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Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
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 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%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“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,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
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,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
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 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%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“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,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
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,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.
Pooled data from 14 randomized controlled trials (RCTs) found a high probability that no or shorter durations of antibiotic prophylaxis are not worse than longer durations in preventing death from any cause in these patients.
The findings suggest that recommendations for routine antibiotic prophylaxis in patients with cirrhosis and upper GI bleeding “should be reassessed,” the authors said.
They acknowledged, however, that the studies were of low-to-moderate quality and higher quality randomized clinical trial data are needed.
The study, with first author Connor Prosty, MD, of McGill University, in Montreal, Quebec, Canada, was published online in JAMA Internal Medicine.
Questionable Benefit?
Antibiotic prophylaxis became standard decades ago, when up to 60% of variceal bleeds were complicated by infections, which were thought to increase the risk for rebleeding and death.
Yet, the evidence to support the recommendation remains limited, and a recent RCT called into question the necessity of prophylaxis. The study showed no statistically significant difference in mortality or infection among patients with Child-Pugh class A cirrhosis randomized to receive no prophylaxis compared to third-generation cephalosporin.
While generally perceived as safe, antibiotics have potential adverse effects and can select for resistant superinfections, Prosty and colleagues pointed out.
They also noted that shorter courses of antibiotics have been proven to be as good, if not better, than longer courses across numerous other infectious indications. Recommendations for primary and secondary antibiotic prophylaxis for spontaneous bacterial peritonitis are being reassessed due to a weak evidence base, lack of mortality benefit, and potential for harm.
To revisit antibiotic prophylaxis for upper GI bleeding in patients with cirrhosis, Prosty and colleagues did a systematic review and meta-analysis of 14 RCTs involving 1322 patients.
Two of the trials compared longer (5-7 days) with shorter (2-3 days) antibiotics, and 12 compared any antibiotic prophylaxis (1-10 days) to none.
The primary outcome was all-cause mortality, with a prespecified noninferiority margin of 5% on the risk difference (RD) scale. Secondary outcomes included early rebleeding and bacterial infections.
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 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%-25.9%). However, the authors cited methodological concerns about the definitions of these infections in the included studies.
The probabilities of noninferiority of shorter durations for mortality, early rebleeding, and bacterial infections were higher in studies published after 2004.
Change Practice Now?
“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,” Prosty and colleagues wrote.
They cautioned, however, that the study quality was “low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions.”
The authors of a commentary published with the study noted that management of upper GI bleeding in cirrhosis patients has “greatly improved” since the 1990s, when some of the trials included in the analysis were conducted.
Hepatologists Catherine Mezzacappa, MD, MPH, and Guadalupe Garcia-Tsao, MD, both at the Yale School of Medicine, New Haven, Connecticut, agree that it “may be time to revisit whether prophylactic antibiotics continue to provide benefit in patients with cirrhosis and upper GI bleeding, and if so, in which patients.”
They caution, however, that the current level of evidence is “inadequate to answer whether it is time to stop this practice, which has become the standard of care.
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,” Mezzacappa and Garcia-Tsao concluded.
The study received no specific funding. The authors and commentary writers had no relevant disclosures.
A version of this article appeared on Medscape.com.