Dalhoff A, Schubert S, Vente A
University Hospital Kiel, Institute for Infection Medicine, Kiel, Germany
University Hospital Kiel, Institute for Infection Medicine, Kiel, Germany.
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02446-16. Print 2017 May.
The pharmacodynamics of finafloxacin, ciprofloxacin, and levofloxacin against extended-spectrum-β-lactamase (ESBL)-producing isolates were compared. Since quinolones lose activity in acidic media, and particularly in urine, their activities were tested in parallel under conventional conditions and in acidic artificial urine. For this purpose, TEM- and SHV-type ESBL-producing and strains and their wild-type counterparts were exposed in a modified Grasso model to simulated concentrations of drugs in serum and urine following oral doses of either finafloxacin at 800 mg once a day (q.d.), immediate-release ciprofloxacin at 500 mg twice a day (b.i.d.), extended-release ciprofloxacin at 1,000 mg q.d., or levofloxacin at 500 or 750 mg q.d. The concentrations of the drugs in urine were fitted by compartmental modeling. Bacteria were cultivated in Mueller-Hinton broth (MHB) at pH 7.2 or 5.8 or in artificial urine at pH 5.8. Bacteria were counted every 2 h until 10 h and at 24 h; the areas under the bacterial-count-versus-time curves were calculated. It was found that finafloxacin eliminated all strains within 2 h under all the conditions studied. At all doses studied, ciprofloxacin and levofloxacin were highly active against wild-type strains in MHB at pH 7.2 but lost activity in MHB, and particularly in urine, at pH 5.8. Viable counts of ESBL producers were reduced for 6 to 8 h by 3 log titers, but the bacteria regrew thereafter. Ciprofloxacin and levofloxacin were almost inactive against the SHV producer grown in artificial urine. We conclude that pharmacodynamic models using artificial urine may mirror the physiology of urinary tract infections more closely than those using conventional media. In contrast to ciprofloxacin and levofloxacin, finafloxacin gained activity in this model at an acidic pH, maintained activity in artificial urine, and was active against TEM and SHV producers.
比较了非那沙星、环丙沙星和左氧氟沙星对产超广谱β-内酰胺酶（ESBL）菌株的药效学。由于喹诺酮类药物在酸性介质中，尤其是在尿液中会失去活性，因此在常规条件下和酸性人工尿液中平行测试了它们的活性。为此，将产TEM型和SHV型ESBL的菌株及其野生型对应菌株在改良的Grasso模型中暴露于口服800 mg非那沙星每日一次（q.d.）、速释环丙沙星500 mg每日两次（b.i.d.）、缓释环丙沙星1000 mg q.d.或左氧氟沙星500或750 mg q.d.后血清和尿液中的模拟药物浓度。通过房室模型拟合尿液中的药物浓度。细菌在pH值为7.2或5.8的 Mueller-Hinton肉汤（MHB）中或pH值为5.8的人工尿液中培养。每2小时计数一次细菌，直至10小时，并在24小时时计数；计算细菌计数-时间曲线下的面积。发现在所有研究条件下，非那沙星在2小时内消除了所有菌株。在所有研究剂量下，环丙沙星和左氧氟沙星在pH值为7.2的MHB中对野生型菌株具有高活性，但在pH值为5.8的MHB中，尤其是在尿液中失去活性。ESBL产生菌的活菌数在6至8小时内降低了3个对数滴度，但此后细菌重新生长。环丙沙星和左氧氟沙星对在人工尿液中生长的SHV产生菌几乎无活性。我们得出结论，与使用传统培养基的药效学模型相比，使用人工尿液的药效学模型可能更能反映尿路感染的生理学情况。与环丙沙星和左氧氟沙星不同，非那沙星在该模型中在酸性pH值下获得活性，在人工尿液中保持活性，并且对TEM和SHV产生菌具有活性。
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