Schlaeffer F, Blaser J, Laxon J, Zinner S
Department of Medicine, Brown University, Roger Williams General Hospital, Providence, R.I. 02908.
J Antimicrob Chemother. 1990 Jun;25(6):941-8. doi: 10.1093/jac/25.6.941.
In vitro exposure to aminoglycosides and quinolones may select resistant subpopulations, although this is not a common clinical problem. This study was designed to determine whether aminoglycoside and quinolone resistant bacteria are more susceptible to leucocyte (WBC) killing. Cultures of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were pretreated with aminoglycosides (netilmicin, amikacin) and quinolones (enoxacin, ciprofloxacin) at 1/2 MIC for 24 h. The median susceptibility of bacteria selected during antibiotic exposure was reduced four-fold. These resistant subpopulations (10(6) cfu/ml) were exposed to 10(7) human WBC/ml for 6 h in antibiotic free cell culture media with 10% fresh human serum. Enhanced WBC activity was observed against all antibiotic pretreated bacteria in comparison with untreated controls (P less than 0.01). After 4 h of exposure to WBC, aminoglycoside or quinolone pretreated cultures of P. aeruginosa were reduced by 1.3-1.7 log, in comparison with a reduction of only 0.5 log in control cultures. These observations may explain in part the infrequent therapeutic failure with these drugs in hosts with competent neutrophils despite the potential of these drugs to select resistant strains in vitro.
体外暴露于氨基糖苷类和喹诺酮类药物可能会筛选出耐药亚群，尽管这并非常见的临床问题。本研究旨在确定对氨基糖苷类和喹诺酮类耐药的细菌是否对白细胞（WBC）杀伤更敏感。将铜绿假单胞菌、大肠杆菌和金黄色葡萄球菌培养物用氨基糖苷类药物（奈替米星、阿米卡星）和喹诺酮类药物（依诺沙星、环丙沙星）在1/2 MIC浓度下预处理24小时。抗生素暴露期间筛选出的细菌的中位敏感性降低了四倍。将这些耐药亚群（10⁶ cfu/ml）在含有10%新鲜人血清的无抗生素细胞培养基中与10⁷ 人白细胞/ml一起孵育6小时。与未处理的对照相比，观察到针对所有经抗生素预处理的细菌白细胞活性增强（P < 0.01）。暴露于白细胞4小时后，铜绿假单胞菌经氨基糖苷类或喹诺酮类预处理的培养物减少了1.3 - 1.7个对数，而对照培养物仅减少0.5个对数。这些观察结果可能部分解释了尽管这些药物在体外有筛选出耐药菌株的可能性，但在中性粒细胞功能正常的宿主中使用这些药物时治疗失败很少见的原因。
