A study today in JAMA Internal Medicine casts doubt on the recommendation for routine preventive (prophylactic) antibiotics for upper-gastrointestinal (GI) bleeding in patients with cirrhosis.
Current guidelines for patients with cirrhosis and upper-GI bleeding recommend 5 to 7 days of antibiotic prophylaxis to prevent bacterial infections and associated complications. But the evidence for the recommendation is limited, and recent data have raised questions about the need to reassess the practice.
To determine whether the current evidence continues to support the recommendation, or whether shorter or even no antibiotic prophylaxis may be acceptable, researchers from McGill University Health Centre and the University of Southern California conducted a systematic review and meta-analysis of 14 randomized controlled trials (RCTs) involving 1,322 patients. The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleed and bacterial infections.
Shorter durations likely to be noninferior
Of the 14 RCTs included in the analysis, two compared longer (5 to 7 days) with shorter (2 to 3 days) antibiotics and 10 compared any antibiotic prophylaxis (1 to 10 days) to none. Overall, shorter antibiotic durations (including none) had a 97.3% probability of noninferiority to longer durations for all-cause mortality (RD, 0.9%; 95% credible interval [CrI], –2.6% to 4.9%).
Shorter durations had only a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, −4.2% to 10.0%) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0% to 25.9%), though the study authors argue that there are methodological concerns about the definitions of these infections in the included studies. The probabilities of noninferiority of shorter durations for all three outcomes were higher in studies published after 2004.
"Our findings re-open the discussion surrounding the long-standing and firmly-held belief that antibiotic prophylaxis has a mortality benefit in patients with cirrhosis presenting with upper gastrointestinal bleeds," the study authors wrote.
The authors add that the evidence base was of low to moderate quality, "underscoring the evidence limitations on which current guideline recommendations are made."
"Until additional studies are completed, clinicians should be aware that the existing guideline recommendations are based on low to moderate quality evidence that when aggregated does not support the present recommendations," they concluded.
In an accompanying commentary, experts from Yale School of Medicine say management of upper GI bleeding in cirrhosis patients has improved greatly since the 1990s, when some of the trials included in the analysis were conducted, and that it now may be time to revisit whether prophylactic antibiotics continue to provide benefit. They say new trials for shorter duration and no antibiotic prophylaxis "should be designed in specific patient populations to compare sequelae of antibiotic prophylaxis, including subsequent infections and all-cause mortality."
