Carbapenem-resistant Klebsiella pneumoniae (CRKP) is often highly resistant to most available antimicrobial agents, posing an enormous threat to human health and leading to a high infection-related mortality rate [1]. Clinical studies have shown that the mortality rate caused by CRKP bloodstream infections exceeds 50%, which is two to three times higher than that of carbapenem-susceptible K. pneumoniae [2]. In 2017, the World Health Organization ranked CRKP as one of the antibiotic-resistant bacteria for which new antibiotics are urgently needed [3]. In China, the prevalence of CRKP in children ranges from approximately 13.4% to 23% [4], with New Delhi metallo-beta-lactamase (NDM) being the primary mechanism of carbapenem resistance in infants infected with CRKP. While ST11-KPC-2-CRKP has been isolated mainly from non-infants and can easily cause invasive infection, posing a tremendous challenge to clinical anti-infective treatment [5].

CRKP is often resistant to most commonly used antibiotics, and the treatment options are limited [6,7]. Tigecycline and polymyxin B have been used to treat multidrug-resistant bacterial infections in children because of their potent antibacterial activity [8,9]. However, their clinical use in children has been limited because of their significant side effects. Tigecycline can affect the development of bones and tooth enamel in children [10]. Colistin is mainly associated with nephrotoxicity and neurotoxicity [11]. However, studies have reported that the adverse effects of colistin are less and it appears to be a safe and effective drug for the treatment of multidrug-resistant Gram-negative bacteria infections in children [12]. Ceftazidime-avibactam (CZA), a novel combination of β-lactam and β-lactamase inhibitor, can effectively inhibit the activity of class A, C, and some class D carbapenemases [13]. It was approved in China in 2019 for the treatment of complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP), as well as for infections with drug-susceptible Gram-negative bacilli in adult patients with limited treatment options [14]. In 2022, CZA was approved by the National Medical Products Administration for the treatment of cIAIs in children ≥3 months of age. Compared with other antibiotics, CZA can significantly improve the clinical survival rate of patients infected with CRKP [15]. However, with the widespread clinical use of CZA, reports of resistance have increased continuously [16], [17], [18]. Mutation of blaKPC is a critical resistance mechanism, and more than 180 blaKPC variants have been reported worldwide, according to the NCBI database [19]. Most of the novel blaKPC variants reported in China are mutations of blaKPC-2, of which blaKPC-33 is the predominant one [20]. However, current reports on KPC-33-producing K. pneumonia are limited to adults, and there are no relevant studies on the blaKPC-33-positive K. pneumoniae cause resistance to CZA in children.

In the present study, 12 strains of KPC-producing K. pneumoniae were isolated from the same patient. Antimicrobial susceptibility testing and WGS analysis revealed that KPC-producing K. pneumoniae developed resistant changes during the treatment. Significantly, this is the first report of the emergence of CZA-resistant KPC-33 carbapenemase-producing K. pneumoniae in paediatric patients worldwide.