Archive for October, 2009

Postexposure Prophylaxis for HIV Infection

N Engl J of Medicine  Oct 29, 2009  V.361  N.18  p.1768-1775

Raphael J. Landovitz, M.D., and Judith S. Currier, M.D.

A 24-year-old man presents to an outpatient clinic, reporting that 36 hours previously he had receptive anal intercourse without the use of a condom with an anonymous male partner who was known to have had sex with other men. The patient is known to the clinical practice and has had several negative tests for human immunodeficiency virus (HIV) infection, most recently 6 months previously. How should he be evaluated and treated?




October 29, 2009 at 11:37 am Leave a comment

REVIEW ARTICLE – Norovirus Gastroenteritis

N Engl J of Medicine  Oct 29, 2009  V.361  N.18  p.1776-1785



Roger I. Glass, M.D., Ph.D., Umesh D. Parashar, M.D., M.P.H., and Mary K. Estes, Ph.D.



October 29, 2009 at 11:35 am Leave a comment

Antibiotic Prophylaxis and Recurrent Urinary Tract Infection in Children

N Engl J of Medicine  Oct 29, 2009  V.361  N.18  p.1748-1759

Jonathan C. Craig, M.B., Ch.B., Ph.D., Judy M. Simpson, Ph.D., Gabrielle J. Williams, Ph.D., M.P.H., Alison Lowe, B.Sc., Graham J. Reynolds, M.B., B.S., Steven J. McTaggart, M.B., B.S., Ph.D., Elisabeth M. Hodson, M.B., B.S., Jonathan R. Carapetis, M.B., B.S., Ph.D., Noel E. Cranswick, M.B., B.S., Grahame Smith, M.B., B.S., Les M. Irwig, M.B., B.Ch., Ph.D., Patrina H.Y. Caldwell, Ph.D., Sana Hamilton, M.P.H., Leslie P. Roy, M.B., B.S., for the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators

Background Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.

Methods We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim–sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.

Results From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim–sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P=0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P0.20 for all interactions).

Conclusions Long-term, low-dose trimethoprim–sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups







Antimicrobial Prophylaxis for Urinary Tract Infection in Children

Alejandro Hoberman, M.D., and Ron Keren, M.D., M.P.H.



October 29, 2009 at 11:34 am Leave a comment

Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis

Antimicrobial Agents and Chemotherapy  1 Nov 2009  V.53  N.11  p.4772-4777

Juan C. Martínez-Pastor,1 Ernesto Muñoz-Mahamud,1 Félix Vilchez,1 Sebastián García-Ramiro,1 Guillem Bori,1 Josep Sierra,2 José A. Martínez,2 Lluis Font,1 Josep Mensa,2 and Alex Soriano2*

Department of Orthopaedics of Hospital Clinic of Barcelona,1 Department of Infectious Diseases of Hospital Clínic of Barcelona, Hospital Clínic Universitari, IDIBAPS, Barcelona, Spain2

The aim of our study was to evaluate the outcome of acute prosthetic joint infections (PJIs) due to gram-negative bacilli (GNB) treated without implant removal. Patients with an acute PJI due to GNB diagnosed from 2000 to 2007 were prospectively registered. Demographics, comorbidity, type of implant, microbiology data, surgical treatment, antimicrobial therapy, and outcome were recorded. Classification and regression tree analysis, the Kaplan-Meier survival method, and the Cox regression model were applied. Forty-seven patients were included. The mean age was 70.7 years, and there were 15 hip prostheses and 32 knee prostheses. The median number of days from the time of arthroplasty was 20. The most frequent pathogens were members of the Enterobacteriaceae family in 41 cases and Pseudomonas spp. in 20 cases. Among the Enterobacteriaceae, 14 were resistant to ciprofloxacin, while all Pseudomonas aeruginosa isolates were susceptible to ciprofloxacin. The median durations of intravenous and oral antibiotic treatment were 14 and 64 days, respectively. A total of 35 (74.5%) patients were in remission after a median follow-up of 463 days (interquartile range, 344 to 704) days. By use of the Kaplan-Meier survival curve, a C-reactive protein (CRP) concentration of 15 mg/dl (P = 0.03) and receipt of a fluoroquinolone, when all GNB isolated were susceptible (P = 0.0009), were associated with a better outcome. By use of a Cox regression model, a CRP concentration of 15 mg/dl (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.05 to 12.5; P = 0.043) and receipt of a fluoroquinolone (OR, 9.09; 95% CI, 1.96 to 50; P = 0.005) were independently associated with better outcomes. Open debridement without removal of the implant had a success rate of 74.5%, and the factors associated with good prognosis were a CRP concentration at the time of diagnosis 15 mg/dl and treatment with a fluoroquinolone.



