Response to Re: Tokyo Guidelines 2018: antimicrobial therapy for
acute cholangitis and cholecystitis
© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery
We thank Guerin and Regimbeau  for their interest in
our Tokyo Guidelines 2018: antimicrobial therapy for
acute cholangitis and cholecystitis , and their comments
and clariﬁcation about Question 4. We would like to reply
to their comments. The randomized studies we cited in
answering Question 4 included three studies [3–5].
Among them, Regimbeau et al.  and Loozen et al. 
were included for meta-analysis . The non-inferiority
margins varied widely between Regimbeau et al.’s  and
Loozen et al.’s  studies (11% vs. 5%). In general, there
are several ways to deﬁne the non-inferiority margin 
and the margins deﬁned in Regimbeau et al.’s and Loozen
et al.’s studies were both reasonable enough. When we
adopted Loozen et al.’s narrower non-inferiority margin
, non-inferiority was not proven in either study. How-
ever, we completely agree that non-inferiority was proven
with its own non-inferiority margin in Regimbeau et al.’s
study, as the authors suggested. Either way, the differ-
ences in outcomes between the two patient groups with
no postoperative antimicrobial use and with postoperative
antimicrobial use were not clinically signiﬁcant. There-
fore, we have recommended not using postoperative
antimicrobial therapy for Grade I and II acute cholecysti-
tis. We hope this further clariﬁes our recommendations
and its scientiﬁc rationale.
1. Guerin O, Regimbeau JM. Re: Tokyo Guidelines 2018: antimi-
crobial therapy for acute cholangitis and cholecystitis. J Hepato-
biliary Pancreat Sci. 2018;25:E5.
2. 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.
3. Regimbeau JM, Fuks D, Pautrat K, Mauvais F, Haccart V, Msika
S, et al. Effect of postoperative antibiotic administration on post-
operative infection following cholecystectomy for acute calculous
cholecystitis: a randomized clinical trial. JAMA. 2014;312:
4. 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–e7.
5. Mazeh H, Mizrahi I, Dior U, Simanovsky N, Shapiro M, Freund
HR, et al. Role of antibiotic therapy in mild acute calculus chole-
cystitis: a prospective randomized controlled trial. World J Surg.
6. Althunian TA, de Boer A, Groenwold RHH, Klungel OH. Deﬁn-
ing the noninferiority margin and analysing noninferiority: an
overview. Br J Clin Pharmacol. 2017;83:1636–42.
H. Gomi (
Ofﬁce of Medical Education, International University of Health and
Welfare, Chiba, Japan
Department of Surgery, Center for Gastroenterology and Liver
Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan
Division of Public Health, Osaka Institute of Public Health, Osaka,
Department of Surgery, Teikyo University School of Medicine,
J Hepatobiliary Pancreat Sci (2018) 25:E6
LETTER TO THE EDITOR