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Antibiotic prophylaxis in emergency cholecystectomy for mild to moderate acute cholecystitis: a systematic review and meta-analysis of randomized controlled trials

Perioperative Medicine volume 13, Article number: 87 (2024) Cite this article

Abstract

Background

Emergency cholecystectomy is the mainstay in treating acute cholecystitis (AC). In actual practice, perioperative prophylactic antibiotics are used to prevent postoperative infectious complications (PIC), but their effectiveness lacks evidence. We aim to investigate the efficacy of prophylactic antibiotics in emergency cholecystectomy.

Methods

We searched PubMed, Embase, Cochrane CENTRAL, Web of Science (WOS), and Scopus up to June 14, 2023. We included randomized controlled trials (RCTs) that involved patients diagnosed with mild to moderate AC according to Tokyo guidelines who were undergoing emergency cholecystectomy and were administered preoperative and/or postoperative antibiotics as an intervention group and compared to a placebo group. For dichotomous data, we applied the risk ratio (RR) and the 95% confidence interval (CI), while for continuous data, we used the mean difference (MD) and 95% CI.

Results

We included seven RCTs encompassing a collective sample size of 1747 patients. Our analysis showed no significant differences regarding total PIC (RR = 0.84 with 95% CI (0.63, 1.12), P = 0.23), surgical site infection (RR = 0.79 with 95% CI (0.56, 1.12), P = 0.19), distant infections (RR = 1.01 with 95% CI (0.55, 1.88), P = 0.97), non-infectious complications (RR = 0.84 with 95% CI (0.64, 1.11), P = 0.22), mortality (RR = 0.34 with 95% CI (0.04, 3.23), P = 0.35), and readmission (RR = 0.69 with 95% CI (0.43, 1.11), P = 0.13).

Conclusion

Perioperative antibiotics in patients with mild to moderate acute cholecystitis did not show a significant reduction of postoperative infectious complications after emergency cholecystectomy. (PROSPERO registration number: CRD42023438755).

Introduction

Acute cholecystitis (AC) is an inflammatory disease of the gallbladder caused by gallstone obstruction of the cystic duct in 90% to 95% of cases, while acute acalculous cholecystitis accounts for 5% to 10% (Indar and Beckingham 2002). When the cystic duct is blocked, it causes high pressure in the gallbladder. This, combined with bile concentrated with cholesterol, starts an immediate inflammatory reaction (Gallaher and Charles 2022). Roughly 20% of people with AC also develop bacterial infections from enteric organisms like E. coli, Klebsiella, and Streptococcus faecalis (Kaplan et al. 2021).

AC is responsible for 20% of all cholecystectomy operations and is the third cause of all emergency admissions to surgical wards. Moreover, it accounts for 3% to 5% of hospitalizations worldwide (Payen et al. 2011). In the United States, approximately 10% of adults suffer from cholelithiasis, and the most common complication is acute calculous cholecystitis. The costs associated with this condition exceed $6.3 billion annually, making it a significant burden. Over the past 30 years, there has been a more than 20% increase in cases, further highlighting the severity of the issue (Shaffer 2005; Kimura et al. 2007).

Emergency cholecystectomy within three days of diagnosis is the mainstay in treating AC (Gallaher and Charles 2022). The complication rate after emergency cholecystectomy varies from 15 to 30%, with postoperative infectious complications (PIC) being the most common (Cao et al. 2015). In actual practice, perioperative antibiotics are used to prevent complications, but their effectiveness lacks evidence (Gomi et al. 2018).

In elective cholecystectomy, there are recommendations for the use of prophylactic preoperative antibiotics to reduce the incidence of PIC. However, in emergency cholecystectomy, the evidence is still scarce (Yan et al. 2011; Sharma et al. 2010; Vohra et al. 2017; Gomez-Ospina et al. 2018). Although the Surgical Infection Society and the Tokyo Guidelines recommend the use of antibiotic prophylaxis in emergency cholecystectomy, these recommendations are not supported with sufficient evidence (Gomi et al. 2018; Mazuski et al. 2017). A randomized trial by Regimbeau et al. (2014) concluded that there is no significant difference in PIC with or without antibiotics (Jaafar et al. 2020).

We hypothesized that administering perioperative prophylactic antibiotics in emergency cholecystectomy in patients with AC may be ineffective due to the inflammatory rather than infectious nature of the condition. In this line, we conducted this study to test our hypothesis by gathering all published randomized controlled trials (RCTs) in this meta-analysis.

