Single versus combination intravenous antibiotic therapy for people with cystic fibrosis.
BACKGROUND
Choice of antibiotic, and the use of single or combined therapy are controversial areas in the treatment of respiratory infection in Cystic Fibrosis (CF). Advantages of combination therapy include wider range of modes of action, possible synergy and reduction of resistant organisms; advantages of monotherapy include lower cost, ease of administration and reduction of drug related toxicity. Current evidence does not provide a clear answer and therefore the use of intravenous antibiotic therapy in CF requires further evaluation.


OBJECTIVE
To assess the effectiveness of single compared to combination intravenous antibiotic therapy in the treatment of patients with CF.


METHODS
The Cochrane CF and Genetic Disorders Group Specialised Register of Controlled Trials and the abstract books of the three major CF conferences were searched to identify randomised controlled trials. The register was compiled by conducting detailed computer searches of Medline from 1966-present and Embase 1974-1995.


METHODS
Randomised controlled trials comparing a single intravenous antibiotic with a combination of that antibiotic plus a second antibiotic in patients with CF.


METHODS
Two reviewers independently assessed trial quality and extracted data.


RESULTS
A total of nine studies including 386 patients compared a single agent to a combination of the same antibiotic and one other. There was a wide variation in the individual antibiotics used in each study. In total, the studies included eight comparisons of a beta-lactam antibiotic (penicillin-related or third generation cephalosporin) with a beta-lactam-aminoglycoside combination and three comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination. These two groups of studies were analysed as separate subgroups. There was considerable heterogeneity amongst these trials which led to difficulties in performing the review and interpreting the results. The meta-analysis did not demonstrate any significant differences between monotherapy and combination therapy, in terms of lung function, symptom scores and adverse effects. Single therapy was associated with an increase in the number of patients with resistant strains of Ps. aeruginosa at two to eight weeks follow-up. This is an important preliminary finding which needs further clarification with a good quality long-term study. These results should be interpreted with caution. All but two of the included trials were published between 1977 and 1988; these were single centre studies with flaws in the randomisation process and small sample size. Overall, the methodological quality was poor.


CONCLUSIONS
The results of this systematic review of monotherapy versus combination therapy for pulmonary exacerbations in CF are inconclusive. The review raises important methodological issues. There is a need for a randomised controlled trial which needs to be well designed in terms of adequate randomisation allocation, blinding, power and long-term follow up. Results need to be standardised to a consistent method of reporting, in order to validate the pooling of results from multiple studies.
Institute of Child Health, Alder Hey Children's Hospital, Eaton Road, Liverpool, UK. helphick@liverpool.ac.uk
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D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002511:Cephalosporins / Q000008:administration & dosage; D003550:Cystic Fibrosis / Q000150:complications*; D004359:Drug Therapy, Combination / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000188:drug therapy*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins