Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis

Waters, Valerie, Ratjen, Felix

Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis (CF) is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with CF with acute exacerbations. This is an updated version of a previously published review. To compare antibiotic therapy based on conventional antimicrobial susceptibility testing to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with CF and chronic infection with P. aeruginosa. We identified relevant trials from the Group's Cystic Fibrosis Trials Register.Latest search: 27 July 2015. Randomised and quasi-randomised controlled trials of antibiotic therapy based on conventional antimicrobial susceptibility testing compared to antibiotic therapy based on combination antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in CF due to chronic infection with P. aeruginosa. Both authors independently selected trials, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information. The search identified one study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing (MCBT) improved clinical outcomes in participants with acute pulmonary exacerbations of CF who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the participants who were only infected with P. aeruginosa for the primary outcome: time until next pulmonary exacerbation. For "Time to next pulmonary exacerbation" in the participants specifically infected with only P. aeruginosa, the hazard ratio was 0.82, favouring the control group (95% CI 0.44 to 1.51) (P = 0.52). The data did not provide evidence that combination susceptibility testing was superior to conventional susceptibility testing. The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with CF with chronic P. aeruginosa infection. A large international and multicentre trial is needed to further investigate this issue.The only trial included in the review was published in 2005, and we have not identified any relevant trials up to September 2011. We therefore do not plan to update this review until new trials are published, although we will search the Group's Cystic Fibrosis Trials Register on a two-yearly cycle.