Drago L, De Vecchi E, Nicola L, Legnani D, Lombardi A, Gismondo M R
Lab Clinical Microbiology, Dept Clinical Science L Sacco, Via GB Grassi 74, 20157 Milano, Italy.
J Chemother. 2005 Feb;17(1):46-53. doi: 10.1179/joc.2005.17.1.46.
This study compared the potential synergy of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin/tazobactam or amikacin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli by using checkerboard and time kill studies. Moreover, selection of resistance was determined by frequency of mutations and by calculating the increase in minimum inhibitory concentrations (MICs) after five serial subcultures on antibiotic-containing plates. Synergy occurred more often with levofloxacin combined with imipenem (7/10 strains) and with levofloxacin or ciprofloxacin with amikacin (10/10) than for the other combinations. Time kill studies showed synergy for levofloxacin combined with amikacin, ceftazidime, imipenem or piperacillin/tazobactam, and for ciprofloxacin combined with amikacin, cefepime or imipenem. Antibiotic combinations selected for resistance less frequently than antibiotics alone. Mutation frequency was <10(-12) for all combinations. In conclusion, the combination of a fluoroquinolone with a beta-lactam or amikacin may provide improved antimicrobial activity and help limit the occurrence of resistance in ESBL-producing E. coli strains.
本研究通过棋盘法和时间杀菌试验，比较了左氧氟沙星和环丙沙星分别与头孢吡肟、头孢他啶、亚胺培南、哌拉西林/他唑巴坦或阿米卡星联合使用时，对产超广谱β-内酰胺酶（ESBL）的大肠埃希菌的潜在协同作用。此外，通过突变频率以及计算在含抗生素平板上连续传代五次后最低抑菌浓度（MIC）的增加情况来确定耐药性的选择。与其他组合相比，左氧氟沙星与亚胺培南联合（10株中有7株）以及左氧氟沙星或环丙沙星与阿米卡星联合（10/10）时协同作用更常见。时间杀菌试验表明，左氧氟沙星与阿米卡星、头孢他啶、亚胺培南或哌拉西林/他唑巴坦联合，以及环丙沙星与阿米卡星、头孢吡肟或亚胺培南联合均有协同作用。抗生素联合用药产生耐药性的频率低于单独使用抗生素。所有组合的突变频率均<10^(-12)。总之，氟喹诺酮类与β-内酰胺类或阿米卡星联合使用可能会提高抗菌活性，并有助于限制产ESBL大肠埃希菌菌株耐药性的发生。
