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Background Optimal timing for rifampicin combination therapy in patients with staphylococcal vascular graft/endograft infection (S-VGEI) is unknown. Experts recommend adding rifampicin after lowering bacterial load by surgery and wound closure. Objectives To assess predictors of rifampicin resistance among staphylococci isolated from patients in the Vascular Graft Infection Cohort Study. Methods We included prospective patients with S-VGEI diagnosis from 1 January 2002 to 30 June 2020. We retrospectively assessed determinants of rifampicin resistance using exact logistic regression and described survival with Kaplan–Meier curves. Results We analysed 513 Staphylococcus spp. among 143 predominantly male (82%) patients with a median age of 68 years (IQR 60–75). Thereof, 82 (57%) received a rifampicin combination therapy and 61 (43%) received an antimicrobial therapy without rifampicin. Among 82 patients with rifampicin, 26/26 patients with any rifampicin resistance had open wounds with a strong association of rifampicin resistance with rifampicin treatment while having open wounds (OR 37, 95% CI 6.1 to ∞). Among 75 patients with a rifampicin combination therapy and rifampicin-susceptible staphylococci at S-VGEI diagnosis, 12/12 patients with a secondary rifampicin-resistant isolate had an open wound (OR 14, 95% CI 2.1 to ∞). Conclusions Rifampicin should be started after wound closure due to increased risk of rifampicin resistance observed while having open wounds or second-look surgeries among patients with S-VGEI.

Open wounds and rifampicin therapy are associated with rifampicin resistance among staphylococcal vascular graft/endograft infections