Sixteen-Year Trends in Antimicrobial Resistance among Enterobacteriaceae Causing Bloodstream Infections in a Tertiary Teaching Hospital in Iran: A Joinpoint Regression Analysis

Background Bloodstream infections caused by Enterobacteriaceae are an important global health concern, particularly in the context of increasing antimicrobial resistance. Long-term surveillance is essential in regions where systematic longitudinal data are limited. This study investigated 16-year trends in antimicrobial resistance among Enterobacteriaceae causing BSIs in a tertiary referral setting in southern Iran. Methods We retrospectively analyzed non-duplicate Enterobacteriaceae blood-culture isolates collected from March 2010 through December 2025 at the Professor Alborzi Clinical Microbiology Research Center, affiliated with Shiraz University of Medical Sciences. Species identification and antimicrobial susceptibility testing were performed using conventional microbiological methods according to CLSI criteria applicable to each study year. Resistance data were analyzed using WHONET 5.6. Temporal trends were evaluated using Joinpoint regression analysis, to identify significant changes in resistance trajectories. Results Among 3,860 isolates, Escherichia coli (38.1%), Klebsiella spp. (30.0%), and Enterobacter spp. (19.0%) were predominant. Overall resistance was highest to ampicillin (93.1%), followed by amoxicillin–clavulanic acid (80.7%), tetracycline (73.8%), cefuroxime (71.3%), and third-generation cephalosporins (64.1%). Extended-spectrum β-lactamase production was detected in 64.0% of isolates. Carbapenem resistance was 25.6% overall and reached 44.7% in 2025. Joinpoint analysis demonstrated significant changes in species distribution, including a decline in E. coli from 2010 to 2020 (APC − 6.14%, P = 0.01), an increase in Klebsiella spp. from 2010 to 2016 (APC 9.68%, P = 0.01), and a subsequent increase from 2019 to 2025 (APC 10.50%, P = 0.02). Species-specific resistance trends included significant increases in resistance to multiple agents among Klebsiella spp., a significant increase in imipenem resistance among Enterobacter spp., and an increasing trend in cefuroxime resistance across Enterobacteriaceae. In contrast, resistance to trimethoprim–sulfamethoxazole, tobramycin, gentamicin, and chloramphenicol declined significantly among E. coli . Conclusions Enterobacteriaceae causing BSIs showed persistently high resistance to commonly used antimicrobials, particularly β-lactams, accompanied by a high prevalence of ESBL production and increasing carbapenem resistance. Joinpoint regression identified heterogeneous temporal patterns across species and antimicrobial agents that may not be evident from overall resistance estimates alone. Sustained microbiological surveillance and strengthened antimicrobial stewardship are warranted to monitor evolving resistance and inform empirical treatment strategies.