Prevalence, Antimicrobial Susceptibility, and Molecular Characteristics of Ceftazidime-Avibactam-Resistant Klebsiella pneumoniae in a Chinese Hospital.

BACKGROUND

The mechanisms underlying ceftazidime-avibactam resistance in carbapenem-resistant Klebsiella pneumoniae (CRKPCZA-R) remain to be elucidated.

METHODS

CRKPCZA-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 CRKPCZA-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 CRKPCZA-R. The susceptibility rates of CRKPCZA-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 CRKPCZA-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 CRKPCZA-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 CRKPCZA-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 CRKPCZA-R co-harboring both bla KPC-2 and bla NDM-1 should be closely monitored.