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 Staphylococcus aureus (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.
- Cystic Fibrosis
- Bacterial Infection
- Infection Control
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Collaborators STAR-too study team Investigators: Study Acronym STAR-too: STaph Aureus Resistance—treat or observe. Participating Sites: Site (Investigator and lead Research Coordinator): University of Washington (Christopher H Goss, Debbie Ng); Minneapolis Children's Affiliate (John McNamara, Mahrya Johnson); Texas Children's Hospital (Silby Moonnumakal, Nicoline Schaap); University of Colorado (Edith Zemanick, Meg Anthony); University of Cincinnati (John P Clancy); Seattle Children's Hospital (Ronald Gibson, Sharon McNamara); Washington University, St. Louis Children's (Peter Michelson, Tina Hicks); University of Texas Southwestern (Preeti Sharma, Andrew Hebert); University of Alabama at Birmingham (Wynton Hoover, Katie Brand); University of Florida at Gainesville (Pamela Schuler, Dawn Baker); University of Michigan (Amy Filbrun, Marisa Linn); University of Nebraska (Paul Sammut, Raquel Telfer); University of North Carolina at Chapel Hill (Marianne Muhlebach, Kelly Moormann); Ft. Worth Cook Children's Hospital (Karen Schultz, Heather Urbanek). Data and Safety Monitoring Board/DMC: Margaret Guill, MD, DMC Chair; Dartmouth-Hitchcock Medical Center, Pediatric Pulmonary Medicine. John J LiPuma, MD, Pediatric Infectious Disease Medicine, University of Michigan. Marci Sontag, PhD, Epidemiology/Community Health, Preventive Medicine/Biometrics, The Children's Hospital, Aurora, Colorado. Susan Murray, ScD, University of Michigan, School of Public Health, Department of Biostatistics (CFFT DMC Ad-hoc Specialist, Sequential Monitoring). Miriam Hunt, CFFT DMC, Prog. Coord., Sr. CFF Therapeutics Development Coordinating Center: Dianne L. Howe, Jasna Hocevar-Trnka, Rose Mitchell, Lynette Browne.
Contributors MSM: inception of study, study design, supervising conduction of study, discussion of data and writing, revising manuscript; communication with all authors and Thorax. EP contributed to protocol development; performed all laboratory analyses on bacterial samples. MBM: Contributed to design of the microbiology end points and provided oversight of all MRSA related processing and interpretation of MRSA typing results. PC contributed to the study inception and ongoing advice during the trial. WCH contributed to patient recruitment and enrolment at his study site, provided input for study modification and ongoing feedback on the protocol; participated in review and modifications of the final manuscript. ETZ contributed to patient recruitment and enrolment at her study site, provided input for study modification and ongoing feedback on the protocol; participated in review and modifications of the final manuscript. CHG, NM-H and JMVD contributed to study conception and study design. NM-H, VB and AB participated in data management and statistical analyses. All authors participated in data analysis/interpretation, drafting and/or revising the manuscript for intellectual content, and editing the manuscript for final approval.
Funding The research for this article was supported by the Cystic Fibrosis Foundation grant number STAR10K, and CTSA at individual sites: UL1TR001111, UL1 TR000433, UL1 TR000077, UL1 TR000423, NCT02249182, UL1 TR001417, UL1 TR000448, UL1 TR001082, UL1 RR025780. CHG receives funding from the Cystic Fibrosis Foundation, the NIH (R01HL103965, R01HL113382, R01AI101307, U M1HL119073, P30DK089507) and the FDA (R01FD003704).
Competing interests None declared.
Patient consent Obtained.
Ethics approval The institutional review board of each study site.
Provenance and peer review Not commissioned; externally peer reviewed.