Laboratory-based surveillance of antimicrobial non-susceptibility in Enterobacter species over 12 years at a tertiary-care hospital in Saudi Arabia

BACKGROUND: Enterobacter species are increasingly associated with antimicrobial non-susceptibility, but long-term surveillance of temporal trends across antibiotic classes is limited in southern Saudi Arabia. METHODS: We retrospectively studied non-duplicate Enterobacter isolates from adults at a tertiary-care hospital in southern Saudi Arabia (August 2012-August 2024), interpreted by contemporaneous CLSI criteria. Temporal trends were modelled by logistic regression as the annual percent change (APC) in the odds of non-susceptibility, adjusted for care setting, specimen source, age, and sex. Carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistance (DTR; Kadri criteria) were analysed over time; sensitivity analyses excluded partial years and used breakpoint-comparable periods. RESULTS: Of 1,319 Enterobacter isolates, 91.8% belonged to the Enterobacter cloacae complex. Adjusted trends declined for amikacin (APC -6.1%), gentamicin (-9.4%) and cefepime (-9.1%) and rose for carbapenems (+13.1% to +15.8%), levofloxacin (+6.3%) and piperacillin-tazobactam (+7.0%), with ciprofloxacin stable. The levofloxacin and piperacillin-tazobactam increases did not persist in breakpoint-comparable analyses and are not unequivocal biological increases. Inpatient isolates were more non-susceptible than outpatient isolates by approximately 16-39 percentage points (gentamicin 31.7% vs 14.8%; piperacillin-tazobactam 38.7% vs 23.1%; cefotaxime 63.9% vs 41.5%; cefepime 45.7% vs 28.8%; ceftazidime 61.4% vs 35.3%; ceftriaxone 57.4% vs 18.8%; all p ≤ 0.003). CRE rose early and remained common (APC + 22.8%; 28.7% overall), whereas DTR rose later and stayed infrequent (7.5% of eligible isolates; APC + 16.4%; highest annual value 20.2% in 2023); this difference in timing and overall frequency, not the partially sampled year 2024, indicates dissociation between carbapenem non-susceptibility and loss of all first-line agents. CONCLUSION: Non-susceptibility among Enterobacter species was heterogeneous and antibiotic-specific. The dissociation between CRE and DTR in timing and overall frequency supports using clinically meaningful phenotypes alongside antibiotic-specific trend analysis for stewardship and reporting; the levofloxacin and piperacillin-tazobactam increases warrant caution, as they did not persist in breakpoint-comparable analyses.