Archive for January, 2014

Methicillin-Resistant Staphylococcus aureus – An Evolving Pathogen

Clinical Infectious Diseases January 2014 V.58 Suppl.1 P.10-19

Martin E. Stryjewski1 and G. Ralph Corey2,3

1Department of Medicine and Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina

2Division of Infectious Diseases, Duke Clinical Research Institute

3Duke University Medical Center, Durham, North Carolina

Correspondence: Martin E. Stryjewski, MD, MHS, Department of Internal Medicine and Division of Infectious Diseases, CEMIC, Las Heras 2939, 3rd floor, Department of Medicine, Ciudad Autonoma de Buenos Aires (1425) Buenos Aires, Argentina (


The horizontal transmission of methicillin resistance to Staphylococcus aureus (MRSA) in hospital and community settings, and growing prevalence of these strains, presents a significant clinical challenge to the management of serious infections worldwide.

While infection control initiatives have stemmed the rising prevalence, MRSA remains a significant pathogen.  More recently, evidence that MRSA is becoming resistant to glycopeptides and newer therapies raises concern about the use of these therapies in clinical practice.

Vancomycin resistance has become evident in select clinical settings through rising MICs, growing awareness of heteroresistance, and emergence of intermediate-resistant and fully resistant strains.

While resistance to linezolid and daptomycin remains low overall, point mutations leading to resistance have been described for linezolid, and horizontal transmission of cfr-mediated resistance to linezolid has been reported in clinical isolates.

These resistance trends for newer therapies highlight the ongoing need for new and more potent antimicrobial therapies.


January 30, 2014 at 8:58 pm

FDA Guidance for ABSSSI Trials – Implications for Conducting and Interpreting Clinical Trials

Clinical Infectious Diseases January 2014 V.58 Suppl.1 P.4-9

Kamal M. F. Itani1 and Andrew F. Shorr2

1Department of Surgery, VA Boston Healthcare System, Boston University and Harvard University Schools of Medicine, Boston, Massachusetts

2Department of Pulmonary and Critical Care, Washington Hospital Center, Washington, District of Columbia

Correspondence: Kamal M. F. Itani, MD, VA Boston Healthcare System, West Roxbury Campus, 1400 VFW Parkway, West Roxbury, MA 02132 (

Recent guidance from the US Food and Drug Administration (FDA) on the conduct of clinical trials for acute bacterial skin and skin structure infection (ABSSSI) has changed the framework for clinical trial design and conduct. Notable changes included new disease state definitions, new primary endpoint definitions and the timing of assessments at these endpoints, and updated guidance on patient inclusion/exclusion criteria.

Supportive evidence and statistical justification for the proposed noninferiority margins were described in detail. Although the updated guidelines are still considered drafts and have been adopted in some trials, they serve as the basis for study protocol discussions between pharmaceutical companies and the FDA in advancing the development of promising new agents.

Not only will the new trial designs impact researchers and sponsors responsible for drug development programs, but they will also affect healthcare providers participating in clinical trials and the ways in which clinicians develop patient treatment plans based on the results of those trials.

This review provides a summary of key changes that will impact future clinical trial design and outcomes.



January 30, 2014 at 8:55 pm

Tedizolid – A Novel Oxazolidinone for Gram-Positive Infections

Clinical Infectious Diseases January 2014 V.58 Suppl.1 P.1-3

Robert C. Moellering Jr1,2

1Harvard Medical School

2Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Correspondence: Robert C. Moellering Jr, MD, Department of Medicine, Beth Israel Deaconess Medical Center, 110 Francis St, Ste 6A, Boston, MA 02215 (

Despite the concerted efforts of modern medicine, infections due to gram-positive bacteria, such as skin and soft tissue infections, pneumonia, bacteremia, and endocarditis, continue to pose many challenges to achieving successful treatment outcomes. A good case in point is found in the emergence and spread of methicillin resistance in Staphylococcus aureus. The first strains of methicillin-resistant S. aureus (MRSA) were discovered a half-century ago in a hospital in London, just 2 years after the first clinical use of methicillin …


