Association of prompt phenotype-desirable antimicrobial therapy with short-term mortality and hospital-onset Clostridioides difficile infection among adults with community-onset bacteraemia.

BACKGROUND

Phenotype-desirable antimicrobial therapy (PDAT) has recently been proposed to improve prognosis in patients with Enterobacterales bacteraemia. However, focusing on overall bacteraemia, the association of prompt PDAT with short-term mortality and the risk of hospital-onset Clostridioides difficile infection (hCDI) remains uncertain.

METHODS

Among treatment-naïve adults with community-onset bacteraemia, clinical variables were retrospectively collected. Etiologic pathogens were prospectively preserved to accurately determine the timepoints of effective antimicrobial therapy and PDAT initiation. After stratifying patients into four groups by PDAT delays (<2.0 d, 2.0-5.9 d, ≥6.0 d, and no PDAT), a time-dependent Cos-regression model was used to investigate the association of prompt PDAT with 30-d crude mortality and hCDI development, after, respectively adjusting for the independent predictors identified.

RESULTS

Of the total 3815 patients, with the no-PDAT group (n = 195) as the reference, patients with PDAT delays of <2.0 d (n = 1819), 2.0-5.9 d (n = 1197), and ≥6 d (n = 604) were at significantly reduced risks of 30-d mortality and hCDI. For these categories, adjusted hazard ratios for 30-d mortality were 0.32, 0.35, and 0.63, respectively, and those for hCDI were 0.03, 0.19, and 0.44, respectively. Across all subgroups, prompt PDAT was consistently associated with reduced risks of 30-d mortality and hCDI development.

CONCLUSIONS

Prompt PDAT was associated with reduced risks of short-term mortality and hCDI. These findings highlight the indispensability of the timely administration of pathogen-targeted narrow-spectrum antimicrobials, particularly in high-risk patients, and support the integration of this strategy into antimicrobial stewardship programmes.