The role of extended infusion β-lactams in the treatment of bloodstream infections in patients with liver cirrhosis.

Bloodstream infections (BSIs) in patients with liver cirrhosis are associated with significant morbidity and mortality. Early appropriated antibiotic treatment is essential for the correct management of these patients. Areas covered: This review covers several aspects of how the pharmacokinetic/pharmacodynamic behavior of antimicrobials may change in patients with liver cirrhosis. Common features of cirrhosis, including hypoproteinemia, third space expansion and impairment of renal function may alter drug distribution in patients receiving hydrophilic drugs like β-lactams, which are often frontline agents. β-lactams exhibit time-dependent pharmacodynamics and achieve maximal bacterial killing when serum drug and tissue concentrations exceed a multiple of the minimal inhibitory concentration (MIC) during the dosing interval (%fT>MIC). Administration of β-lactams by extended infusion strategies improves the rate of this pharmacodynamic target attainment and has been associated with improved outcomes in several randomized trials in critically-ill patients. Expert commentary: Observational studies have suggested that cirrhotic patients have improved outcomes when beta-lactam therapy is administered by extended or continuum infusion. Given the multiple pathophysiological features of liver cirrhosis that impact antimicrobial behavior and the high incidence of multidrug resistance in this population, additional studies are needed to understand how cirrhosis affects the pharmacokinetics and pharmacodynamics of antibacterial therapy.