Abstract
Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial agents, including mupirocin, for 403 MRSA isolates collected longitudinally from a naive population at the Veterans Affairs Puget Sound Health Care System. The MICs for retapamulin had a unimodal distribution, ranging from 0.008 to 0.5 μg/ml. One isolate had an MIC of >16 μg/ml, was also resistant to clindamycin and erythromycin, and was recovered from the nares of a patient undergoing hemodialysis. Twenty-four isolates (6%) and 11 isolates (3%) demonstrated low-level resistance (MICs of 8 to 64 μg/ml) and high-level resistance (MICs of ≥ 512 μg/ml), respectively, to mupirocin. Isolates were recovered from 10 patients both before and after mupirocin therapy. Of those, isolates from 2 patients demonstrated MIC changes postmupirocin therapy; in both cases, however, strain typing demonstrated that the pre- and postmupirocin strains were different. A total of 386 isolates (96%) had vancomycin MICs of ≤ 1.0 μg/ml; 340 isolates (84%) were resistant to levofloxacin, 18 isolates (4.5%) were resistant to trimethoprim-sulfamethoxazole, and 135 isolates (33%) had elevated MICs of 4 μg/ml for linezolid. The baseline levels of resistance were low for mupirocin (9%) and even lower for retapamulin (0.25%) Although the use of mupirocin is currently the standard therapy for decolonization practices, the activity of retapamulin warrants its consideration as an alternative therapy in MRSA decolonization regimens.
Highlights
Retapamulin is a semisynthetic derivative of the compound pleuromutilin, which binds to and prevents formation of the active 50S ribosomal subunit, inhibiting bacterial protein synthesis [1]
Decolonization using mupirocin is not a standardized practice within the Veterans Affairs (VA) health care system, and baseline levels of mupirocin resistance have never been determined at our facility
We determined the in vitro activity of retapamulin, mupirocin, and a select panel of antimicrobials against methicillin-resistant Staphylococcus aureus (MRSA) isolates selected from targeted groups of veteran patients, including patients who had significant infections caused by MRSA, were at risk for long-term colonization or recolonization with MRSA, and/or were potential candidates for or were receiving decolonization treatment
Summary
Retapamulin is a semisynthetic derivative of the compound pleuromutilin, which binds to and prevents formation of the active 50S ribosomal subunit, inhibiting bacterial protein synthesis [1]. Approved in 2007 and licensed as Altabax in the United States, retapamulin is currently indicated for the topical treatment of impetigo due to methicillin-susceptible Staphylococcus aureus and Streptococcus pyogenes [2,3,4] It has not been approved for use against methicillin-resistant Staphylococcus aureus (MRSA), as in vitro susceptibility data did not correlate with clinical efficacy for open wounds [5]. The purpose of this study was to determine the in vitro activities of retapamulin and mupirocin for MRSA isolates that we considered extensively drug-resistant (XDR) (defined on the basis of resistance to one or more drug classes in addition to -lactams, macrolides/lincosamides, and fluoroquinolones) or from groups of patients for whom topical therapy might be beneficial. We evaluated these isolates using a panel of antimicrobials to establish a baseline “antibiogram” for these patient groups at our facility, as many of our patients have had repeated hospital exposures and may be at risk for nosocomial acquisition of MRSA
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