Assessment of Prophylactic Carbapenem Antibiotics Administration for Severe Acute Pancreatitis: An Updated Systematic Review and Meta-Analysis

Abstract

<b><i>Background:</i></b> The effectiveness of prophylactic antibiotics in severe acute pancreatitis (SAP) remains a debatable issue. This meta-analysis aimed to determine the efficacy of prophylactic carbapenem antibiotics in SAP. <b><i>Methods:</i></b> This meta-analysis of prophylactic carbapenem antibiotics for SAP was conducted in PubMed, EMBASE, Web of Science, MEDLINE, and Cochrane Library up to February 2021. The related bibliographies were manually searched. The primary outcomes involved infected pancreatic or peripancreatic necrosis, mortality, complications, infections, and organ failure. <b><i>Results:</i></b> Seven articles comprised 5 randomized controlled trials and 2 retrospective observational studies, including 3,864 SAP participants. Prophylactic carbapenem antibiotics in SAP were associated with a statistically significant reduction in the incidence of infections (odds ratio [OR]: 0.27; <i>p</i> = 0.03) and complications (OR: 0.48; <i>p</i> = 0.009). Nevertheless, no statistically significant difference was demonstrated in the incidence of infected pancreatic or peripancreatic necrosis (OR: 0.74; <i>p</i> = 0.24), mortality (OR: 0.69; <i>p</i> = 0.17), extrapancreatic infection (OR: 0.64, <i>p</i> = 0.54), pulmonary infection (OR: 1.23; <i>p</i> = 0.69), blood infection (OR: 0.60; <i>p</i> = 0.35), urinary tract infection (OR: 0.97; <i>p</i> = 0.97), pancreatic pseudocyst (OR: 0.59; <i>p</i> = 0.28), fluid collection (OR: 0.91; <i>p</i> = 0.76), organ failure (OR: 0.63; <i>p</i> = 0.19), acute respiratory distress syndrome (OR: 0.80; <i>p</i> = 0.61), surgical intervention (OR: 0.97; <i>p</i> = 0.93), dialysis (OR: 2.34; <i>p</i> = 0.57), use of respirator or ventilator (OR: 1.90; <i>p</i> = 0.40), intensive care unit treatment (OR: 2.97; <i>p</i> = 0.18), and additional antibiotics (OR: 0.59; <i>p</i> = 0.28) between the experimental and control groups. <b><i>Conclusions:</i></b> It is not recommended to administer routine prophylactic carbapenem antibiotics in SAP.

A nomogram for predicting the risk of mortality in patients with acute pancreatitis and Gram-negative bacilli infection

“…It has been reported that carbapenem has been considered as the last-line regimen for AP patients with “suspected” pancreatic infections ( Guo et al., 2022 ). Due to relative resistance to hydrolysis by most β-lactamases, carbapenems are regarded as the most active and potent agents against multidrug-resistant (MDR) gram-negative pathogens with a wide antibacterial spectrum ( El-Gamal et al., 2017 ).However, the inappropriate use of the antimicrobial drugs has led to the rise of the drug-resistant pathogens, which, according to the reporting frequency, are sorted from high to low as Carbapenem-resistant Enterobacteria (CRE), Carbapenem-resistant Pseudomonas aeruginosa (CRPA), and Carbapenem-resistant Acinetobacter baumannii (CRAB) complex ( Tacconelli et al., 2018 ).…”

Diagnosis, severity stratification and management of adult acute pancreatitis–current evidence and controversies

“…Ukai et al [ 64 ] in 2015 analysed 6 randomized controlled trials (RCTs) with 397 ANP patients and showed that early prophylactic antibiotics (within 72 h from onset of symptoms or 48 h after admission) was associated with lower mortality (prophylactic antibiotics: 7.4% vs no antibiotics: 14.4%, OR: 0.48, 95%CI: 0.25-0.94) and reduced incidence of infected pancreatic necrosis (prophylactic antibiotics: 16.3% vs no antibiotics: 25.1%, OR: 0.55, 95%CI: 0.33-0.92) compared to no antibiotics use[ 64 ]. However, a recent meta-analysis on the use of prophylactic carbapenem antibiotics by Guo et al [ 65 ] on 6 studies (5 RCTs, 1 retrospective observational study) showed similar mortality (prophylactic antibiotics: 11.0% ( n = 29/264) vs no prophylactic antibiotics: 15.4% ( n = 38/246), OR: 0.69, 95%CI: 0.41-1.16, P = 0.17) and incidence of infected pancreatic necrosis [prophylactic antibiotics: 12.5% ( n = 33/264) vs no prophylactic antibiotics: 15.9% ( n = 39/246), OR: 0.74, 95%CI: 0.44-1.23, P = 0.24][ 65 ]. Guo et al [ 65 ] included studies with heterogeneity in the timing of prophylactic antibiotics administration: One study started antibiotics within 48 h of symptom onset[ 66 ], three studies within 72 h of symptom onset[ 67 - 69 ] and one study within 120 h of symptom onset[ 70 ].…”

“…However, a recent meta-analysis on the use of prophylactic carbapenem antibiotics by Guo et al [ 65 ] on 6 studies (5 RCTs, 1 retrospective observational study) showed similar mortality (prophylactic antibiotics: 11.0% ( n = 29/264) vs no prophylactic antibiotics: 15.4% ( n = 38/246), OR: 0.69, 95%CI: 0.41-1.16, P = 0.17) and incidence of infected pancreatic necrosis [prophylactic antibiotics: 12.5% ( n = 33/264) vs no prophylactic antibiotics: 15.9% ( n = 39/246), OR: 0.74, 95%CI: 0.44-1.23, P = 0.24][ 65 ]. Guo et al [ 65 ] included studies with heterogeneity in the timing of prophylactic antibiotics administration: One study started antibiotics within 48 h of symptom onset[ 66 ], three studies within 72 h of symptom onset[ 67 - 69 ] and one study within 120 h of symptom onset[ 70 ]. Unlike Guo et al [ 65 ] who analysed only patients with prophylactic carbapenem, Ukai et al [ 64 ] included studies with cefuroxime[ 71 ], and ciprofloxacin[ 72 ].…”

“…Guo et al [ 65 ] included studies with heterogeneity in the timing of prophylactic antibiotics administration: One study started antibiotics within 48 h of symptom onset[ 66 ], three studies within 72 h of symptom onset[ 67 - 69 ] and one study within 120 h of symptom onset[ 70 ]. Unlike Guo et al [ 65 ] who analysed only patients with prophylactic carbapenem, Ukai et al [ 64 ] included studies with cefuroxime[ 71 ], and ciprofloxacin[ 72 ]. In addition, while the populations examined are similar between the two studies, ANP (study by Ukai et al [ 64 ]) is not synonymous with SAP (study by Guo et al [ 65 ]).…”

“…Unlike Guo et al [ 65 ] who analysed only patients with prophylactic carbapenem, Ukai et al [ 64 ] included studies with cefuroxime[ 71 ], and ciprofloxacin[ 72 ]. In addition, while the populations examined are similar between the two studies, ANP (study by Ukai et al [ 64 ]) is not synonymous with SAP (study by Guo et al [ 65 ]). Moderately-SAP is defined as presence of local complications which include acute necrotic collection (ANC), peri-pancreatic collection, or walled-off necrosis (WON).…”