Muranaka K, Greenwood D
Department of Microbiology, University Hospital, Queen's Medical Centre, Nottingham, UK.
J Antimicrob Chemother. 1988 May;21(5):545-54. doi: 10.1093/jac/21.5.545.
The response to three quinolones of a clinical isolate of Streptococcus faecalis was studied by continuous turbidimetric monitoring, by viable counting, and in an in-vitro model of the treatment of bacterial cystitis. Dense populations (c. 8 x 10(6) cfu/ml) responded to ciprofloxacin, norfloxacin and enoxacin at concentrations below the conventionally determined MIC, but variants, shown to exhibit decreased susceptibility, emerged during overnight incubation. The variants were cross-resistant to each of the three quinolones, but the resistance was lost on subculture in drug-free broth. At a concentration of ten-fold MIC, ciprofloxacin was more bactericidal than norfloxacin or enoxacin. In experiments in the bladder model, doses of ciprofloxacin achieving a peak concentration of 10, 50 or 250 mg/l suppressed bacterial growth for 20 h or more. The doses of norfloxacin or enoxacin required to achieve a comparable effect were higher than those of ciprofloxacin. A reduction in susceptibility, as judged by comparative disc testing, occurred after two cycles of exposure to norfloxacin or enoxacin in experiments in which the peak concentration achieved was 50 mg/l, but not when the peak was 250 mg/l. Reduced susceptibility to ciprofloxacin developed only in experiments in which a lower peak concentration of 10 mg/l was achieved.
通过连续比浊法监测、活菌计数以及在细菌性膀胱炎体外治疗模型中,研究了粪肠球菌临床分离株对三种喹诺酮类药物的反应。高密度菌液(约8×10⁶ cfu/ml)在低于常规测定的最低抑菌浓度(MIC)时对环丙沙星、诺氟沙星和依诺沙星有反应,但在过夜培养期间出现了显示敏感性降低的变异株。这些变异株对三种喹诺酮类药物均呈交叉耐药,但在无药肉汤中继代培养后耐药性消失。在十倍MIC浓度下,环丙沙星比诺氟沙星或依诺沙星更具杀菌作用。在膀胱模型实验中,环丙沙星剂量达到10、50或250 mg/l的峰值浓度时可抑制细菌生长20小时或更长时间。达到类似效果所需的诺氟沙星或依诺沙星剂量高于环丙沙星。在峰值浓度达到50 mg/l的实验中,经比较纸片试验判断,在接触诺氟沙星或依诺沙星两个周期后敏感性降低,但在峰值为250 mg/l时未出现这种情况。仅在峰值浓度较低为10 mg/l的实验中出现了对环丙沙星敏感性降低的情况。