Archive for August, 2008

Interventions to control MRSA: high time for time-series analysis?

Journal of Antimicrobial Chemotherapy  Sept 2008  V.62  N.3  p.431-433

S. Harbarth1,* and M. H. Samore2,3

1 Infection Control Program, University of Geneva Hospitals and Medical School, CH-1211 Geneva 14, Switzerland 2 VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA 3 Division of Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84108, USA

Time-series methods are useful in quasi-experimental study designs in which rates of antibiotic-resistant infections are ascertained before and after an intervention. However, uncertainties remain regarding the use of time-series analysis as an appropriate research methodology for analysing the effect of infection control interventions and antibiotic policies on the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). In particular, there is still a substantial gap in our understanding of what actually happens to MRSA incidence when a planned intervention is made on use of one or more antibiotic drug classes.

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August 29, 2008 at 10:14 pm Leave a comment

Short- versus long-duration antimicrobial treatment for exacerbations of chronic bronchitis: a meta-analysis

Journal of Antimicrobial Chemotherapy  Sept 2008  V.62  N.3  p.442-450

Systematic review

Matthew E. Falagas1,2,3,*, Sofia G. Avgeri1, Dimitrios K. Matthaiou1, George Dimopoulos1,4 and Ilias I. Siempos1

1 Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece 2 Department of Medicine, Tufts University School of Medicine, Boston, MA, USA 3 Department of Medicine, Henry Dunant Hospital, Athens, Greece 4 Intensive Care Unit, ‘Attikon’ University Hospital, Athens, Greece

Objectives: The aim of this study was to evaluate the comparative effectiveness and safety of short (5 days) and long (7 or 10 days) duration antimicrobial treatment of patients with acute exacerbations of chronic bronchitis (AECB).

Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing regimens of the same antibiotic (same dosage and same route of administration) administered for a different time period. We searched PubMed, the Cochrane Central Register of Controlled Trials and reference lists from publications, with no language restrictions.

Results: Of the 1031 reports retrieved initially, seven RCTs, enrolling 3083 patients with AECB, met our inclusion criteria. The antimicrobials studied in these seven RCTs were quinolones, cefixime and clarithromycin. There was no difference between the short- and long-duration therapies with regard to treatment success in intention-to-treat [relative risk (RR) = 0.99, 95% confidence interval (CI) 0.95–1.03], clinically evaluable (RR = 0.99, 95% CI 0.96–1.02) or microbiologically evaluable (RR = 0.98, 95% CI 0.93–1.02) patients. Short-duration treatment, when compared with long, was associated with fewer adverse events (RR = 0.84, 95% CI 0.72–0.97).

Conclusions: Short-duration treatment seems to be as effective as and safer than long-duration antimicrobial treatment of patients with AECB. Additional research is required to clarify the long-term outcomes (namely the exacerbation-free interval after the resolution of an initial episode) of the compared regimens.


August 29, 2008 at 10:11 pm Leave a comment

Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland

Journal of Antimicrobial Chemotherapy  Sept 2008  V.62  N.3  p.490-494

Helen M. Palmer1,*, Hugh Young1, Andrew Winter2 and Jayshree Dave1

1 Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL), Department of Medical Microbiology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 5SA, UK 2 Sandyford Initiative, 2-6 Sandyford Place, Glasgow G3 7NB, UK

Objectives: The aim of this study was to analyse the trend in azithromycin susceptibility (AzDS) of Neisseria gonorrhoeae in Scotland between April 2004 and December 2007, and to characterize isolates exhibiting decreased AzDS or high-level azithromycin resistance (AzHLR).

Methods: Antibiotic susceptibility testing and N. gonorrhoeae multiantigen sequence typing (NG-MAST) were performed on all gonococcal isolates received by the Scottish Bacterial Sexually Transmitted Infections Reference Laboratory (SBSTIRL) during the study period.

Results: AzHLR isolates were observed for the first time in 2004 and increased from 0.3% to 3.9% in 2007. AzDS declined from 2.1% to 1.3% in the same period. Taken together, AzDS and AzHLR isolates accounted for 5.2% of the gonococcal infections in Scotland in 2007. NG-MAST revealed that only a small number of sequence types (STs) contained AzHLR and AzDS isolates; these STs also included azithromycin-susceptible isolates. Most STs containing AzHLR isolates were genetically related on the basis of their por and tbpB alleles; however, demographic data suggested that they formed discrete sexual networks.

Conclusions: AzHLR strains of N. gonorrhoeae are increasing in Scotland. A 1 g dose of azithromycin should not be considered as an alternative antibiotic therapy for gonococcal infections. The use of azithromycin to treat chlamydia in patients co-infected with N. gonorrhoeae results in a level of azithromycin in vivo that is sublethal for N. gonorrhoeae, which may lead to resistance.


