1218. Retapamulin as a Potential Decolonizing Agent: Activity against Mupirocin-Resistant Strains from Pediatric Patients with Methicillin-Resistant Staphylococcus aureus infection
Session: Poster Abstract Session: Healthcare Epidemiology: MSSA, MRSA and Other Gram Positive Infections
Friday, October 5, 2018
Room: S Poster Hall
Background:

Controlling methicillin-resistant Staphylococcus aureus (MRSA) colonization is a common strategy to prevent transmission and recurrent infection. Standard decolonization regimens include nasal application of mupirocin ointment, however, increasing rates of mupirocin-resistance (Mup-R) have been noted globally. At our institution there has been an increase in community-acquired MRSA (CA-MRSA) infections among children living in Brooklyn, New York. A genotypic geographic cluster of an outbreak clone of the CA-MRSA strain USA 300 with a high rate (>85%) of mupirocin resistance, mediated by the plasmid borne mupA gene, was identified prompting investigation into an alternative decolonizing agent. We sought to investigate retapamulin, a topical pleuromutilin antibiotic, which has been shown to be effective against S.aureus with in vitro and in vivo activity against MRSA and a low propensity to develop resistance.

Methods:

Broth microdilution was used to determine the minimum inhibitory concentrations (MIC) of retapamulin against 53 Mup-R MRSA isolates collected from pediatric patients (aged 9 months -17 years) presenting to our institution over an 18 month period with clinical MRSA infection. Susceptibility defined as ≤0.5 mg/L susceptible (EUCAST). Whole genome sequence data was analyzed for the presence of rplC and cfr gene mutations known to confer resistance to retapamulin.

Results:

All 53 isolates were susceptible to retapamulin. 49/53 (92%) strains were inhibited at MIC 0.25 mg/L, 2/53 (4%) at MIC 0.125 mg/L, and 2/53 (4%) at MIC 0.5 mg/L. DNA sequence analysis showed that one isolate had a first-step mutation in the rplC gene, but it was not associated with reduced phenotypic susceptibility to retapamulin, as the MIC of that isolate was 0.25 mg/L.

Conclusion:

Retapamulin demonstrated excellent in vitro activity against a genotypic cluster of Mup-R isolates from pediatric patients presenting to our institution with MRSA infection. These data suggest that retapamulin may be a promising alternative decolonization therapy for MRSA and a viable option to prevent the spread of mupirocin-resistant MRSA clones. Further research includes an ongoing randomized, placebo-controlled trial testing the in vivo efficacy of retapamulin as a nasal and perirectal decolonizing agent in children.

Ami Patel, MD, MPH1, Jennifer Lighter-Fisher, MD2, Yi Fulmer, PhD3, Richard Copin, PhD4, Adam Ratner, MD, MPH3 and Bo Shopsin, MD, PhD5, (1)Pediatrics, Infectious Diseases, New York University School of Medicine/NYU Langone Health, New York, NY, (2)Infection Prevention and Control, NYU Langone Medical Center, New York, NY, (3)New York University School of Medicine, New York, NY, (4)Microbiology, New York University Langone Medical Center, New York, NY, (5)New York University School of Medicine, New Yok, NY

Disclosures:

A. Patel, Aqua Pharmaceuticals: Investigator inititiated grant , Research grant .

J. Lighter-Fisher, Aqua Pharmaceuticals: Investigator Initiated Grant , Research grant .

Y. Fulmer, None

R. Copin, None

A. Ratner, None

B. Shopsin, None

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