Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection.
BACKGROUND
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.
Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington; Seattle Children's Hospital, Seattle, Washington. smoskowitz@partners.org
Samuel M
SM
Moskowitz
Julia C
JC
Emerson
Sharon
S
McNamara
Richard D
RD
Shell
David M
DM
Orenstein
Daniel
D
Rosenbluth
Marcia F
MF
Katz
Richard
R
Ahrens
Douglas
D
Hornick
Patricia M
PM
Joseph
Ronald L
RL
Gibson
Moira L
ML
Aitken
Wade W
WW
Benton
Jane L
JL
Burns
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects*; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005540:Forced Expiratory Flow Rates; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods; D010865:Pilot Projects; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D013183:Sputum / Q000187:drug effects / Q000382:microbiology; D013845:Thienamycins / Q000627:therapeutic use; D055815:Young Adult
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000077731:Meropenem