August 29, 2008 at 10:09 pm Leave a comment

Pneumonia in HIV-infected Persons

American Journal of Respiratory and Critical Care Medicine  15 Sept 2008  V.178  N.6  p.630-636

Original Article

Increased Risk with Cigarette Smoking and Treatment Interruption

Fred M. Gordin1, Mollie P. Roediger2, Pierre-Marie Girard3, Jens D. Lundgren4, Jose M. Miro5, Adrian Palfreeman6, Maria C. Rodriguez-Barradas7, Marcelo J. Wolff8, Philippa J. Easterbrook9, Kate Clezy10 and Leonard N. Slater11

1 Veterans Affairs Medical Center and George Washington University, Washington, DC; 2 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota; 3 Service des Maladies Infectieuses et Tropicales–Hôpital Saint-Antoine, Université Pierre et Marie Curie, and Institut Médecine et d’Epidémiologie Appliquée, Paris, France; 4 Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark; 5 Hospital Clinic–Institut d’Investigacions Biomèdiques August Pi-Sunyer, University of Barcelona, Barcelona, Spain; 6 University Hospitals of Leicester, Leicester, and Medical Research Council, London, United Kingdom; 7 Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; 8 University of Chile School of Medicine and Arriaran Foundation, Santiago, Chile; 9 Department of HIV and Genitourinary Medicine, Kings College, London, United Kingdom; 10 University of New South Wales, Sydney, Australia; 11 University of Oklahoma College of Medicine and Veterans Affairs Medical Center, Oklahoma City, Oklahoma

Rationale: Bacterial pneumonia is a major cause of morbidity for HIV-infected persons and contributes to excess mortality in this population.

Objectives: To evaluate the frequency and risk factors for occurrence of bacterial pneumonia in the present era of potent antiretroviral therapy.

Methods: We evaluated data from a randomized trial of episodic antiretroviral therapy. The study, Strategies for Management of Antiretroviral Therapy, enrolled 5,472 participants at 318 sites in 33 countries. Study patients had more than 350 CD4 cells at baseline. Diagnosis of bacterial pneumonia was confirmed by a blinded clinical-events committee.

Measurements and Main Results: During a mean follow-up of 16 months, 116 participants (2.2%) developed at least one episode of bacterial pneumonia. Patients randomized to receive episodic antiretroviral therapy were significantly more likely to develop pneumonia than patients randomized to receive continuous antiretroviral therapy (hazard ratio, 1.55; 95% confidence interval, 1.07–2.25; P = 0.02). Cigarette smoking was a major risk factor: Current-smokers had more than an 80% higher risk of pneumonia compared with never-smokers (hazard ratio, 1.82; 95% confidence interval, 1.09–3.04; P = 0.02). Participants who were on continuous HIV treatment and were current smokers were three times more likely to develop bacterial pneumonia than nonsmokers. Current smoking status was significant, but a past history of smoking was not.

Conclusions: Bacterial pneumonia is a major source of morbidity, even for persons on potent antiretroviral therapy, including those with high CD4 cells. Efforts to reduce this illness should stress the importance of uninterrupted antiretroviral therapy and attainment and/or maintenance of nonsmoking status.


August 29, 2008 at 6:12 pm Leave a comment

The AIDS Epidemic — A Progress Report from Mexico City

N Engl J of Medicine August 28, 2008  V.359  N.9  p.885-887

Robert Steinbrook, M.D.



August 28, 2008 at 5:24 pm Leave a comment

An HIV Vaccine — Challenges and Prospects

N Engl J of Medicine  August 28, 2008  V.359  N.9  p.888-890


Margaret I. Johnston, Ph.D., and Anthony S. Fauci, M.D.



August 28, 2008 at 5:22 pm Leave a comment

Chronic Hepatitis C Virus Genotype 6 Infection: Response to Pegylated Interferon and Ribavirin

Journal of Infectious Diseases  15 September 2008  V.198  N.6  p.808–812

James Fung, Ching-Lung Lai, Ivan Hung, John Young, Charles Cheng, Danny Wong, and Man-Fung Yuen

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong Special Administrative Region, China

Background.  To date, no study has evaluated pegylated interferon for the treatment of chronic infection with hepatitis C virus (HCV) genotype 6. We aimed to determine the efficacy of pegylated interferon plus ribavirin for treating infection with genotype 6 versus genotype 1.

Methods.  Forty-two patients chronically infected with HCV (for genotype 1, n=21 ; for genotype 6, n=20  ) were treated with pegylated interferon a-2a (n=20) or a-2b (n=22) combined with oral ribavirin for 48 weeks.

Results.  There was no difference between genotypes 1 and 6 in the rates of early virological response (76% vs. 81%; P>.05) and end-of-treatment response (71% vs. 81%; P>.05). Patients infected with genotype 6 had a higher rate of sustained virological response (SVR) than did patients infected with genotype 1 (86% vs. 52%; P=.019). The overall adverse-effects profile was similar in both genotype groups. There was no significant difference in the rate of SVR between patients receiving pegylated interferon a-2a and those receiving a-2b. Multivariate analysis showed that genotype was the only significant factor associated with SVR (P=-039).