Methods

We conducted our systematic review and meta-analysis following the Cochrane Handbook for Systematic Reviews of Intervention (Shea et al. 2007) and the AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews 2) Guidelines (Shea et al. 2007). We strictly followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline (Moher et al. 2009) when reporting this meta-analysis. We registered the protocol of this study in the International Prospective Register of Systematic Reviews (PROSPERO) prior to conducting our study (registration number: CRD42023438755).

Search strategy

We searched PubMed, Embase, Cochrane CENTRAL, Web of Science (WOS), and Scopus up to June 14, 2023. We used keywords of cholecystectomy, acute, emergency, and antibiotic to find relevant studies comparing perioperative antibiotic administration with placebo in patients undergoing emergency cholecystectomy. No filters were used when searching databases. The full strategy is summarized in Supplementary Table S1.

Eligibility criteria

We included RCTs that involved patients diagnosed with mild to moderate AC according to Tokyo guidelines (Gomi et al. 2018) who were undergoing emergency cholecystectomy and were administered preoperative and/or postoperative antibiotics as an intervention group and compared to a placebo group. The main outcome of interest was the occurrence of PIC. Observational studies, case reports, case series, book chapters, research using non-human participants, studies not presented in the English language, and conference abstracts were not included.

Studies selection

To eliminate duplicates, we utilized the EndNote Reference Library (EndNote X9 Version, Clarivate, Philadelphia, PA, USA). Next, we uploaded the studies to the Rayyan website (Ouzzani et al. 2016) for screening, which was performed by two teams, each consisting of two members. With the blinding feature enabled, we conducted title and abstract screening. Afterwards, we proceeded to conduct full-text screening for the included studies before finalizing our selection. The decision for each study was made independently by at least two authors, with another member responsible for reviewing any conflicts.

Quality assessment

To assess the quality of the RCTs included in our study, we used the Cochrane Collaboration Risk of Bias Assessment Tool 2 (ROB2) (2023), which evaluates the following domains: randomization, deviations from intended interventions, missing outcome data, measurement of the outcome, selection of the reported result, and overall bias. We classified the outcome of the process as low, unclear, or high risk. Two reviewers conducted the risk of bias assessment independently. In case of any discrepancies, we resolved them by team discussion.

Data extraction

The data extracted were as follows: (1) a summary of included studies, e.g., title, study design, country, duration, inclusion and exclusion criteria, antibiotic name, dosage, route of administration, and follow-up, and (2) baseline characteristics of the enrolled patients, e.g., sample size, age, sex, and body mass index (BMI). We extracted data on these outcomes: total PIC, surgical site infection (SSI), superficial SSI, deep SSI, organ and/or space SSI, postoperative distant infections, pneumonia, urinary tract infection (UTI), mortality, readmission, length of hospital stay, operation time, and total postoperative non-infectious complications.

Statistical analysis

To conduct our analysis, we utilized the Review Manager software (RevMan for Windows, version 5.4, the Cochrane Collaboration, 2020). For dichotomous data, we applied the risk ratio (RR) and the 95% confidence interval (CI), while for continuous data, we used the mean difference (MD) and 95% CI. Statistical significance was considered if the p value was less than 5%. To assess statistical heterogeneity among the pooled results, we used the I-squared test (I2). If the I2 statistic exceeded 50% or the corresponding p-value was less than 0.1, the pooled results were considered heterogeneous, and we used the random effect model. Otherwise, we utilized the fixed-effect model. We conducted a subgroup analysis of antibiotic administration timing, grouping them as preoperative or postoperative. We conducted a sensitivity analysis using the leave-one-out model to account for significant heterogeneity.

Adherence to the registered protocol

In the protocol registered in the PROSPERO register, it was not planned to conduct a subgroup analysis. We decided to conduct the subgroup analysis on the timing of antibiotic administration during the data extraction phase. This decision was made to investigate whether different timings might yield varied outcomes. Initially, we were unsure if the available data would support this analysis, which is why it was not included in the original study protocol registered on PROSPERO.

Clarity of the evidence

Two researchers evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) (2023) through the GRADE Pro online website tool (GRADEpro 2023). We assessed the quality of the evidence and the confidence in the effect estimates based on study design, risk of bias, inconsistency, indirectness, imprecision, and others. The scale was stratified as follows: high quality, which means no further research is needed and unlikely to change the confidence of the effects estimations; moderate quality, which means that further studies may affect the confidence of the effects estimation; low quality, which means further research is likely to have a crucial impact on the confidence of the effects estimation and may change the estimation; and very low quality, which means that we cannot be certain about this estimation (Table 1).

