Batard Eric, Jacqueline Cedric, Boutoille David, Hamel Antoine, Drugeon Henri B, Asseray Nathalie, Leclercq Roland, Caillon Jocelyne, Potel Gilles, Bugnon Denis
Laboratoire d'Antibiologie, Faculté de Médecine, Université de Nantes, Nantes, France.
Antimicrob Agents Chemother. 2002 Jul;46(7):2174-8. doi: 10.1128/AAC.46.7.2174-2178.2002.
The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested against two strains of gentamicin- and dalfopristin-susceptible methicillin-resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides, lincosamides, and streptogramin B type antibiotics (MLS(B)), and the other was constitutively resistant to these antibiotics by virtue of the ermA gene. The checkerboard method and time-kill curves showed that the combination of Q-D and gentamicin was indifferent. A rabbit endocarditis model simulated the pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5 mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For the MLS(B)-susceptible strain, a 4-day regimen reduced mean bacterial titers (MBT) in vegetations from 8.5 +/- 0.8 log CFU/g (control group) to 4.1 +/- 2.6 (gentamicin), 3.0 +/- 0.9 (Q-D), and 2.6 +/- 0.5 log CFU/g (Q-D plus gentamicin). For the strain constitutively resistant to MLS(B), a 4-day regimen reduced MBT in vegetations from 8.7 +/- 0.9 log CFU/g (control group) to 5.0 +/- 2.2 (gentamicin), 5.2 +/- 2.2 (Q-D), and 5.1 +/- 2.4 log CFU/g (Q-D plus gentamicin). The differences between control and treatment groups were significant for both strains (P < 0.0001), although there was no significant difference between treatment groups. No resistant variant was isolated from vegetations, and no significant difference in MBT in vegetations of treatment groups after 1-day regimens was observed. This experimental study found no additive benefit in combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible MRSA.
对喹奴普丁-达福普汀（Q-D）与庆大霉素联合用药针对两株对庆大霉素和达福普汀敏感的耐甲氧西林金黄色葡萄球菌（MRSA）进行了测试。其中一株对大环内酯类、林可酰胺类和链阳菌素B型抗生素（MLS(B)）敏感，另一株因ermA基因而对这些抗生素呈组成型耐药。棋盘法和时间杀菌曲线表明Q-D与庆大霉素联合用药效果不佳。兔心内膜炎模型模拟了接受静脉注射Q-D（7.5mg/kg体重，每日3次）和庆大霉素（3mg/kg，每日1次）的人体所达到的药代动力学。对于MLS(B)敏感菌株，4天疗程可使赘生物中的平均细菌滴度（MBT）从8.5±0.8 log CFU/g（对照组）降至4.1±2.6（庆大霉素组）、3.0±0.9（Q-D组）和2.6±0.5 log CFU/g（Q-D加庆大霉素组）。对于对MLS(B)呈组成型耐药的菌株，4天疗程可使赘生物中的MBT从8.7±0.9 log CFU/g（对照组）降至5.0±2.2（庆大霉素组）、5.2±2.2（Q-D组）和5.1±2.4 log CFU/g（Q-D加庆大霉素组）。两株菌株的对照组与治疗组之间差异均有统计学意义（P<0.0001），尽管治疗组之间无显著差异。未从赘生物中分离出耐药变体，且在1天疗程后治疗组赘生物中的MBT无显著差异。该实验研究发现，Q-D与庆大霉素联合用于对达福普汀和庆大霉素敏感的MRSA并无额外益处。
