Comparison of a beta-lactam alone versus beta-lactam and an aminoglycosidefor pulmonary exacerbation in cystic fibrosis

We determined whether a beta-lactam and an aminoglycoside have efficacy gre ater than a beta-lactam alone in the management of a pulmonary exacerbation in patients with cystic fibrosis. Study design: Azlocillin and placebo or azlocillin and tobramycin were admi nistered to 76 patients with a pulmonary exacerbation caused by Pseudomonas aeruginosa in a randomized double-blind, third-party monitored protocol. I mprovement was assessed by standardized clinical evaluation, pulmonary func tion 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, fo rced expiratory volume in second 1, or peak expiratory flow rate at the end of treatment (33 receiving azlocillin alone and 43 both antibiotics); adve rse reactions were equivalent in each group. Sputum P. aeruginosa density d ecreased more with combination therapy (P = .034). On follow-up evaluation, an average of 26 days after the end of treatment, all outcome indicators h ad worsened in both groups. Time to readmission for a new pulmonary exacerb ation was significantly longer in the group receiving azlocillin plus tobra mycin (P < .001). Treatment-emergent tobramycin resistance occurred in both groups and was more frequent with combination therapy. Conclusion: We conclude that the combination of a beta-lactam and an aminog lycoside produces a longer clinical remission than a beta-lactam alone and slightly better initial improvement.