Table 1 Certainty of evidence according to the grading of recommendations assessment, development, and evaluation (GRADE) scale
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Results

Search literature results

Our search resulted in a total of 4506 records; after the duplicates were removed, 1918 records entered the process of title and abstract screening. Twenty-six articles were eligible for the full-text screening, and finally, seven studies (Jaafar et al. 2020; Regimbeau et al. 2014; Braak et al. 2022; Park et al. 2023; Kim et al. 2017; Loozen et al. 2017; Santibañes et al. 2018) were available to enter our meta-analysis. The selection process of the included studies is shown in Fig. 1.

Fig. 1
figure 1

PRISMA flow diagram of the included studies

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Characteristics of the included studies

Out of the seven studies, two were conducted in South Korea (Park et al. 2023; Kim et al. 2017), two in the Netherlands (Braak et al. 2022; Loozen et al. 2017), and one in Argentina (Santibañes et al. 2018), France (Regimbeau et al. 2014), and Sweden (Jaafar et al. 2020). These studies encompassed a time frame spanning from 2009 to 2021 and had a collective sample size of 1747 patients. Of these patients, 866 were administered antibiotics, while the remaining 881 patients constituted the control group. All included patients had mild to moderate AC. Laparoscopic cholecystectomy (LC) was the surgical technique employed in all of the studies included in the analysis. Regimbeau et al. (2014) utilized open cholecystectomy in 6.8% (14 patients) in the antibiotic group and 5.3% (11 patients) in the control group. Jaafar et al. (2020) included four patients who were initially scheduled to have LC; nevertheless, as a result of technical concerns, the surgeon decided to do an open surgical procedure instead. The summary of included studies and baseline characteristics are reported in Tables 2, and 3.

Table 2 Summary of the included studies
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Table 3 Baseline characteristics of the included studies
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Risk of bias assessment results

According to ROB2 (2023), four studies showed a low risk of bias (Braak et al. 2022; Park et al. 2023; Kim et al. 2017; Santibañes et al. 2018), while three showed a high risk (Jaafar et al. 2020; Regimbeau et al. 2014; Loozen et al. 2017). Jaffar et al. (2020) did not report some of the secondary outcomes as planned in their protocol, which introduces a significant risk of reporting bias. Loozen et al. (2017) had concerns regarding the randomization process; neither the patients nor the investigators were blinded to the allocation process. Furthermore, the study conducted by Regimbeau et al. (2014) revealed a higher proportion of patients with diabetes mellitus in the treatment group (27%) compared to the control group (13%). This discrepancy raises concerns regarding potential biased allocation and divergence from the planned study arm. The quality assessment of the included studies is shown in Fig. 2.

Fig. 2
figure 2

Risk of bias assessment of the included studies according to Cochrane risk of bias assessment tool 2

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Postoperative infectious complications

Our analysis resulted in no significant difference regarding total PIC (RR = 0.84 with 95% CI (0.63, 1.12), P = 0.23) (I2 = 0%, P = 0.67), preoperatively administered antibiotics (RR = 0.69 with 95% CI (0.45, 1.08), P = 0.10) (I2 = 8%, P = 0.34), and postoperatively administered antibiotics (RR = 0.96 with 95% CI (0.66, 1.40), P = 0.85) (I2 = 0%, P = 0.88), as shown in Fig. 3.

Fig. 3
figure 3

Forest plot of total postoperative infectious complications

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Surgical site infection

There were no significant differences regarding total SSI (RR = 0.79 with 95% CI (0.56, 1.12), P = 0.19) (I2 = 0%, P = 0.44), preoperatively administered antibiotics (RR = 0.66 with 95% CI (0.27, 1.59), P = 0.06) (I2 = 63%, P = 0.10), and postoperatively administered antibiotics (RR = 0.98 with 95% CI (0.61, 1.56), P = 0.23) (I2 = 0%, P = 0.96), as shown in Fig. 4A. Also, there were no significant differences in each type of SSI: superficial SSI (RR = 0.97 with 95% CI (0.58, 1.64), P = 0.92) (I2 = 0%, P = 0.53), preoperatively administered antibiotics (RR = 0.73 with 95% CI (0.36, 1.48, P = 0.38) (I2 = 0%, P = 0.44), and postoperatively administered antibiotics (RR = 1.37 with 95% CI (0.64, 2.94), P = 0.42) (I2 = 0%, P = 0.68), as shown in Fig. 4B; deep SSI (RR = 0.38 with 95% CI (0.09, 1.52), P = 0.17) (I2 = 0%, P = 0.52), preoperatively administered antibiotics (RR = 0.17 with 95% CI (0.02, 1.40), P = 0.10) (I2 = 0%, P = 0.89), and postoperatively administered antibiotics (RR = 0.70 with 95% CI (0.11, 4.40), P = 0.70) (I2 = 19%, P = 0.27), as shown in Fig. 4C; organ and/or space SSI (RR = 0.64 with 95% CI (0.32, 1.26), P = 0.20) (I2 = 10%, P = 0.34), preoperatively administered antibiotics (RR = 1.19 with 95% CI (0.09, 15.94), P = 0.89) (I2 = 67%, P = 0.08), and postoperatively administered antibiotics (RR = 0.69 with 95% CI (0.29, 1.62), P = 0.39) (I2 = 0%, P = 0.65), as shown in Fig. 4D.

