VERAPAMIL-TOBRAMYCIN SYNERGY IN PSEUDOMONAS-CEPACIA BUT NOT PSEUDOMONAS-AERUGINOSA IN-VITRO
VERAPAMIL-TOBRAMYCIN SYNERGY IN PSEUDOMONAS-CEPACIA BUT NOT PSEUDOMONAS-AERUGINOSA IN-VITRO
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DOI：
10.1159/000239363
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发表时间：
1995-09-01
期刊：
影响因子：
3.3
通讯作者：
PUTNAM, RW
中科院分区：
文献类型：
--
作者：
COHN, RC;RUDZIENSKI, L;PUTNAM, RW
几乎所有囊性纤维化（CF）患者都死于慢性进行性肺部感染引起的呼吸衰竭。铜绿假单胞菌和洋葱假单胞菌是导致这些患者肺部恶化的两种主要细菌病原体。妥布霉素对这些微生物有不同的抑制作用，但在许多分离株中，这种抑制作用在体外通过暴露于利尿剂阿米洛利而增加。雾化阿米洛利已被证明是CF的临床效益。这种协同作用的基础尚不清楚。为了检查阿米洛利-妥布霉素协同作用通过多药耐药（mdr）蛋白介导的细菌外排机制介导的可能性，我们使用标准MIC和协同作用测试研究了维拉帕米（一种已知的mdr抑制剂）对铜绿假单胞菌和洋葱假单胞菌中妥布霉素MIC的抑制作用。维拉帕米对铜绿假单胞菌的妥布霉素MIC没有影响，但能够与妥布霉素协同作用，显著降低所有受试洋葱假单胞菌分离株的妥布霉素MIC。这种药物组合可能值得研究作为耐药洋葱青霉菌感染的新治疗策略。
Virtually all patients with cystic fibrosis (CF) die of respiratory failure resulting from chronic progressive pulmonary infections. Pseudomonas aeruginosa and Pseudomonas (Burkholderia) cepacia are the two major bacterial pathogens responsible for the pulmonary deterioration in these patients. Tobramycin has variable inhibitory effects on these organisms, but in many isolates this inhibition is increased in vitro by exposure to the diuretic, amiloride. Aerosolized amiloride has been shown to be of clinical benefit in CF. The basis for this synergy is unknown. To examine the possibility that amiloride-tobramycin synergy is mediated through a bacterial efflux mechanism mediated by a multidrug resistant (mdr) protein, we studied the inhibitory effect of verapamil, a known mdr inhibitor on the tobramycin MIC in P. aeruginosa and P. cepacia using standard MIC and synergy testing. Verapamil had no effect on the tobramycin MIC in P. aeruginosa but was able to act synergistically with tobramycin in reducing the tobramycin MIC markedly in all isolates of P. cepacia tested. This combination of drugs may be worth studying as a new treatment strategy for resistant P. cepacia infections.