October 28, 2009 at 6:06 pm Leave a comment

Penetration of Colistin into Cerebrospinal Fluid

Antimicrobial Agents and Chemotherapy  1 Nov 2009  V.53  N.11  p.4907-4910

S. L. Markantonis,1* N. Markou,2 M. Fousteri,1 N. Sakellaridis,3 S. Karatzas,4 I. Alamanos,2 E. Dimopoulou,2 and G. Baltopoulos4

University of Athens, Faculty of Pharmacy, Laboratory of Biopharmaceutics and Pharmacokinetics, 157.71 Athens, Greece,1 ICU-B, KAT Hospital, 2 Nikis Str. Kifissia, 145.61 Athens, Greece,2 Department of Neurosurgery, KAT Hospital, 2 Nikis Str. Kifissia, 145.61 Athens, Greece,3 University of Athens School of Nursing ICU, KAT Hospital, 2 Nikis Str. Kifissia, 145.61 Athens, Greece4

Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.



October 28, 2009 at 6:05 pm Leave a comment

VanA-Type Vancomycin-Resistant Staphylococcus aureus

Antimicrobial Agents and Chemotherapy  1 Nov 2009  V.53  N.11


Bruno Périchon and Patrice Courvalin*

Institut Pasteur, Unité des Agents Antibactériens, Paris, France

Since 2002, nine methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains that are also resistant to vancomycin (VRSA) have been reported in the United States, including seven clinical isolates from Michigan. The strains harbor a plasmid-borne Tn1546 element following conjugation from a glycopeptide-resistant Enterococcus strain. In the second step, Tn1546 transposed to a resident plasmid in five strains; the acquired plasmid behaved as a suicide gene delivery vector, and the incoming DNA had been rescued by illegitimate recombination. Surprisingly, combination of a glycopeptide with a β-lactam has a strong synergistic effect against VRSA, both in vitro and in an animal model, despite resistance of the strains to both drug classes when administered separately. This results from the fact that the late peptidoglycan precursors ending in D-alanine-D-lactate (D-Ala-D-Lac) that are mainly synthesized in the presence of glycopeptide inducers are not substrates for PBP2′, which is the only transpeptidase that remains active in the presence of oxacillin. One VRSA strain is partially dependent on vancomycin for growth due to a mutation in the host D-Ala:D-Ala ligase, thus having to rely on the inducible resistance pathway for cell wall synthesis. Competition growth experiments in the absence of inducer between the MRSA recipient and isogenic VRSA transconjugant revealed a disadvantage for the transconjugant, accounting, in part, for the low level of dissemination of the VRSA clinical isolates. The association of multiple molecular and environmental factors has been implicated in the regional emergence of VRSA in Michigan.


October 28, 2009 at 6:04 pm Leave a comment

Occurrence of vancomycin-tolerant and heterogeneous vancomycin-intermediate strains (hVISA) among Staphylococcus aureus causing bloodstream infections in nine USA hospitals

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.1024-1028

Helio S. Sader1,*, Ronald N. Jones1, Kerri L. Rossi2 and Michael J. Rybak2

1 JMI Laboratories, North Liberty, IA, USA 2 Wayne State University, Detroit, MI, USA

Background: The bactericidal activities of vancomycin and daptomycin were evaluated in a large collection of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia strains from nine major USA medical centres.

Objectives: To evaluate the occurrence of heterogeneous vancomycin-intermediate S. aureus (hVISA) among MRSA strains tolerant to vancomycin and/or with increased vancomycin or daptomycin MIC values. The accuracy of the macro Etest method (MET) compared with population analysis profiling (PAP) for the detection of hVISA was also assessed.

Methods: A total of 1800 MRSA strains were collected from bloodstream infections at the nine sites (40 strains per year, per medical centre during the 2002–06 study period). Vancomycin and daptomycin MIC testing was performed by reference broth microdilution (all strains) and MBC tests on 50% of strains (randomly selected). A subset of isolates (n = 268) having an increased vancomycin MBC (16 mg/L), an increased vancomycin MIC (1 mg/L) and/or an increased daptomycin MIC (>0.5 mg/L) were tested for susceptibility to vancomycin and teicoplanin by MET.

