Published online Nov 27, 2023. doi: 10.4254/wjh.v15.i11.1226
Peer-review started: July 8, 2023
First decision: August 15, 2023
Revised: September 5, 2023
Accepted: October 23, 2023
Article in press: October 23, 2023
Published online: November 27, 2023
Processing time: 138 Days and 13.3 Hours
Rifaximin is frequently administered to critically ill patients with liver disease and hepatic encephalopathy, but patients currently or recently treated with antibiotics were frequently excluded from studies of rifaximin efficacy. Due to overlapping spectrums of activity, combination therapy with broad-spectrum antibiotics and rifaximin may be unnecessary. A pharmacist-driven protocol was piloted to reduce potentially overlapping therapy in critically ill patients with liver disease. It was hypothesized that withholding rifaximin during broad-spectrum antibiotic therapy would be safe and reduce healthcare costs.
To determine the clinical, safety, and financial impact of discontinuing rifaximin during broad-spectrum antibiotic therapy in critically ill liver patients.
This was a single-center, quasi-experimental, pre-post study based on a pilot pharmacist-driven protocol. Patients in the protocol group were prospectively identified via the medical intensive care unit (ICU) (MICU) protocol to have rifaximin withheld during broad-spectrum antibiotic treatment. These were compared to a historical cohort who received combination therapy with broad-spectrum antibiotics and rifaximin. All data were collected retrospectively. The primary outcome was days alive and free of delirium and coma (DAFD) to 14 d. Safety outcomes included MICU length of stay, 48-h change in vasopressor dose, and ICU mortality. Secondary outcomes characterized rifaximin cost savings and protocol adherence. Multivariable analysis was utilized to evaluate the association between group assignment and the primary outcome while controlling for potential confounding factors.
Each group included 32 patients. The median number of delirium- and coma-free days was similar in the control and protocol groups [3 interquartile range (IQR 0, 8) vs 2 (IQR 0, 9.5), P = 0.93]. In multivariable analysis, group assignment was not associated with a reduced ratio of days alive and free of delirium or coma at 14 d. The protocol resulted in a reduced median duration of rifaximin use during broad-spectrum antibiotic therapy [6 d control (IQR 3, 9.5) vs 1 d protocol (IQR 0, 1); P < 0.001]. Rates of other secondary clinical and safety outcomes were similar including ICU mortality and 48-h change in vasopressor requirements. Overall adherence to the protocol was 91.4%. The median estimated total cost of rifaximin therapy per patient was reduced from $758.40 (IQR $379.20, $1200.80) to $126.40 (IQR $0, $126.40), P < 0.01.
The novel pharmacist-driven protocol for rifaximin discontinuation was associated with significant cost savings and no differences in safety outcomes including DAFD.
Core Tip: Critically ill patients with liver disease receiving broad-spectrum antibiotic therapy have been frequently excluded from clinical trials of rifaximin efficacy. Therefore, despite overlapping spectrums of antibacterial activity, it is not known if rifaximin provides additional clinical benefit in these patients. In this study, pharmacist-guided rifaximin discontinuation during broad-spectrum antibiotic therapy resulted in significant cost savings and was not associated with negative short-term cognitive effects or adverse events.