Klebsiella pneumoniae carbapenemase variants: the new threat to global public health

Abstract

SUMMARY Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild bla KPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 bla KPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting bla KPC variants, treatment options, and future perspectives of bla KPC variants worldwide to alert this new great public health threat.

Comparing antibiotic resistance and virulence profiles of Enterococcus faecium, Klebsiella pneumoniae, and Pseudomonas aeruginosa from environmental and clinical settings

“…The absence of this gene in most of the isolates analysed in the current study, corresponds to the Kirby-Bauer assay results, where none of the isolates were resistant to any of the tested carbapenems (i.e., imipenem, meropenem, doripenem). Nonetheless, KPC-producing bacteria are becoming an emerging threat due to their increased resistance profiles, and significant association with increased morbidity and mortality [ 114 , 115 ]. In comparison to E. faecium and K. pneumoniae , none of the environmental or clinical P. aeruginosa isolates ( n = 16), possessed the bla KPC gene.…”

“…Klebsiella carbapenemase (KPC; Ambler class A β-lactamase) has however, been reported in P. aeruginosa strains [ 116 ]. Thus, while none of the clinical or environmental P. aeruginosa isolates possessed the bla KPC gene in this study, it is possible for P. aeruginosa to possess KPC gene variations [ 115 ].…”

ESKAPE in China: epidemiology and characteristics of antibiotic resistance

“…Over the past decade, no matter in all clinical samples or in bloodstream infection samples, K. pneumoniae has exhibited an overall steady rise of resistance to cephalosporins, aminoglycosides, fluoroquinolones, polymyxins and tigecycline [ 9 , 19 ]. In special, the increasing isolation rate of carbapenem-resistant K. pneumoniae (CRKP) is concerning [ 75 ]. Furthermore, K. pneumoniae demonstrates relatively high sensitivity to tigecycline, polymyxin, and ceftazidime-avibactam, with nationwide surveillance in 2022 indicating resistance rates of 2.6%, 2.8%, and 6.2% for these antibiotics (CHINET data) ( Figure 5 ), respectively.…”

“…CAZ/AVI resistance primarily due to mutations in the bla KPC gene and alterations in outer membrane porins [ 75 , 113 ]. To date, over 150 variants of bla KPC have been reported globally, with the majority of new variants identified in the last three years, warranting public concern [ 75 ].…”

“…CAZ/AVI resistance primarily due to mutations in the bla KPC gene and alterations in outer membrane porins [ 75 , 113 ]. To date, over 150 variants of bla KPC have been reported globally, with the majority of new variants identified in the last three years, warranting public concern [ 75 ]. The variant KPC protein increases its affinity to ceftazidime while reducing its affinity to avibactam through structural changes, thereby facilitating bacterial resistance to CZA [ 75 ].…”