Microbiological efficacy of early MRSA treatment in cystic fibrosis in a randomised controlled trial

Thorax. 2017 Apr;72(4):318-326. doi: 10.1136/thoraxjnl-2016-208949. Epub 2016 Nov 15.

Abstract

Objective: To evaluate microbiological effectiveness, that is, culture negativity of a non-blinded eradication protocol (Rx) compared with observation (Obs) in clinically stable cystic fibrosis participants with newly positive methicillin resistant Staphylococcusaureus (MRSA) cultures.

Design: This non-blinded trial randomised participants ages 4-45 years with first or early (≤2 positive cultures within 3 years) MRSA-positive culture without MRSA-active antibiotics within 4 weeks 1:1 to Rx or Obs. The Rx protocol was: oral trimethoprim-sulfamethoxazole or if sulfa-allergic, minocycline plus oral rifampin; chlorhexidine mouthwash for 2 weeks; nasal mupirocin and chlorhexidine body wipes for 5 days and environmental decontamination for 21 days. The primary end point was MRSA culture status at day 28.

Results: Between 1 April 2011 to September 2014, 45 participants (44% female, mean age 11.5 years) were randomised (24 Rx, 21 Obs). At day 28, 82% (n=18/22) of participants in the Rx arm compared with 26% (n=5/19) in the Obs arm were MRSA-negative. Adjusted for interim monitoring, this difference was 52% (95% CI 23% to 80%, p<0.001). Limiting analyses to participants who were MRSA-positive at the screening visit, 67% (8/12) in the Rx arm and 13% (2/15) in the Obs arm were MRSA-negative at day 28, adjusted difference: 49% (95% CI 22% to 71%, p<0.001). Fifty-four per cent in the Rx arm compared with 10% participants in the Obs arm remained MRSA-negative through day 84. Mild gastrointestinal side effects were higher in the Rx arm.

Conclusions: This MRSA eradication protocol for newly acquired MRSA demonstrated microbiological efficacy with a large treatment effect.

Trial registration number: NCT01349192.

Keywords: Bacterial Infection; Cystic Fibrosis; Infection Control.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents, Local / therapeutic use
  • Child
  • Child, Preschool
  • Chlorhexidine / therapeutic use
  • Cystic Fibrosis / microbiology*
  • Female
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification*
  • Middle Aged
  • Minocycline / therapeutic use
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology*
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents, Local
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Minocycline
  • Chlorhexidine

Associated data

  • ClinicalTrials.gov/NCT01349192