Fig. 4
figure 4

Forest plot of surgical site infections. a Total surgical site infections; b superficial surgical site infection; c deep surgical site infection; d organ and/or space surgical site infection

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Distant infections

We found no significant difference in the total number of postoperative distant infections (RR = 1.01 with 95% CI (0.55, 1.88), P = 0.97) (I2 = 0%, P = 0.72) (I2 = 0%, P = 0.72), preoperatively administered antibiotics (RR = 3.68 with 95% CI (0.61, 22.28), P = 0.16) (I2 = 0%, P = 0.87), and postoperatively administered antibiotics (RR = 0.85 with 95% CI (0.44, 1.65), P = 0.64) (I2 = 0%, P = 0.89), as shown in Fig. 5A. Similarly, there were no significant differences in pneumonia (RR = 0.55 with 95% CI (0.17, 1.80), P = 0.33) (I2 = 0%, P = 0.64), preoperatively administered antibiotics (RR = 1.61 with 95% CI (0.20, 12.98), P = 0.66) (I2 = 0%, P = 0.63), and postoperatively administered antibiotics (RR = 0.34 with 95% CI (0.08, 1.41), P = 0.14) (I2 = 0%, P = 0.96), as shown in Fig. 5B. Our analysis did not show any significant difference in UTI (RR = 0.81 with 95% CI (0.25, 2.64), P = 0.73) (I2 = 0%, P = 0.59), preoperatively administered antibiotics (RR = 3.07 with 95% CI (0.13, 74.87), P = 0.49) and postoperatively administered antibiotics (RR = 0.66 with 95% CI (0.19, 2.34), P = 0.52) (I2 = 0%, P = 0.56), as shown in Fig. 5C.

Fig. 5
figure 5

Forest plot of postoperative distant infections. a Total number of postoperative distant infections; b pneumonia; c urinary tract infection

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Non-infectious complications

Our analysis indicated that there were no significant differences in the overall incidence of postoperative non-infectious complications (RR = 0.84 with 95% CI (0.64, 1.11), P = 0.22) (I2 = 0%, P = 0.61), preoperatively administered antibiotics (RR = 0.85 with 95% CI (0.61, 1.17), P = 0.31) (I2 = 0%, P = 0.32), and postoperatively administered antibiotics (RR = 0.82 with 95% CI (0.46, 1.47), P = 0.51), (I2 = 0%, P = 0.46), as shown in Fig. 6A.

Fig. 6
figure 6

Forest plots of noninfectious morbidity and mortality. a The overall incidence of postoperative non-infectious complications; b mortality; c readmission; d operation time (minutes); e length of hospital stay (days)

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We found no significant difference in mortality (RR = 0.34 with 95% CI (0.04, 3.23), P = 0.35) (I2 = 0%, P = 0.99), preoperatively administered antibiotics (RR = 0.34 with 95% CI (0.01, 8.32), P = 0.51), and postoperatively administered antibiotics (RR = 0.33 with 95% CI (0.01, 8.14), P = 0.50), as shown in Fig. 6B.

The pooled result of the meta-analysis showed comparable readmission rates in both groups (RR = 0.69 with 95% CI (0.43, 1.11), P = 0.13) (I2 = 0%, P = 0.92), preoperatively administered antibiotics (RR = 0.57 with 95% CI (0.30, 1.07), P = 0.08) (I2 = 0%, P = 0.89), and postoperatively administered antibiotics (RR = 0.88 with 95% CI (0.44, 1.78), P = 0.72) (I2 = 0%, P = 0.94), as shown in Fig. 6C.

Operation time showed no change with either group (MD = 0.98 min with 95% CI (-1.49, 3.45), P = 0.44) (I2 = 0%, P = 0.46), preoperatively administered antibiotics (MD = -0.80 min with 95% CI (-4.05, 2.46), P = 0.63) (I2 = 16%, P = 0.27), and postoperatively administered antibiotics (MD = 3.40 min with 95% CI (-0.39, 7.20), P = 0.08) (I2 = 0%, P = 0.86), as shown in Fig. 6D.

