Introduction

Carbapenems are broad-spectrum beta-lactam antibiotics used to treat severe infections caused by MDR Enterobacterales. Their use as a therapeutic option of choice has lately been extended because of an increase in the prevalence of MDR Enterobacterales in many countries [1]. Concurrently, the increasing global burden of carbapenem-resistant Enterobacterales has become a major public health concern. This concern is due to the resistance profile of CRE, limited therapeutic options, adverse impacts on patient outcomes, and an associated increase in morbidity and mortality, especially in health care settings [2] (see Fig. 1, Fig. 2).

Fig. 1: Prevalence of CRE among Enterobacterales isolates.

Fig. 2: Distribution of CRE-positive isolates by specimen source.

CRE emergence is mediated by the acquisition and expression of carbapenemase enzymes encoded by genes spanning three Ambler classes: KPC (Klebsiella pneumoniae carbapenemase; class A); IMP (Imipenemase), NDM-1 (New Delhi metallo-β-lactamase), and VIM (Verona integron-encoded metallo-β-lactamase; class B); and OXA-48-like (OXA: oxacillinase) carbapenemases (class D) [3]. Non-enzymatic mechanisms contributing to carbapenem resistance include loss or mutation of porin-encoding genes and the overexpression of efflux pump–encoding genes [4].

CRE isolates are predominantly represented by Klebsiella pneumoniae. On a global scale, KPC is the most common carbapenemase and is usually plasmid-mediated in Klebsiella pneumoniae [5]. In Saudi Arabia, however, the leading carbapenemases are OXA-48, followed by NDM [6].

KPC is a β-lactamase that hydrolyzes carbapenem antibiotics and can thereby contribute to treatment failure in severe infections. It is encoded by the blaKPC gene and is produced by several bacterial species belonging to the Enterobacterales group [7]. The main aim of this study was to determine the frequency with which Enterobacterales clinical isolates show resistance to carbapenems. It also aimed to describe them at the molecular level, with particular reference to resistance mechanisms and factors. It is important to understand the molecular nature of CRE infections.