Emerging Issues in the Diagnosis and Management of Infections Caused by Multi-Drug-Resistant, Gram-Positive Cocci

Abstract

Rising rates of multi-drug-resistant, gram-positive cocci (e.g., methicillin-resistant Staphylococcus aureus [MRSA], vancomycin-resistant Enterococcus spp. [VRE]) have created treatment challenges for clinicians in both the hospital and community settings. These organisms have become especially problematic for hospitalized patients with pneumonia, complicated intra-abdominal infections, and skin and skin-structure infections (SSSIs). A review of the recent literature (1990 onwards) was undertaken in order to review the epidemiology, diagnostic issues, and clinical trial data of available and forthcoming therapies for the treatment of multi-drug resistant, gram-positive isolates, with an emphasis on selected MRSA infections (i.e., pneumonia, SSSI, diabetic foot infections, blood stream) and infections caused by VRE. The rate of healthcare-associated MRSA in 2004 rose to an incidence of 59.5% in the United States compared with data from 1998-2002, making MRSA the predominant gram-positive etiology of S. aureus infections in hospitalized patients. Methicillin-resistant S. aureus has also emerged as an important pathogen in both the non-ICU and community settings. Similarly, 28.5% of all enterococcal isolates were identified as vancomycin-resistant in 2003 (a 12% increase). However, these rates may be underestimated, as detection methods for determining susceptibility have proved to be inadequate. Recognition that prior inadequate antibiotic therapy is common in patients with antibiotic-resistant bacteria, and is associated with higher mortality rates, emphasizes the importance of selecting appropriate empiric therapy. Currently available therapies for resistant gram-positive infections include quinupristin-dalfopristin, linezolid, and daptomycin, although each of these agents has limitations (e.g., daptomycin is not indicated for MRSA pneumonia due to inadequate lung tissue penetration and inactivation by surfactant). Three agents with broad-spectrum activity against gram-positive organisms that are at an advanced stage of testing include two new glycopeptides (oritavancin and dalbavancin), and a first-in-class glycylcycline (tigecycline). These agents have demonstrated efficacy in the treatment of SSSIs, including those caused by MRSA. New antimicrobial agents are needed to combat the increasing prevalence of multi-drug-resistant, gram-positive pathogens such as MRSA. The emergence of resistance to available therapies such as vancomycin underscores this urgency.