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Intervention Review

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Interventions for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis

  1. David KH Lo1,*,
  2. Matthew N Hurley2,
  3. Marianne S Muhlebach3,
  4. Alan R Smyth1

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 24 JAN 2013

DOI: 10.1002/14651858.CD009650.pub2


How to Cite

Lo DKH, Hurley MN, Muhlebach MS, Smyth AR. Interventions for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD009650. DOI: 10.1002/14651858.CD009650.pub2.

Author Information

  1. 1

    University of Nottingham, Department of Child Health, School of Clinical Sciences & Nottingham Respiratory BRU, Nottingham, UK

  2. 2

    University of Nottingham, Department of Child Health, School of Clinical Sciences, Nottingham, UK

  3. 3

    University of North Carolina, Department of Pediatrics, Division of Pulmonary Medicine, Chapel Hill, North Carolina, USA

*David KH Lo, Department of Child Health, School of Clinical Sciences & Nottingham Respiratory BRU, University of Nottingham, E Floor East Block, Queens Medical Centre, Derby Road, Nottingham, NG7 2UH, UK. david.lo@nottingham.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 28 FEB 2013

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This is not the most recent version of the article. View current version (24 FEB 2015)

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Adeboyeku 2001Not a relevant intervention - tolerability study of differing dosages of nebulised colistin.

Amelina 2000Not a relevant intervention or participants - difference in quality of life between home versus hospital IV treatment.

Carswell 1987Not relevant participants - trial of P. aeruginosa treatment.

Chua 1990Not a relevant intervention - used differing tonicities of inhaled antibiotics to assess airway responsiveness.

Conway 1996Not relevant participants - did not differentiate between organisms causing exacerbation leading to inclusion into the trial.

Cooper 1985Not relevant participants - trial of P. aeruginosa treatment.

Davis 1987Pharmocokinetic study.

Degg 1996Not a relevant intervention or relevant participants - study on long-term effects of gentamicin on hearing. Patients not selected on basis of microbial colonisation.

Dodd 1997Not a relevant intervention or relevant participants - testing differences in lung function relating to tonicity of nebulised colistin.

Dodd 1998Not a relevant intervention or relevant participants - a compliance study. No suitable control.

Garske 2004An observational study.

Geller 2004Pharmocokinetic study.

Goldfarb 1986Pharmocokinetic study.

Griffith 2008Pharmocokinetic/tolerability study.

Gulliver 2003Not a relevant intervention or relevant participants - testing whether nebulised IV tobramycin solution induced cough or bronchoconstriction or both.

Heininger 1993Not relevant participants - trial of P. aeruginosa treatment.

Hjelte 1988Not relevant participants - investigated affect of home IV antibiotics for P. aeruginosa on quality of life.

Huang 1979Not relevant participants - did not differentiate between organisms causing exacerbation leading to inclusion into trial.

Huls 2000Pharmocokinetic study.

Junge 2001Not relevant participants - investigating risk of ototoxicity or cochlea damage in once daily versus 3-times daily IV tobramycin.

Kapranov 1995Not relevant participants - trial of P. aeruginosa treatment.

Keel 2011Pharmocokinetic study.

Keller 2010Pharmocokinetic study.

Knight 1979Not relevant participants - trial of P. aeruginosa treatment.

Labiris 2004Not a relevant intervention or relevant participants - objective was to determine whether preservative containing inhaled tobramycin causes airway inflammation.

Loening -Bauke 1979Not a relevant intervention - used cephalexin as prophylaxis.

Macfarlane 2007An observational study.

Maiz 1998A case report of one 10-year old boy.

Nathanson 1985Not relevant participants - trial of P. aeruginosa treatment.

Nolan 1982Not a relevant intervention - prophylaxis rather than eradication.

Pai 2006Pharmocokinetic study.

Postnikov 2000Not relevant participants - compared children with CF and aplastic anaemia

Postnikov 2001aNot a relevant intervention or relevant participants - describes risk of quinolone arthropathy in children.

Postnikov 2001bNot a relevant intervention or relevant participants - investigated the effect on growth with the addition of ciprofloxacin to the treatment of children with CF.

Ramstrom 2000Not a relevant intervention - compared quality of life scores in patients who received pre-made infusion devices compared to those who reconstituted drugs themselves.

Roberts 1993Pharmocokinetic study.

Romano 1991Not relevant participants - trial of P. aeruginosa treatment.

Rosenfeld 2006Pharmocokinetic study.

Sahl 1992Not relevant participants - MRSA not required for entry into trial.

Shapera 1981Not relevant participants - did not differentiate between MRSA and MSSA in inclusion criteria. Unclear how randomisation was achieved.

Smith 1997Pharmocokinetic study.

Solis 2003Retrospective study.

Stutman 1987Not relevant participants - pharmacokinetic study of P. aeruginosa treatment.

Vitti 1975Pharmocokinetic study.

