Antimicrobial prophylaxis for 1 day versus 3 days in liver cancer surgery: a randomized controlled non-inferiority trial
This study compared the effectiveness of 1-day vs 3-days antibiotic regimen to prevent surgical site infection (SSI) in open liver resection.
We performed a randomized controlled non-inferiority trial in 480 patients at 39 hospitals across Japan (registered as UMIN000002852). Patients with hepatocellular carcinoma scheduled to undergo resection were randomly assigned to receive either a 1-day regimen for antimicrobial prophylaxis, or a 3-day regimen. The primary endpoint was the incidence of SSI.
Among 480 randomized patients, 232 assigned to the 1-day regimen and 235 to the 3-day regimen were included in the full analysis set. Baseline characteristics of the two groups were well balanced. SSI was diagnosed in 22 patients (9.5%) in the 1-day group vs 23 patients (9.8%) in the 3-day group (difference, – 0.30; 90% CI – 4.80 to 4.19% [95% CI – 5.66% to 5.05%]; one-sided P = 0.001 for non-inferiority), meeting the non-inferiority hypothesis. In both groups, remote site infection (16 [6.9%] vs 22 [9.4%], P ˂ 0.001 for non-inferiority) and drain-related infection (5 [2.2%] vs 4 [1.7%], P ˂ 0.001 for non-inferiority) were comparable.
To prevent SSI in liver cancer surgery, a 1-day regimen of flomoxef sodium is recommended for antimicrobial prophylaxis because of confirming the non-inferiority to longer usage.
KeywordsLiver surgery Hepatocellular carcinoma Surgical site infection Antimicrobial prophylaxis Randomized controlled non-inferiority trial
The Centers for Disease Control and Prevention
Magnetic resonance imaging
Surgical site infection
Investigators who participated in this study: T. Itamoto (Hiroshima University Hospital, Hiroshima); O. Masaaki (Yamaguchi University Hospital, Yamaguchi); M. Shimada (Tokushima University Hospital, Tokushima); S. Isaji (Mie University Hospital, Mie); T. Kanematsu (Nagasaki University Hospital, Nagasaki); S. Kubo (Osaka City University Hospital, Osaka); K. Chijiiwa (Miyazaki University Hospital, Miyazaki); K. Dono (Toyonaka Municipal Hospital, Osaka); K. Yanaga (Jikei Medical University Hospital, Tokyo); Y. Doki (Osaka University Hospital, Osaka); I. Koyama (Saitama Medical University Hospital, Saitama); K. Hirata (Sapporo Medical University Hospital, Hokkaido); J. Iseki (Shizuoka General Hospital, Shizuoka); K. Miyazaki (Saga University Hospital, Saga); Yamaue (Wakayama Medical University Hospital, Wakayama); M. Miyazaki (Chiba University Hospital, Chiba); S. Uemoto (Kyoto University Hospital, Kyoto); Y. Nakajima (Nara Medical University Hospital, Nara); M. Unno (Tohoku University Hospital, Miyagi); H. Saitsu (National Kyushu Medical Center, Fukuoka); M. Yamamoto (Tokyo Women's Medical University Hospital, Tokyo); S. Kudo (Showa University Hospital, Yokohama); M. Watanabe (Kitasato University Hospital, Kanagawa); J. Nagao (Toho University Hospital Ohashi Medical Center, Tokyo); T. Nonami (Aichi Medical University Hospital, Aichi); S. Ono (National Defense Medical College Hospital, Saitama); M. Shibazaki (Tokyo Yamate Medical Center, Tokyo); K. Yamaguchi (University of Occupational and Environmental Health, Fukuoka); H. Baba (Kumamoto University Hospital, Kumamoto); I. Endo (Yokohama City University Hospital, Kanagawa); Y. Kitagawa (Keio University Hospital, Tokyo); S. Natsugoe (Kagoshima University Hospital, Kagoshima); K. Shirouzu (Kurume University Hospital, Fukuoka); G. Wakabayashi (Iwate Medical University Hospital, Iwate); H. Fujii (University of Yamanashi Hospital, Yamanashi); K. Hanazaki (Kochi Medical University Hospital, Kochi); Y. Sasaki (Yao Municipal Hospital, Osaka); K. Yoshida (Gifu University Hospital, Gifu).
We thank all patients and their relatives for participating in this study, and all medical staff at the 39 participating sites for their cooperation. We also thank Prof Yasuhiko Mohri, Department of Gastrointestinal and Pediatric Surgery, Mie University for his assistance with data management, Prof Yukinori Kurokawa, Department of Gastroenterological Surgery, Osaka University for providing a study protocol on antimicrobial prophylaxis in gastric cancer surgery, Prof Mitsuru Yanai, Department of General Medicine, Nihon University for his assistance with data interpretation, Prof Masashi Fujii, Department of Digestive Surgery, Nihon University for his statistical review, and Prof. Satoshi Hori, Department of Infection Control Science, Juntendo University for his critical review.
Concept and design: TT, MO, HM, and YS. Acquisition or interpretation of data: TT, MO, TI, MS, SI, TK, and SK. Drafting of the manuscript: TT, and OA. Critical revision of the manuscript: TT, MO, Shibata, MK, and YS. Statistical analysis: TS.
This trial was funded by a grant from the Japan Society for Surgical Infection, Tokyo, Japan, which is a non-profit organization established to control surgery-related infections, initiated and sponsored this study, but had no role in the study design or the collection, analysis, and interpretation of data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
All authors declare no conflicts of interest.
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