January 30, 2014 at 8:53 pm

Tedizolid Phosphate for the Management of Acute Bacterial Skin and Skin Structure Infections – Safety Summary

Clinical Infectious Diseases January 2014 V.58 Suppl.1 P.51-57

Debaditya Das1, Paul M. Tulkens1,2, Purvi Mehra3, Edward Fang4, and Philippe Prokocimer4

1Cellular and Molecular Pharmacology

2Center for Clinical Pharmacy; Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium

3eStudySite, San Diego

4Cubist Pharmaceuticals, San Diego, California

Correspondence: Philippe Prokocimer, Cubist Pharmaceuticals, 6310 Nancy Ridge Dr, Ste 101, San Diego, CA 92121 (


The novel oxazolidinone tedizolid phosphate is in late-stage clinical development. In an effort to improve efficacy and safety, the adverse event profile and safety aspects of tedizolid phosphate have been evaluated in several preclinical animal models and through ongoing clinical trials.

Early dose-ranging studies demonstrated a favorable overall adverse event profile and low thrombocytopenia rates, which have been consistently confirmed in phase 2 and 3 clinical trials.

Pharmacokinetic modeling suggests a lower potential for monoamine oxidase interaction, and animal and human subject testing has confirmed these predictions. Studies in special patient populations showed a consistent and predictable pharmacokinetic profile across age groups and comorbid conditions, without evidence of increased incidence of adverse effects over matched controls.

The favorable safety profile makes tedizolid phosphate an important new option for the management of serious Gram-positive infections, including those caused by methicillin-resistant Staphylococcus aureus.



January 28, 2014 at 9:06 am

Primary Care Guidelines for the Management of Persons Infected With HIV – 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Clinical Infectious Diseases January 1, 2014 V.58 N.1 P.1-10

Executive Summary

Judith A. Aberg1, Joel E. Gallant2,3, Khalil G. Ghanem3, Patricia Emmanuel4, Barry S. Zingman5, and Michael A. Horberg6

1Division of Infectious Diseases and Immunology, New York University School of Medicine, Bellevue Hospital Center, New York

2Southwest CARE Center, Santa Fe, New Mexico

3Johns Hopkins University School of Medicine, Baltimore, Maryland

4Department of Pediatrics, University of South Florida Health, Tampa

5Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York

6Mid-Atlantic Permanente Research Institute, Rockville, Maryland

Correspondence: Judith A. Aberg, MD, New York University School of Medicine, 550 First Ave, BCD 5 (Rm 558), New York, NY 10016 (


Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America.

These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve.

However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009–2013 has been incorporated into this document.


January 28, 2014 at 9:04 am

Effect of Influenza Vaccination of Healthcare Personnel on Morbidity and Mortality Among Patients: Systematic Review and Grading of Evidence

Clinical Infectious Diseases January 1, 2014 V.58 N.1 P.50-57

Faruque Ahmed1, Megan C. Lindley1, Norma Allred1, Cindy M. Weinbaum2, and Lisa Grohskopf3

1Immunization Services Division, National Center for Immunization and Respiratory Diseases

2Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases

3Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

Correspondence: Faruque Ahmed, PhD, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS A-19, Atlanta, GA 30333 (



Influenza vaccination of healthcare personnel (HCP) is recommended in >40 countries. However, there is controversy surrounding the evidence that HCP vaccination reduces morbidity and mortality among patients. Key factors for developing evidence-based recommendations include quality of evidence, balance of benefits and harms, and values and preferences.


We conducted a systematic review of randomized trials, cohort studies, and case-control studies published through June 2012 to evaluate the effect of HCP influenza vaccination on mortality, hospitalization, and influenza cases in patients of healthcare facilities. We pooled trial results using meta-analysis and assessed evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.