Our results showed that the length of hospital stay was equal in both groups (MD = 0.89 day with 95% CI (-0.14, 1.92), P = 0.09) (I2 = 98%, P < 0.00001), preoperatively administered antibiotics (MD = 3.67 day with 95% CI (-4.04, 11.37), P = 0.35) (I2 = 90%, P = 0.001), and postoperatively administered antibiotics subgroup (MD = 0.78 day with 95% CI (-0.55, 2.10), P = 0.25) (I2 = 98%, P < 0.00001), as shown in Fig. 6E. Heterogeneity within the postoperatively administered antibiotics were addressed when excluding results of Santibanes et al. (2018) (I2 = 0%, P = 0.32), and the results did not change in this subgroup (MD = 0.21 day with 95% CI (-0.22, 0.48), P = 0.09).

Discussion

In this systematic review and meta-analysis, we aimed to assess the efficacy of perioperative antibiotic administration in reducing PIC in patients with AC undergoing emergency cholecystectomy. We found no significant difference in total PIC, SSI, or any of its components separately (superficial, deep, and organ or space SSI), distant infections or any of its components (pneumonia and UTI), non-infectious complications, mortality, hospital readmission, and operation time either with perioperative antibiotic or with no antibiotic. Additionally, there was no difference in outcomes based on whether antibiotics were administered before or after surgery. The results of the pooled studies were homogenous in nearly all outcomes, which reflects the agreement of pooled results.

Braak et al. (2022), Park et al. (2023), Jaafar et al. (2020), Kim et al. (2017), Loozen et al. (2017), Regimbeau et al. (2014), and de Santibañes et al. (2018) found in their RCTs that there is no significant difference between the antibiotic and control groups regarding PIC. Choudhary et al. (2008) reported in their meta-analysis that there is no significant difference in total infection risk between the antibiotic and control group after emergency cholecystectomy.

Regarding SSI, our results indicated that there is no statistically significant difference between the antibiotics and control groups. These results are in line with the RCTs of Jaafar et al. (2020), Kim et al. (2017), Loozen et al. (2017), Regimbeau et al. (2014), and de Santibañes et al. (2018). Furthermore, Hajibandeh et al. (2019) conducted a meta-analysis of four RCTs to assess the effectiveness of antibiotics in reducing postoperative SSI and found no association. La Regina and colleagues (2019) reported in their meta-analyses of three RCTs that postoperative antibiotics do not reduce SSI. However, Braak et al. (2022) reported that SSI may have a higher predominance among the control group. It should be noted that the control group in Braak et al. (2022) had a higher white blood cell count upon admission, which could lead to biased observation.

In terms of distant infections, we found that there is no statistically significant difference between the antibiotic and control groups. Also, our results are aligned with Braak et al. (2022), Choudhary et al. (2008), and Hajibandeh et al. (2019) regarding postoperative distant infections.

Although up to 20% of patients with AC may experience bacterial infection due to cystic duct obstruction and bile stasis, AC is still primarily an inflammatory process, and that may explain why antibiotic administration did not lead to lower rates of infection in our study or the literature van Dijk (2016). Moreover, in patients with positive bile culture, antibiotic treatment does not always prevent complications in patients with AC (Galili et al. 2008). Despite the 2018 Tokyo guidelines (Gomi et al. 2018) recommending the use of preoperative and intraoperative antibiotics for uncomplicated cholecystitis patients, the current study and existing literature suggest that such antibiotics do not provide protective benefits against infections. This raises concerns about the routine use of antibiotics in such procedures and calls for a reevaluation of current practices. Given these findings, it is crucial to adopt a cautious and selective approach to antibiotic use, particularly considering the growing challenge of antibiotic resistance (Llor and Bjerrum 2014). Instead, we recommend focusing on enhancing surgical techniques and providing quality postoperative care. These measures aim to improve patient outcomes while reducing the need for antibiotics.

Our research has significant implications for the economy, potentially reducing hospital stays and antibiotic expenses, easing the burden on healthcare systems, and preventing future antibiotic resistance. This supports the aims and goals of antibiotic stewardship programs (ASPs) (Karanika et al. 2016). It highlights the need for a thoughtful approach to antibiotic use in cholecystectomy procedures. These insights are important not only for medical professionals but also for healthcare quality improvement and sustainability researchers.

