Havlichek D, Saravolatz L, Pohlod D
Department of Medicine, Henry Ford Hospital, Detroit, Michigan 48202.
Antimicrob Agents Chemother. 1987 Oct;31(10):1529-34. doi: 10.1128/AAC.31.10.1529.
We evaluated the in vitro susceptibility of Legionella pneumophila ATCC 33152 (serogroup I) to 13 antibiotics alone and in combination with rifampin (0.1 mg/liter) by three methods. Extracellular susceptibility was determined by MIC determinations and time kill curves in buffered yeast extract broth, while intracellular susceptibility was determined by peripheral human monocytes in RPMI 1640 culture medium. Antibiotic concentrations equal to or greater than the broth dilution MIC inhibited or killed L. pneumophila by the time kill method, except this was not the case for trimethoprim-sulfamethoxazole. Antibiotic concentrations below the broth dilution MIC did not inhibit Legionella growth. The only antibiotic-rifampin combinations which produced improved killing of L. pneumophila by the time kill method were those in which the logarithmic growth of L. pneumophila occurred during the experiment (rosoxacin, amifloxacin, cinoxacin, trimethoprim-sulfamethoxazole, clindamycin, and doxycycline). Neither direct MICs nor time kill curve assays accurately predicted intracellular L. pneumophila susceptibility. Rifampin, erythromycin, ciprofloxacin, rosoxacin, enoxacin, amifloxacin, gentamicin, clindamycin, and doxycycline all inhibited intracellular L. pneumophila growth at readily achievable concentrations in serum. Cefoxitin and thienamycin showed no inhibition of growth, although they were present extracellularly at concentrations that were 20 to 1,000 times their broth dilution MICs. Clindamycin was the only antibiotic that was able to inhibit intracellular L. pneumophila growth at an extracellular concentration below its MIC. The gentamicin (5 mg/liter)-rifampin combination was the only antibiotic-rifampin combination which demonstrated decreased cell-associated Legionella survival in this model of in vitro susceptibility.
我们通过三种方法评估了嗜肺军团菌ATCC 33152（血清群I）对13种抗生素单独及与利福平（0.1毫克/升）联合使用时的体外敏感性。细胞外敏感性通过在缓冲酵母提取物肉汤中进行的最低抑菌浓度（MIC）测定和时间杀菌曲线来确定，而细胞内敏感性则通过在RPMI 1640培养基中的人外周血单核细胞来确定。除甲氧苄啶 - 磺胺甲恶唑外，等于或高于肉汤稀释MIC的抗生素浓度通过时间杀菌法抑制或杀死了嗜肺军团菌。低于肉汤稀释MIC的抗生素浓度未抑制军团菌生长。通过时间杀菌法能提高嗜肺军团菌杀灭效果的唯一抗生素 - 利福平组合是那些在实验期间嗜肺军团菌出现对数生长的组合（罗索沙星、阿米氟沙星、西诺沙星、甲氧苄啶 - 磺胺甲恶唑、克林霉素和强力霉素）。直接MIC测定和时间杀菌曲线分析均不能准确预测细胞内嗜肺军团菌的敏感性。利福平、红霉素、环丙沙星、罗索沙星、依诺沙星、阿米氟沙星、庆大霉素、克林霉素和强力霉素在血清中易于达到的浓度下均能抑制细胞内嗜肺军团菌生长。头孢西丁和硫霉素虽在细胞外以高于其肉汤稀释MIC 20至1000倍的浓度存在，但未显示出对生长的抑制作用。克林霉素是唯一一种在细胞外浓度低于其MIC时仍能抑制细胞内嗜肺军团菌生长的抗生素。在这个体外敏感性模型中，庆大霉素（5毫克/升） - 利福平组合是唯一显示出细胞相关军团菌存活率降低的抗生素 - 利福平组合。
