Comprehensive review on antimicrobial resistance: mechanisms, clinical challenges

Abstract

Antimicrobial resistance (AMR) poses a growing global health threat, necessitating a deeper understanding of its mechanisms and clinical implications. This review investigates three critical resistance phenomena: extended-spectrum β-lactamases (ESBLs) in gram-negative bacilli, penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). We synthesize clinical, microbiological, and molecular data from hospital outbreaks,surveillance programs to elucidate the evolutionary and epidemiological drivers of resistance. ESBL-producing Klebsiella pneumoniae and Escherichia coli emerged through plasmid-mediated gene transfer and transposon mobility, with hospital outbreaks linked to prolonged antibiotic use and invasive procedures. PRSP strains acquired mosaic genes encoding altered penicillin-binding proteins, retaining virulence despite resistance, while VRE outbreaks were fueled by van operon dissemination via plasmids, leading to high mortality rates. The study reveals convergent resistance mechanisms across pathogens, underscoring the limitations of current therapies. Moreover, it highlights the efficacy of carbapenems and β-lactam–β-lactamase inhibitors against ESBLs, the geographic variability of PRSP serotypes, and the urgent need for infection-control measures to curb VRE transmission. Our findings emphasize the necessity of multidisciplinary interventions, including antibiotic stewardship, vaccine development, and novel therapeutic strategies, to mitigate AMR's escalating impact. This research contributes a comprehensive analysis of resistance dynamics, offering actionable insights for clinicians, policymakers, and researchers to address one of the most pressing public health challenges of our time.