Safety and Efficacy of Intranasal and Topical Mupirocin in Eradicating Colonization With Staphylococcus Aureus (SA) in Critically Ill Infants - a Phase 2, Multi-Center, Open Label, Randomized Trial

This is a Phase 2, open label, multi-center, randomized trial to determine the safety and
efficacy of mupirocin in eradicating colonization with Staphylococcus aureus (SA) and
preventing the occurrence of invasive and other clinically significant SA infections among
critically ill infants in the ICU. Infants hospitalized in an ICU at any one of the 6
participating centers with a positive nasal culture for SA will be eligible to enroll.
Infants will be stratified by birth gestational age (< 28 weeks and <8 weeks of post-natal
life or > /= 28 weeks / < 28 weeks and > /=8 weeks of post-natal life) and colonizing strain
methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-sensitive Staphylococcus
aureus (MSSA) and then randomized 1:1 to receive a 5 day course of mupirocin applied to the
nares, umbilicus and perianal (NUP) areas every 8 hours (+/= 2 hours) vs. no treatment.
(Stratification by birth gestational age is performed to minimize bias that could result
from a higher risk for developing infection due to prematurity or prolonged length of stay
due to prematurity.) The primary objectives of this study are to 1) evaluate the safety and
clinical acceptability of a 5-day course of mupirocin applied every 8 hours (± 2 hours) to
the nares, umbilical and perianal areas of infants residing in the ICU 2) to examine the
efficacy of mupirocin in eradicating SA colonization of infants in the ICU, defined as the
absence of SA in cultures of the nares, umbilical, and perianal areas on day 8 (± 2)
(primary decolonization) 3) to examine the efficacy of mupirocin in achieving persistent
eradication of SA colonization among infants residing in the ICU, defined as the absence of
SA in cultures of the nares, umbilical, and perianal areas on days 8 (±2) and 22 (±2)
(persistent decolonization). The secondary objectives of this study are to 1) To examine the
efficacy of mupirocin in preventing clinical SA infection during days 1-22 or until
discharge, whichever occurs first, among SA colonized infants who are residing in the ICU 2)
To compare time until SA decolonization between the mupirocin and placebo groups: Time from
Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and
perianal areas 3) To examine whether mupirocin affects the frequency of non-SA clinical
infections by comparing the frequency of these infections in the treatment and control
groups during the 85 day observation period 4) To examine whether mupirocin affects the
frequency of severe (stage II-III) necrotizing enterocolitis by comparing the frequency of
occurrence in the treatment and control groups during the 85 day observation period.

Each participant will be enrolled for up to 12 weeks (Day 85) or until the time of discharge
from the hospital, death or withdrawal from further participation, whichever occurs first.
It is anticipated that it will take at least 2 years to enroll all participants. Study
duration is 36 months. Enrolled infants will continue to receive medical care as they
otherwise would if they were not enrolled in the trial. The study will be powered toward the
primary endpoint with 126 participants. Enrollment may continue up to a maximum of 500
participants to inform the secondary and exploratory endpoints and to help design any
subsequent study.

Inclusion Criteria:

1. Currently admitted to a NICU or ICU at a participating site

2. Chronological age less than 24 months

3. Evidence of colonization with SA (MRSA or MSSA) based on a positive nasal
surveillance culture. Randomization must occur within 7 days (168 hours) of when the
site's laboratory reports the first SA positive nasal surveillance swab

4. The attending neonatologist/ intensivist anticipates that the infant will remain in
the ICU for a minimum of 14 days after enrollment

5. Parent or legal guardian agrees that the infant will not participate in a research
trial involving the administration of an investigational drug for 14 days following
enrollment

Exclusion Criteria:

1. Receipt of an investigational drug as part of a research trial within the past 14
days

2. Previously enrolled and participated in this trial

3. Has an active or previous SA infection

4. Currently receiving topical or intranasal mupirocin

5. Has a rash in an area to which mupirocin will be directly applied

6. Has any of the following congenital abnormalities:

- A congenital skin disorder (i.e. - epidermolysis bullosa, icthyosis)

- An opened neural tube defect

- Confirmed or suspected choanal atresia

- Any of the following abdominal wall defects: wound dehiscence, gastroschisis,
open abdominal wound (small abdominal wall defects such as ostomy sites or
peritoneal drain sites are not exclusionary)

7. Is nasally intubated

8. Known hypersensitivity to the trial product or its constituents

9. Known or suspected immune deficiency. Infants born to HIV-seropositive mothers with
the following risk factors for intrapartum transmission will not be eligible to
participate:

- Mother's most recent viral load within the past 3 months was > 1,000 copies/ml
or

- Mother's viral load is not known or has has not been measured in the past 3
months.

10. Any other condition(s) that in the opinion of the investigator would jeopardize the
safety or rights of a participant or would render the participant unable to comply
with the protocol