The Impact of Early Empirical Antibiotic Therapy on the Mortality of Bacteremia Patients with Klebsiella Infection: A Retrospective Cohort Study

<b>Background:</b><i>Klebsiella</i> species are a leading cause of Gram-negative bacteremia associated with nosocomial infections. They exhibit higher antimicrobial resistance compared to other Enterobacterales, emphasizing their role as a "sentinel organism". While the impact of inappropriate empiric therapy has been studied, data specific to <i>Klebsiella</i> bacteremia are limited due to small sample sizes. This study aims to provide high-resolution data on <i>Klebsiella</i> bacteremia and assess the impact of appropriate empirical therapy on clinical outcomes. <b>Methods:</b> We conducted a retrospective study of patients with <i>Klebsiella</i> bacteremia hospitalized at Beilinson Hospital between 2012 and 2022. Patients were categorized into two groups based on the appropriateness of empiric therapy. The primary outcome was 30-day all-cause mortality; subgroup analyses evaluated mortality in ESBL bacteremia treated with either carbapenems or piperacillin-tazobactam, and carbapenems versus aminoglycosides. Propensity score weighting and inverse probability treatment-weighted models were used to adjust for confounding. <b>Results:</b> Among 1132 patients, 79% received appropriate empirical therapy. This therapy was associated with reduced 30-day mortality (OR = 0.59, 95% CI: 0.46-0.76) and a shorter hospital stay (median 7 vs. 11 days, <i>p</i> < 0.001). Other significant risk factors for mortality included a higher Charlson comorbidity score (OR = 1.06), assistance with ADL (OR = 2.16), prior hospitalization (OR = 1.31), and a higher SOFA score (OR = 1.32). No significant mortality differences were observed in ESBL subgroups treated with carbapenems versus piperacillin-tazobactam (<i>p</i> = 0.2) or carbapenems versus aminoglycosides (<i>p</i> = 0.9). <b>Conclusions:</b> Early appropriate empirical therapy significantly reduces 30-day mortality in <i>Klebsiella</i> bacteremia. These findings highlight the importance of timely, appropriate empirical therapy and suggest choosing less broad-spectrum therapy. However, the lack of molecular data on resistance mechanisms limits the ability to assess strain-specific outcomes and may affect generalizability. Despite this, the study offers valuable insights for optimizing empirical therapy and advancing antimicrobial stewardship in the era of rising resistance.