IL-10 Stratifying Tool for Towards Antibiotic Selection for MRSaB

Patients with MRSaB have primary therapeutic failure rates of 40-50% and high mortality rate
of 10-50% when treated with the recommended standard antimicrobial therapy. (Sharp) local
data for MRSaB for 2014 shows an all-cause mortality rate of 29%. Recent studies have been
published that utilize the predictive biomarker, IL-10, aiding the understanding for the wide
variability in mortality. Further studies are needed to elucidate the clinical relevance of
utilizing IL-10 levels to optimize MRSaB management and whether or not patient outcomes are
enhanced.

Under current standard treatment strategies, vancomycin 15 mg/kg IVPB every 12 hrs following
a 30 mg/kg IVPB loading dose is the first line of antibiotic therapy initiated with known or
suspected MRSaB. Only when patients have showed an unsatisfactory clinical response such as
prolonged bacteremia and/or continued clinical signs of uncontrolled infection are more
potent/aggressive and more expensive antibiotic choices considered in most cases. Even the
time for consideration of such a switch is a matter of controversy, with current MRSA
treatment guidelines recommending a switch after 7-days of failure.

Several recent studies have shown that an elevated IL-10 level is an independent risk factor
of mortality. In animal models, it has been shown that the bacterial cell wall of
Staphylococcus aureus stimulates the production of IL-10. A small study by Rose et al. showed
that this observation is consistent in humans. In another study, the authors concluded that
elevated IL-10 at the time of presentation is a predictive value of mortality in patients
with MRSaB4. In addition, the authors concluded that IL-10 may serve as a biomarker for very
early risk stratification, with selection of standard therapy for low-risk patients and more
potent, expensive, and cumbersome antibiotic therapies reserved for the high-risk patients.
Furthermore, it is postulated that treating high risk patients with aggressive/intensified
therapy earlier may improve economic and microbiological outcomes, such as a decreased length
of treatment, decreased time in the Intensive Care Unit, decreased length of stay in the
hospital, and decreased duration of bacteremia.

The aim in this study is to compare the outcomes for patients with elevated IL-10 levels (≥ 8
pg/mL) when treated with standard antibiotic therapy versus early aggressive therapy for the
treatment of MRSaB. Aggressive therapy is defined in study to be daptomycin (6-8mg/kg/day)
with ceftaroline (600 mg q8hr).

Inclusion Criteria:

- Adult (≥ 18 years of age) men or women.

- Diagnosis of MRSaB

- Has not been treated with antibiotics for MRSaB within 7 days of admission

- Has been on standard antibiotics for < 72hrs prior to randomization

- In the opinion of the investigator, the subject must require and be a suitable
candidate for IV antibiotic therapy.

Exclusion Criteria:

- Medical history of hypersensitivity or allergic reaction to vancomycin, or vancomycin
derivatives, daptomycin or ceftaroline

- Severe allergy to cephalosporins, i.e. Type 1 reaction, especially IgE mediated
anaphylaxis

- Comfort care patients

- Death within 72hrs of the start of antibiotic therapy

- Polymicrobial bacteremia: Staphylococcus aureus and another gram positive, gram
negative or anaerobic pathogen

- Burns covering ≥ 10% of body.

- Pt currently enrolled in an investigational study