Cohn R C, Rudzienski L
Department of Pediatrics, Children's Medical Center of Dayton, OH 45404-1815.
Pediatr Pulmonol. 1994 Jun;17(6):366-9. doi: 10.1002/ppul.1950170605.
Amiloride (A) for aerosolized therapy in cystic fibrosis (CF) is under investigation. Antipseudomonal properties of A and A analogs in vitro have recently been described. This study was performed to determine if there was suppression of P. cepacia growth after a limited 2-hour exposure to (subinhibitory) concentrations of A +/- tobramycin (T) or to the analog 5-(N,N-hexamethylene) amiloride (HMA) in vitro. The MIC of each drug against five different P. cepacia strains was determined. Cells were prepared in Mueller Hinton broth to [10(6)] colony forming units (CFU)/mL and incubated at 35 degrees C for 2 hours in the presence and absence of subinhibitory A, HMA, T, or A+T. The CFU were measured before and at 1-hour intervals after dilutional removal of drug. The post-antibiotic effect (PAE) was defined as the time (in minutes) required for the test culture counts to increase 10-fold minus the time required for control counts to increase 10-fold. At 400 micrograms/mL or 200 micrograms/mL, the PAE for A against five different strains was 139 +/- 23 and 83 +/- 24 (mean +/- SD) minutes, respectively. For 100 micrograms/mL and 50 mu cg/mL HMA, the PAE was 122 +/- 38 and 65 +/- 25 minutes. For T and A+T (200 micrograms/mL + 32 micrograms/mL) the PAE ws 168 +/- 30 and 258 +/- 30 minutes. We conclude that A and the analog HMA in (subinhibitory) concentrations have a suppressive effect on P. cepacia after drug removal and potentiate the effect of T in vitro.
氨氯吡咪(A)用于囊性纤维化(CF)雾化治疗的研究正在进行中。近期已有关于A及其类似物体外抗铜绿假单胞菌特性的描述。本研究旨在确定在体外有限接触(亚抑菌)浓度的A ± 妥布霉素(T)或类似物5 -(N,N - 六亚甲基)氨氯吡咪(HMA)2小时后,洋葱伯克霍尔德菌的生长是否受到抑制。测定了每种药物对五种不同洋葱伯克霍尔德菌菌株的最低抑菌浓度(MIC)。将细胞在米勒 - 欣顿肉汤中制备至[10⁶]菌落形成单位(CFU)/mL,并在有或无亚抑菌浓度的A、HMA、T或A + T存在的情况下于35℃孵育2小时。在通过稀释去除药物之前以及之后每隔1小时测量CFU。抗生素后效应(PAE)定义为测试培养物计数增加10倍所需的时间(以分钟为单位)减去对照计数增加10倍所需的时间。在400微克/毫升或200微克/毫升时,A对五种不同菌株的PAE分别为139 ± 23和83 ± 24(平均值 ± 标准差)分钟。对于100微克/毫升和50微克/毫升的HMA,PAE分别为122 ± 38和65 ± 25分钟。对于T和A + T(200微克/毫升 + 32微克/毫升),PAE分别为168 ± 30和258 ± 30分钟。我们得出结论,(亚抑菌)浓度的A和类似物HMA在去除药物后对洋葱伯克霍尔德菌有抑制作用,并在体外增强了T的作用。