Wood 1996Not a relevant intervention - compared aminoglycoside toxicity in twice and 3-times daily dosing regimens.

 
Characteristics of ongoing studies [ordered by study ID]
PMEP

Trial name or titlePersistent methicillin-resistant Staphylococcus aureus eradication protocol.

MethodsRandomised, placebo-controlled parallel trial.

Duration 28 days with additional 3-month follow-up.

Participants will be assigned in a 1:1 ratio to either treatment or control group.

Participants40 patients with persistent respiratory tract MRSA infection will be enrolled in this trial.

Inclusion criteria:

  1. male or female ≥ 12 years of age;
  2. confirmed diagnosis of CF based on the following criteria: positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with 2 identifiable mutations consistent with CF or abnormal NPD, and 1 or more clinical features consistent with the CF phenotype;
  3. written informed consent (and assent when applicable) obtained from participant or participants's legal representative and ability for participant to comply with the requirements of the study;
  4. 2 positive MRSA respiratory cultures in the last 2 years at least 6 months apart, plus a positive MRSA respiratory culture at screening visit and run-in (day 14) visit;
  5. at least 50% of respiratory cultures from the time of the first MRSA culture (in the last 2 years) have been positive for MRSA;
  6. FEV1 > 30% of predicted normal for age, gender, and height at screening;
  7. females of childbearing potential must agree to practice 1 highly effective method of birth control, including abstinence. Note: highly effective methods of birth control are those, alone or in combination, that result in a failure rate less than 1% per year when used consistently and correctly. Female patients who utilize hormonal contraceptives as a birth control method must have used the same method for at least 3 months before study dosing. If the patient is using a hormonal form of contraception, patients will be required to also use barrier contraceptives as rifampin can affect the reliability of hormone therapy. Barrier contraceptives such as male condom or diaphragm are acceptable if used in combination with spermicides.

InterventionsTreatment group: 28-day course of inhaled vancomycin for inhalation (250 mg twice-a-day) plus oral rifampicin and oral TMP/SMX.

Control group: taste-matched inhaled placebo (sterile water) plus oral rifampicin and oral TMP/SMX.

In addition, both groups will receive oral rifampin, a second oral antibiotic (TMP-SMX or doxycycline, protocol determined), mupirocin intranasal cream and chlorhexidine body washes.

OutcomesPrimary objectives

1. To determine the efficacy of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF.

2. To determine the safety of an aggressive treatment protocol in eradicating persistent MRSA infection in individuals with CF.

Secondary objectives

1. To determine the efficacy of an aggressive treatment protocol in improving FEV1, time to next exacerbation, and quality of life in individuals with CF and persistent MRSA infection.

2. To determine if there is benefit to adding nebulized vancomycin to an aggressive oral antibiotic treatment protocol in eradicating persistent MRSA infection in individuals with CF.

Starting dateOct 2012.

Contact informationMichael Boyle, Associate Professor of Medicine, Johns Hopkins University.

NotesStudy first registered on www.clinicaltrials.gov - 7th May 2012.

STAR-Too

Trial name or titleEarly methicillin-resistant Staphylococcus aureus (MRSA) therapy in cystic fibrosis (CF).

MethodsRandomized, open-label, multicentre study comparing use of an eradication protocol to an observational group receiving the current standard of care, i.e. treatment for MRSA only with pulmonary exacerbations.

ParticipantsParticipants will include people ≥4 and ≤45 years with CF and new isolation of MRSA from their respiratory culture on a routine clinic visit. Estimated enrolment - 80.

InterventionsEradication protocol: 14-day oral rifampicin plus TMP-SMX or minocycline in patients with contraindications to TMP-SMX.

Observational group: current standard of care, i.e. treatment for MRSA only with pulmonary exacerbations.

Drug: rifampin (adult dose: 300 mg twice 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 twice daily for 14 days; paediatric dose: <40 kg: 8 mg/kg trimethoprim, >40 mg/kg sulfamethoxazole twice daily for 14 days).
Drug: minocycline (only participants greater or equal to 8 years of age, who are not able to tolerate TMP/SMX or whose screening MRSA is resistant to TMP/SMX, should be prescribed minocycline. Adult dose: 100 mg orally twice daily for 14 days. Paediatric dose: <50 kg: 2 mg/kg orally twice daily for 14 days not to exceed 200 mg per 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).
Behavioral: 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 once weekly for 3 weeks).

OutcomesPrimary outcome measure

1. Proportion of participants in each arm with MRSA-negative respiratory cultures at day 28.

Secondary outcome measures

1. Proportion of participants treated with oral, inhaled, and IV antibiotics over the 6-month study and number of days of use.

2. Proportion of participants with a protocol-defined pulmonary exacerbation between baseline and day 28 who are treated with antibiotics active against MRSA.

Starting dateApril 2011

Contact informationMarianne S Muhlebach, MD, University of North Carolina, Chapel Hill.

NotesCurrently recruiting. Estimated completion date is December 2013.