Lim Tze-Peng, Ho Jun-Yuan, Teo Jocelyn Qi-Min, Sim James Heng-Chiak, Tan Si-Hui, Tan Thuan-Tong, Kwa Andrea Lay-Hoon
Department of Pharmacy, Singapore General Hospital, 10 Hospital Boulevard, Singapore 168582, Singapore.
SingHealth Duke-NUS Pathology Academic Clinical Programme, 20 College Road, Singapore 169856, Singapore.
Microorganisms. 2023 Aug 25;11(9):2158. doi: 10.3390/microorganisms11092158.
The emergence of carbapenem-resistant Enterobacterales (CRE) has been recognized as a significant concern globally. Ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor that has demonstrated activity against isolates producing class A, C, and D β-lactamases. Here-in, we evaluated the in vitro activity of CZA and comparator antimicrobial agents against 858 CRE isolates, arising from the Southeast Asian region, collected from a large tertiary hospital in Singapore. These CRE isolates mainly comprised (50.5%), (29.4%), and complex (17.1%). Susceptibility rates to levofloxacin, imipenem, meropenem, doripenem, aztreonam, piperacillin/tazobactam, cefepime, tigecycline, and polymyxin B were low. CZA was the most active β-lactam agent against 68.9% of the studied isolates, while amikacin was the most active agent among all comparator antibiotics (80% susceptibility). More than half of the studied isolates (51.4%) identified were carbapenemase (KPC)-2 producers, 25.9% were New Delhi metallo-β-lactamase (NDM) producers, and Oxacillinase (OXA)-48-like producers made up 10.7%. CZA was the most active β-lactam agent against KPC-2, OXA-48-like, and Imipenemase (IMI) producers (99.3% susceptible; MIC: ≤1/2 mg/L). CZA had excellent activity against the non-carbapenemase-producing CRE (91.4% susceptible; MIC: ≤1/8 mg/L). Expectedly, CZA had no activity against the metallo-β-lactamases (MBL)-producing CRE (NDM- and Imipenemase MBL (IMP) producers; 27.2% isolates), and the carbapenemase co-producing CRE (NDM + KPC, NDM + OXA-48-like, NDM + IMP; 3.0% isolates). CZA is a promising addition to our limited armamentarium against CRE infections, given the reasonably high susceptibility rates against these CRE isolates. Careful stewardship and rational dosing regimens are required to preserve CZA's utility against CRE infections.
耐碳青霉烯类肠杆菌科细菌（CRE）的出现已被公认为全球关注的重大问题。头孢他啶/阿维巴坦（CZA）是一种新型β-内酰胺/β-内酰胺酶抑制剂，已显示出对产生A类、C类和D类β-内酰胺酶的分离株具有活性。在此，我们评估了CZA和对照抗菌药物对从新加坡一家大型三级医院收集的858株源自东南亚地区的CRE分离株的体外活性。这些CRE分离株主要包括（50.5%）、（29.4%）和复合体（17.1%）。对左氧氟沙星、亚胺培南、美罗培南、多利培南、氨曲南、哌拉西林/他唑巴坦、头孢吡肟、替加环素和多粘菌素B的敏感率较低。CZA是对68.9%的研究分离株最具活性的β-内酰胺类药物，而阿米卡星是所有对照抗生素中最具活性的药物（敏感率80%）。鉴定出的超过一半的研究分离株（51.4%）是碳青霉烯酶（KPC）-2生产者，25.9%是新德里金属β-内酰胺酶（NDM）生产者，奥沙西林酶（OXA）-48样生产者占10.7%。CZA是对KPC-2、OXA-48样和亚胺培南酶（IMI）生产者最具活性的β-内酰胺类药物（99.3%敏感；MIC：≤1/2mg/L）。CZA对不产生碳青霉烯酶的CRE具有优异的活性（91.4%敏感；MIC：≤1/8mg/L）。不出所料，CZA对产生金属β-内酰胺酶（MBL）的CRE（NDM和亚胺培南酶MBL（IMP）生产者；27.2%分离株）以及共同产生碳青霉烯酶的CRE（NDM+KPC、NDM+OXA-48样、NDM+IMP；3.0%分离株）无活性。鉴于对这些CRE分离株有相当高的敏感率，CZA是我们对抗CRE感染的有限药物库中一个有前景的补充。需要谨慎管理和合理给药方案以保持CZA对CRE感染的效用。
