Loading dose plus continuous/extended infusion versus intermittent bolus of β-lactams for the treatment of Gram-negative bacteria bloodstream infections: a propensity score-adjusted retrospective cohort study

Background Optimal & beta;-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated. Methods This is a retrospective observational study enrolling patients with GNB-BSIs treated with & beta;-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model. Results Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. & beta;-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, & beta;-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011). Conclusions The use of LD + EI/CI of & beta;-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.

Automated summary

This study compared the efficacy and safety of a loading dose followed by extended/continuous infusion (EI/CI) and intermittent bolus (IB) of β-lactam drugs for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs). The results showed that the LD + EI/CI regimen was associated with a lower mortality rate, especially in severely immunocompromised patients, patients with a higher severity of infection, and patients with septic shock.