Archive for March, 2011

Systematic Review and Meta-Analysis of the Efficacy of Appropriate Empiric Antibiotic Therapy for Sepsis

Antimicrobial Agents and Chemotherapy 1 Nov. 2010 V.54 N.11 P.4851-4863

Mical Paul, Vered Shani, Eli Muchtar, Galia Kariv, Eyal Robenshtok, and Leonard Leibovici

Unit of Infectious Diseases, Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Quantifying the benefit of early antibiotic treatment is crucial for decision making and can be assessed only in observational studies. We performed a systematic review of prospective studies reporting the effect of appropriate empirical antibiotic treatment on all-cause mortality among adult inpatients with sepsis. Two reviewers independently extracted data. Risk of bias was assessed using the Newcastle-Ottawa score. We calculated unadjusted odds ratios (ORs) with 95% confidence intervals for each study and extracted adjusted ORs, with variance, methods, and covariates being used for adjustment. ORs were pooled using random-effects meta-analysis. We examined the effects of methodological and clinical confounders on results through subgroup analysis or mixed-effect meta-regression. Seventy studies were included, of which 48 provided an adjusted OR for inappropriate empirical antibiotic treatment. Inappropriate empirical antibiotic treatment was associated with significantly higher mortality in the unadjusted and adjusted comparisons, with considerable heterogeneity occurring in both analyses (I2 > 70%). Study design, time of mortality assessment, the reporting methods of the multivariable models, and the covariates used for adjustment were significantly associated with effect size. Septic shock was the only clinical variable significantly affecting results (it was associated with higher ORs). Studies adjusting for background conditions and sepsis severity reported a pooled adjusted OR of 1.60 (95% confidence interval = 1.37 to 1.86; 26 studies; number needed to treat to prevent one fatal outcome, 10 patients [95% confidence interval = 8 to 15]; I2 = 46.3%) given 34% mortality with inappropriate empirical treatment. Appropriate empirical antibiotic treatment is associated with a significant reduction in all-cause mortality. However, the methods used in the observational studies significantly affect the effect size reported. Methods of observational studies assessing the effects of antibiotic treatment should be improved and standardized.



March 27, 2011 at 5:21 pm Leave a comment

Current and potential usefulness of pneumococcal urinary antigen detection in hospitalized patients with community-acquired pneumonia to guide antimicrobial therapy.

Arch Intern Med. 2011 Jan 24 V.171 N.2 P.166-72.

Sordé R, Falcó V, Lowak M, Domingo E, Ferrer A, Burgos J, Puig M, Cabral E, Len O, Pahissa A.

Department of Infectious Diseases, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Spain.

Comment in:

Arch Intern Med. 2011 Jan 24 V.171 N.2 P.172-3.



The role of pneumococcal urinary antigen detection in the treatment of adults with community-acquired pneumonia (CAP) is not well defined. We assessed the usefulness of pneumococcal urinary antigen detection in the diagnosis and antimicrobial guidance in patients hospitalized with CAP.


A prospective study of all adults hospitalized with CAP was performed from February 2007 through January 2008. To evaluate the accuracy of the test, we calculated its sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios. The gold standard used for diagnosis of pneumococcal pneumonia was isolation in blood or pleural fluid (definite diagnosis) and isolation in sputum (probable diagnosis). Antibiotic modifications, complications, and mortality were analyzed.


A total of 474 episodes of CAP were included. Streptococcus pneumoniae was the causative pathogen in 171 cases (36.1%). It was detected exclusively by urinary antigen test in 75 cases (43.8%). Sixty-nine patients had CAP caused by a pathogen other than S pneumoniae. Specificity was 96%, positive predictive value ranged from 88.8% to 96.5%, and the positive likelihood ratio ranged from 14.6 to 19.9. The results of the test led the clinicians to reduce the spectrum of antibiotics in 41 patients. Pneumonia was cured in all of them. Potentially, this optimization would be possible in the 75 patients diagnosed exclusively by the test.


