Muhlebach 2017.
Methods | RCT (open‐label). Design: parallel. Location: multicentre (14 centres) in USA. Duration: 14 days treatment, follow up to 6 months. |
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Participants | People with first or early (≤ 2 positive cultures within 3 years) MRSA‐positive culture without MRSA active antibiotics within 4 weeks. Between 1 April 2011 to September 2014, 45 participants were randomised 1:1 to treatment or control (24 in the treatment group, 21 in the control group). Age (mean): 11.5 years (6.1) (ages 4 – 45 years were eligible for inclusion). Gender: 44% female. No significant differences in lung function, weight or Pseudomonas aeruginosa status between treatment arms |
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Interventions |
Eradication protocol: 14‐day oral rifampicin plus TMP‐SMX or minocycline in people with contraindications to TMP‐SMX; chlorhexidine mouthwash for 2 weeks; nasal mupirocin and chlorhexidine body wipes for 5 days and, in addition, environmental decontamination (wipe down high‐touch surfaces and medical equipment with surface disinfecting wipes daily for the first 21 days. Wash all linens and towels in hot water 1x weekly for 3 weeks). Drug: rifampin (adult dose: 300 mg 2x daily for 14 days; paediatric dose: <40 kg: 15 mg/kg daily for 14 days divided every 12 hours). Drug: TMP‐SMX (adult dose: 320/1600 orally 2x daily for 14 days; paediatric dose: < 40 kg: 8 mg/kg trimethoprim, > 40 mg/kg sulfamethoxazole twice daily for 14 days). Drug: minocycline (only for participants ≥ 8 years of age, who can not tolerate TMP‐SMX or whose screening MRSA is resistant to TMP/SMX. Adult dose: 100 mg orally 2x daily for 14 days. Paediatric dose: < 50 kg: 2 mg/kg orally twice daily for 14 days not to exceed 200 mg/day). Drug: mupirocin (1 g 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 14 days). Drug: chlorhexidine gluconate oral rinse (0.12% chlorhexidine gluconate oral rinse twice daily for 14 days). Drug: 2% chlorhexidine solution wipes (whole body wash solution wipes once daily for the first 5 days). Control group: observation with current standard of care, i.e. treatment for MRSA only with pulmonary exacerbations. |
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Outcomes |
Primary outcome measure 1. Proportion of participants in each arm with MRSA‐negative respiratory cultures at day 28. Secondary outcome measures 1. Safety and tolerability of treatment regime 2. Protocol adherence 3. Duration of microbiological effect 4. Number of pulmonary exacerbations 5. Use of antibiotics 6. Change in spirometry (FEV1) 7. Respiratory symptoms as measured by the CF‐specific patient outcomes: Cystic Fibrosis Questionnaire Revised respiratory domain scores and Cystic Fibrosis Respiratory Symptom Diary Chronic Respiratory Infection Symptom Scale 8. Weight |
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Notes | ||
Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | Quote: "Participants were randomised (1:1) to an MRSA eradication protocol...or to no treatment" using a secure web‐based randomisation system. |
Allocation concealment (selection bias) | Low risk | Quote: "Randomisation assignments were generated via a centralised, secure web based randomisation system for each enrolled subject" |
Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Study personnel and participants were not blinded to the treatment regimen". |
Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Clinical evaluations, physical examination and spirometry were performed on day 1 (randomisation), day 15, day 28, day 84 and day 168; but not details of blinding of outcome assessors given. |
Incomplete outcome data (attrition bias) All outcomes | Low risk | 47 participants were randomised. 2 withdrew immediately post randomisation. Of the remaining 45 participants, 4 had "missing" MRSA culture results at day 28 (2 from each arm) and so not included in ITT‐E analysis. All missing participants accounted for. |
Selective reporting (reporting bias) | Low risk | No selective reporting identified. Reported outcomes matched stated outcomes on clinical trials registry. |
Other bias | Unclear risk | Trial stopped early based on recommendations of data monitoring committee due to treatment efficacy, so did not reach planned recruitment target. |