IS ONE DOSE NON-INFERIOR TO FOUR DOSES OF SYSTEMIC ANTIBIOTIC PROPHYLAXIS AGAINST PERIPROSTHETIC JOINT INFECTION IN PRIMARY ARTHROPLASTY?

Aim The current recommendation in Norway is to use four doses of a first-generation cephalosporin (cefazolin or cephalotin) as systemic antibiotic prophylaxis (SAP) the day of surgery in primary joint arthroplasty. Due to shortage of supply, scientific development, changed courses of treatment and improved antibiotic stewardship, this recommendation has been disputed. We therefore wanted to assess if one dose of SAP was non-inferior to four doses in preventing periprosthetic joint infection (PJI) in primary joint arthroplasty. Method We included patients with primary hip- and knee arthroplasties from the Norwegian Arthroplasty Register and the Norwegian Hip Fracture Register for the period 2005-2023. We included the most used SAPs (cephalotin, cefazolin, cefuroxime, cloxacillin and clindamycin), administered as the only SAP in 1-4 doses, starting preoperatively. Risk of revision (Hazard rate ratio; HRR) for PJI was estimated by Cox regression analyses with adjustment for sex, age, ASA class, duration of surgery, reason for- and type of arthroplasty, and year of primary arthroplasty. The outcome was 1-year reoperation or revision for PJI. Non-inferiority margins were calculated for 1, 2 and 3 doses versus reference of 4 doses of SAP at the day of surgery, against a predetermined limit of 15% increased risk of PJI. Results In total 274,188 primary arthroplasties (total hip 133,985, hemi hip 51,442, and total knee 88,761) were included. Of these primary arthroplasties, 2,996 (1.1%) had subsequent revisions for PJI during the first postoperative year. One dose of SAP was given in 9,603 arthroplasties, two doses in 10,068, three doses in 18,351, and four doses in 236,166 arthroplasties. With the recommended four doses as reference, the HRR (95% CI) for 1-year revision for infection was 0.9 (0.7-1.1) for one dose, 1.0 (0.8-1.2) for two doses, and 0.9 (0.8-1.1) for three doses. The corresponding adjusted 1-year revision incidences for PJI was 0.9 (0.7-1.1), 1.0 (0.8-1.2), 0.9 (0. 8-1.1) and 1.0 (1.0-1.1) for one, two, three and four doses respectively, and less than four doses was found to be non-inferior. Conclusions One preoperative dose of SAP in primary joint arthroplasty surgery seems to be non-inferior to the current recommendation of four doses of a first-generation cephalosporin as PJI-prophylaxis. This finding may simplify the course of treatment for arthroplasty patients, save costs, and improve antibiotic stewardship.