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

BACKGROUND: Optimal ß-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 ß-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. ß-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, ß-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 ß-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.

Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study.

INTRODUCTION: Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. METHODS: This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. RESULTS: Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1-q3) age was 70 (62-79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00-1.05), septic shock (aHR = 1.93, 95% CI 1.05-3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11-5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25-0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27-0.98). CONCLUSIONS: Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.