Bauernfeind A, Eberlein E, Hörl G
Max von Pettenkofer-Institut, München, Federal Republic of Germany.
J Antimicrob Chemother. 1988 Oct;22 Suppl D:81-9. doi: 10.1093/jac/22.supplement_d.81.
From in-vitro data, recommendations for dosing with fleroxacin are presented. Serum pharmacokinetics of 250, 400, 500, 800, 1000 and 1500 mg once daily dosages were simulated in bacterial cultures. The bactericidal kinetics of clinical isolates of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus with MICs for fleroxacin similar to MIC90 or above were investigated. Bacterial populations of all strains with MICs equal to or below 2 mg/l were reduced by at least 99% by a once daily dosage of 400 mg of fleroxacin. 500 mg once per day was high enough to induce a two log reduction of P. aeruginosa MIC 4 mg/l. At a 250 mg dosing mutants with MICs four times above the MICs of the initial strains were selected. The increased concentrations of fleroxacin after multiple dosing enhanced bactericidal activity. Once daily dosing increased the initial rate of killing but reduced the extent of inactivation in comparison with twice daily dosing of the same total amount. From our in-vitro investigation a once daily dosage of 400 mg of fleroxacin should be effective against causative organisms with an MIC of up to 2 mg/l, both in the rate and extent of killing and to minimize the risk for selection of resistant mutants.
根据体外实验数据，给出了氟罗沙星的给药建议。在细菌培养物中模拟了每日一次250、400、500、800、1000和1500毫克剂量的血清药代动力学。研究了对氟罗沙星的最低抑菌浓度（MIC）与MIC90或更高相似的大肠杆菌、铜绿假单胞菌和金黄色葡萄球菌临床分离株的杀菌动力学。每日一次400毫克氟罗沙星剂量可使所有MIC等于或低于2毫克/升的菌株的细菌数量减少至少99%。每天一次500毫克足以使MIC为4毫克/升的铜绿假单胞菌数量减少两个对数。在250毫克剂量时，选择了MIC比初始菌株高四倍的突变体。多次给药后氟罗沙星浓度增加增强了杀菌活性。与相同总量的每日两次给药相比，每日一次给药增加了初始杀灭率，但降低了失活程度。根据我们的体外研究，每日一次400毫克氟罗沙星剂量在杀灭速率和程度方面应能有效对抗MIC高达2毫克/升的致病微生物，并将选择耐药突变体的风险降至最低。
