Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) has been increasingly highlighted as a major threat to global public health due to the high mortality rates and huge financial burden of infections [[1], [2], [3], [4]]. In China, Kp sequence type 11 (ST11) has been recognised as the dominant clone responsible for KPC dissemination [4,5]. Ceftazidime-avibactam (CZA) is a β-lactam/β-lactamase inhibitor (BL/BLI) combination which was approved by the FDA in 2015 for complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) clinical practice [6,7]. This novel BL/BLI has demonstrated activity against common Gram-negative HAP/VAP pathogens, including certain drug-resistant (ESBL- and KPC-producing) Enterobacterales and MDR Pseudomonas aeruginosa strains. The recommended duration of therapy for FDA-approved indications is 5 to 14 days for complicated intra-abdominal infections and 7 to 14 days for complicated urinary tract infections and HAP/VAP [8,9].

The emergence of CZA resistance in KPC-Kp isolates has been increasingly reported with its extensive usage [[10], [11], [12], [13], [14], [15]]. Notably, mutations in the KPC enzyme have been demonstrated to mainly contribute to the CZA resistance [10,[12], [13], [14],[16], [17], [18], [19], [20]]. To date, 230 KPC variants have been identified worldwide (https://www.ncbi.nlm.nih.gov/pathogens/isolates#/refgene/KPC). One or more amino acid mutations on loops (Ω-loop 164-179, loop 237-243 and loop 267–275) in the KPC variants were responsible for the CZA resistance [21].

In the present study, a total of 11 Kp isolates were recovered successively from bronchoalveolar lavage fluid (BALF) samples after transplantation. Among these, four representative Kp isolates were selected for further investigation based on their antimicrobial resistance phenotypes: two CZA-susceptible strains (Kp36854 and Kp37523) and two CZA-resistant strains (Kp38097 and Kp38935). One CZA-resistant Kp carried a newly-designated blaKPC-102 gene, whereas the other harboured an increased copy number of blaKPC-33 gene. The resistance profiles and mechanisms in these strains evolved within this host were further analysed. This study will help understand the complexity of the in-host evolution of blaKPC genes in KPC-Kp strains and how they tried to survive under the pressure of CZA.