Hospital-Based Surveillance of Klebsiella pneumoniae and Other Klebsiella species in Southern Saudi Arabia (2012–2024): Escalating Carbapenem and DTR Resistance with Species-Specific Phenotypes and Genotypes

Background: Klebsiella species, particularly Klebsiella pneumoniae , are major healthcare-associated infections showing increasing resistance to carbapenems and other antibiotics. In Saudi Arabia, rising antimicrobial resistance (AMR) and the emergence of difficult-to-treat resistance (DTR) phenotypes pose significant clinical challenges. Methods: A 12-year retrospective surveillance study (2012– 2024) of 9790 non-duplicate Klebsiella isolates from Aseer Central Hospital in southern Saudi Arabia. Species-level identification, antimicrobial susceptibility testing for each isolate was done. Molecular characterization of carbapenemase genes for selected isolates were performed. Temporal resistance trends were assessed using logistic regression. Results: K. pneumoniae accounted for 93.0% of isolates, with non-pneumoniae species showing distinct resistance profiles. Carbapenem resistance surged from 12.4% in 2012 to 69.3% in 2021, while DTR prevalence rose to 50.7%. ICU and inpatient settings exhibited the highest resistance rates. Molecular testing revealed widespread bla_OXA-48-like (35.7%), bla_NDM (17.9%), and emerging bla_KPC (14.3%) genes, with 25% of isolates co-harboring multiple carbapenemases. Progression from colonization to bloodstream infection occurred in 1.7% of K. pneumoniae cases, primarily from respiratory and urinary sources. Conclusion: This study highlights escalating carbapenem and DTR resistance among Klebsiella species in southern Saudi Arabia, driven by species-specific mechanisms and widespread carbapenemase gene dissemination. Findings underscore the need for species-level diagnostics, expanded molecular surveillance, and integrated stewardship strategies to curb the spread of multidrug-resistant Klebsiella . Keywords: Klebsiella pneumoniae , carbapenem-resistant enterobacterales, difficult-to-treat resistance, antimicrobial resistance surveillance, carbapenemase genes, Saudi Arabia