The global incidence of multidrug-resistant (MDR) ESKAPE pathogens—comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species—has surged alarmingly in recent years, posing a significant challenge to healthcare systems worldwide. These organisms are notorious for their capacity to evade the effects of multiple classes of antibiotics, leading to treatment failures, increased morbidity and mortality, and escalating healthcare costs, all of which have placed unprecedented strain on existing infection control measures. This review encapsulates the progress in target-driven vaccine research, including the genomic discovery of highly conserved surface antigens, iron acquisition systems, biofilm- and quorum-sensing-related proteins, and computationally predicted epitopes, which are considered the most attractive targets for broad-spectrum vaccination. Novel vaccine platforms, such as outer membrane vesicles (OMVs), mRNA technologies, and multi-epitope constructs, will rapidly drive the translation of these targets into next-generation vaccine formulations. Nevertheless, challenges such as antigenic variation and immune evasion, as well as the need for a robust mucosal and cross-protective immune response, persist. The sustainability in interdisciplinary investigations are required, along with adjunctive measures and investment in the development of advanced discovery and delivery systems, to achieve the ultimate goal of successful vaccines against MDR ESKAPE infections and to mitigate the worldwide burden of antimicrobial resistance.

The rising incidence of Escherichia coli ( E. coli ) strains harbouring ESBL enzymes in healthcare environment including hospitals poses significant public health concerns. This study sought to assess the occurrence of E. coli strains that carry ESBL enzymes in clinical isolates from patients at hospitals in Tabuk, Saudi Arabia, focusing on the responsible genes and antibiotic susceptibility profiles. The 100 clinical samples positive for these ESBL genes were collected from the different Tabuk hospitals’ in-patients for a 6-month period only, with multiplex PCR used to identify genes that encode ESBLs ( bla _TEM , bla _SHV , bla _{CTX-M-group 1} , bla _{CTX-M-group 9} , and bla _{CTX-M-group 25} ). These results yielded that 24% of the clinical isolates exhibited positive for ESBL, with the CTX-M-1 gene having the highest prevalence (67% of ESBL-positive samples). This study underscores the high occurrence of the CTX-M-1 gene isolated in ESBL (+) E. coli within the Tabuk region, providing critical insights into local antibiotic resistance patterns. While these findings enhance our understanding of regional dynamics, they also reaffirm existing knowledge regarding global trends in ESBL gene prevalence. Other genes detected included bla _SHV (46%), bla _TEM (50%), bla _CTX-M-9 (63%), and bla _CTX-M-25 (50%). Co-occurrence of bla _SHV and bla _CTX-M-1 genes was observed in 42% of isolates, while bla _TEM and bla _SHV co-occurred in 12.5%. These ESBL-positive E.coli were primarily isolated from urine (70.8%), wound (12.5%) and blood (16.5%). While these enzymes confer resistance to many beta-lactam classes, they generally remain sensitive to carbapenems, cephamycin and certain β-lactamase inhibitors, while cefoxitin showed 95.8% resistance in this study. Although the study was conducted over a limited six-month duration with a relatively small sample size, the isolation of these specific strains is nonetheless significant. These outcomes highlight the necessity for ongoing surveillance studies and robust infection control programs to combat antibiotic resistance in healthcare settings. To address the study’s objectives, it is recommended to develop targeted antibiotic stewardship programs that align with local resistance patterns, enhance surveillance systems to monitor ESBL-producing bacteria, and implement stringent infection control protocols in healthcare settings. Additionally, launching educational initiatives for healthcare professionals and the public, promoting research on resistance mechanisms, and collaborating with public health authorities will ensure that findings inform evidence-based policies. Finally, fostering multidisciplinary approaches will help create comprehensive strategies for effectively managing antibiotic resistance at both local and global levels.