One of the best approaches we have for dealing with in-hospital antimicrobial resistance is stewardship - using antibiotics only when the patient is most likely to benefit. It's been known for a long time that there is little benefit in extending prophylactic antibiotics beyond the end of surgery, yet this practice still persists. Imamura et al. just published an RCT in Lancet ID that examined the possible benefits of extending prophylaxis in patients with gastric cancer undergoing distal gastrectomy for cure.
The trial was an open-label, stratified (by ASA score) randomized trial in seven hospitals. All patients were assigned (1:1) to receive cefazolin 1g before incision and every 3 hours. Those in the extended prophylaxis group received 1g at closure and twice daily for two postoperative days. Using CDC definitions, infection control staff monitored for SSI while in hospital and surgeons monitored post-discharge for 30 days.
In the intention-to-treat analysis, 176 patients received standard prophylaxis and 179 received extended prophylaxis. Randomization appeared adequate with similar operative times and estimated blood loss in each arm; however, 4 patients in the extended prophylaxis arm received transfusions versus none in the standard arm. I've pasted Table 2 above, so you can see the results broken down into superfical and deep SSI. Twice as many patients in the extended arm developed an SSI (RR 0.51 95% CI 0.22-1.16), but this was not statistically significant. Caveats: open-label study and SSI not monitored by independent researchers after discharge.
The authors and the accompanying editorial (both behind a paywall) each conclude that extended prophylaxis is not recommended. Although it is likely true, as Hedrick and Sawyer state in their editorial, that "the study is unlikely to have a major impact in the USA and other countries where the maximum duration of perioperative antibiotics is limited to 24 h and is carefully monitored and regulated."