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. Plain Language Summary: The resistance mechanisms of CRKP CZA-R remain to be uncovered. In our study, the detection rate of CRKP CZA-R was relatively high due to the metallo-β-lactamase-producing isolates. The sensitivity of CRKP CZA-R to antibacterial agents was evaluated in vitro, and revealed high susceptibility to aztreonam-avibactam, cefiderocol, polymyxin B, and tigecycline. The enzyme inhibitor enhancement method plays an important role in guiding the selection of clinical antibiotics due to its high sensitivity and specificity. Specifically, when the inhibition zone diameter of K-B method CZA is 20-22 mm, CZA can be used alone if it produces serine enzyme, but not if it produces metalloenzyme. Patients infected with CRKP CZA-R harboring both bla KPC-2 and bla NDM-1 were older and experienced more serious illness compared to those infected with other drug-resistant isolates, and should therefore be monitored more closely. Keywords: carbapenem-resistant Klebsiella pneumoniae , ceftazidime–avibactam, resistance mechanism, homology
Li et al. (Sun,) studied this question.