NOSOCOMIAL ENTEROBACTER INFECTIONS: MECHANISMS OF RESISTANCE, CLINICAL IMPACT, AND INFECTION CONTROL STRATEGIES

Enterobacter species, particularly Enterobacter cloacae complex and Enterobacter aerogenes (reclassified as Klebsiella aerogenes), represent significant opportunistic pathogens responsible for an increasing proportion of nosocomial infections worldwide. Their propensity to colonize immunocompromised individuals and patients in intensive care units (ICUs) presents a major clinical challenge. This review provides a comprehensive analysis of the core resistance mechanisms, clinical implications, and infection control strategies associated with nosocomial Enterobacter infections. Mechanistically, Enterobacter species possess a formidable array of intrinsic and acquired resistance determinants. Central to their drug-resistant phenotype is the inducible, chromosomally encoded AmpC β-lactamase. Exposure to β-lactam antibiotics frequently selects for derepressed mutants that constitutively overproduce AmpC, conferring resistance to third-generation cephalosporins and monobactams. Furthermore, the rapid dissemination of plasmid-mediated resistance genes—including extended-spectrum β-lactamases (ESBLs) and carbapenemases (such as KPC, NDM, VIM, and OXA-48-like variants)—has severely compromised carbapenem utility. Coupled with efflux pump overexpression, porin mutations, and aminoglycoside-modifying enzymes, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains have emerged rapidly. Clinically, Enterobacter infections manifest primarily as ventilator-associated pneumonia, central line-associated bloodstream infections, catheter-associated urinary tract infections, and surgical site infections. These infections are correlated with prolonged hospital stays, heightened healthcare costs, and elevated morbidity and mortality, particularly when inappropriate empirical antimicrobial therapy is administered. The narrow range of remaining effective therapeutic options—often restricted to newer β-lactam/β-lactamase inhibitor combinations, cefiderocol, polymyxins, or tigecycline—underscores the critical nature of these pathogens.