PDF(Pubmed)
Abstract：
Carbapenem-resistant Klebsiella pneumoniae (CPKP) infections seriously threaten global public health. The main objective of this study was to assess the in-vitro synergistic activity of ceftazidime-avibactam (CZA) in combination with colistin (COL), amikacin (AK), gentamicin (GEN), and fosfomycin (FOS) against CPKP isolates. The secondary goal was to determine the antibiotic susceptibility performance of BD Phoenix. OXA-48 (49.1%) was the predominant carbapenemase, followed by KPC (29.1%). We used the broth microdilution (BMD) method to determine the minimum inhibitory concentrations (MICs) of CZA, COL, AK, and GEN. Meanwhile, the MICs of FOS were determined by the agar dilution (AD) method. To examine the antibacterial activity of CZA, we conducted a checkerboard assay (CBA) with COL, AK, GEN, and FOS against CRKP isolates. We randomly selected three strains and performed synergy testing via time-kill assay (TKA). CRKP isolates were 89.1% susceptible to CZA, 16.4% to COL, 21.8% to GEN, and 29.1% to AK using BMD, 47.3% to FOS by AD. The most synergistic effects were observed in the combination of CZA-COL (78.2%) and CZA-FOS (63.6%). Given the limited therapeutic options for treating severe CRKP infections, combining CZA with COL and FOS may enhance in-vitro activity against clinical CRKP isolates.
摘要：
耐碳青霉烯类肺炎克雷伯菌(CPKP)感染严重威胁全球公众健康。这项研究的主要目的是评估头孢他啶-阿维巴坦（CZA）与粘菌素（COL）组合的体外协同活性，阿米卡星（AK），庆大霉素（GEN），和磷霉素（FOS）对CPKP分离株。次要目标是确定BDPhoenix的抗生素敏感性表现。OXA-48（49.1%）是主要的碳青霉烯酶，其次是KPC(29.1%)。我们使用肉汤微量稀释（BMD）方法来确定CZA的最低抑制浓度（MIC），COL,AK,和GEN。同时,通过琼脂稀释（AD）法测定FOS的MIC。为了检查CZA的抗菌活性，我们用COL进行了棋盘试验(CBA)，AK,GEN,和针对CRKP分离株的FOS。我们随机选择了三个菌株，并通过时间杀伤测定（TKA）进行了协同作用测试。CRKP分离株对CZA的敏感性为89.1%,对COL的16.4%，占GEN的21.8％，和29.1%的AK使用BMD，广告对FOS的影响为47.3%。在CZA-COL(78.2%)和CZA-FOS(63.6%)的组合中观察到最多的协同作用。鉴于治疗严重CRKP感染的治疗选择有限，将CZA与COL和FOS组合可能会增强针对临床CRKP分离株的体外活性。
