Multidrug Resistance, Antimicrobial Therapy, and In-Hospital Mortality in Patients with Healthcare-Associated Infections: A Retrospective Cohort Study

Background: Healthcare-associated infections (HAIs), particularly those caused by antimicrobial-resistant pathogens, remain an important cause of adverse outcomes among hospitalized patients. The combined contribution of antimicrobial resistance, clinical characteristics, and antimicrobial treatment to mortality requires further evaluation. This study aimed to investigate factors associated with in-hospital mortality among patients with HAIs, with particular emphasis on multidrug resistance (MDR) and post-culture antimicrobial treatment. Methods: We conducted a retrospective observational cohort study that included 192 patients with 242 documented HAI episodes in a hospital in Târgu-Mureș, Romania. Demographic and clinical characteristics, invasive procedures, microbiological findings, antimicrobial resistance phenotypes, antimicrobial exposure, and in-hospital outcome were evaluated. Comparisons between survivors and non-survivors were performed using the Mann–Whitney U test, Pearson’s chi-square test, or Fisher’s exact test, as appropriate. Factors associated with in-hospital mortality were investigated using univariable and multivariable logistic regression. Results: Overall, 161/192 patients (83.9%) died during hospitalization. Non-survivors were significantly older than survivors [median: 71 (IQR: 62–78) vs. 62 (50.5–72) years; p = 0.025]. MDR organisms were more common among non-survivors (51.6% vs. 22.6%; p = 0.003), and MDR phenotype was associated with increased odds of mortality in univariable analysis (OR = 3.65, 95% CI: 1.49–8.95; p = 0.005). After adjustment for age, mechanical ventilation, and recent surgery, MDR remained independently associated with in-hospital mortality (aOR = 3.58, 95% CI: 1.42–8.98; p = 0.007). In the treatment-focused model, aminopenicillin exposure (aOR = 0.21, 95% CI: 0.07–0.64; p = 0.006), second-generation aminoglycosides (aOR = 0.23, 95% CI: 0.06–0.97; p = 0.045), and third-generation cephalosporins (aOR = 0.35, 95% CI: 0.14–0.88; p = 0.025) were associated with lower odds of mortality. No significant association was observed between time to specific antimicrobial therapy and mortality (p = 0.541). Conclusions: MDR was the main antimicrobial-resistance factor independently associated with in-hospital mortality among patients with HAIs. Although several antimicrobial classes were associated with lower odds of death, these observational associations should not be interpreted as causal treatment effects. The findings emphasize the importance of antimicrobial resistance surveillance, rapid microbiological diagnosis, antimicrobial stewardship, and timely access to active antimicrobial therapy.