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

Abstract

Background: 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, MIC 50 and MIC 90 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, bla kpc-2 (n=5) being predominant, followed by bla NDM-1 (n=4) and bla NDM-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 bla SHV and bla CTX-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.

Infection with Carbapenem-resistant Hypervirulent Klebsiella Pneumoniae: clinical, virulence and molecular epidemiological characteristics

“…Due to express carbapenemase and extended-spectrum β-lactamase, CR-KP strains are resistant to most general antibacterial drugs [ 30 ]. Here, the antimicrobial susceptibility testing showed that all the CR-KP strains were highly or completely resistant to general antibacterial drugs, such as piperacillin-tazobactam, cefoxitin, cefepime, aztreonam, amikacin, gentamicin, tobramycin, sulfamethoxazole and cefperazone-sulbactam, while the resistance rate to ceftazidime/avibactam was relatively low, accounting for 26.1%, which is higher than the results of Zhou et al [ 31 ]. As reported in previous studies, colistin and tigecycline were still a good choice for the treatment of CR-KP infection [ 32 , 33 ].…”

Clinical Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Among Pediatric Patients in Jiangsu Province, China

“…Up to now, only one KPC-2 and IMP-4 co-producing CRKP isolate and one strain harbored bla KPC-2 and bla NDM-5 have been identified from children. 26 , 27 To our knowledge, this is the first report of the dissemination of Klebsiella pneumoniae coproducing KPC-2 and IMP-4 clones among children. Something of concern is that these two pediatric patients died of severe lung infection, which suggests that the Klebsiella pneumoniae isolates coproducing two carbapenemases may pose a significant health risk to pediatric patients.…”

Carbapenem-Resistant Klebsiella pneumoniae Osteomyelitis Treated with Ceftazidime-Avibactam in an Infant: A Case Report

“…However, early susceptibility testing is still essential to determine the proper treatment as incidences of CAZ-AVI resistant CR-KP have been previously reported. 16 …”