When its findings are positive, the pneumococcal urinary antigen test is a useful tool in the treatment of hospitalized adult patients with CAP because it may allow the clinician to optimize antimicrobial therapy with good clinical outcomes.


March 27, 2011 at 5:19 pm Leave a comment

Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children: Executive Summary

Clinical Inectious Diseases 1 Feb 2011 V.52 N.3 P.285-292


Catherine Liu1, Arnold Bayer3,5, Sara E. Cosgrove6, Robert S. Daum7, Scott K. Fridkin8, Rachel J. Gorwitz9, Sheldon L. Kaplan10, Adolf W. Karchmer11, Donald P. Levine12, Barbara E. Murray14, Michael J. Rybak12,13, David A. Talan4,5, and Henry F. Chambers1,2

1Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California

2Division of Infectious Diseases, San Francisco General Hospital, San Francisco, CA

3Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA

4Divisions of Emergency Medicine and Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA

5Department of Medicine, David Geffen School of Medicine at University of California- Los Angeles

6Division of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, Maryland

7Department of Pediatrics, Section of Infectious Diseases, University of Chicago, Chicago, Illinois


9Division of Healthcare Quality Promotion, Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

10Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas

11Division of Infectious Diseases, Beth Israel Deaconess Medicine Center, Harvard Medical School, Boston, Massachusetts

12 Department of Medicine, Division of Infectious Diseases, Wayne State University, Detroit Receiving Hospital and University Health Center, Detroit, Michigan

13Deparment of Pharmacy Practice, Wayne State University, Detroit Michigan

14Division of Infectious Diseases and Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Medical School, Houston, Texas


Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.



March 25, 2011 at 3:41 pm Leave a comment

Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia

Chest Dec 2010 V.138 N.6 p.1356-62

Nadia Z. Haque, PharmD, Lizbeth Cahuayme Zuniga, MD, Paula Peyrani, MD, Katherine Reyes, MD, Lois Lamerato, PhD, Carol L. Moore, PharmD, Shruti Patel, MD, Marty Allen, MD, Edward Peterson, PhD, Timothy Wiemken, MPH, Ennie Cano, PharmD, Julie E. Mangino, MD, Daniel H. Kett, MD, Julio A. Ramirez, MD, Marcus J. Zervos, MD and the Improving Medicine through Pathway Assessment of Critical Therapy of Hospital-Acquired Pneumonia (IMPACT-HAP) Investigators

From the Henry Ford Health System (Drs Haque, Cahuayme Zuniga, Reyes, Lamerato, Moore, Patel, Peterson, and Zervos), and the School of Medicine (Dr Zervos), Wayne State University, Detroit, MI; the University of Louisville (Drs Peyrani, Allen, and Ramirez and Mr Wiemken), Louisville, KY; the Ohio State University (Dr Mangino), Columbus, OH; and the University of Miami Miller School of Medicine and Jackson Memorial Hospital (Drs Cano and Kett), Miami, FL.



Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined.


Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables.


The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality.


Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.


Part of this article was published previously in abstract form (Haque NZ, Cahuayme Zuniga L, Osaki Kiyan P, et al; IMPACT-HAP Study Group. Relationship of MIC to vancomycin on outcome of methicillin-resistant Staphylococcus aureus health care-associated and hospital-acquired pneumonia. In: 48th Annual ICAAC/IDSA 46th Annual Meeting; October 25-28, 2008; Washington, DC. Abstract K-531).

Funding/Support: This work was supported by a grant from Pfizer Inc US Medical.


March 25, 2011 at 2:56 pm Leave a comment

Pyogenic Liver Abscess

N Engl J of Medicine 24 March 2011 V.364  N.  p.1154

Images in Clinical Medicine

Chin-Wei Yu, M.D., and Ching-Hsing Lee, M.D.

