Evaluating the Role of Antibiotics in Patients Admitted to Hospital With Decompensated Cirrhosis: Lessons From the ATTIRE Trial

Abstract

Hospital-acquired infections (HAI) are common in cirrhosis with antibiotics frequently used to prevent infections, but their efficacy for this role is unknown. To investigate this, we used Albumin to Prevent Infection in Chronic Liver Failure (ATTIRE) data to evaluate whether antibiotic use in patients without infection prevented HAI. METHODS:In ATTIRE patients without infection at baseline grouped by antibiotic prescription or not, we studied HAI during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. RESULTS:Two hundred three of 408 patients prescribed antibiotics at enrollment did not have infection and they were more unwell than noninfected patients not given antibiotics. There were no differences in subsequent HAI comparing antibiotic treated (39/203, 19.2%) to nonantibiotic treated (73/360, 20.3%; P 5 0.83). Twenty-eight-day mortality was higher in antibiotic-treated patients (P 5 0.004) likely reflecting increased disease severity. Matching groups using propensity scoring revealed no differences in HAI or mortality. In noninfected patients at enrollment treated with/without rifaximin, there were no differences in HAI (P 5 0.16) or mortality, confirmed with propensity matching. Patients given long-term antibiotic prophylaxis at discharge had no differences in 6-month mortality compared with nonantibiotic patients, although antibiotic-treated patients had more infections at trial entry, with numbers too small for matching. DISCUSSION:Half of antibiotics at study entry were given to patients without an infection diagnosis which did not reduce the overall risk of HAI or improve mortality. This supports prompt de-escalation or discontinuation of antibiotics guided by culture sensitivities at 24-48 hours after commencement if no infection and the patient is improving.

The Role of Prophylactic Antibiotics for Patients With Severe Alcohol-Related Hepatitis

“…The current clinical trial by Louvet et al suggests no role for prophylactic prescription of antibiotics when treating all patients who have alcohol-related hepatitis with corticosteroids . This finding was similar to observations from a post hoc analysis of hospitalized patients with decompensated cirrhosis in the ATTIRE clinical trial, many of whom had alcohol-related liver disease . In this study, prescription of antibiotics in 777 patients hospitalized with decompensated cirrhosis without documented infection did not improve survival compared with those who did not receive antibiotics .…”

“…This finding was similar to observations from a post hoc analysis of hospitalized patients with decompensated cirrhosis in the ATTIRE clinical trial, many of whom had alcohol-related liver disease . In this study, prescription of antibiotics in 777 patients hospitalized with decompensated cirrhosis without documented infection did not improve survival compared with those who did not receive antibiotics . For patients with alcohol-related hepatitis, developing infection while taking corticosteroids is an indicator of poor prognosis and should be treated .…”

“…12 In this study, prescription of antibiotics in 777 patients hospitalized with decompensated cirrhosis without documented infection did not improve survival compared with those who did not receive antibiotics. 12 For patients with alcohol-related hepatitis, developing infection while taking corticosteroids is an indicator of poor prognosis and should be treated. 13 This may be particularly relevant for patients without a Lille score biochemical response to corticosteroids, since these patients have an increased rate of infection compared with those with a biochemical response (42.5% vs 11.1% in responders; P < .001).…”

In search of a roadmap towards improving care of patients with cirrhosis and ascites, could a platform trial design transform clinical research?

“…This emphasises the need to reduce unnecessary antibiotic prescriptions to prevent these life-saving drugs becoming ineffective. Further analyses of the ATTIRE patients not considered by their clinicians to have an infection revealed no differences in subsequent HAI comparing antibiotic treated to nonantibiotic treated (approximately 20% for both) ( 4 , 5 ). Twenty-eight-day mortality was significantly higher in antibiotic-treated patients, likely reflecting their increased disease severity and when we matched groups using propensity scoring, there were no differences in HAI or mortality.…”

Challenges and recommendations when selecting empirical antibiotics in patients with cirrhosis

“…Given the high incidence and severe impact of bacterial infections in patients with cirrhosis, it is likely that antibiotics are overused in this population. In fact, a recent sub-analysis of the ATTIRE clinical trial suggested that half of the antibiotics prescribed to hospitalized patients with decompensated cirrhosis might not be necessary[ 43 ].…”