Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial.
BACKGROUND
We did a randomised, double-blind, controlled clinical trial to prospectively assess whether use of combination antibiotic susceptibility testing improved clinical outcomes in patients with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria.


METHODS
251 patients with cystic fibrosis who were chronically infected with multiresistant gram negative bacteria gave sputum at 3-month intervals for conventional culture and sensitivity tests and for combination antibiotic susceptibility tests using multiple combination bactericidal antibiotic testing (MCBT). Patients who developed an exacerbation of pulmonary disease were randomised to receive a 14-day course of any two blinded intravenous antibiotics chosen on the basis of either results from conventional sputum culture and sensitivity testing or the result of MCBT. The primary outcome was time from randomisation until the patient's next pulmonary exacerbation. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN60187870.


RESULTS
132 patients had a pulmonary exacerbation and were randomised during the 4.5-year study period. The time to next pulmonary exacerbation was not prolonged in the MCBT-treated group (hazard ratio 0.86 in favour of the conventionally-treated group, 95% CI 0.60-1.23, p=0.40). There was no difference between the groups in treatment failure rate. After 14 days of intravenous antibiotic therapy, changes in lung function, dyspnoea, and sputum bacterial density were similar in both groups.


CONCLUSIONS
Antibiotic therapy directed by combination antibiotic susceptibility testing did not result in better clinical and bacteriological outcomes compared with therapy directed by standard culture and sensitivity techniques. The non-bactericidal effects of antibiotic therapy might play an important part in determining improvement in patients with cystic fibrosis pulmonary exacerbations.
Aaron
Shawn D
SD
The Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada. saaron@ottawahospital.on.ca
Vandemheen
Katherine L
KL
Ferris
Wendy
W
Fergusson
Dean
D
Tullis
Elizabeth
E
Haase
David
D
Berthiaume
Yves
Y
Brown
Neil
N
Wilcox
Pearce
P
Yozghatlian
Veronica
V
Bye
Peter
P
Bell
Scott
S
Chan
Francis
F
Rose
Barbara
B
Jeanneret
Alphonse
A
Stephenson
Anne
A
Noseworthy
Mary
M
Freitag
Andreas
A
Paterson
Nigel
N
Doucette
Steve
S
Harbour
Colin
C
Ruel
Michel
M
MacDonald
Noni
N
D000208:Acute Disease; D000328:Adult; D000900:Anti-Bacterial Agents; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D004311:Double-Blind Method; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*; D013183:Sputum / Q000382:microbiology
D000900:Anti-Bacterial Agents