On the other hand, Yang et al. (2021) conducted a meta-analysis on patients with mild to moderate cholecystitis undergoing elective LC and reported that the administration of perioperative antibiotics could effectively reduce infections, including SSI and distant infections. The reason why antibiotics show efficacy with patients undergoing elective LC in the study of Yang et al. (2021) but not here in our study on patients undergoing emergency cholecystectomy is a very interesting question. One reason could be credited to the different pathologies between acute and chronic cholecystectomy. In contrast, a long period of bile stasis in chronic cholecystitis can predispose to organism growth; the relatively short period of AC is not always associated with colonization or bacteriobilia. We hypnotize that this different outcome may be attributed to a distinct feature in Yang et al. (2021). They included 14 RCTs, and of them, 6 (43%), including 2573 patients (59% of the meta-analysis sample size), were conducted in Asia, and a subgroup analysis found the antibiotics are effective in reducing total infections (P = 0.003), SSI (P = 0.006), and distant infections (P = 0.005) only in studies from Asia, but not from Europe or America. The reason why antibiotics are effective in Asian patients is yet to be studied.

Interestingly, our investigation revealed a notable finding: The utilization of antibiotics was associated with a 25% increase in the duration of hospital stays. This finding represents a good example of ASPs, which aim to improve antimicrobial use to improve patient outcomes, reduce antibiotic costs, and minimize the side effects associated with antimicrobial use, including drug resistance. Additionally, certain cases might exhibit hypersensitivity reactions to specific antibiotics, necessitating an extended stay for closer observation.

Furthermore, our study’s other outcomes showed no statistically significant differences concerning readmission rates, occurrences of non-infectious complications, and the duration of the surgical procedure. These results align with the findings from Hajibandeh et al. (2019).

Strengths

We are reporting a very important example of antimicrobial overuse with no obvious benefits in patients undergoing emergency cholecystectomy. We included seven RCTs, and their pooled results were homogenous, which robustness the agreement on the uselessness of antimicrobial treatment. We did a subgroup analysis depending on the time of antibiotic administration, and we found similar results, which was a limitation of a previous meta-analysis (Hajibandeh et al. 2019).

Limitations

However, it is essential to acknowledge the limitations inherent in our study. Specifically, three of the included RCTs are potentially susceptible to bias. The previous bias might influence the robustness of our conclusions. Our meta-analysis only included RCTs published in English, potentially excluding relevant studies published in other languages. Also, some studies used different antibiotic regimens. Braak et al. (2022) and Loozen et al. (2017) used 2 g of first-generation cephalosporin; Jaafar et al. (2020) used 4 g of piperacillin/tazobactam, and Kim et al. (2017) used 1.0 g of second-generation cephalosporin. While Park et al. (2023) used 1.0 g of first-generation cephalosporin, Regimbeau et al. (2014) used an amoxicillin regimen, and Santibañes et al. (2018) used an ampicillin/sulbactam regimen. These limitations may impact the overall comprehensiveness of our meta-analysis and underscore the necessity for cautious interpretation and consideration when evaluating the scope and applicability of our results. There were no studies that reported on the occurrence of antibiotic-associated (pseudomembranous) colitis caused by Clostridium difficile. We were unable to conduct a subgroup analysis on the severity of AC as there were no sufficient data available. Two of the included studies (Jaafar et al. 2020; Regimbeau et al. 2014) included patients undergoing open cholecystectomy, which may introduce a confounding variable; however, the percentage was very small.

Conclusion

The current evidence on the administration of prophylactic perioperative antibiotics in patients with mild to moderate acute cholecystitis did not show a significant reduction of postoperative infectious complications after emergency cholecystectomy. This meta-analysis recommends revising the current guidelines on the use of antibiotics in acute cholecystitis, especially with the growing challenges of antimicrobial resistance.

Availability of data and materials

All raw data presented or analyzed in this article are available on request from the corresponding author.

Competing interests

The authors declare no competing interests.

Abbreviations

AC:

Acute cholecystitis

PIC:

Postoperative infectious complications

RCTs:

Randomized controlled trials

AMSTAR-2:

Assessing the Methodological Quality of Systematic Reviews 2

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO:

International Prospective Register of Systematic Reviews

WOS:

Web of Science

ROB2:

Cochrane Collaboration Risk of Bias Assessment Tool 2

BMI:

Body mass index

SSI:

Surgical site infection

UTI:

Urinary tract infection

RR:

Risk ratio

CI:

Confidence interval

MD:

Mean difference

GRADE:

Recommendations Assessment, Development, and Evaluation of evidence

LC:

Laparoscopic cholecystectomy

ASPs:

Antibiotic stewardship programs

References

  • Cao AM, Eslick GD, Cox MR. Early cholecystectomy is superior to delayed cholecystectomy for acute cholecystitis: a meta-analysis. J Gastrointest Surg. 2015;19(5):848–57.

