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Physicians: .25 AMA PRA Category I CreditsTM
Family Physicians: .25 Prescribed credits
Nurse Practitioners: .25 Contact hours

Release Date: June 11, 2014
Expiration Date: June 11, 2015

Estimated Completion Time: 15 minutes

There is no fee for this activity.

To Receive Credit

In order to receive your certificate of participation, you should read the information about this activity, including the disclosure statements, review the entire activity, take the post-test, and complete the evaluation form. You may then follow the directions to print your certificate of participation. To begin, click the CME icon above.

Program Overview

Learning Objectives

Upon successful completion of this educational program, the reader should be able to:

1. Discuss the significance of this article as it relates to your clinical practice.
2. Be able to apply this knowledge to your patient's diagnosis, treatment and management.

Faculty Information

Alan Ehrlich, MD
Assistant Clinical Professor in Family Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA; Senior Deputy Editor, DynaMed, Ipswich, Massachusetts, USA

Michael Fleming, MD, FAAFP
Assistant Clinical Professor of Family Medicine and Comprehensive Care, LSU Health Science Center School of Medicine, Shreveport, Louisiana, USA; Assistant Clinical Professor of Family Medicine, Department of Family and Community Medicine, Tulane University Medical School, New Orleans, Louisiana, USA; Chief Medical Officer, Amedisys, Inc. & Antidote Education Company


Dr. Ehrlich, Dr. Fleming, DynaMed Editorial Team members, and the staff of Antidote Education Company have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

No commercial support has been received for this activity.

Accreditation Statements

ACCME: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Antidote Education Company and EBSCO Publishing. Antidote is accredited by the ACCME to provide continuing medical education for physicians. Antidote Education Company designates this enduring activity for a maximum of 0.25 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

AAFP: This enduring material activity, DynaMed EBM Focus Volume 9, has been reviewed and is acceptable for up to 15.25 Prescribed credits by the American Academy of Family Physicians. AAFP certification begins March 5, 2014. Term of approval is for one year from this date. Each EBM Focus is approved for .25 Prescribed credits. Credit may be claimed for one year from the date of each update. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AANP: This program is approved for 0.25 contact hour(s) of continuing education by the American Association of Nurse Practitioners. This program was planned in accordance with AANP CE Standards and Policies and AANP Commercial Support Standards.

Program ID: 1405237E

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We are currently seeking subspecialty reviewers for our Patient Education Resource Center (PERC). PERC provides fact sheets and discharge instructions for patients leaving the hospital or emergency room. These hand-outs fulfill the meaningful use requirements for the Medicare & Medicare Services Incentive Programs.

Click here to speak with us about becoming a peer reviewer.

Last week 505 journal articles were evaluated via DynaMed's Systematic Literature Surveillance and summaries of 225 articles were added to DynaMed content.

Based on criteria for selecting "articles most likely to change clinical practice," one article was selected by the DynaMed Editorial Team.

Dalbavancin and Oritavancin Each Have Similar Efficacy to Vancomycin in Patients with Serious Bacterial Skin and Skin Structure Infections
Reference: N Engl J Med 2014 Jun 5;370(23):2169, N Engl J Med 2014 Jun 5;370(23):2180 (level 1 [likely reliable] evidence)

Skin and skin-structure infections are common and represent a significant burden for hospitals and primary care practices. A recent population-based study in the United States estimated that there were 496 clinically diagnosed skin or soft tissue infections per 10,000 person-years, which translates to more than 15 million new cases annually in the U.S. (BMC Infect Dis 2013 May 30;13(1):252 full-text). Staphylococcus aureus is an important causative agent of these infections, and methicillin-resistant S. aureus, or MRSA, can be particularly difficult to treat. When MRSA is suspected among hospitalized patients with complicated skin and skin tissue infections, such as purulent cellulitis, the glycopeptide antibiotic vancomycin is a treatment option (Clin Infect Dis 2011 Feb;52(3):e18 full-text). Lipoglycopeptide analogs such as dalbavancin (an analog of teicoplanin) and oritavancin (an analog of vancomycin) share a similar mechanism to their glycopeptide counterparts, but have important differences in pharmacologic properties. Two recent studies, one evaluating dalbavancin and the other evaluating oritavancin, assessed whether these analogs were noninferior to vancomycin in patients with acute bacterial skin and skin-structure infections.

Dalbavancin was evaluated in a pooled analysis of 2 randomized noninferiority trials with a total of 1,312 adults (mean age 50 years) with acute bacterial skin and skin structure infections. Patients were randomized to dalbavancin 1 g IV on day 1 and 500 mg on day 8 vs. vancomycin 1 g or 15 mg/kg IV twice daily for ≥ 3 days and followed to 70 days. Patients in the vancomycin group had the option to switch to linezolid 600 mg orally twice daily to complete 10-14 days therapy. 54% of patients had cellulitis, 25% had major abscess, and 21% had a wound or surgical site infection. All patients had lesions with ≥ 75 cm2 of erythema plus systemic and symptomatic signs of infection. In patients with a pathogen isolated at baseline, 24% had MRSA and 53% had methicillin-susceptible S. aureus (MSSA). A total of 45 patients (3.4%) had Gram-positive bacteremia, including 20 patients with S. aureus bacteremia. The primary outcome was early clinical response, which was defined as cessation of spread of infection-related erythema plus absence of fever at 48-72 hours. The noninferiority criterion was defined as a lower limit of 95% CI ≤ 10% for differences between groups in early clinical response.

A total of 85% of patients were included in the per-protocol analysis, and 92% were included in the modified intention-to-treat analysis. Early clinical response was observed in 79.7% with dalbavancin vs. 79.8% with vancomycin-linezolid in the modified intention-to-treat analysis (noninferiority met). The overall clinical response rate at the end of treatment was 90.7% with dalbavancin vs. 92.1% with vancomycin-linezolid in the per-protocol analysis (not significant), with consistent results in the intention-to-treat analysis.

