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Randomized Controlled Trial
. 2022 Apr 1;5(4):e226095.
doi: 10.1001/jamanetworkopen.2022.6095.

Effect of Antimicrobial Prophylaxis Duration on Health Care-Associated Infections After Clean Orthopedic Surgery: A Cluster Randomized Trial

Kosei Nagata  1 , Koji Yamada  2 , Tomohiro Shinozaki  3 , Tsuyoshi Miyazaki  4 , Fumiaki Tokimura  4 , Yasuhito Tajiri  5 , Takuya Matsumoto  6 , Kiyofumi Yamakawa  7 , Hiroyuki Oka  8 , Akiro Higashikawa  2 , Toshihide Sato  5 , Kenichi Kawano  5 , Tatsuro Karita  6 , Takuya Koyama  7 , Takahiro Hozumi  7 , Hiroaki Abe  2 , Makoto Hodohara  5 , Kazuhiro Kohata  6 , Masato Toyonaga  2 , Yasushi Oshima  1 , Sakae Tanaka  1 , Hiroshi Okazaki  2 ; OSSI investigators
Collaborators, Affiliations
Randomized Controlled Trial

Effect of Antimicrobial Prophylaxis Duration on Health Care-Associated Infections After Clean Orthopedic Surgery: A Cluster Randomized Trial

Kosei Nagata et al. JAMA Netw Open. .

Abstract

Importance: Postoperative health care-associated infections are associated with a greater deterioration in patients' general health status and social and economic burden, with at least 1 occurring in approximately 4% of acute care hospital patients. Antimicrobial prophylaxis prevents surgical site infections in various orthopedic procedures; however, its relationship with health care-associated infections remains unknown.

Objective: To examine whether a shorter antimicrobial prophylaxis duration of less than 24 hours after surgery is not inferior to a longer duration in preventing health care-associated infections after clean orthopedic surgery.

Design, setting, and participants: This open-label, multicenter, cluster randomized, noninferiority clinical trial was conducted in 5 tertiary referral hospitals in greater Tokyo metropolitan area, Japan, from May to December 2018. Adult patients undergoing clean orthopedic surgery were recruited until the planned number of participants was achieved (500 participants per group). Statistical analysis was conducted from July to December 2019.

Interventions: Antimicrobial prophylaxis was discontinued within 24 hours after surgery in group 24 and 24 to 48 hours after surgery in group 48. Group allocation was switched every 2 or 4 months according to the facility-based cluster rule. Study-group assignments were masked from participants.

Main outcomes and measures: The primary outcome was the incidence of health care-associated infections requiring antibiotic therapies within 30 days after surgery. The noninferiority margin was 4%.

Results: Of the 1211 participants who underwent cluster allocation, 633 participants were in group 24 (median [IQR] age, 73 [61-80] years; 250 men [39.5%] and 383 women [60.5%]), 578 participants were in group 48 (median [IQR] age, 74 [62-81] years; 204 men [35.3%] and 374 women [64.7%]), and all were eligible for the intention-to-treat analyses. Health care-associated infections occurred in 29 patients (4.6%) in group 24 and 38 patients (6.6%) in group 48. Intention-to-treat analyses showed a risk difference of -1.99 percentage points (95% CI, -5.05 to 1.06 percentage points; P < .001 for noninferiority) between groups, indicating noninferiority. Results of adjusted intention-to-treat, per-protocol, and per designated procedure population analyses supported this result, without a risk of antibiotic resistance and prolonged hospitalization.

Conclusions and relevance: This cluster randomized trial found noninferiority of a shorter antimicrobial prophylaxis duration in preventing health care-associated infections without an increase in antibiotic resistance risk. These findings lend support to the global movement against antimicrobial resistance and provide additional information on adequate antimicrobial prophylaxis for clean orthopedic surgery.

Trial registration: Identifier: UMIN000030929.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Yamada reported receiving speaker fees from Johnson & Johnson K.K., Pfizer Japan, 3M Japan, Stryker Japan, Taisho Toyama Pharmaceutical, MSD K.K., Hisamitsu, Kaken Pharmaceutical, Astellas Pharma Inc, Smith & Nephew Japan, Speaker fee, and Daiichi Sankyo Company outside the submitted work. Dr Tanaka reported receiving personal fees and other from Asahi Kasei Pharma Co, personal fees and other from Amgen Astellas BioPharma K.K., personal fees and other from Astellas Pharma Inc, personal fees from Ayumi Pharmaceutical Corporation, personal fees from TSUMRA & Co, personal fees and other from Daiichi Sankyo Company Limited, personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees and other from Chugai Pharmaceutical Co, Ltd, personal fees and other from Teijin Pharma Ltd, personal fees from Eli Lilly Japan K.K., personal fees from Hisamitsu Pharmaceutical Co, Inc, personal fees from Pfizer Japan, personal fees from Bristol-Myers Squibb, personal fees from Taisho Pharmaceutical Co, other from Gilead Science Inc, other from Taiho Pharmaceutical Co, other from Zimmer Biomet G.K., other from Merry Life Co., Ltd., grants from Japan Society for the Promotion of Science (JSPS), grants from The Japan Agency for Medical Research and Development (AMED), and grants from The Ministry of Health Labour and Welfare outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Diagram of Participant Flow Through Trial
Figure 2.
Figure 2.. Differences in Risk According to the Analysis Performed
The point estimates for the differences in the occurrence of health care–associated infections (HAIs) (panel A) and surgical site infections (panel B) are shown with 2-sided 95% CIs. The vertical dotted line indicates the noninferiority margin. Noninferiority was consistent in both the intention-to-treat (ITT) and per-protocol populations in terms of HAIs. For the ITT populations, model A was adjusted for operation type. For model B, in addition to the operation type, the following variables were included: age (<65 vs ≥65 years), sex, diabetes, American Society of Anesthesiologists score (grouping 1 and 2, and 3 and 4), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) (<30 vs ≥30), operative time (<150 min vs ≥150 min), and estimated blood loss (<1000 mL vs ≥1000 mL). For model C, general anesthesia (any vs none) and use of urinary catheter (any vs none) were also included.
Figure 3.
Figure 3.. Cumulative Incidence Probability of Health Care–Associated Infections and Surgical Site Infections in Group 24 and Group 48
The hazard ratio of group 24 vs group 48 was estimated using the Cox proportional hazard model in the intention-to-treat population for health care–associated infections (HAIs) (panel A) and surgical site infections (SSIs) (panel B).
See this image and copyright information in PMC

References

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