Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study

Abstract

Background We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). Methods The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. Results Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11–0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9–32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06–0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03–0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08–0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06–2.47]). Conclusions C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

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“…Moreover, two recent meta-analyses have shown an association between prolonged infusion of BLA and lower mortality rates [10,11]. Similar results have also been observed in a non-randomised prospective study in cirrhotic patients with bloodstream infections, in whom prolonged infusion of BLA was associated with improved survival [12]. Nevertheless, earlier studies addressing this issue have mainly focussed on the general non-severely immunocompromised population.…”

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“…12,53,83 A recent prospective multicentre study in patients with cirrhosis and BSI showed that a loading dose followed by continuous infusion of b-lactams improves 30-day survival compared to traditional dosing schedules. 84 Most high-dose antibiotic strategies are off label and their safety profile needs to be proven in patients with cirrhosis.…”