Oritavancin was evaluated in a randomized noninferiority trial of 968 adults (mean age 45 years) with acute bacterial skin and skin structure infections. Patients were randomized to a single dose of oritavancin 1,200 mg IV vs. vancomycin 1 g or 15 mg/kg IV twice daily for 7-10 days with serum trough monitoring, and followed to 60 days. 50% of patients had cellulitis, 30% had abscess, and 20% had wound infection. MRSA was isolated in 21% of patients, and MSSA was isolated in 23%. All patients had lesions surrounded by erythema, edema, or induration ≥ 75 cm2 plus signs and symptoms of systemic inflammation. The primary outcome was a composite of cessation of spreading or decrease in lesion size, absence of fever, and lack of need for rescue antibiotic at 48-72 hours. The noninferiority criterion was defined as a lower limit of 95% CI ≤ 10% for differences between groups in the primary outcome.

A total of 791 patients (82%) were clinically evaluable, and 954 patients (98.5%) were included in a modified intention-to-treat analysis. The primary outcome occurred in 82.3% with oritavancin vs. 78.9% with vancomycin (noninferiority met). An investigator-assessed clinical cure occurred in 79.6% with oritavancin vs. 80% with vancomycin (not significant). A decrease in lesion area of at least 20% at 48-72 hours was observed in 86.9% with oritavancin vs. 82.9% with vancomycin (not significant). There were no significant differences in the primary outcome in subgroup analyses separately evaluating patients with MRSA or MSSA.

The findings from these randomized trials demonstrate that dalbavancin and oritavancin have comparable clinical response rates compared to vancomycin in the management of acute bacterial skin and skin-structure infections. Dalbavancin has been approved by the U.S. Food and Drug Administration for treatment of adults with acute bacterial skin and skin structure infections caused by certain susceptible bacteria, including MRSA and MSSA (FDA Press Release 2014 May 23). Cost information was not reported for either agent, and pricing information does not yet appear to be available. In these trials, dalbavancin was administered once weekly and oritavancin was administered as a single dose, whereas vancomycin was administered every 12 hours. The less frequent administration required for dalbavancin and oritavancin, and the lack of need to monitor serum levels, may make it possible to treat some of these infections on an outpatient basis when they might otherwise have been treated in-hospital. This could dramatically reduce both the costs and risks of hospitalization. However, the longer duration of action may prove to be a safety concern as well, since any toxic effects may continue for weeks until the agents have been cleared. It is also important to keep in mind that these trials were designed to compare these lipoglycopeptide agents to vancomycin, and do not represent a comparison to standard practice in some cases. For example, in patients with MSSA bacteremia, retrospective cohort studies have demonstrated that nafcillin and cefazolin are associated with reduced mortality compared to vancomycin (BMC Infect Dis 2011 Oct 19;11:279 full-text, Antimicrob Agents Chemother 2008 Jan;52(1):192 full-text). For patients with bacteremia who are later shown to have MSSA, itís not clear how these agents compare to standard practice, and the longer half-life of these agents may make switching to optimal treatment more difficult. In addition, itís not clear that a full 14 days of therapy is warranted in all cases, and treatment with a long-acting agent might expose a patient to antibiotics for longer than needed. Longer duration of therapy may also augment the emergence of vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus.

For more information see the Cellulitis, Skin abscess, and Treatment of MRSA skin and soft tissue infections topics in DynaMed.

Special thanks to Ben Smith and Deborah Orosz of Harvard Medical School for their contributions to this week's article.

Earn CME Credit for reading this e-Newsletter. For more information on this educational activity, see the CME sidebar.

EBSCO Health Launches Pediatric Clinical Information Mobile App

PEMSoft Now Available For iPhone, iPad, and Android Devices

A mobile app designed specifically for pediatricians, emergency department physicians, physicians-in-training and other medical providers caring for children with acute illnesses and injury, is now available from EBSCO Health, the leading provider of clinical decision support solutions for the healthcare industry.

Designed by pediatricians, emergency physicians and other medical specialists, PEMSoft is a pediatric evidence-based point-of-care medical reference tool for hospitals, emergency departments, clinics, pediatric group practices, transport services, and medical schools. The vast content in PEMSoft addresses the entire spectrum of neonatal, infant, child, adolescent and young adult health. PEMSoft authors adhere to a strict evidence-based editorial policy focused on systematic identification, evaluation and consolidation of practice-changing clinical literature.

The PEMSoft Mobile app includes explicit step-by-step emergency critical care procedures, information about common pediatric signs and symptoms and content covering pediatric injuries and management approaches. More than 3,000 evidence-based pediatric topics and a similar number of medical illustrations, clinical images and videos are also available via the mobile app.

The PEMSoft Mobile App is accessible from both Apple and Android devices.

For more information and technical support, visit the PEMSoft Mobile Access page. To view the official press release, click here.

DynaMed Events

Medical Marijuana: Regs, Responsibilities & Communication
June 18, 2014 / 8am-12:30pm

Senior Deputy Editor Alan Ehrlich, MD, will be presenting Medical Marijuana: An Evidenced-Based Assessment of Efficacy and Harms at the Massachusetts Medical Society (MMS) CME Event and Conference.

The conference, Medical Marijuana: Regulations, Responsibilities & Communication, will be held at the MMS Headquarters at Waltham Woods in Waltham, Massachusetts. DynaMed Representatives will also be available to discuss peer review, mobile access, and free trial information.

Visit the MMS website to learn more about the event and for registration information.

If you would like to meet with a DynaMed representative at any of our conferences, please contact us at DyndMedCommunity@ebscohost.com.