Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents
Carbapenem-Resistant Klebsiella pneumoniae Strains Exhibit Diversity in Aminoglycoside-Modifying Enzymes, Which Exert Differing Effects on Plazomicin and Other Agents
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DOI：
10.1128/aac.00099-14
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发表时间：
2014-08-01
影响因子：
4.9
通讯作者：
Nguyen, M. Hong
中科院分区：
文献类型：
--
作者：
Almaghrabi, Reem;Clancy, Cornelius J.;Nguyen, M. Hong
我们测量了下一代氨基糖苷类药物普拉佐霉素和其他氨基糖苷类药物对来自两个中心的50株碳青霉烯类耐药肺炎克雷伯菌的体外活性，并将结果与各种氨基糖苷类修饰酶（艾姆斯）的存在相关联。94%的菌株为序列类型258（ST 258）克隆，表现出5种ompK 36基因型; 80%和10%的菌株分别产生肺炎克雷伯菌碳青霉烯酶2（KPC-2）和KPC-3。98%的菌株具有艾姆斯，包括AAC（6 '）-Ib（98%）、APH（3'）-Ia（56%）、AAC（3）-IV（38%）和ANT（2（“））-Ia（2%）。庆大霉素、妥布霉素和阿米卡星的不敏感率分别为40%、98%和16%。普拉佐霉素MIC范围为0.25至1 μ g/ml。妥布霉素和普拉佐霉素MIC与庆大霉素MIC相关（r分别为0.75和0.57）。帕唑霉素对17%（1 × MIC）和94%（4 × MIC）的菌株具有杀菌活性。所有携带AAC（6 '）-Ib的菌株均对妥布霉素耐药，16%对阿米卡星不敏感。AAC（6=）-Ib联合另一种AME与比AAC（6=）-Ib单独使用更高的庆大霉素、妥布霉素和普拉佐霉素MIC相关（分别为P = 0.01、0.0008和0.046）。菌株中AAC（3）-IV的存在也与更高的庆大霉素、妥布霉素和普拉佐霉素MIC相关（分别为P = 0.0006、P < 0.0001和P = 0.01）。AAC（6 '）-Ib和另一种AME的组合、AAC（3）IV的存在和APH（3'）-Ia的存在均与庆大霉素耐药性相关（分别为P = 0.0002、0.003和0.01）。综上所述，耐碳青霉烯类K.肺炎菌株（包括ST 258克隆）表现出高度多样的抗微生物剂抗性基因型和表型。普拉佐霉素可能提供一种治疗选择，对其他氨基糖苷类耐药菌株。预测碳青霉烯类耐药克雷伯氏菌抗菌反应的分子检测方法的发展。肺炎菌株应该是研究的重点。
We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenem- resistant Klebsiella pneumoniae strains from two centers and correlated the results with the presence of various aminogly-coside- modifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10% of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6')-Ib (98%), APH(3')-Ia (56%), AAC(3)-IV (38%), and ANT(2("))-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 mu g/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r = 0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1 x MIC) and 94% (4 x MIC) of strains. All strains with AAC(6')-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6=)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6=)-Ib alone (P = 0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P = 0.0006, P < 0.0001, and P = 0.01, respectively). The combination of AAC(6')-Ib and another AME, the presence of AAC(3)IV, and the presence of APH(3')-Ia were each associated with gentamicin resistance (P = 0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K. pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant K. pneumoniae strains should be a research priority.