Antibiotic dosing in cirrhosis

Abstract

Purpose: Published evidence regarding the influence of cirrhosis on the clinical pharmacokinetics of antibacterial agents is reviewed; dosing recommendations and a decision algorithm are provided.

Summary: A systematic PubMed search (1960-2013) was conducted to identify literature pertaining to the use of antibacterials with hepatobiliary clearance in adult patients with cirrhosis. Clinical drug databases, conference abstracts, and package inserts were also reviewed for pertinent information. Twenty-two antibiotics that undergo hepatic or mixed renal-hepatobiliary clearance were identified. Overall, published pharmacokinetic data to guide antibiotic dosing in adults with cirrhosis are sparse, and many relevant studies were conducted before wide adoption of the Child-Pugh method for classifying the severity of cirrhosis. Dose adjustments should be considered in the setting of decompensated liver disease, particularly with antibiotics that undergo phase I metabolism, have high protein binding, or are associated with a high frequency of hepatotoxicity or other concentration-dependent toxicities. Individualization of dosing regimens should take into account a number of variables: the intent of therapy (treatment versus prophylaxis); the duration of therapy; the site and severity of infection; the degree of organ dysfunction, as indicated by Child-Pugh class; the patient's immune status, weight, and fluid status; and the pharmacokinetic and pharmacodynamic properties of the antibacterial agents under consideration.

Conclusion: Cirrhosis has multiple effects on the disposition of a wide range of antibacterial agents. Appropriate antibiotic therapy selection and individualized dosing can contribute to optimal clinical outcomes while decreasing the risk of hepatotoxicity.