Peleg Anton Y, Potoski Brian A, Rea Rhonda, Adams Jennifer, Sethi Jigme, Capitano Blair, Husain Shahid, Kwak Eun J, Bhat Sunil V, Paterson David L
Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
J Antimicrob Chemother. 2007 Jan;59(1):128-31. doi: 10.1093/jac/dkl441. Epub 2006 Nov 1.
Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed.
The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor.
Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively.
To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.
替加环素已显示出对鲍曼不动杆菌的体外活性。然而，缺乏在临床试验之外使用替加环素的已发表临床经验。我们首次描述了在因其他适应症接受替加环素治疗的患者中，由对替加环素不敏感的鲍曼不动杆菌引起的血流感染。探讨了耐药的可能机制和该药物的药代动力学局限性。
系统回顾了相关患者的临床记录。最初使用Etest方法进行替加环素敏感性测试，并通过琼脂稀释法进行确认。对相关分离株进行脉冲场凝胶电泳（PFGE）和外排泵抑制剂苯丙氨酸 - β - 萘酰胺（PAbetaN）的暴露试验。
两名患者在接受替加环素治疗时发生了鲍曼不动杆菌血流感染。在鲍曼不动杆菌感染发生前，替加环素分别因其他适应症使用了9天和16天。患者1死于严重的鲍曼不动杆菌感染，患者2在抗生素治疗改变后康复。替加环素的最低抑菌浓度（MIC）分别为4 mg/L和16 mg/L。两种分离株均具有多重耐药表型，且基因型不相关。暴露于PAbetaN后，MIC分别降至1 mg/L和4 mg/L。
据我们所知，这是对替加环素不敏感的鲍曼不动杆菌引起的血流感染的首次临床描述。这种耐药性似乎至少部分归因于外排泵机制。鉴于报道的替加环素血清水平较低，我们在使用该药物治疗鲍曼不动杆菌血流感染时敦促谨慎。