    Article  PubMed  Google Scholar 

  • Choudhary A, Bechtold ML, Puli SR, Othman MO, Roy PK. Role of prophylactic antibiotics in laparoscopic cholecystectomy: a meta-analysis. J Gastrointest Surg. 2008;12(11):1847–53.

    Article  PubMed  Google Scholar 

  • de Santibañes M, Glinka J, Pelegrini P, Alvarez FA, Elizondo C, Giunta D, et al. Extended antibiotic therapy versus placebo after laparoscopic cholecystectomy for mild and moderate acute calculous cholecystitis: a randomized double-blind clinical trial. Surgery. 2018;S0039–6060(18):30030–8.

    Google Scholar 

  • Galili O, Eldar S, Matter I, Madi H, Brodsky A, Galis I, et al. The effect of bactibilia on the course and outcome of laparoscopic cholecystectomy. Eur J Clin Microbiol Infect Dis off Publ Eur Soc Clin Microbiol. 2008;27(9):797–803.

    Article  CAS  Google Scholar 

  • Gallaher JR, Charles A. Acute Cholecystitis: A Review. JAMA. 2022;327(10):965–75.

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Ospina JC, Zapata-Copete JA, Bejarano M, García-Perdomo HA. Antibiotic prophylaxis in elective laparoscopic cholecystectomy: a systematic review and network meta-analysis. J Gastrointest Surg off J Soc Surg Aliment Tract. 2018;22(7):1193–203.

    Article  Google Scholar 

  • Gomi H, Solomkin JS, Schlossberg D, Okamoto K, Takada T, Strasberg SM, et al. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepato-Biliary-Pancreat Sci. 2018;25(1):3–16.

    Article  Google Scholar 

  • GRADE handbook [Internet]. [cited 2023 Oct 29]. Available from: https://gdt.gradepro.org/app/handbook/handbook.html#h.g2dqzi9je57e

  • GRADEpro [Internet]. [cited 2023 Oct 21]. Available from: https://www.gradepro.org/.

  • Hajibandeh S, Popova P, Rehman S. Extended postoperative antibiotics versus no postoperative antibiotics in patients undergoing emergency cholecystectomy for acute calculous cholecystitis: a systematic review and meta-analysis. Surg Innov. 2019;26(4):485–96.

    Article  PubMed  Google Scholar 

  • Indar AA, Beckingham IJ. Acute cholecystitis. BMJ. 2002;325(7365):639–43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jaafar G, Sandblom G, Lundell L, Hammarqvist F. Antibiotic prophylaxis in acute cholecystectomy revisited: results of a double-blind randomised controlled trial. Langenbecks Arch Surg. 2020;405(8):1201–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaplan U, Handler C, Chazan B, Weiner N, Hatoum OA, Yanovskay A, et al. The bacteriology of acute cholecystitis: comparison of bile cultures and clinical outcomes in diabetic and non-diabetic patients. World J Surg. 2021;45(8):2426–31.

    Article  PubMed  Google Scholar 

  • Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic review and meta-analysis of clinical and economic outcomes from the implementation of hospital-based antimicrobial stewardship programs. Antimicrob Agents Chemother. 2016;60(8):4840–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim EY, Yoon YC, Choi HJ, Kim KH, Park JH, Hong TH. Is there a real role of postoperative antibiotic administration for mildmoderate acute cholecystitis? A prospective randomized controlled trial. J Hepato-Biliary-Pancreat Sci. 2017;24(10):550–8.

    Article  Google Scholar 

  • Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):15–26.

    Article  PubMed  PubMed Central  Google Scholar 

  • La Regina D, Di Giuseppe M, Cafarotti S, Saporito A, Ceppi M, Mongelli F, et al. Antibiotic administration after cholecystectomy for acute mild-moderate cholecystitis: a PRISMA-compliant meta-analysis. Surg Endosc. 2019;33(2):377–83.

    Article  PubMed  Google Scholar 

  • Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Loozen CS, Kortram K, Kornmann VNN, Van Ramshorst B, Vlaminckx B, Knibbe CAJ, et al. Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis. Br J Surg. 2017;104(2):e151–7.

    Article  PubMed  CAS  Google Scholar 

  • Mazuski JE, Tessier JM, May AK, Sawyer RG, Nadler EP, Rosengart MR, et al. The surgical infection society revised guidelines on the management of intra-abdominal infection. Surg Infect. 2017;18(1):1–76.

    Article  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097.

  • Ouzzani M, Hammady H, Fedorowicz Z, et al. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5:210. https://doi.org/10.1186/s13643-016-0384-4.

  • Park SE, Choi HJ, You YK, Hong TH. Clinical significance of preoperative antibiotic use in mild to moderate acute inflammatory gallbladder disease: a randomized controlled trial. J Hepato-Biliary-Pancreat Sci. 2023;30(4):482–92.

