Azithromycin may antagonize inhaled tobramycin when targeting Pseudomonas aeruginosa in cystic fibrosis.
BACKGROUND
Recent studies of inhaled tobramycin in subjects with cystic fibrosis (CF) find less clinical improvement than previously observed. Nonhuman data suggest that in some strains of Pseudomonas aeruginosa, azithromycin can antagonize tobramycin.


OBJECTIVE
We tested the hypothesis that concomitant azithromycin use correlates with less improvement in key outcome measures in subjects receiving inhaled tobramycin while not affecting those receiving a comparative, nonaminoglycoside inhaled antibiotic.


METHODS
We studied a cohort of 263 subjects with CF enrolled in a recent clinical trial comparing inhaled tobramycin with aztreonam lysine. We performed a secondary analysis to examine key clinical and microbiologic outcomes based on concomitant, chronic azithromycin use at enrollment.


RESULTS
The cohort randomized to inhaled tobramycin and reporting azithromycin use showed a significant decrease in the percent predicted FEV1 after one and three courses of inhaled tobramycin when compared with those not reporting azithromycin use (28 d: -0.51 vs. 3.43%, P < 0.01; 140 d: -1.87 vs. 6.07%, P < 0.01). Combined azithromycin and inhaled tobramycin use was also associated with earlier need for additional antibiotics, lesser improvement in disease-related quality of life, and a trend toward less reduction in sputum P. aeruginosa density. Subjects randomized to inhaled aztreonam lysine had significantly greater improvement in these outcome measures, which were unaffected by concomitant azithromycin use. Outcomes in those not using azithromycin who received inhaled tobramycin were not significantly different from subjects receiving aztreonam lysine. Azithromycin also antagonized tobramycin but not aztreonam lysine in 40% of P. aeruginosa clinical isolates tested in vitro.


CONCLUSIONS
Oral azithromycin may antagonize the therapeutic benefits of inhaled tobramycin in subjects with CF with P. aeruginosa airway infection.
1 Department of Medicine.
Jerry A
JA
Nick
Samuel M
SM
Moskowitz
James F
JF
Chmiel
Anna V
AV
Forssén
Sun Ho
SH
Kim
Milene T
MT
Saavedra
Lisa
L
Saiman
Jennifer L
JL
Taylor-Cousar
David P
DP
Nichols
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000150:complications*; D004347:Drug Interactions; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D011788:Quality of Life; D014031:Tobramycin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D001398:Aztreonam; D014031:Tobramycin