We identified 4 cluster randomized trials and 4 observational studies conducted in long-term care or hospital settings. Pooled risk ratios across trials for all-cause mortality and influenza-like illness were 0.71 (95% confidence interval [CI], .59–.85) and 0.58 (95% CI, .46–.73), respectively; pooled estimates for all-cause hospitalization and laboratory-confirmed influenza were not statistically significant. The cohort and case-control studies indicated significant protective associations for influenza-like illness and laboratory-confirmed influenza. No studies reported harms to patients. Using GRADE, the quality of the evidence for the effect of HCP vaccination on mortality and influenza cases in patients was moderate and low, respectively. The evidence quality for the effect of HCP vaccination on patient hospitalization was low. The overall evidence quality was moderate.


The quality of evidence is higher for mortality than for other outcomes. HCP influenza vaccination can enhance patient safety.



Editorial Commentary: Influenza Vaccination of Healthcare Workers: Making the Grade for Action

Marie R. Griffin

Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee

Correspondence: Marie R. Griffin, MD, MPH, Department of Preventive Medicine, Vanderbilt University Medical Center, 1500 21st Ave S, Nashville, TN 37212 (

It is reasonable to ask what type of evidence is needed to recommend or require annual influenza vaccination of healthcare workers to help prevent transmission of influenza to vulnerable hospitalized patients and to residents of long-term care facilities. To make such a recommendation, one would want to know the risks and consequences of influenza in such patients, the safety of the vaccine and its efficacy in preventing influenza in healthcare workers, and the likelihood that vaccinating such workers could prevent the spread of influenza within these facilities in addition to costs and feasibility …


January 28, 2014 at 9:01 am

Emergence of high-level resistance to gentamicin and streptomycin in Streptococcus agalactiae in Buenos Aires, Argentina.

Rev Esp Quimioter. 2013 Jun;26(2):112-5.

Article in Spanish

Villar HE, Jugo MB.



Streptococcus agalactiae has become recognized as a cause of serious illness in newborns, pregnant women, and adults with chronic medical conditions.

Optimal antimicrobial therapy for serious infections requires the use of synergistic combinations of a cell wall-active agent, such as a penicillin, with an aminoglycoside, which results in bactericidal activity against this organism.

The synergistic effect is eliminated by the acquisition of high-level resistance (HLR) to aminoglycosides. The aim of our study was to determine the prevalence of HLR to gentamicin (GEN) and streptomycin (EST).The ability to detect HLR using a standard agar screen plate and high-content discs was investigated.


This study was conducted with 141 strains of S. agalactiae isolated from vaginal and rectal swabs of pregnant women at term. Minimum inhibitory concentrations (MICs) to GEN and STR were determined by the E-test method. Disks of GEN (120 μg) and STR (300 μg) were used to detect HLR. Agar screening plates were performed with GEN 100 mg/L, GEN 500 mg/L and STR 2000 mg/L.


The HLR to GEN and STR was detected in 13.5% and 16.3% of the isolates respectively. Among 141 strains, 7.8% were simultaneously resistant to GEN and STR. With 120-μg GEN and 300-μg STR disks, strains for which MICs were ≥ 512 mg/L and ≥ 1024 mg/L had no zones of inhibition. Isolates with inhibitory zones for GEN and STR of ≥13 mm showed a MICs ≤ 64 mg/L and ≤ 512 mg/L. All the screening plates were negative for these isolates. HLR to aminoglycosides was associated (83.9%) with resistance to erythromycin and/or clindamycin.


This study highlights the emergence of strains with HLR to aminoglycosides. The disk-agar diffusion test performed with high-content aminoglycoside disks and screening plates can provide laboratories with a convenient and reliable method for detecting S. agalactiae isolates that are resistant to aminoglycoside-betalactam synergy.


January 27, 2014 at 2:54 pm

Spinal epidural abscesses in children – A 15-year experience and review of the literature.

