The purpose of this study was to investigate the bactericidal effects of levofloxacin and ceftazidime as both monotherapy and combination therapy, and to determine their effects on resistance suppression in patients with normal and abnormal (Ccr:16–20 mL/min) renal function. Common clinical administration regimens to provide reference values were further evaluated. The 7-d hollow-fiber infection model was used to inject the Pseudomonas aeruginosa standard strain (ATCC27853), which simulated common clinical administration regimens for patients with different renal function. Ten regimens were stratified into 2 categories based on renal function, and each category contained 3 monotherapy regimens and 2 combination therapy regimens. Total and resistant populations were quantified. Drug concentrations were determined by high-performance liquid chromatography (HPLC). Monotherapy regimens resulted in about 0.5-log-CFU/mL bacterial kill in the total population at 6 or 8 h, whilst combination regimens resulted in 2- to 3-log-CFU/mL within 2 days. For levofloxacin monotherapy regimens in patients with normal renal function, resistance emergence was seen after 6 h, and was seen at 0 h in the ceftazidime monotherapy regimen, as well as in all regimens of patients with abnormal renal function. Although resistant subpopulation in combination regimens with abnormal renal function began to increase at 0 h, there was a definite downward trend after 8 h, while resistant population in the normal renal function group increased after 16 h. Combination therapy had greater bactericidal efficacy and resistance inhibition compared with monotherapy. Studying combination regimens in randomized clinical trials is warranted.

中文翻译：

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左氧氟沙星-头孢他啶的给药方案在模拟重症患者肾功能异常的中空纤维感染模型中对抗铜绿假单胞菌

这项研究的目的是研究左氧氟沙星和头孢他啶作为单一疗法和联合疗法的杀菌作用，并确定它们对正常和异常（Ccr：16-20 mL / min）肾功能患者的耐药性抑制作用。进一步评估提供参考值的常见临床给药方案。使用7天空心纤维感染模型注射铜绿假单胞菌标准菌株（ATCC27853），该菌株模拟了针对不同肾功能患者的常见临床给药方案。根据肾功能，将10种方案分为2类，每类包含3种单一疗法和2种联合疗法。定量总种群和耐药种群。通过高效液相色谱法（HPLC）测定药物浓度。单一疗法在6或8 h导致总种群中细菌杀灭量约为0.5 log CFU / mL，而联合疗法在2天内导致2到3 log CFU / mL。对于左氧氟沙星单药治疗方案，在肾功能正常的患者中，在6 h后出现耐药性出现，在头孢他啶单药治疗方案以及所有肾功能异常患者的治疗中于0 h出现耐药性。尽管肾功能异常的联合治疗方案中的耐药人群在0 h开始增加，但在8 h后有明显的下降趋势，而正常肾功能组的耐药人群在16 h后有所增加。与单一疗法相比，联合疗法具有更大的杀菌效力和耐药性抑制作用。必须在随机临床试验中研究联合用药方案。