Antibiotic prophylaxis for prevention of bacterial infections and death in cirrhotic patients with upper gastrointestinal bleeding

Patients with liver cirrhosis have an impaired immune response. Often, liver cirrhosis patients experience complications from portal hypertension, such as gastroesophageal varices. These varices can bleed, increasing the risk of infection and death in a short period of time, despite proper endoscopic management. Patients who develop bacterial infections during hospitalisation for gastroesophageal haemorrhage are at increased risk of dying. Twelve trials (1241 patients) assessing several antibiotic prophylaxis regimens versus no intervention or placebo were analysed, showing that antibiotic prophylaxis successfully reduced the incidence of bacterial infections. Antibiotic prophylaxis was also associated with a reduction in mortality, mortality from bacterial infections, rebleeding rate, and days of hospitalisation. The prophylactic treatment was not associated with important adverse effects. Five trials (650 patients) assessed one antibiotic regimen compared with another. All antibiotic regimens provided similar benefits and none seemed superior. Thus, to this point there is no evidence to recommend one specific antibiotic regimen over the other. All trials analysed were subject to bias; thus, results should be interpreted carefully.

Authors' conclusions: 

Prophylactic antibiotic use in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and seems to have reduced all-cause mortality, bacterial infection mortality, rebleeding events, and hospitalisation length. These benefits were observed independently of the type of antibiotic used; thus, no specific antibiotic can be preferred. Therefore, antibiotic selection should be made considering local conditions such as bacterial resistance profile and treatment cost.

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Background: 

Bacterial infections are a frequent complication in patients with cirrhosis and upper gastrointestinal bleeding. Antibiotic prophylaxis seems to decrease the incidence of bacterial infections. Oral antibiotics, active against enteric bacteria, have been commonly used as antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding. This is an update of a Cochrane review first published in 2002.

Objectives: 

To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with upper gastrointestinal bleeding.

Search strategy: 

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index EXPANDED until June 2010. In addition, we handsearched the references of all identified studies.

Selection criteria: 

Randomised clinical trials comparing different types of antibiotic prophylaxis with no intervention, placebo, or another antibiotic to prevent bacterial infections in cirrhotic patients with upper gastrointestinal bleeding.

Data collection and analysis: 

Three authors independently assessed trial quality, risk of bias, and extracted data. We contacted study authors for additional information. Association measures were relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes.

Main results: 

Twelve trials (1241 patients) evaluated antibiotic prophylaxis compared with placebo or no antibiotic prophylaxis. All trials were at risk of bias. Antibiotic prophylaxis compared with no intervention or placebo was associated with beneficial effects on mortality (RR 0.79, 95% CI 0.63 to 0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19 to 0.97), bacterial infections (RR 0.36, 95% CI 0.27 to 0.49), rebleeding (RR 0.53, 95% CI 0.38 to 0.74), days of hospitalisation (MD -1.91, 95% CI -3.80 to -0.02), bacteraemia (RR 0.25, 95% CI 0.15 to 0.40), pneumonia (RR 0.45, 95% CI 0.27 to 0.75), spontaneous bacterial peritonitis (RR 0.29, 95% CI 0.15 to 0.57), and urinary tract infections (RR 0.23, 95% CI 0.12 to 0.41). No serious adverse events were reported. The trials showed no significant heterogeneity of effects. Another five trials (650 patients) compared different antibiotic regimens. Data could not be combined as each trial used different antibiotic regimen. None of the examined antibiotic regimen was superior to the control regimen regarding mortality or bacterial infections.