Genetic Basis of Multidrug Resistance in Acinetobacter Clinical Isolates in Taiwan

Genetic Basis of Multidrug Resistance in Acinetobacter Clinical Isolates in Taiwan
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DOI:
10.1128/aac.01398-09
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发表时间:
2010-05-01
影响因子:
4.9
通讯作者:
Li, Shu-Ying
Li, Shu-Ying
中科院分区:
医学2区
文献类型:
--
作者:
Lin, Yu-Chi;Hsia, Ko-Chiang;Li, Shu-Ying

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多重耐药(MDR)不动杆菌属对公众健康构成了威胁我们调查了来自台湾一家医院的75株临床分离的不动杆菌中涉及氟喹诺酮类、氨基糖苷类、头孢菌素类和碳青霉烯类耐药的各种基因。检测所有分离株的gyrA突变、是否存在整合子、(bla)AmpC和碳青霉烯类耐药基因。GyrA基因的Ser 83 Leu突变是导致氟喹诺酮类药物耐药的主要原因。含有氨基糖苷类修饰酶的整合子的存在与庆大霉素和妥布霉素的耐药性有关,但与阿米卡星的耐药性无关。ISAba 1元件上游(bla)AmpC的存在与头孢菌素耐药性相关。尽管大多数ISAba 1-bla(OXA-51样)鲍曼不动杆菌分离株对碳青霉烯类耐药,但一些分离株仍对碳青霉烯类敏感。通过将ISAba 1-bla(OXA-23)或ISAba 1-bla(OXA-66)引入A.鲍曼不动杆菌ATCC 15151(CIP 70.10)分别导致OXA-23或OXA-66的过表达,表明ISAba 1元件作为强启动子的作用。这两个转化体对哌拉西林-他唑巴坦、亚胺培南和美罗培南的抗性显著增加。ISAba 1-bla(OXA-23)对头孢吡肟耐药的影响以及ISAba 1-bla(OXA-66)对碳青霉烯耐药的影响。鲍曼不动杆菌属首次报道。耐多药不动杆菌耐药基因的连续监测。并且阐明它们的抗生素抗性机制对于开发治疗方案和防止这些抗生素抗性基因的进一步传播是至关重要的。
Multidrug-resistant (MDR) Acinetobacter spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical Acinetobacter isolates from a Taiwanese hospital. All isolates were tested for the gyrA mutations, the presence of integrons, (bla)AmpC, and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not with resistance to amikacin. The presence of an ISAba1 element upstream of (bla)AmpC was correlated with cephalosporin resistance. Although most Acinetobacter baumannii isolates with ISAba1-bla(OXA-51-like) were resistant to carbapenems, several isolates remained susceptible to carbapenems. Transformation by the introduction of ISAba1-bla(OXA-23) or ISAba1-bla(OXA-66) into A. baumannii ATCC 15151 (CIP 70.10), resulting in the overexpression of OXA-23 or OXA-66, respectively, suggested the role of the ISAba1 element as a strong promoter. The two transformants showed significantly increased resistance to piperacillin-tazobactam, imipenem, and meropenem. The cefepime resistance conferred by ISAba1-bla(OXA-23) and the impact of ISAba1-bla(OXA-66) on carbapenem resistance in A. baumannii are reported here for the first time. Continuous surveillance of antibiotic resistance genes in MDR Acinetobacter spp. and elucidation of their antibiotic resistance mechanisms are crucial for the development of therapy regimens and for the prevention of further dissemination of these antibiotic resistance genes.