A 44-year-old man with diabetes mellitus presented to our hospital after 4 days of fever and abdominal pain. The initial evaluation revealed tachycardia (heart rate, 137 beats per minute), hypotension (blood pressure, 81/44 mm Hg), and abdominal discomfort in the right upper quadrant. There was no rebound tenderness. A lesion with heterogeneous radiodensity was noted in the right upper abdomen on chest radiography (Panel A, arrowheads). Computed tomographic imaging revealed an intrahepatic lesion containing gas and fluid (Panel B, arrowheads). A pyogenic liver abscess was suspected. Blood cultures ultimately grew Klebsiella pneumoniae, which can be gas-producing. Diabetes is an important risk factor for this condition. Despite fluid resuscitation and treatment with inotropic agents and antibiotics, the patient’s clinical condition deteriorated, and he died within 48 hours after admission.



March 24, 2011 at 12:00 pm Leave a comment

Emerging mutations at virological failure of HAART combinations containing tenofovir and lamivudine or emtricitabine.

AIDS. 2010 Apr 24  V.24 N.7 p.1013-8.

Maserati R, De Silvestri A, Uglietti A, Colao G, Di Biagio A, Bruzzone B, Di Pietro M, Re MC, Tinelli C, Zazzi M; ARCA Collaborative Group.

Department of Infectious Disease, Foundation IRCCS San Matteo Hospital, Pavia, Italy.



To compare the emergence of drug-resistant HIV variants at failure of lamivudine (3TC)/tenofovir (TDF)-containing or emtricitabine (FTC)/TDF-containing HAART as a consequence of the different 3TC and FTC intracellular half-lives.


Retrospective evaluation of 859 patients selected from an Italian HIV resistance database (Antiretroviral Resistance Cohort Analysis).


Patients were selected for analysis if treated with a HAART whose nucleoside/nucleotide reverse transcriptase inhibitor backbone was either 3TC/TDF or FTC/TDF; if they experienced a virological failure after at least 6 months of plasma HIV-RNA undetectability; and if HIV genotypes before treatment and at failure were available. Univariate and multivariate logistic regression analyses were done to detect predictors of resistance mutations emerging at failure.


Of 714 patients failing with 3TC/TDF and 145 with FTC/TDF, 35.8 and 21.1% were in Centers for Disease Control and Prevention stage C, and 8.8 and 15.2% were on first-line HAART, respectively. At multivariate analysis, the emergence of K70R (P = 0.002), M184V (P = 0.031), T215F (P = 0.020) and Y181C (P = 0.005) was significantly more common in 3TC-treated than in FTC-treated patients, with an odds ratio of 4, 1.56, 1.89 and 3.84, respectively.


Despite their close structural similarity, 3TC and FTC are associated with a significantly different rate of drug resistance at treatment failure when combined with TDF in HAART regimens independently of the third drug used.


March 24, 2011 at 11:56 am Leave a comment


The Lancet, Early Online Publication, 18 March 2011

Stephen D Lawn MRCP a b, Prof Alimuddin I Zumla FRCP

Tuberculosis results in an estimated 1·7 million deaths each year and the worldwide number of new cases (more than 9 million) is higher than at any other time in history. 22 low-income and middle-income countries account for more than 80% of the active cases in the world. Due to the devastating effect of HIV on susceptibility to tuberculosis, sub-Saharan Africa has been disproportionately affected and accounts for four of every five cases of HIV-associated tuberculosis. In many regions highly endemic for tuberculosis, diagnosis continues to rely on century-old sputum microscopy; there is no vaccine with adequate effectiveness and tuberculosis treatment regimens are protracted and have a risk of toxic effects. Increasing rates of drug-resistant tuberculosis in eastern Europe, Asia, and sub-Saharan Africa now threaten to undermine the gains made by worldwide tuberculosis control programmes. Moreover, our fundamental understanding of the pathogenesis of this disease is inadequate. However, increased investment has allowed basic science and translational and applied research to produce new data, leading to promising progress in the development of improved tuberculosis diagnostics, biomarkers of disease activity, drugs, and vaccines. The growing scientific momentum must be accompanied by much greater investment and political commitment to meet this huge persisting challenge to public health. Our Seminar presents current perspectives on the scale of the epidemic, the pathogen and the host response, present and emerging methods for disease control (including diagnostics, drugs, biomarkers, and vaccines), and the ongoing challenge of tuberculosis control in adults in the 21st century…


March 23, 2011 at 11:17 am Leave a comment

Incidence and clearance of genital human papillomavirus infection in men (HIM): a cohort study.

