Vouillamoz Jacques, Moreillon Philippe, Giddey Marlyse, Entenza José M
Laboratory of Infectious Diseases and Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
J Antimicrob Chemother. 2008 Feb;61(2):371-4. doi: 10.1093/jac/dkm459. Epub 2007 Nov 22.
To test the activity of tigecycline combined with 16 antimicrobials in vitro against 22 gram-positive and 55 gram-negative clinical isolates.
Antibiotic interactions were determined by chequerboard and time-kill methods.
By chequerboard, of 891 organism-drug interactions tested, 97 (11%) were synergistic, 793 (89%) were indifferent and 1 (0.1%) was antagonistic. Among gram-positive pathogens, most synergisms occurred against Enterococcus spp. (7/11 isolates) with the tigecycline/rifampicin combination. No antagonism was detected. Among gram-negative organisms, synergism was observed mainly with trimethoprim/sulfamethoxazole against Serratia marcescens (5/5 isolates), Proteus spp. (2/5) and Stenotrophomonas maltophilia (2/5), with aztreonam against S. maltophilia (3/5), with cefepime and imipenem against Enterobacter cloacae (3/5), with ceftazidime against Morganella morganii (3/5), and with ceftriaxone against Klebsiella pneumoniae (3/5). The only case of antagonism occurred against one S. marcescens with the tigecycline/imipenem combination. Selected time-kill assays confirmed the bacteriostatic interactions observed by the chequerboard method. Moreover, they revealed a bactericidal synergism of tigecycline with piperacillin/tazobactam against one penicillin-resistant Streptococcus pneumoniae and with amikacin against Proteus vulgaris.
Combinations of tigecycline with other antimicrobials produce primarily an indifferent response. Specific synergisms, especially against enterococci and problematic gram-negative isolates, might be worth investigating in in vitro models and/or in animal models simulating the human environment.
检测替加环素与16种抗菌药物联合应用对22株革兰氏阳性和55株革兰氏阴性临床分离菌株的体外活性。
采用棋盘法和时间杀菌法测定抗生素相互作用。
通过棋盘法，在测试的891种菌株-药物相互作用中，97种（11%）为协同作用，793种（89%）为无关作用，1种（0.1%）为拮抗作用。在革兰氏阳性病原体中，替加环素/利福平联合用药对肠球菌属（11株分离菌株中的7株）产生的协同作用最多。未检测到拮抗作用。在革兰氏阴性菌中，主要观察到甲氧苄啶/磺胺甲恶唑对粘质沙雷氏菌（5株分离菌株中的5株）、变形杆菌属（5株中的2株）和嗜麦芽窄食单胞菌（5株中的2株）有协同作用，氨曲南对嗜麦芽窄食单胞菌（5株中的3株）有协同作用，头孢吡肟和亚胺培南对阴沟肠杆菌（5株中的3株）有协同作用，头孢他啶对摩根氏摩根菌（5株中的3株）有协同作用，头孢曲松对肺炎克雷伯菌（5株中的3株）有协同作用。唯一的拮抗作用案例是替加环素/亚胺培南联合用药对一株粘质沙雷氏菌产生的。选定的时间杀菌试验证实了棋盘法观察到的抑菌相互作用。此外，试验还揭示了替加环素与哌拉西林/他唑巴坦联合对一株耐青霉素肺炎链球菌以及与阿米卡星联合对普通变形杆菌有杀菌协同作用。
替加环素与其他抗菌药物联合应用主要产生无关反应。特定的协同作用，尤其是对肠球菌和有问题的革兰氏阴性分离菌株的协同作用，可能值得在体外模型和/或模拟人类环境的动物模型中进行研究。
