Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection

Abstract

Rationale: In cystic fibrosis (CF), conventional antibiotic susceptibility results correlate poorly with clinical outcomes. We hypothesized that biofilm testing would more accurately reflect the susceptibilities of bacteria infecting CF airways.

Methods: A multicenter randomized pilot trial was conducted to assess the efficacy and safety of using biofilm susceptibility testing of Pseudomonas aeruginosa sputum isolates to guide antibiotic regimens for chronic airway infections in clinically stable adolescent and adult CF patients. Thirty-nine participants were randomized to biofilm or conventional treatment groups; 14-day courses of two antibiotics were selected according to an activity-based algorithm using the corresponding susceptibility results.

Results: Of the agents tested, meropenem was most active against biofilm-grown bacteria, and was included in regimens for about half of each study group. For 19 of 39 randomized participants, randomization to the other study group would not have changed the antibiotic classes of the assigned regimen. Study groups were comparable at baseline, and had similar mean decreases in bacterial density, measured in log(10) colony forming units per gram of sputum (biofilm, -2.94 [SD 2.83] vs. conventional, -3.27 [SD 3.09]), and mean increases in forced expiratory volume in 1 sec, measured in liters (0.18 [SD 0.20] vs. 0.12 [SD 0.22]).

Conclusions: In this pilot study, antibiotic regimens based on biofilm testing did not differ significantly from regimens based on conventional testing in terms of microbiological and clinical responses. The predictive value of biofilm testing may nonetheless warrant evaluation in an adequately powered clinical trial in younger CF patients or those experiencing acute pulmonary exacerbation.

Figure 1. Flow of participants through each stage of the protocol

*Repeat screenings were allowed. Most common reasons for screen failures included multi-resistant bacteria (n=11), insufficient bacterial density or lack of growth (n=5), inadequate biofilm growth (n=5), history of antibiotic allergy or intolerance (n=4), insufficient susceptibility data (n=3), and acute pulmonary exacerbation (n=3). **The 39 randomized participants included 1 individual who was randomized twice: when first randomized, the individual was withdrawn prior to initiating treatment owing to decline in lung function; six months later the same individual was re-screened and randomized a second time, and treatment was initiated and completed. Treatment group and assigned antibiotic regimen were the same for both randomizations (MIC group; meropenem/tobramycin). Data for the second randomization are summarized in the flow chart. ^†Completion of treatment was defined as having received at least 10 days of the assigned antibiotic regimen.