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

Valerie Waters, Felix Ratjen

Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis 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 cystic fibrosis 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 cystic fibrosis and chronic infection with Pseudomonas aeruginosa. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 19 December 2016.We also searched ongoing trials registries. Date of latest search: 08 March 2017. Randomised and quasi-randomised controlled studies 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 cystic fibrosis due to chronic infection with Pseudomonas aeruginosa. Both authors independently selected studies, assessed their quality and extracted data from eligible studies. Additionally, the authors contacted the study investigators to obtain further information. The search identified one multicentre study eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants. 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 cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue.The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.