Use of Pseudomonas biofilm susceptibilities to assign simulated antibiotic regimens for cystic fibrosis airway infection.
OBJECTIVE
Increasing evidence indicates that Pseudomonas aeruginosa grows as a biofilm in the lungs of cystic fibrosis (CF) patients. In contrast, the bacterial inoculum used in conventional susceptibility testing is composed of planktonic cells. As a prelude to a clinical trial of biofilm susceptibility testing in CF, simulated antibiotic regimens based on either biofilm or conventional susceptibility testing of CF patient isolates were compared.


METHODS
Biofilm and conventional susceptibilities were determined for P. aeruginosa isolate sets from 40 CF patients. An algorithm was used to assign simulated regimens of two anti-pseudomonal antibiotics for each patient/susceptibility method dataset. For agents with equivalent activity, the algorithm included a drug selection hierarchy, the rationale for which was suppression of chronic infection. Substitution of an alternative hierarchy, based on treatment of acute exacerbation, was used to evaluate the robustness of the regimen assignments.


RESULTS
For both drug-ranking schemes, all 40 simulated regimens based on conventional susceptibilities included a beta-lactam antibiotic. In contrast, based on biofilm testing, only 43% of chronic regimens and 65% of acute regimens included a beta-lactam. Moreover, the conventional and biofilm regimens assigned to individual patients were discordant, with only 20% and 40% of chronic and acute regimens, respectively, consisting of drugs in the same two mechanistic classes by both methods.


CONCLUSIONS
Biofilm susceptibility testing of CF P. aeruginosa isolate sets leads to different antibiotic assignments than conventional testing, with no single two-drug regimen predicted to provide optimal anti-biofilm activity against the majority of isolate sets.
Moskowitz
Samuel M
SM
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA. sam.moskowitz@seattlechildrens.org
Foster
Jessica M
JM
Emerson
Julia C
JC
Gibson
Ronald L
RL
Burns
Jane L
JL
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology*; D004338:Drug Combinations; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011549:Pseudomonas / Q000187:drug effects* / Q000254:growth & development; D047090:beta-Lactams / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D018942:Macrolides; D047090:beta-Lactams