    Article  Google Scholar 

  • Payen JL, Muscari F, Vibert É, Ernst O, Pelletier G. Lithiase biliaire. Presse Med. 2011;40(6):567–80.

    Article  PubMed  Google Scholar 

  • Regimbeau JM, Fuks D, Pautrat K, Mauvais F, Haccart V, Msika S, et al. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis. JAMA. 2014;312(2):145–145.

    Article  PubMed  Google Scholar 

  • RoB 2: A revised Cochrane risk-of-bias tool for randomized trials | Cochrane Bias [Internet]. [cited 2023 Oct 2]. Available from: https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials.

  • Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep. 2005;7(2):132–40.

    Article  PubMed  Google Scholar 

  • Sharma N, Garg PK, Hadke NS, Choudhary D. Role of prophylactic antibiotics in laparoscopic cholecystectomy and risk factors for surgical site infection: a randomized controlled trial. Surg Infect. 2010;11(4):367–70.

    Article  Google Scholar 

  • Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  • van Braak WG, Ponten JEH, Loozen CS, Schots JPM, van Geloven AAW, Donkervoort SC, et al. Antibiotic prophylaxis for acute cholecystectomy: PEANUTS II multicentre randomized non-inferiority clinical trial. Br J Surg. 2022;109(3):267–73.

    Article  PubMed  Google Scholar 

  • van Dijk AH, de Reuver PR, Tasma TN, van Dieren S, Hugh TJ, Boermeester MA. Systematic review of antibiotic treatment for acute calculous cholecystitis. Br J Surg. 2016;103(7):797–811.

    Article  PubMed  Google Scholar 

  • Vohra RS, Hodson J, Pasquali S, Griffiths EA. Effectiveness of antibiotic prophylaxis in non-emergency cholecystectomy using data from a population-based cohort study. World J Surg. 2017;41(9):2231–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan RC, Shen SQ, Chen ZB, Lin FS, Riley J. The role of prophylactic antibiotics in laparoscopic cholecystectomy in preventing postoperative infection: a meta-analysis. J Laparoendosc Adv Surg Tech A. 2011;21(4):301–6.

    Article  PubMed  Google Scholar 

  • Yang J, Gong S, Lu T, Tian H, Jing W, Liu Y, et al. Reduction of risk of infection during elective laparoscopic cholecystectomy using prophylactic antibiotics: a systematic review and meta-analysis. Surg Endosc. 2021;35(12):6397–412.

    Article  PubMed  Google Scholar 

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Acknowledgements

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Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB). This research did not receive any funding.

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Authors and Affiliations

  1. Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Mohamed Hamouda Elkasaby & Mohamed Abdalla Rashed

  2. Faculty of Medicine, Tanta University, Tanta, Egypt

    Hesham Elsayed

  3. General Surgery Department, Ministry of Health, Latakia, Syria

    Dilawer Chofan Charo

  4. Faculty of Medicine, Suez University, Suez, Egypt

    Omar Elkoumi

  5. Faculty of Medicine, Al-Azhar University, Damietta, Egypt

    Islam Mohsen Elhaddad

  6. Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Ahmed Gadallah

  7. Faculty of Medicine, South Valley University, Qena, Egypt

    Alaa Ramadan

  8. Medical Research Group of Egypt (MRGE), Cairo, Egypt

    Mohamed Hamouda Elkasaby, Hesham Elsayed, Dilawer Chofan Charo, Mohamed Abdalla Rashed, Omar Elkoumi, Islam Mohsen Elhaddad, Ahmed Gadallah & Alaa Ramadan

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Contributions

MHE was the lead author of this review, conceived and delineated the hypotheses, designed the study, wrote the first draft, and edited the final manuscript. HE conceived and delineated the hypotheses, extracted data, and wrote the first draft. DCC and MAR took part in screening and data extraction and performed quality of bias assessment. OE wrote the first draft and edited the final manuscript. IME and AG took part in screening and data extraction. MAR and AR performed data analysis. AR wrote the first draft and edited the final manuscript. All authors revised the final manuscript and accepted it for publication.

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Correspondence to Mohamed Hamouda Elkasaby.

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Elkasaby, M.H., Elsayed, H., Charo, D.C. et al. Antibiotic prophylaxis in emergency cholecystectomy for mild to moderate acute cholecystitis: a systematic review and meta-analysis of randomized controlled trials. Perioper Med 13, 87 (2024). https://doi.org/10.1186/s13741-024-00441-4

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Keywords

Perioperative Medicine

ISSN: 2047-0525