Clinical and Molecular Epidemiologic Characteristics of Ceftazidime/Avibactam-Resistant Carbapenem-Resistant Klebsiella pneumoniae in a Neonatal Intensive Care Unit in China

Abstract

Juanjuan Zhou,1,2,* Junwen Yang,1,2,* Fupin Hu,3,4 Kaijie Gao,1,2 Jiufeng Sun,5 Junmei Yang1,2 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Laboratory Medicine, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 3Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, People’s Republic of China; 5Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junmei YangZhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, 33M Waihuan East Road, Longhu, Zhengzhou 450018, People’s Republic of ChinaTel [phone]Email [email protected] SunGuangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, 160M. Qunxian Road, Guangzhou 510300, People’s Republic of ChinaTel [phone]Email [email protected]: Ceftazidime/avibactam (CZA)-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) infections occur in adults worldwide but are rarely observed in neonates. We evaluated the activities of CZA against CRKP and described the clinical and molecular epidemiology of CZA-resistant CRKP in a NICU prior to CZA approval in China.Methods: A laboratory-based surveillance of CRKP was conducted from July 2017 to June 2018. Clinical data were initially reviewed. Antimicrobial susceptibility was determined by the broth microdilution method. CZA-resistant CRKP isolates were submitted to carbapenemase types screening and multilocus sequence typing.Results: Over 23.3% (10/43) of CRKP strains were resistant to CZA, MIC50 and MIC90 values being 0.5 μg/mL and > 32μg/mL, respectively. Most neonates shared similar clinical features with cesarean (n=8), preterm birth (n=6), low birth weight (n=5), and exposure to carbapenems/β-lactam (n=8). All CZA-resistant CRKP isolates were highly resistant to most tested drugs except for polymyxin B (POL) and tigecycline (TGC). CZA-resistant CRKP isolates showed greater sensitivity to amikacin (AMK), nitrofurantoin (NIT), levofloxacin (LVX) and ciprofloxacin (CIP), compared with CZA-sensitive CRKP. All CZA-resistant CRKP isolates harbored carbapenemase genes, blakpc-2 (n=5) being predominant, followed by blaNDM-1 (n=4) and blaNDM-5 (n=2). Among these CZA-resistant CRKP isolates, a total of eight different STs were identified. CRKP harboring KPC belonged to ST1419, ST37 and ST11, while NDM types were assigned to ST784, ST1710, ST37 and ST324. Furthermore, other β-lactamase genes including blaSHV and blaCTX-M were also found.Conclusion: Over 23.3% of CRKP strains isolated from neonates were resistant to CZA. Cesarean, preterm birth, low birth weight, and exposure to carbapenems/β-lactam were similar clinical features of most neonates with CZA-resistant CRKP. The predominant carbapenemases of CZA-resistant CRKP were KPC-2 and NDM-1, and KPC-2 producing K. pneumoniae assigned into 3 STs, which indicate the genetic diversity of clinical CZA-resistant CRKP isolates.Keywords: ceftazidime/avibactam, neonate, drug resistance, clinical features, blaKPC

Keywords

• ceftazidime/avibactam
• neonate
• drug resistance
• clinical features
• blakpc