Lancet. 2011 Mar 12 V.377  p.932

Giuliano AR, Lee JH, Fulp W, Villa LL, Lazcano E, Papenfuss MR, Abrahamsen M, Salmeron J, Anic GM, Rollison DE, Smith D.

H Lee Moffitt Cancer Center, Tampa, FL, USA.



Human papillomaviruses (HPVs) cause genital warts and cancers in men. The natural history of HPV infection in men is largely unknown, and that information is needed to inform prevention strategies. The goal in this study was to estimate incidence and clearance of type-specific genital HPV infection in men, and to assess the associated factors.


Men (aged 18-70 years), residing in Brazil, Mexico, and the USA, who were HIV negative and reported no history of cancer were recruited from the general population, universities, and organised health-care systems. They were assessed every 6 months for a median follow-up of 27·5 months (18·0-31·2). Specimens from the coronal sulcus, glans penis, shaft, and scrotum were obtained for the assessment of the status of HPV genotypes.


In 1159 men, the incidence of a new genital HPV infection was 38·4 per 1000 person months (95% CI 34·3-43·0). Oncogenic HPV infection was significantly associated with having a high number of lifetime female sexual partners (hazard ratio 2·40, 1·38-4·18, for at least 50 partners vs not more than one partner), and number of male anal-sexual partners (2·57, 1·46-4·49, for at least three male partners vs no recent partners). Median duration of HPV infection was 7·52 months (6·80-8·61) for any HPV and 12·19 months (7·16-18·17) for HPV 16. Clearance of oncogenic HPV infection decreased in men with a high number of lifetime female partners (0·49, 0·31-0·76, for at least 50 female partners vs not more than one partner), and in men in Brazil (0·71, 0·56-0·91) and Mexico (0·73, 0·57-0·94) compared with the USA. Clearance of oncogenic HPV was more rapid with increasing age (1·02, 1·01-1·03).


The data from this study are useful for the development of realistic cost-effectiveness models for male HPV vaccination internationally.


National Cancer Institute.



Lancet. 2011 Mar 12 V.377  p.881

Genital infection with HPV in men: research into practice.

Monsonego J.

Department of Colposcopy, Institute of the Cervix, 75017 Paris, France.


March 22, 2011 at 5:36 pm Leave a comment

The influence of abacavir and other antiretroviral agents on virological response to HCV therapy among antiretroviral-treated HIV-infected patients.

Antivir Ther. 2010  V.15 N.1  p.91-9.

Amorosa VK, Slim J, Mounzer K, Bruno C, Hoffman-Terry M, Dorey-Stein Z, Ferrara T, Kostman JR, Lo Re V 3rd.

Division of Infectious Diseases, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.



It remains unclear if certain antiretroviral medications, particularly abacavir, compromise response to HCV therapy. Such data could inform the selection of appropriate antiretrovirals in HIV/HCV-coinfected patients. The aim of this study was to determine if use of abacavir, as well as other antiretrovirals, was associated with reduced response to pegylated interferon (PEG-IFN) plus ribavirin.


A cohort study was performed among antiretroviral-treated HIV/HCV-coinfected patients initiating PEG-IFN plus ribavirin between January 2001 and June 2007 at six sites in the United States. Abacavir and other antiretrovirals represented exposures of interest. Study outcomes included an early virological response (> or =2 log IU/ml decrease in HCV viral load at 12 weeks) and sustained virological response (undetectable HCV viral load 24 weeks after treatment discontinuation).


