Is current guidance for cloxacillin prophylaxis dosages in hip and knee arthroplasty adequate? Evidence from a prospective Swedish cohort

OBJECTIVES: Perioperative antibiotic prophylaxis is crucial for preventing detrimental postoperative prosthetic joint infections (PJIs). Guidelines aim to prevent infection with methicillin-susceptible staphylococci-in Sweden through administering cloxacillin, at fixed doses with minimal consideration to kidney function or patient weight. Over- and under-dosing could have adverse effects, negative effects on the microbiome, or increase the risk of PJI. We aimed primarily to evaluate whether the current uniform prophylactic regimen of cloxacillin in hip and knee arthroplasty is adequate. PATIENTS AND METHODS: Patients subjected to elective prosthetic joint surgery (N = 204) were included in a prospective study. Free plasma concentrations of cloxacillin were measured on three occasions throughout arthroplasty surgery. Samples were analysed using a validated HPLC-MS/MS method. A free concentration of 90 mL/min/1.73 m2, body weight >100 kg and long duration of surgery significantly predicted suboptimal concentrations. CONCLUSIONS: Current cloxacillin dosing in hip and knee arthroplasty surgery results in a risk for subtherapeutic levels in patients with high body weight and preserved renal function. Therefore, dosing guidelines for cloxacillin prophylaxis in arthroplasty should be reviewed.