Clin Infect Dis. 2001 Jan;32(1):9-16.

Auletta JJ, John CC.


We reviewed medical records and laboratory and diagnostic evaluations for 8 pediatric patients with spinal epidural abscesses who were treated during the last 15 years at our institution.

Staphylococcus aureus was isolated from 5 of 8 epidural abscesses, including 2 abscesses with methicillin-resistant S. aureus. Unusual isolates were group B Streptococcus in a patient with chronic vesicouretral reflux associated with the posterior urethral valves and Aspergillus flavus in a patient with acute myelogenous leukemia.

An analysis incorporating our results and a review of the English-language literature about abscesses in children and adults revealed differences related to age. Abscesses in children were more posterior in epidural location, had greater spinal column extension, and were associated with more favorable clinical outcomes than were abscesses in adults.

Magnetic resonance imaging is the diagnostic procedure of choice; however, radionuclide bone scans should be considered for associated distant osteomyelitis in children. Prompt diagnosis and combined medical and surgical treatment remain the cornerstones for the prevention of adverse outcomes.


January 27, 2014 at 2:51 pm

Group B streptococcal infections in elderly adults.

Clin Infect Dis. 2005 Sep 15;41(6):839-47.

Edwards MS, Baker CJ.


Elderly adults account for >40% of persons with invasive group B streptococcal (GBS) disease and for >50% of GBS-associated deaths in the United States.

The prevalence of colonization among healthy elderly adults (approximately 25%) is similar to that among women of childbearing age. Delineating contributions of comorbid conditions, altered integrity of anatomical barriers, and abnormalities in immune responses caused by immune senescence to pathogenesis require further investigation.

Delayed clinical recognition of illness may contribute to poor outcome. Skin and soft-tissue infections and bacteremia with no identified focus are common manifestations of infection in elderly adults and younger nonpregnant adults.

Urinary tract infection and pneumonia are presentations more often encountered in elderly persons than in younger adults. The safety and immunogenicity of GBS serotype V-tetanus toxoid conjugate vaccine in healthy elderly persons suggest the potential for vaccination as an approach to prevention of invasive GBS infections in elderly persons.



January 27, 2014 at 2:50 pm

Pyogenic vertebral osteomyelitis – A review of 14 cases.

J Orthop Surg (Hong Kong). 2005 Dec;13(3):240-4.

Nather A, David V, Hee HT, Thambiah J.



To review and evaluate the management of 14 patients with pyogenic vertebral osteomyelitis at National University Hospital, Singapore between 1998 and 2001.


Demographic pattern, predisposing factors, clinical presentation, co-morbidities, microbiology, treatment, and complications of 14 patients were retrospectively reviewed.


The mean age at presentation was 62.5 years and the male to female ratio was 6:1. The mean follow-up duration was 12.5 months.

The most common predisposing condition was diabetes mellitus (n=5).

The most common site of infection was the lumbar spine (n=8), followed by the thoracic (n=4) and cervical (n=2) spine.

Staphylococcus aureus was the most common causative organism isolated (n=9), followed by methicillin-resistant S aureus (n=3), Pseudomonas pseudomallei (n=1), and Streptococcus agalactiae (n=1). 12 patients were treated surgically: 8 by an anterior approach, 3 by a posterior approach, and one by a combination of the 2.

The mean period of antibiotic use was 11.4 weeks. One patient with melioidosis involving the T9 to T11 vertebrae caused by P pseudomallei died of empyema and septicaemia 22 months after presentation.


Pyogenic vertebral osteomyelitis is not uncommon in the elderly, especially those with predisposing conditions such as diabetes mellitus. Computed tomography-guided needle biopsy is recommended to investigate causative microorganisms. Aggressive surgical debridement and prolonged antibiotic therapy were necessary in patients with methicillin-resistant S aureus, P pseudomallei, and S agalactiae.


January 27, 2014 at 2:48 pm

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