Among 212 patients, 74 (35%) received abacavir. For patients infected with HCV genotype 1 or 4, no differences were observed between abacavir users and non-users in early virological response (26 [40%] versus 53 [44%]; adjusted odds ratio [OR] 1.00; 95% confidence interval [CI] 0.50-2.00) or sustained virological response (8 [13%] versus 13 [12%]; adjusted OR 1.34; 95% CI 0.50-3.62). Among genotype 2 and 3 patients, rates of early virological response (7 [78%] versus 16 [89%]; OR 0.44; 95% CI 0.05-3.76) and sustained virological response (3 [33%] versus 8 [44%]; OR 0.63; 95% CI 0.12-3.32) were also similar between abacavir users and non-users. No association was found between other antiretrovirals and a lack of early or sustained response.


Use of abacavir or other antiretroviral medications was not associated with reduced early or sustained virological response rates.



March 22, 2011 at 5:28 pm Leave a comment

Does This Patient Have Malaria?

JAMA Nov 10, 2010  V.304  N.18  p.2048-2056

Steve M. Taylor, MD, MPH; Malcolm E. Molyneux, MD, FRCP; David L. Simel, MD, MHS; Steven R. Meshnick, MD, PhD; Jonathan J. Juliano, MD, MSPH

Division of Infectious Diseases and International Health (Dr Taylor) and Department of Medicine (Dr Simel), Duke University Medical Center, Durham, North Carolina; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi (Dr Molyneux); School of Tropical Medicine, University of Liverpool, Liverpool, England (Dr Molyneux); Durham Department of Veterans Affairs Medical Center, Durham, North Carolina (Dr Simel); and Department of Epidemiology, Gillings School of Global Public Health (Drs Taylor and Meshnick), and Division of Infectious Diseases, School of Medicine (Dr Juliano), University of North Carolina, Chapel Hill.


Malaria commonly infects residents of and travelers to tropical regions. The clinical features of infection are notoriously nonspecific but have not been comprehensively evaluated.


To systematically review and synthesize data related to the predictive value of clinical findings for the diagnosis of malaria in endemic areas and in travelers returning from endemic areas.

Data Sources, Study Selection, and Data Extraction

The databases of MEDLINE and EMBASE (1950-July 2010) were searched to identify studies published in the English language of endemic and “imported” (acquired during travel) malaria. Additional studies were identified from reference lists. Studies were included that had patients suspected of having acute malaria (usually because of fever) and compared the presence or absence of clinical findings with blood smear confirmation. Two authors independently identified studies, appraised study quality, and extracted data on the patient population, outcome assessment, and clinical findings. Differences between reviewers were resolved by consensus.

Data Synthesis

Fourteen studies for endemic malaria were identified that met review criteria. Individual symptoms are of limited diagnostic utility but presence of splenomegaly (summary likelihood ratio [LR], 3.3; 95% confidence interval [CI], 2.0-4.7) or hepatomegaly (summary LR, 2.4; 95% CI, 1.6-3.6) make malaria more likely. Combinations of findings can affect the likelihood of malaria, but their performance varies by setting. Seven studies of imported malaria were identified. The presence of fever (LR, 5.1; 95% CI, 4.9-5.3), splenomegaly (summary LR, 6.5; 95% CI, 3.9-11.0), hyperbilirubinemia (LR, 7.3; 95% CI, 5.5-9.6), or thrombocytopenia (summary LR, 5.6; 95% CI, 4.1-7.5) make malaria more likely.


In endemic areas, the likelihood of malaria is increased by the presence of splenomegaly and hepatomegaly but individual findings are of limited utility and cannot reliably exclude malaria; combinations of findings may be useful to stratify risk in patients. In returning travelers, the clinical assessment can provide substantial diagnostic benefit, although all patients still require laboratory testing because malaria can be rapidly fatal.


March 20, 2011 at 3:42 pm Leave a comment

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