Infectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
University General Hospital "ATTIKON", Rimini 1, 124 62, Chaidari, Greece.
BMC Infect Dis. 2019 Feb 15;19(1):167. doi: 10.1186/s12879-019-3801-1.
To evaluate the in vitro activities of plazomicin and comparator aminoglycosides and elucidate the underlying aminoglycoside resistance mechanisms among carbapenemase-producing K. pneumoniae isolates collected during a nationwide surveillance study in Greek hospitals.
Three hundred single-patient carbapenemase-producing K. pneumoniae isolates were studied, including 200 KPC-, 50 NDM-, 21 VIM-, 14 KPC & VIM-, 12 OXA-48-, two NDM & OXA- and one KPC & OXA-producing isolates. Susceptibility testing was performed by broth microdilution, and minimum inhibitory concentrations (MICs) interpreted per EUCAST breakpoints. Carbapenemase-, aminoglycoside modifying enzyme- and 16S rRNA methylase- encoding genes were detected by PCR.
Of 300 isolates tested, 5.7% were pandrug resistant and 29.3% extensively drug resistant. Plazomicin inhibited 87.0% of the isolates at ≤2 mg/L, with MIC/MIC of 0.5/4 mg/L. Apramycin (a veterinary aminoglycoside) inhibited 86.7% of the isolates at ≤8 mg/L and was the second most active drug after plazomicin, followed by gentamicin (S, 43%; MIC/MIC, 4/> 256) and amikacin (S, 18.0%; MIC/MIC, 32/128). Twenty-three (7.7%) isolates (16 KPC-, 6 VIM- and one KPC & OXA-48-producers) exhibited MICs ≥64 mg/L for plazomicin, and harbored rmtB (n = 22) or armA (n = 1). AAC(6')-Іb was the most common aminoglycoside modifying enzyme (84.7%), followed by AAC(3΄)-IIa (25.3%), while those two enzymes were co-produced by 21.4% of the isolates.
Plazomicin retains activity against most carbapenemase-producing K. pneumoniae isolated from Greek hospitals, with MICs consistently lower than those of the other aminoglycosides, even in the presence of aminoglycoside modifying enzymes. Dissemination of 16S- rRNA methylases in 8% of the isolates is an unwelcome event that needs strict infection control measures and rigorous stewardship interventions.
为了评估普拉佐米星和比较氨基糖苷类药物的体外活性，并阐明在希腊医院进行的全国性监测研究中收集的产碳青霉烯酶肺炎克雷伯菌分离株中潜在的氨基糖苷类耐药机制。
研究了 300 株单株产碳青霉烯酶肺炎克雷伯菌分离株，包括 200 株 KPC-、50 株 NDM-、21 株 VIM-、14 株 KPC & VIM-、12 株 OXA-48-、2 株 NDM & OXA-和 1 株 KPC & OXA-株。通过肉汤微量稀释法进行药敏试验，并按 EUCAST 折点解释最小抑菌浓度（MIC）。通过 PCR 检测碳青霉烯酶、氨基糖苷修饰酶和 16S rRNA 甲基化酶编码基因。
在 300 株被检测的分离株中，有 5.7%为泛耐药，29.3%为广泛耐药。普拉佐米星在≤2 mg/L 时抑制了 87.0%的分离株，MIC/MIC 为 0.5/4 mg/L。大观霉素（一种兽用氨基糖苷类药物）在≤8 mg/L 时抑制了 86.7%的分离株，是仅次于普拉佐米星的第二大活性药物，其次是庆大霉素（S，43%；MIC/MIC，4/>256）和阿米卡星（S，18.0%；MIC/MIC，32/128）。有 23 株（16 株 KPC-、6 株 VIM-和 1 株 KPC & OXA-48-株）分离株对普拉佐米星的 MIC 值≥64 mg/L，携带 rmtB（n=22）或 armA（n=1）。AAC(6')-Ib 是最常见的氨基糖苷修饰酶（84.7%），其次是 AAC(3΄)-IIa（25.3%），而这两种酶在 21.4%的分离株中同时产生。
普拉佐米星对从希腊医院分离的大多数产碳青霉烯酶肺炎克雷伯菌保持活性，其 MIC 值始终低于其他氨基糖苷类药物，即使存在氨基糖苷类修饰酶也是如此。在 8%的分离株中发现的 16S rRNA 甲基化酶的传播是一个不受欢迎的事件，需要严格的感染控制措施和严格的管理干预。
