Azithromycin may antagonize inhaled tobramycin when targeting Pseudomonas aeruginosa in cystic fibrosis.
Azithromycin may antagonize inhaled tobramycin when targeting Pseudomonas aeruginosa in cystic fibrosis.
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DOI：
10.1513/annalsats.201310-352oc
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发表时间：
2014-03-01
影响因子：
8.3
通讯作者：
Nichols, David P
中科院分区：
文献类型：
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作者：
Nick, Jerry A;Moskowitz, Samuel M;Nichols, David P
依据：最近在囊性纤维化（CF）受试者中进行的吸入妥布霉素研究发现，临床改善程度低于先前观察到的结果。非人类数据表明，在某些铜绿假单胞菌菌株中，阿奇霉素可以拮抗妥布霉素。结论：我们检验了以下假设，即阿奇霉素的伴随使用与吸入妥布霉素受试者的关键结局指标改善较少相关，而不影响那些接受比较的非氨基糖苷类吸入抗生素的受试者。我们研究了263名CF患者，他们参加了最近的一项比较吸入妥布霉素和氨曲南赖氨酸的临床试验。我们进行了二次分析，以检查关键的临床和微生物学结果的基础上，伴随，长期使用阿奇霉素在enrollment.MEASUREMENTS和主要结果：队列随机吸入妥布霉素和报告阿奇霉素的使用表明，百分预测值FEV 1吸入妥布霉素后一个和三个疗程，与那些没有报告阿奇霉素的使用相比，显着下降（28 d：-0.51vs3.43%，P < 0.01; 140 d：-1.87vs6.07%，P < 0.01）。阿奇霉素和妥布霉素吸入联合使用也与早期需要额外抗生素、疾病相关生活质量改善较少以及痰液铜绿假单胞菌密度降低较少的趋势相关。随机接受吸入性氨曲南赖氨酸的受试者在这些结局指标方面有显著更大的改善，而这些指标不受阿奇霉素联合使用的影响。接受妥布霉素吸入治疗的未使用阿奇霉素的患者与接受氨曲南赖氨酸治疗的患者的结局无显著差异。阿奇霉素也拮抗妥布霉素，但不是氨曲南赖氨酸在40%的铜绿假单胞菌的临床分离株tested in vitro.CONCLUSIONS：口服阿奇霉素可能拮抗吸入妥布霉素在CF与铜绿假单胞菌呼吸道感染的受试者的治疗益处。
RATIONALE: 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.OBJECTIVES: 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.MEASUREMENTS AND MAIN 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.