Cohn R C, Rudzienski L, Putnam R W
Department of Pediatrics, Wright State University, Dayton, Ohio, USA.
Chemotherapy. 1995 Sep-Oct;41(5):330-3. doi: 10.1159/000239363.
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.
几乎所有囊性纤维化（CF）患者都死于慢性进行性肺部感染导致的呼吸衰竭。铜绿假单胞菌和洋葱伯克霍尔德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具有不同的抑制作用，但在许多分离株中，通过暴露于利尿剂氨氯地平，这种抑制作用在体外会增强。雾化吸入氨氯地平已被证明对CF患者有临床益处。这种协同作用的基础尚不清楚。为了研究氨氯地平 - 妥布霉素协同作用是否通过多药耐药（mdr）蛋白介导的细菌外排机制介导，我们使用标准的最低抑菌浓度（MIC）和协同试验，研究了已知的mdr抑制剂维拉帕米对铜绿假单胞菌和洋葱伯克霍尔德菌中妥布霉素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，但在所有测试的洋葱伯克霍尔德菌分离株中，它能够与妥布霉素协同作用，显著降低妥布霉素的MIC。这种药物组合作为耐药洋葱伯克霍尔德菌感染的一种新治疗策略可能值得研究。
