Assessment of Prophylactic Antibiotics Administration for Acute Pancreatitis: A Meta-Analysis of Randomized Controlled Trials
Acute pancreatitis (AP) is a common gastrointestinal disease characterized by inflammation of the pancreas, often caused by gallstones or excessive alcohol consumption. AP is classified as mild, moderate, or severe based on the 2012 revised Atlanta classification. Mild AP is typically self-limiting, with recovery occurring within the first week, while severe AP (SAP) is associated with systemic inflammatory response, pancreatic and peripancreatic necrosis, organ failure, and high mortality rates. Approximately 20% to 40% of SAP patients develop infected pancreatic necrosis, which is a leading cause of death. The role of prophylactic antibiotics in AP remains controversial, with conflicting evidence on their efficacy in reducing mortality, morbidity, and infection rates.
Background and Rationale
The use of prophylactic antibiotics in AP has been debated for decades. Early studies suggested that antibiotic prophylaxis could reduce the incidence of infected pancreatic necrosis and improve outcomes. However, more recent evidence has challenged this notion, indicating that prophylactic antibiotics do not significantly decrease mortality or morbidity. Clinical guidelines also vary in their recommendations, with some advising against routine antibiotic prophylaxis in AP. Despite this, some physicians continue to administer prophylactic antibiotics, highlighting the need for a comprehensive assessment of their efficacy.
This meta-analysis aimed to evaluate the benefits of prophylactic antibiotics in AP by analyzing randomized controlled trials (RCTs) that assessed outcomes such as infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infections. The study also explored specific infections, including pneumonia, urinary tract infections (UTIs), positive blood cultures, and fungal infections, to provide a more nuanced understanding of the role of antibiotic prophylaxis in AP.
Methods
A systematic literature search was conducted using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The search included RCTs published from inception to June 2019 that evaluated the prophylactic use of antibiotics in patients with AP or SAP. Studies were included if they met the following criteria: (1) aimed to assess prophylactic antibiotic use, (2) written in any language, (3) included patients with AP, SAP, or acute necrotizing pancreatitis, (4) described the name and dose of antibiotics used, and (5) were RCTs.
The primary outcomes of interest were the incidence of infected pancreatic necrosis and mortality. Secondary outcomes included surgical intervention, non-pancreatic infections, pneumonia, UTIs, positive blood cultures, and fungal infections. Data were extracted independently by two authors, and disagreements were resolved through consensus. The quality of the included studies was assessed using the Cochrane Collaboration’s Risk of Bias Tool, and statistical analysis was performed using Review Manager 5.3 software. Odds ratios (ORs) were calculated using the Mantel-Haenszel method, and heterogeneity was assessed using the I² statistic. Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity.
Results
A total of 11 RCTs involving 747 participants were included in the meta-analysis. The intervention group (prophylactic antibiotics) comprised 376 patients, while the control group included 371 patients. The analysis revealed no significant differences between the groups in terms of infected pancreatic necrosis (OR, 0.74; 95% CI, 0.50–1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62–1.38; P = 0.70), or mortality (OR, 0.71; 95% CI, 0.44–1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infections (OR, 0.59; 95% CI, 0.42–0.84; P = 0.004).
Further analysis of specific non-pancreatic infections showed that prophylactic antibiotics did not significantly reduce the incidence of pneumonia (OR, 0.61; 95% CI, 0.32–1.14; P = 0.12), positive blood cultures (OR, 0.61; 95% CI, 0.29–1.30; P = 0.20), or fungal infections (OR, 0.95; 95% CI, 0.30–3.03; P = 0.94). However, a significant reduction was observed in the incidence of UTIs (OR, 0.44; 95% CI, 0.22–0.89; P = 0.02).
Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity. The Egger’s test indicated no publication bias, and the sensitivity analysis showed stable outcomes. Subgroup analysis revealed no significant differences based on study year, sample size, or type of antibiotic used. However, a significant difference was observed between single-center and multicenter studies, with antibiotic prophylaxis showing a greater reduction in non-pancreatic infections in multicenter trials.
Discussion
The findings of this meta-analysis suggest that prophylactic antibiotics do not significantly reduce the incidence of infected pancreatic necrosis, surgical intervention, or mortality in patients with AP. However, antibiotic prophylaxis was associated with a reduction in non-pancreatic infections, particularly UTIs. These results are consistent with previous studies that have questioned the efficacy of prophylactic antibiotics in AP.
The lack of benefit in reducing infected pancreatic necrosis and mortality may be due to several factors. First, the pathogenesis of infected pancreatic necrosis is complex and may not be entirely preventable with antibiotics. Second, the timing of antibiotic administration and the choice of antibiotics may influence outcomes. Third, the heterogeneity of the included studies, including differences in patient populations, disease severity, and study design, may have contributed to the observed results.
The reduction in non-pancreatic infections, particularly UTIs, suggests that prophylactic antibiotics may have a role in preventing secondary infections in AP patients. However, the clinical significance of this finding is limited, as non-pancreatic infections are generally less severe than pancreatic infections and can often be managed with targeted antibiotic therapy.
The subgroup analysis revealed that antibiotic prophylaxis was more effective in reducing non-pancreatic infections in multicenter studies compared to single-center studies. This may be due to differences in medical practices, patient populations, or study protocols between single-center and multicenter trials. Further research is needed to explore these differences and their impact on outcomes.
Limitations
This meta-analysis has several limitations. First, the included studies exhibited heterogeneity in terms of antibiotic type, dosage, timing of administration, and patient populations. Second, some studies had small sample sizes, which may have limited the power to detect significant differences. Third, the analysis did not account for differences in the etiology of pancreatitis or disease severity, which may have influenced outcomes. Finally, the study did not evaluate the potential adverse effects of prophylactic antibiotics, such as the development of antibiotic resistance or fungal infections.
Conclusion
In conclusion, this meta-analysis found that prophylactic antibiotics do not significantly reduce the incidence of infected pancreatic necrosis, surgical intervention, or mortality in patients with AP. However, antibiotic prophylaxis was associated with a reduction in non-pancreatic infections, particularly UTIs. These findings suggest that the routine use of prophylactic antibiotics in AP is not justified, as it does not provide significant clinical benefits. Future research should focus on identifying patient subgroups that may benefit from antibiotic prophylaxis and exploring alternative strategies for preventing and managing infections in AP.
doi.org/10.1097/CM9.0000000000000603
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