Results: Overall, 181 of 900 (20.1%) MRSA tested exhibited vancomycin tolerance, varying from 10% to 43% among the medical centres evaluated, and from 11.7% in 2004 to 27.8% in 2005. No resistance trend was observed in any medical centre or in the overall study data. Daptomycin showed bactericidal activity against all strains tested. The accuracy of MET for identifying hVISA strains varied significantly with the criteria applied for positivity.

Conclusions: The most frequently used criteria to define hVISA, i.e. MET reading values 8 mg/L for both vancomycin and teicoplanin or 12 mg/L for teicoplanin only, detected 20 of 36 PAP-positive strains (55.6% sensitivity), indicating that the prevalence of hVISA could be higher than currently appreciated. Daptomycin was bactericidal against hVISA strains.


October 27, 2009 at 3:29 pm Leave a comment

Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.1091-1095

Michael C. Ober1, Torsten Hoppe-Tichy1, Jörg Köninger2, Oliver Schunter3, Hans-Günther Sonntag4, Markus A. Weigand5, Jens Encke6, Carsten Gutt2 and Stefanie Swoboda1,*

1 Pharmacy Department, University Hospital of Heidelberg, Im Neuenheimer Feld 670, D-69120 Heidelberg, Germany 2 Department of Surgery, University Hospital of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany 3 Hospital Bietigheim-Bissingen, Riedstr. 12, D-74321 Bietigheim-Bissingen, Germany 4 Department of Medical Microbiology and Hygiene, Institute of Hygiene, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany 5 Department of Anaesthesiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany 6 Department of Gastroenterology and Hepatology, University Hospital of Heidelberg, Im Neuenheimer Feld 410, D-69129 Heidelberg, Germany

Objectives: Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication.

Patients and methods: Hospitalized patients with acute cholecystitis received a single, 1 h infusion of 400 mg of moxifloxacin before cholecystectomy. Serum and gallbladder wall tissue samples were collected during surgery, and the moxifloxacin concentrations were measured by HPLC.

Results: Sixteen patients (eight men and eight women) were included between January 2007 and April 2008. The time between start of infusion and gallbladder removal ranged from 50 min to 21 h 10 min. The serum concentration at the time of cholecystectomy was between 0.39 and 4.37 mg/L, and the tissue concentration between 1.73 and 17.08 mg/kg. The tissue-to-serum concentration ratio ranged from 1.72 to 6.33.

Conclusions: The results show that moxifloxacin penetrates well into gallbladder tissue and is therefore a therapeutic option for biliary tract infection. The highest concentrations in serum and gallbladder tissue were measured shortly after the end of a 1 h infusion. As perioperative prophylaxis, moxifloxacin should therefore be administered 30–60 min before the first surgical incision.


October 27, 2009 at 3:28 pm Leave a comment

Has the publication of methicillin-resistant Staphylococcus aureus (MRSA) treatment guidelines increased the survival associated with MRSA bacteraemia?

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.1111-1113

Richard Brindle* and on behalf of Wessex Microbiologists

Department of Microbiology, Portsmouth Hospitals, Portsmouth PO6 3LY, UK

Objectives: To establish whether local practice review and national methicillin-resistant Staphylococcus aureus (MRSA) treatment guidelines have increased the survival of patients with MRSA bacteraemia.

Methods: A multisite retrospective analysis of survival of patients with MRSA bacteraemia, which included patients from March 1995 to December 2008. Periods before and after the publication of UK guidelines were compared.

Results: Data were analysed for 1675 patients with a mean age of 69.8 years. Survival for the period up to and including 2003 was 64.3%, and was 62.8% for both 2004–2005 and 2006–2008.

Conclusions: No significant difference in survival in relation to local practice review or the publication of national guidelines was detected.


October 27, 2009 at 3:26 pm Leave a comment

Introduction and Transmission of 2009 Pandemic Influenza A (H1N1) Virus — Kenya, June–July 2009

MMWR Weekly  Oct 23, 2009  V.58  N.41  p.1143-1146


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October 27, 2009 at 3:24 pm Leave a comment

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