultation with the patient, taking into account their aims and realistic goals. This review provides an overview of current understanding regarding diagnosis and treatment of prosthetic joint infections and suggests a treatment algorithm.


January 26, 2012 at 7:44 pm Leave a comment

Prosthetic joint infections: single versus combination therapy

Journal of Antimicrobial and Chemotherapy January 2010 V.65 N.1 P.18-23


Prosthetic joint replacement is increasingly used to alleviate pain and increase mobility. Bone and joint infections remain a therapeutic dilemma for healthcare providers in all fields. Antimicrobial agents combined with appropriate surgical techniques play a vital role in eradicating infections associated with prosthetic joints. The question still remains whether monotherapy or combination therapy is effective in this situation because there is a paucity of well-defined comparative studies. We reviewed in vitro and in vivo studies evaluating the effectiveness of various antimicrobial agents either as single agents or in combination.




January 25, 2012 at 6:51 pm Leave a comment

Treatment of acute hepatitis C in HIV infection

Journal of Antimicrobial and Chemotherapy January 2010 V.65 N.1 P.4-9

Martin Vogel and Jürgen K. Rockstroh*

Department of Internal Medicine I, Bonn University, Bonn, Germany

*Corresponding author. Tel: +49-228-287-16558; Fax: +49-228-287-15034; E-mail:


Within Europe and recently in theUSAandAustraliaan ongoing epidemic of acute hepatitis C virus (HCV) infections among HIV-positive individuals, mainly men who have sex with men, has been observed. Other concomitant sexually transmitted diseases and sexual practices with a high risk of mucosal trauma and damage have been established as risk factors for sexual transmission. In HIV-positive patients the diagnosis of acute HCV infection may be obscured by delayed anti-HCV antibody seroconversion, and HCV RNA testing may be warranted. It is estimated that up to 85% of HIV-positive patients take a chronic course after acute HCV infection, and early treatment of acute HCV infection within 12 weeks after the presumed date of infection is recommended unless spontaneous clearance of HCV has occurred. A watch and wait strategy for 4–8 weeks after the date of diagnosis with 4 weekly HCV RNA controls may help to distinguish patients who will spontaneously clear acute HCV infection from those who will not. Treatment of acute HCV infection with interferon-based therapy has been shown to be highly efficacious, with sustained virological response rates in between 60% and 70% of HIV-positive individuals. Though data are sparse, controlling treatment response at weeks 4 and 12 may further help to individualize therapy, and patients who have not reached a negative HCV RNA by week 12 may benefit from prolonged treatment beyond 24 weeks.




January 25, 2012 at 6:48 pm Leave a comment

Oseltamivir (Tamiflu) and its use against seasonal, avian and pandemic strains of influenza

JAC April 2010 Suppl                      FREE

January 23, 2012 at 6:25 pm Leave a comment

Staphylococcus aureus with reduced glycopeptide susceptibility in Liverpool, UK

Journal of Antimicrobial and Chemotherapy April 2010 V.65 N.4 P.721-724

Andrew Kirby1,*, Robert Graham2, Nicola J. Williams3, Mandy Wootton4, Caroline M. Broughton1, Mishaal Alanazi1, James Anson2, Timothy J. Neal2 and Christopher M. Parry1

1School of Infection and Host Defence,DuncanBuilding,UniversityofLiverpool,Daulby Street,LiverpoolL69 3GA,UK

2Department of Medical Microbiology, Royal Liverpool andBroadgreenUniversityHospitalTrust,Prescot Street,LiverpoolL7 8XP,UK

3School of Veterinary Science, National Centre for Zoonoses Research, University of Liverpool, Leahurst, Chester High Road, Neston, Wirral CH64 7TE, UK

4Specialist Antimicrobial Chemotherapy Unit, NPHSCardiff,UniversityHospitalofWales,HeathPark,CardiffCF14 4XW,UK

*Corresponding author. Tel: +44-151-706-4396/4410; Fax: +44-151-706-5805; E-mail:



To investigate if colonization with heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA) is associated with hGISA bacteraemia.


Isolates of methicillin-resistant S. aureus (MRSA) from blood cultures and from swabs to detect MRSA colonization were screened for reduced susceptibility to glycopeptides by an agar incorporation method. Isolates detected by this screen were tested for glycopeptide resistance by MacroEtest, standard MIC Etest methods and population analysis profile–AUC (PAP–AUC) analysis. S. aureus isolates with and without reduced glycopeptide susceptibility were characterized by PFGE and spa typing.


MRSA isolates with reduced susceptibility to glycopeptides, as identified by the MacroEtest method, were detected in the colonization screens of 86 of 2550 MRSA-positive patients. The isolates were confirmed by Etest MIC and PAP–AUC analysis as hGISA. A total of 82/86 of the hGISA colonizing isolates were EMRSA-16 by PFGE; the remainder were EMRSA-15. Bacteraemia with hGISA was identified in five patients during the study period; two isolates were EMRSA-16 and three were EMRSA-15. hGISA colonization could not be linked to hGISA bacteraemia and hGISA bacteraemia could not be linked to hGISA colonization. Four of the five hGISA bacteraemias developed following teicoplanin therapy for a central venous catheter-associated MRSA bacteraemia.


Laboratory strategies to reduce morbidity associated with hGISA should focus on testing for hGISA in bacteraemic (rather than colonizing) MRSA isolates in patients with recurrent S. aureus bacteraemia following glycopeptide exposure.




January 23, 2012 at 6:23 pm Leave a comment

Integrase inhibitors in the treatment of HIV-1 infection


J of Antimicr Chemoth Dec 2010 V.65 N.12 P.2485-2488


William G. Powderly*


School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland

*Tel: +353-1-7166609; Fax: +353-1-7166585; E-mail:



Agents active against HIV type 1 (HIV-1) that target the viral integrase by inhibiting the strand transfer step of integration have now entered the clinical arena. Raltegravir is the first in this new class. Clinical trials in treatment-experienced and in treatment-naive patients have shown that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated. Drug resistance emerges relatively frequently in patients who fail therapy and is associated with mutations in the gene encoding the integrase enzyme. Although such mutations often confer cross-resistance to other integrase inhibitors, newer agents in development, such as S/GSK1349572, show promise as potential second-generation integrase inhibitors. Given their potency, safety and novel mechanism of action, integrase inhibitors represent an important advance in HIV-1 therapy.





January 22, 2012 at 10:03 pm Leave a comment

Streptococcal toxic shock-like syndrome.

Intern Med. 2000 Mar V.39 N.3 P.195-6.

Shimizu Y.

Comment on

Intern Med. 2000 Mar;39(3):266-9.


January 22, 2012 at 3:16 pm Leave a comment

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