Re: Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis
© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery
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 .
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-infer-
iority was not proven in either RCT, there was no clini-
cally 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 = [À8.2%; 8.9%] (P = 0.2%). The non-
inferiority margin of this study was 5% . 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-infer-
iority, 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 = [À8.98%;
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 = [À5.0%;
6.3%] in the per protocol analysis (P = 0.3%) . Then,
the non-inferiority of the absence of antibiotic therapy and
the POI has been proven.
Our department is involved in the approach of simpliﬁ-
cation of care of patients with acute calculous cholecysti-
tis (ACC) and we are going in the same direction as your
guidelines in addition to early cholecystectomy: no post-
operative antibiotic therapy in patients with mild or mod-
erate ACC [1, 3], no drainage  and short length of
hospital stay .
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.
1. Gomi H, Solomkin JS, Schlossberg D, Okamoto K, Takada T,
Strasberg SM, et al. Tokyo Guidelines 2018: antimicrobial ther-
apy for acute cholangitis and cholecystitis. J Hepatobiliary Pan-
creat Sci. 2018;25:3–16.
2. Loozen CS, Kortram K, Kornmann VN, van Ramshorst B, Vlam-
inckx B, Knibbe CA, et al. Randomized clinical trial of extended
versus single-dose perioperative antibiotic prophylaxis for acute
calculous cholecystitis. Br J Surg. 2017;104:e151–7.
3. Regimbeau JM, Fuks D, Pautrat K, Mauvais F, Haccart V, Msika
S, et al. Effect of postoperative antibiotic administration on postop-
erative infection following cholecystectomy for acute calculous
cholecystitis: a randomized clinical trial. JAMA. 2014;312:145–54.
4. Prevot F, Fuks D, Coss
e C, Pautrat K, Msika S, Mathonnet M,
et al. The value of abdominal drainage after laparoscopic chole-
cystectomy for mild or moderate acute calculous cholecystitis: a
post hoc analysis of a randomized clinical trial. World J Surg.
5. Fuks D, Coss
e C, Regimbeau JM. Antibiotic therapy in acute cal-
culous cholecystitis. J Visc Surg. 2013;150:3–8.
J.-M. Regimbeau (
Department of Digestive Surgery, Amiens University Hospital,
e Laennec, F-80054 Amiens Cedex 01, France.
Simpliﬁcation of Care of Complex Surgical Patients, Unit of
Clinical Research, University of Picardie Jules Verne, Amiens,
J Hepatobiliary Pancreat Sci (2018) 25:E5
LETTER TO THE EDITOR