In vitro activity of tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumannii
In vitro activity of tigecycline in combination with various antimicrobials against multidrug resistant Acinetobacter baumannii
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DOI：
10.1186/1476-0711-8-18
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发表时间：
2009-01-01
影响因子：
5.7
通讯作者：
Visca, Paolo
中科院分区：
文献类型：
--
作者：
Principe, Luigi;D'Arezzo, Silvia;Visca, Paolo
背景资料：多重耐药和泛耐药鲍曼不动杆菌感染已成为重症监护病房面临的一个挑战性问题。替加环素为MDR A的治疗提供了新的希望。鲍曼不动杆菌感染，但在许多国家出现了显示敏感性降低的分离株，进一步限制了治疗选择。经验性联合治疗已成为治疗MDR A感染患者的常见做法。鲍曼不动杆菌，尽管支持其功效的微生物和临床证据有限。在这里，替加环素与七种常用的抗不动杆菌药物的体外相互作用进行了评估。检测了重症监护病房（ICU）患者的鲍曼不动杆菌分离株和欧洲克隆谱系I和II的两种参考菌株（分别包括对替加环素耐药、中度和敏感的3、15和6株分离株）。抗菌药物包括：替加环素、左氧氟沙星、哌拉西林-他唑巴坦、阿米卡星、亚胺培南、利福平、氨比西林-舒巴坦和粘菌素。通过肉汤微量稀释法测定MIC。抗生素的相互作用，确定棋盘和时间杀死测定。只有抗生素组合显示协同作用或拮抗作用，在棋盘和时间杀灭试验被接受为真实的协同或拮抗作用，分别为relevant.Results：考虑到所有的抗菌药物与替加环素，棋盘分析显示5.9%的协同作用，85.7%的冷漠，和8.3%的拮抗作用。替加环素与左氧氟沙星、阿米卡星、亚胺培南、粘菌素等药代动力学指标的协同作用分别为4株（16.6%）、2株（8.3%）、2株（8.3%）。观察到替加环素/哌拉西林-他唑巴坦联合用药的拮抗作用（8株; 33.3%）。仅在替加环素非敏感菌株中检测到协同作用。时间杀灭试验证实替加环素与左氧氟沙星、阿米卡星、亚胺培南和粘菌素对7株分离株中的5株具有协同作用。结论：替加环素与粘菌素、左氧氟沙星、阿米卡星和亚胺培南联合应用对5株替加环素不敏感的A.鲍曼不动杆菌菌株，开辟了一条道路，以更合理的临床评估新的联合治疗，以打击感染所造成的MDR和泛耐药A。鲍曼不动杆菌。
Background: Infections sustained by multidrug-resistant (MDR) and pan-resistant Acinetobacter baumannii have become a challenging problem in Intensive Care Units. Tigecycline provided new hope for the treatment of MDR A. baumannii infections, but isolates showing reduced susceptibility have emerged in many countries, further limiting the therapeutic options. Empirical combination therapy has become a common practice to treat patients infected with MDR A. baumannii, in spite of the limited microbiological and clinical evidence supporting its efficacy. Here, the in vitro interaction of tigecycline with seven commonly used anti-Acinetobacter drugs has been assessed.Methods: Twenty-two MDR A. baumannii isolates from Intensive Care Unit (ICU) patients and two reference strains for the European clonal lineages I and II (including 3, 15 and 6 isolates that were resistant, intermediate and susceptible to tigecycline, respectively) were tested. Antimicrobial agents were: tigecycline, levofloxacin, piperacillin-tazobactam, amikacin, imipenem, rifampicin, ampicillin-sulbactam, and colistin. MICs were determined by the broth microdilution method. Antibiotic interactions were determined by chequerboard and time-kill assays. Only antibiotic combinations showing synergism or antagonism in both chequerboard and time-kill assays were accepted as authentic synergistic or antagonistic interactions, respectively.Results: Considering all antimicrobials in combination with tigecycline, chequerboard analysis showed 5.9% synergy, 85.7% indifference, and 8.3% antagonism. Tigecycline showed synergism with levofloxacin (4 strains; 16.6%), amikacin (2 strains; 8.3%), imipenem (2 strains; 8.3%) and colistin (2 strains; 8.3%). Antagonism was observed for the tigecycline/piperacillin-tazobactam combination (8 strains; 33.3%). Synergism was detected only among tigecycline non-susceptible strains. Time-kill assays confirmed the synergistic interaction between tigecycline and levofloxacin, amikacin, imipenem and colistin for 5 of 7 selected isolates. No antagonism was confirmed by time-kill assays.Conclusion: This study demonstrates the in vitro synergistic activity of tigecycline in combination with colistin, levofloxacin, amikacin and imipenem against five tigecycline non-susceptible A. baumannii strains, opening the way to a more rationale clinical assessment of novel combination therapies to combat infections caused by MDR and pan-resistant A. baumannii.