Abstract
BACKGROUND: The mechanisms underlying ceftazidime-avibactam resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP(CZA-R)) remain to be elucidated. METHODS: CRKP(CZA-R) isolates were screened from non-repetitive CRKP isolates at our hospital from January 1, 2018 to October 30, 2021. The antimicrobial susceptibility and molecular characteristics of CRKP(CZA-R) were analyzed by broth microdilution method and next-generation sequencing, respectively. RESULTS: In total, 67 of 623 CRKP isolates (10.8%) were identified as CRKP(CZA-R). The susceptibility rates of CRKP(CZA-R) to polymyxin B, tigecycline, aztreonam-avibactam, and cefiderocol were 97.0% (65/67), 83.6% (56/67), 100.0% (67/67), and 94.0% (63/67), respectively. The most prevalent resistance gene was bla (NDM-1) (44.8%, 30/67), followed by bla (IMP-4) (9.0%, 6/67), bla (NDM-5) (7.5%, 5/67), and bla (NDM-4) (1.5%, 1/67). Furthermore, 37.3% (25/67) of the CRKP(CZA-R) isolates co-harbored more than two carbapenemase-encoding genes, mainly bla (NDM-1) and bla (KPC-2) (31.3%, 21/67). The enzyme inhibitor enhancement method detected carbapenemase activity with high sensitivity, except for isolates carrying two or more carbapenemases. Notably, 21 KL64-ST11 CRKP(CZA-R) isolates presented bla (NDM-1), bla (KPC-2), and ompk36 deletion, and 17 co-harbored two or more high virulence gene markers. Patients infected with these 21 isolates were older and experienced more serious illness compared to those infected with other drug-resistant isolates. CONCLUSION: The detection rate of CRKP(CZA-R) was relatively high due to the metallo-β-lactamase-producing isolates. Although enzyme inhibitor enhancement method can detect carbapenemases with high sensitivity and specificity, and provide an important reference for drug selection, it is not as effective for isolates carrying two or more carbapenemases. Patients infected with CRKP(CZA-R) co-harboring both bla (KPC-2) and bla (NDM-1) should be closely monitored.