Insights into Non-Enzymatic Carbapenem Resistance: Role of Porin Alterations among Klebsiella pneumoniae

Carbapenem resistance in Klebsiella pneumoniae is a growing public health concern, with loss or deficiency of outer membrane porins (OMPs) and β-lactamases production, including extended-spectrum-β-lactamase (ESBL) and cephalosporinases, playing a significant role. K. pneumoniae is often found in urinary tract infections, pneumonia, and severe bacteremia, playing a significant role in hospital-acquired infections worldwide. The emergence of ESBL-producing K. pneumoniae is closely related to the overuse of expanded-spectrum cephalosporins, a critical factor in its rise. Carbapenems were once the last resort against multidrug-resistant strains producing ESBLs. However, their overuse and misuse have led to resistance mechanisms emerging. This has resulted in carbapenem-resistant Enterobacteriaceae becoming a major public health concern, with limited treatment options, fast transmission, and high mortality rates. Resistance to carbapenems may result from the production of carbapenemases or ESBL and/or AmpC β-lactamases in association with alteration in the outer membrane porins. K. pneumoniae, which normally lacks a chromosomally encoded class C β-lactamase, can easily acquire a plasmid encoding AmpC or another broad-spectrum-β-lactamase. These enzymes can confer high-level carbapenem resistance in porin-deficient strains. In addition, ESBL-producing K. pneumoniae with deficiency in OmpK35 and OmpK36 may contribute to the antibiotic resistance. These enzymes can confer high-level carbapenem resistance in porin-deficient strains.