Telavancin for the Treatment of Methicillin-ResistantStaphylococcus aureusInfections

Methicillin-resistant Staphylococcus aureus (MRSA) causes a wide range of infections, including skin and skin-structure infections, pneumonia, bloodstream infections, and endocarditis [1]. Staphylococci, including MRSA, are considered to be a leading cause of healthcare-associated infections [2]. Many of these infections can be life-threatening and cause sepsis and death. The Centers for Disease Control and Prevention estimate that 80 461 severe MRSA infections and 11 285 MRSArelated deaths occur each year in the United States [2]. The changing epidemiology and increasing prevalence of resistant phenotypes of S. aureus, including MRSA, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and, rarely, vancomycin-resistant S. aureus, have spurred the need for new antimicrobial agents to treat serious infections caused by these gram-positive pathogens. Telavancin is a semisynthetic lipoglycopeptide antibacterial with potent bactericidal activity against a broad spectrum of these gram-positive organisms, including MRSA [3]. The recommended dosage regimen for telavancin is 10 mg/kg body weight intravenously infused over a 60-minute period every 24 hours in patients with normal renal function (creatinine clearance [CrCl], >50 mL/min). A dosage adjustment is required for patients with renal impairment (CrCl, ≤50 mL/ min). This supplement provides historical and current perspectives on the present roles of telavancin in clinical practice. The first article in the supplement, which Eric Wenzler and I coauthored, summarizes the discovery and development programs that allowed telavancin to become the first marketed semisynthetic lipoglycopeptide in 2009 [3]. Telavancin is commercially available again after a long and winding road involving regulatory decisions, manufacturing obstacles, and changes in commercialization partners. Importantly, telavancin continues to be supported by ongoing clinical research programs including the Telavancin Observational Use Registry (TOUR; NCT02288234) in the United States and an international phase 3, randomized trial comparing telavancin with standard intravenous antibiotic therapy for the treatment of patients with complicated S. aureus bacteremia, including right-sided endocarditis. The dual mechanism of action and in vitro activity of telavancin against clinically significant wild-type and drug-resistant gram-positive pathogens are outlined in the article by Karlowsky and colleagues [4]. The Clinical and Laboratory Standards Institute revised the broth microdilution susceptibility testing of telavancin in 2014, which resulted in a more accurate method for determining minimum inhibitory concentration [5, 6]. The US Food and Drug Administration has also revised minimum inhibitory concentration interpretive break point criteria for susceptibility to telavancin for S. aureus (≤0.12 μg/mL), Streptococcus pyogenes (≤0.12 μg/mL), Streptococcus agalactiae (≤0.12 μg/mL), Streptococcus anginosus group (≤0.06 μg/mL), and Enterococcus faecalis (vancomycin susceptible, ≤0.25 μg/mL) [5, 6]. The recent in vitro activity of telavancin from 2 large surveillance Correspondence: Keith A. Rodvold, PharmD, FCCP, FIDSA, University of Illinois at Chicago, College of Pharmacy, M/C 886, 833 S Wood St, Rm 164, Chicago, IL 60612 (kar@uic.edu). Clinical Infectious Diseases 2015;61(S2):S35–7 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. DOI: 10.1093/cid/civ524