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

## TL;DR

This study shows that starting the right antibiotics early improves survival in patients with Klebsiella bloodstream infections.

## Contribution

Provides high-resolution data on Klebsiella bacteremia outcomes based on early empirical therapy appropriateness.

## Key findings

- Appropriate empirical therapy reduced 30-day mortality (OR = 0.59) and shortened hospital stays.
- No significant mortality differences were found between carbapenems and piperacillin-tazobactam or aminoglycosides in ESBL subgroups.
- Higher comorbidity scores and prior hospitalization increased mortality risk.

## Abstract

Background: Klebsiella 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 Klebsiella bacteremia are limited due to small sample sizes. This study aims to provide high-resolution data on Klebsiella bacteremia and assess the impact of appropriate empirical therapy on clinical outcomes. Methods: We conducted a retrospective study of patients with Klebsiella 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. Results: 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, p < 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 (p = 0.2) or carbapenems versus aminoglycosides (p = 0.9). Conclusions: Early appropriate empirical therapy significantly reduces 30-day mortality in Klebsiella 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.