AACP Grant Supports Sofjan's Study of Potential Change in Common, But Serious Infection in Cirrhosis Patients

A UH College of Pharmacy researcher is investigating whether an epidemiological shift in the pathogens responsible for a common but serious bacterial infection in patients with liver cirrhosis has taken root in the U.S., which could trigger a significant change in the national therapeutic guidelines.

Supported by a $10,000 New Investigator Award from the American Association of Colleges of Pharmacy, Clinical Assistant Professor Amelia Sofjan, Pharm.D., BCPS, is conducting a retrospective epidemiological study to determine if there has been a change in the types of bacteria that cause a complication called spontaneous bacterial peritonitis (SBP) in patients with end-stage liver disease.

"Spontaneous bacterial peritonitis is an infection of the ascitic fluid produced as a result of liver failure and is traditionally identified by laboratory analysis of the fluid following paracentesis (draining of the ascitic fluid)," Sofjan said. "SBP most commonly manifests in fever, changes in mental status, abdominal pain and discomfort."

The complication is diagnosed in one of four cirrhotic patients hospitalized with bacterial infections, with 30-day mortality rates ranging from one-quarter to one-half of patients. The most common pathogens implicated in SBP have been Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae, with older guidelines recommending treatment with a third-generation cephalosporin antibiotic such as ceftriaxone in patients with SBP.

However, recent studies in Europe, Canada, and Asia have identified an increase in ceftriaxone-resistant pathogens among SBP patients. These findings recently have generated a more cautious approach from the American Association for the Study of Liver Disease (AASLD), which is one of the primary bodies that publishes guideline recommendations for SBP management to U.S. clinicians.

The revised AASLD guidelines now recommend the use of the third-generation cephalosporins as first-line therapy only for those patients with community-acquired SBP who were not previously exposed to broad-spectrum beta-lactam antibiotics. Yet, the AASLD has made not specific treatment recommendations for hospital-associated or hospital-acquired SBP and suggests that empirical therapy is based on local epidemiology. This study aims to provide the local epidemiological data needed to appropriately select alternative empirical therapy.

"There have only been two small studies in the U.S. which assessed the prevalence of ceftriaxone-resistant pathogens in SBP patients, but the rates were significant," Sofjan said. "Although our sample size will be relatively small, it should represent the largest study undertaken thus far in the U.S. Depending on the results of this project, it may warrant further, larger-scale multicenter studies to determine the prevalence of ceftriaxone-resistant pathogens in the U.S.

"Our project will not only identify the ceftriaxone-resistant pathogens, but also the risk factors for developing SBP from these resistant organisms and predictors of patient outcomes. The goal is to develop a prediction score model for ceftriaxone-resistant organisms in cirrhotic patients with SBP and to create an empirical treatment algorithm for these patients."