Re: Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis

It is with a certain interest that we read the new Tokyo Guidelines 2018 about the therapeutic management of acute cholangitis and calculous cholecystitis, especially the article “Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis”, written by Gomi et al. and published in your journal [1]. To answer question 4: “What is the optimal duration of antimicrobial therapy for patients with acute cholecystitis”, the authors reported two randomized clinical trials, one published by Loozen et al. and the other one by our own group [2, 3]. Their conclusion was “Although non-inferiority was not proven in either RCT, there was no clinically significant difference.” It is true that non-inferiority has not been proven in the study by Loozen et al. The results according to the intention-to-treat analysis showed a postoperative complication rate of 4% in both groups with a 95% CI = [ 8.2%; 8.9%] (P = 0.2%). The noninferiority margin of this study was 5% [2]. However, non-inferiority has been proven in our study. Started in 2010, this French multicenter study aimed to show that the absence of antibiotic therapy was not inferior to the antibiotic therapy prescription after cholecystectomy for acute low and moderately severe lithiasic cholecystitis (grade I and grade II): the main evaluation criteria was Post-Operative Infections (POI). To establish the non-inferiority, the upper limit of the 95% confidence interval had to be lower than the non-inferiority margin (11%). In our study, there was no significant difference between the two groups (POI rate of 17% in the antibiotic-free group vs. 15% in the antibiotic group) with a 95% CI = [ 8.98%; 5.12%] in the intention-to-treat analysis (P = 1.93%) and there was no significant difference between the two groups (POI rate of 13% in both groups) with a 95% CI = [ 5.0%; 6.3%] in the per protocol analysis (P = 0.3%) [3]. Then, the non-inferiority of the absence of antibiotic therapy and the POI has been proven. Our department is involved in the approach of simplification of care of patients with acute calculous cholecystitis (ACC) and we are going in the same direction as your guidelines in addition to early cholecystectomy: no postoperative antibiotic therapy in patients with mild or moderate ACC [1, 3], no drainage [4] and short length of hospital stay [5]. Currently, we are in the process of evaluating the implementation of these guidelines in France. Due to the TG13 that remained unclear on the antibiotic treatment, these official new Tokyo Guidelines 2018 are welcome to support our approach.