Conjunto Hospitalar do Mandaqui, São Paulo, SP, Brazil.
Global Medical Affairs, MSD in Brazil, São Paulo, SP, Brazil.
Braz J Infect Dis. 2020 Jul-Aug;24(4):310-321. doi: 10.1016/j.bjid.2020.05.010. Epub 2020 Jul 12.
Multi-drug resistant Gram-negative bacilli (GNB) have been reported as cause of serious hospital-acquired infections worldwide. The aim of this study was to investigate the in vitro activity of ceftolozane-tazobactam compared to other agents against GNB isolated from patients admitted to Brazilian medical centers between the years 2016 and 2017. Presence of β-lactamase encoding genes was also evaluated.
Antimicrobial susceptibility testing of GNB isolated from intra-abdominal (IAI), respiratory (RTI), and urinary tract infections (UTI) was performed according to ISO 227-1 guidelines and interpreted following CLSI and BrCAST/EUCAST guidelines. Qualifying Enterobacteriaceae isolates were screened for the presence of β-lactamase genes by PCR followed by DNA sequencing.
1748 GNB collected from UTI (45.2%), IAI (25.7%) and RTI (29.1%) were evaluated. Ceftolozane-tazobactam remained highly active (94.7%) against E. coli isolates. Among K. pneumoniae, susceptibility rates were 85.9% and 85.4% for amikacin and colistin, whereas ceftolozane-tazobactam (44.1% susceptible) and carbapenems (55.2-62.2% susceptible) showed poor activity due to bla. Against E. cloacae amikacin, imipenem, and meropenem retained good activity (>90%). Ceftolozane-tazobactam was the most potent β-lactam agent tested against P. aeruginosa (90.9% susceptible), including ceftazidime and imipenem resistant isolates. β-lactamase encoding genes testing was carried out in 433 isolates. bla variants were predominant in E. coli, P. mirabilis and E. cloacae. Among the K. pneumoniae molecularly tested, most carried bla (68.5%), with all harboring bla except two isolates carrying bla or bla. ESBL encoding genes, mainly CTX-M family, were frequently detected in K. pneumoniae, plasmid-mediated AmpC were rare. A variety of PDC encoding genes were detected in P. aeruginosa isolates with five isolates harboring MBL and one KPC encoding genes.
Ceftolozane-tazobactam was very active against E. coli, P. mirabilis and P. aeruginosa isolates and could constitute an excellent therapeutic option including for those isolates resistant to extended-spectrum cephalosporins and carbapenems but not producers of carbapenemases.
本研究旨在调查巴西医疗中心 2016 年至 2017 年间住院患者分离的革兰氏阴性菌（GNB）对头孢洛扎他唑巴坦与其他药物的体外活性。还评估了β-内酰胺酶编码基因的存在。
根据 ISO 227-1 指南对来自腹腔内（IAI）、呼吸道（RTI）和尿路感染（UTI）的 GNB 进行了抗菌药敏试验，并根据 CLSI 和 BrCAST/EUCAST 指南进行了解释。通过 PCR 对合格的肠杆菌科分离株进行β-内酰胺酶基因筛选，然后进行 DNA 测序。
共评估了来自 UTI（45.2%）、IAI（25.7%）和 RTI（29.1%）的 1748 株 GNB。头孢洛扎他唑巴坦对大肠埃希菌分离株保持高度活性（94.7%）。在肺炎克雷伯菌中，阿米卡星和粘菌素的敏感性率分别为 85.9%和 85.4%，而头孢洛扎他唑巴坦（44.1%敏感）和碳青霉烯类（55.2-62.2%敏感）由于 bla 的存在，活性较差。对于阴沟肠杆菌，阿米卡星、亚胺培南和美罗培南保留了良好的活性（>90%）。头孢洛扎他唑巴坦是测试的最有效的针对铜绿假单胞菌的β-内酰胺类药物（90.9%敏感），包括头孢他啶和亚胺培南耐药分离株。对 433 株分离株进行了β-内酰胺酶编码基因检测。bla 变体在大肠埃希菌、奇异变形杆菌和阴沟肠杆菌中占优势。在分子检测的肺炎克雷伯菌中，大多数携带 bla（68.5%），除了两个携带 bla 或 bla 的分离株外，所有分离株都携带 bla。ESBL 编码基因主要为 CTX-M 家族，在肺炎克雷伯菌中频繁检测到，质粒介导的 AmpC 很少见。在铜绿假单胞菌分离株中检测到多种 PDC 编码基因，其中 5 株携带 MBL，1 株携带 KPC 编码基因。
头孢洛扎他唑巴坦对大肠埃希菌、奇异变形杆菌和铜绿假单胞菌分离株非常有效，可作为一种极好的治疗选择，包括对那些对头孢菌素和碳青霉烯类药物耐药但不产碳青霉烯酶的分离株。
