Eradication strategy for persistent methicillin-resistant Staphylococcus aureus infection in individuals with cystic fibrosis—the PMEP trial: study protocol for a randomized controlled trial

BACKGROUND: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) respiratory infection in cystic fibrosis (CF) has increased dramatically over the last decade, and is now affecting approximately 25% of patients. Epidemiologic evidence suggests that persistent infection with MRSA results in an increased rate of decline in FEV(1) and shortened survival. Currently, there are no conclusive studies demonstrating an effective and safe treatment protocol for persistent MRSA respiratory infection in CF. METHODS/DESIGN: The primary objective of this study is to evaluate the safety and efficacy of a 28-day course of vancomycin for inhalation in combination with oral antibiotics in eliminating MRSA from the respiratory tract of individuals with CF and persistent MRSA infection. This is a two-center, randomized, double-blind, comparator-controlled, parallel-group study with 1:1 assignment to either vancomycin for inhalation (250 mg twice a day) or taste-matched placebo for 28 days in individuals with cystic fibrosis. In addition, both groups will receive oral rifampin, a second oral antibiotic – trimethoprim/sulfamethoxazole (TMP/SMX) or doxycycline, protocol determined – mupirocin intranasal cream, and chlorhexidine body washes. Forty patients with persistent respiratory tract MRSA infection will be enrolled: 20 will be randomized to vancomycin for inhalation and 20 to a taste-matched placebo. The primary outcome will be the presence of MRSA in sputum respiratory tract cultures 1 month after the conclusion of treatment. Secondary outcomes include the efficacy of the intervention on: FEV(1)% predicted, patient reported outcomes, pulmonary exacerbations, and MRSA colony-forming units found in respiratory tract sample culture. DISCUSSION: Results of this study will provide guidance to clinicians regarding the safety and effectiveness of a targeted eradication strategy for persistent MRSA infection in CF. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT01594827, received 05/07/2012) and is funded by the Cystic Fibrosis Foundation (Grants: PMEP10K1 and PMEP11K1).