Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for pulmonary exacerbation in cystic fibrosis.
We determined whether a beta-lactam and an aminoglycoside have efficacy greater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis.


METHODS
Azlocillin and placebo or azlocillin and tobramycin were administered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. Improvement was assessed by standardized clinical evaluation, pulmonary function testing, sputum bacterial density, sputum DNA content, and time to the next pulmonary exacerbation requiring hospitalization.


RESULTS
No significant difference was seen between the 2 treatment groups in clinical evaluation, sputum DNA concentration, forced vital capacity, forced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adverse reactions were equivalent in each group. Sputum P. aeruginosa density decreased more with combination therapy (P =.034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators had worsened in both groups. Time to readmission for a new pulmonary exacerbation was significantly longer in the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy.


CONCLUSIONS
We conclude that the combination of a beta-lactam and an aminoglycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.
Smith
A L
AL
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, Missouri, USA.
Doershuk
C
C
Goldmann
D
D
Gore
E
E
Hilman
B
B
Marks
M
M
Moss
R
R
Ramsey
B
B
Redding
G
G
Rubio
T
T
Williams-Warren
J
J
Wilmott
R
R
Wilson
H D
HD
Yogev
R
R
D000293:Adolescent; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001390:Azlocillin / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004269:DNA, Bacterial / Q000187:drug effects / Q000302:isolation & purification; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010406:Penicillins / Q000009:adverse effects / Q000627:therapeutic use*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D012129:Respiratory Function Tests; D013183:Sputum / Q000187:drug effects / Q000382:microbiology; D014031:Tobramycin / Q000009:adverse effects / Q000627:therapeutic use*; D014797:Vital Capacity / Q000187:drug effects
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D010406:Penicillins; D001390:Azlocillin; D014031:Tobramycin