Beta-lactam target attainment and associated outcomes in patients with bloodstream infections

Objectives: To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI).Methods: Adult patients who received cefepime, meropenem, or piperacillin/tazobactam for BSI and had concentrations measured were included. Beta-lactam exposure was generated and the time that free concentration remained above the minimum inhibitory concentration ( f T , MIC ) and four multiples of MIC ( f T , 4 xMIC ) were calculated for times 0-24 h and 0-7 days of therapy. Multiple regression analysis was performed to evaluate the impact of PK/PD on microbiological and clinical outcomes.Results: A total of 204 patients and 213 BSI episodes were included. The mean age was 58 years and weight 83 kg. Age, Sequential Organ Failure Assessment (SOFA) score, haemodialysis, Pitt bacteraemia score, and hours of empiric antibiotic therapy were significantly associated with certain outcomes and retained in the final model. In multiple regression analysis, f T , 4 xMIC at 0-24 h and 0-7 days was a significant predictor of negative blood culture on day 7 ( P = 0.0161 and 0.0068, respectively). In the timeto-event analysis, patients who achieved 100% f T , 4 x MIC at 0-24 h and 0-7 day s had a shorter time t o negative blood culture compared with those who did not (log-rank P = 0.0 0 04 and 0.0 014, respectively). No significant associations were identified between PK/PD parameters and other outcomes, including improvement in symptoms at day 7 and 30-day mortality.Conclusion: Early and cumulative achievement of f T , 4 xMIC was a significant predictor of microbiological outcome in patients with BSI.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

The aim of this study was to evaluate the association between early and cumulative β-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI). Multiple regression analysis revealed that achieving a higher percentage of free concentration above the four times the minimum inhibitory concentration (fT/4 xMIC ) at both 0-24 hours and 0-7 days significantly predicted negative blood culture results on day 7.