Michail George, Labrou Maria, Pitiriga Vassiliki, Manousaka Styliani, Sakellaridis Nikolaos, Tsakris Athanasios, Pournaras Spyros
Department of Microbiology, Faculty of Medicine, University of Thessalia, Larissa, Greece.
Antimicrob Agents Chemother. 2013 Dec;57(12):6028-33. doi: 10.1128/AAC.00891-13. Epub 2013 Sep 23.
Limited antimicrobials remain active for treating severe infections due to KPC-producing pathogens, and optimal regimens have not been established. In murine thigh infections caused by nine KPC-producing clinical strains of Enterobacteriaceae (meropenem MICs, 1 to 4 μg/ml), we evaluated the activities of tigecycline, colistin, meropenem, rifampin, and gentamicin in single and combination regimens lasting for 24 h and 48 h. Rifampin, tigecycline, and gentamicin were the most effective monotherapies, reducing significantly the CFU counts yielded from thighs infected by 88.9 to 100%, 77.8 to 88.9%, and 66.7 to 88.9% of strains, respectively; meropenem and colistin alone exhibited considerably lower performance (significant CFU reduction in 33.3% and 22.2 to 33.3% of the strains, respectively). The addition of rifampin or gentamicin to tigecycline produced synergistic effect in most strains, while antagonism was observed in 33.3 to 44.4% of the strains when colistin was added to tigecycline and in 44.4 to 55.5% of the strains for meropenem combination with tigecycline. Tigecycline combinations with gentamicin or with rifampin caused higher CFU reductions than did tigecycline plus colistin or plus meropenem with almost all strains. Furthermore, tigecycline plus gentamicin was significantly more effective than tigecycline plus colistin or tigecycline plus meropenem in 33.3 to 44.4% and 55.5 to 66.7% of the strains, respectively, while tigecycline plus rifampin significantly outperformed tigecycline plus colistin and tigecycline plus meropenem in 33.3% and 66.7 to 77.8% of the strains, respectively. Overall, our in vivo study showed that tigecycline plus rifampin or plus gentamicin is a robust regimen against soft tissue infections caused by KPC-producing strains. The combinations of tigecycline with colistin or meropenem should be considered with caution in clinical practice.
由于产KPC病原体导致的严重感染，可用的有效抗菌药物有限，且尚未确定最佳治疗方案。在由9株产KPC的临床肠杆菌科菌株（美罗培南MICs为1至4μg/ml）引起的小鼠大腿感染中，我们评估了替加环素、黏菌素、美罗培南、利福平及庆大霉素在持续24小时和48小时的单一及联合治疗方案中的活性。利福平、替加环素和庆大霉素是最有效的单一疗法，分别使感染大腿的菌株产生的CFU计数显著降低88.9%至100%、77.8%至88.9%和66.7%至88.9%；单独使用美罗培南和黏菌素的效果则低得多（分别使33.3%和22.2%至33.3%的菌株CFU显著降低）。替加环素联合利福平或庆大霉素对大多数菌株产生协同作用，而替加环素联合黏菌素时，33.3%至44.4%的菌株出现拮抗作用，替加环素联合美罗培南时，44.4%至55.5%的菌株出现拮抗作用。替加环素联合庆大霉素或利福平比替加环素联合黏菌素或美罗培南能使几乎所有菌株的CFU降低更多。此外，替加环素联合庆大霉素分别在33.3%至44.4%的菌株中显著优于替加环素联合黏菌素或替加环素联合美罗培南，替加环素联合利福平分别在33.3%和66.7%至77.8%的菌株中显著优于替加环素联合黏菌素和替加环素联合美罗培南。总体而言，我们的体内研究表明，替加环素联合利福平或庆大霉素是治疗产KPC菌株引起的软组织感染的有效方案。在临床实践中，应谨慎考虑替加环素联合黏菌素或美罗培南的方案。