Conclusions.  Treatment with pegylated interferon and ribavirin for 48 weeks resulted in a significantly higher rate of SVR in patients infected with genotype 6 than in those infected with genotype 1. Further studies are required to determine whether lower dosages and 24 weeks of therapy may be sufficient for the treatment of genotype 6 infection.


August 28, 2008 at 5:20 pm Leave a comment

Opt-Out Testing for Human Immunodeficiency Virus in the United States: Progress and Challenges

JAMA  August 27, 2008  V.300  N.8  p.945-951

Special Communications

John G. Bartlett; Bernard M. Branson; Kevin Fenton; Benjamin C. Hauschild; Veronica Miller; Kenneth H. Mayer

Johns Hopkins University, School of Medicine, Baltimore, Maryland (Dr Bartlett); Centers for Disease Control and Prevention, Atlanta, Georgia (Drs Branson and Fenton); Forum for Collaborative HIV Research and George Washington University, Washington, DC (Mr Hauschild and Dr Miller); and Department of Medicine, Brown University, and Miriam Hospital, Providence, Rhode Island (Dr Mayer).

The Centers for Disease Control and Prevention (CDC) has recommended human immunodeficiency virus (HIV) testing for all persons aged 13 to 64 years in all health care settings. Signed consent would not be required and counseling with referral would be managed as it is for other serious conditions. The goal of the recommendations is to promote earlier entry into care to reduce unnecessary mortality and facilitate prevention by behavioral changes that accompany knowledge of serostatus. Concerns about the change include laws in some states that mandate signed consent and counseling, a perception that counseling is an effective prevention strategy, variability in payment coverage for the test, concerns about the stigma and discrimination that may accompany the HIV diagnosis, and the possibility that other testing policies would be more effective. Eleven of 16 states have changed legislation to reduce barriers to testing, 35 of 74 national professional societies have endorsed the new recommendations, and multiple demonstration projects have shown feasibility. Metrics to evaluate the health outcomes of the CDC’s recommendations for HIV testing have been defined, but the data necessary to determine the effects on early entry into care, the actual reduction in disease incidence, and the unanticipated consequences are not yet available.


August 26, 2008 at 11:49 pm Leave a comment

Delay of Active Antimicrobial Therapy and Mortality among Patients with Bacteremia: Impact of Severe Neutropenia

Antimicrobial Agents and Chemotherapy  1 Sept 2008  V.52  N.9  p.3188-3194

Michael Y. Lin,1,2* Robert A. Weinstein,1,2 and Bala Hota1,2

Section of Infectious Diseases, Rush University Medical Center, Chicago, Illinois,1 Division of Infectious Diseases, John H. Stroger, Jr. (Cook County) Hospital, Chicago, Illinois2

Increasing bacterial antimicrobial resistance has prompted physicians to choose broad-spectrum antimicrobials in order to reduce the likelihood of inactive empirical therapy. However, for bacteremic patients already receiving supportive care, it is unclear whether delay of active antimicrobial therapy significantly impacts patient outcomes. We performed a retrospective cohort study of patients with monomicrobial bloodstream infections at a large urban hospital in the United States from 2001 to 2006. We assessed the impact of delay of active antimicrobial therapy on mortality by using multivariable logistic regression modeling with and without propensity score methodology. We evaluated 1,523 episodes of monomicrobial bacterial bloodstream infections at our institution. Nine hundred eighty-three bacteremic episodes (64.5%) were treated with an active antimicrobial agent within 24 h of the index blood culture; the remaining 540 episodes (35.5%) were considered to have delay of active antimicrobial therapy. In adjusted analysis, among patients in the non-intensive-care-unit setting with an absolute neutrophil count (ANC) of <100 cells/µl, delay was associated with increased mortality (odds ratio [OR], 18.0; 95% confidence interval [CI], 2.84 to 114.5; P < 0.01); among intensive-care-unit patients with an ANC of <100 cells/µl, the effect of delay on mortality was nearly significant (OR, 5.56; 95% CI, 0.85 to 36.3; P = 0.07). However, for patients who were nonneutropenic (ANC, >500 cells/µl) or had ANCs of 100 to 500 cells/µl, delay was not associated with increased mortality. While the delay of active antimicrobial therapy was not significantly associated with higher mortality for most patients in this cohort, patients with severe neutropenia appeared to be vulnerable.


August 26, 2008 at 11:46 pm Leave a comment

Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Escherichia coli: Risk Factors for Inadequate Initial Antimicrobial Therapy

Antimicrobial Agents and Chemotherapy  1 Sept 2008  V.52  N.9  p.3244-3252

Mario Tumbarello,1* Michela Sali,2 Enrico Maria Trecarichi,1 Fiammetta Leone,2 Marianna Rossi,1 Barbara Fiori,2 Gennaro De Pascale,1 Tiziana D’Inzeo,2 Maurizio Sanguinetti,2 Giovanni Fadda,2 Roberto Cauda,1 and Teresa Spanu2

Institute of Infectious Diseases,1 Institute of Microbiology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy2

Extended-spectrum-β-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to 3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient’s history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.


August 26, 2008 at 11:44 pm Leave a comment

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