Retapamulin for Reducing MRSA Nasal Carriage

This study will evaluate the utility of retapamulin, a topical ointment FDA approved for skin
infection, as a novel agent for MRSA decolonization and prevention of healthcare-associated
MRSA infection. Retapamulin is a first-in-class semi-synthetic pleuromutilin antibiotic that
inhibits protein synthesis by interacting with the bacterial ribosome 50S subunit. It
received FDA approval in 2007 for the topical treatment of impetigo in adults and pediatric
patients.

We propose to evaluate retapamulin as an investigational agent for the nasal decolonization
of MRSA carriers whose strains demonstrate low-level and high-level resistance to mupirocin.
Mupirocin resistance is increasingly common and there is no approved substitute topical agent
for decolonization of the MRSA nasal reservoir.

We will conduct a randomized placebo-controlled double-blinded study of nasal decolonization
with retapamulin vs. placebo for the eradication of MRSA nasal carriage among adult carriers
with low-level (MIC 8-256) and high-level mupirocin resistant (MIC >256) strains.
Randomization will be stratified by low vs high level resistance.

Consenting adult (at least 18 years old) subjects will be randomized to 1% retapamulin or
placebo ointment intra-nasally twice a day for 5 days (D1-5) with follow up bilateral nares
swab one week following completion of therapy (~D12) to assess clearance. If follow up swabs
are positive for MRSA, patients will be given a second course of the same agent (retapamulin
or placebo) to begin one week following swab collection (~D19-23) so that up to two
decolonization attempts will be made. A final set of bilateral nares swabs will be obtained
from all subjects six weeks from the completion of initial treatment (~D47).

Consenting adult (at least 18 years old)subjects will be given retapamulin or placebo. At the
time of recruitment, all subjects will complete a detailed survey administered by trained
research staff. This survey will include questions related to self care, home hygiene
practices, and known risk factors for MRSA acquisition. Subject follow up will include repeat
bilateral nares swabs and follow up surveys related to compliance, experience (side
effects/concerns) with the assigned regimen, and ongoing risk factors will occur either
during a home visit (or facility visit if the patient is admitted to a hospital or nursing
home at the time of the required visit) or at the University of California Irvine (UCI)
Institute for Clinical and Translational Science (ICTS), a Clinical and Translational Science
Award (CTSA) site which provides clinic visit support for pilot studies.

Outcomes will include successful nares decolonization at the end of the follow up period
(D47). We will detail the sequence of clearance or re-colonization based upon the two follow
up nares swabs, as well as any adverse events, which are expected to be related to local
irritation in a small percent of subjects.

Inclusion Criteria:

- 18 years of age or older

- Have a type of MRSA that is resistant to mupirocin (a drug used to treat MRSA)

Exclusion Criteria:

- Allergic to retapamulin

- Unable to use retapamulin via your nose (i.e. nose surgery, etc.)

- Are pregnant and/or breastfeeding