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

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 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 <2 mg/L was deemed a theoretically appropriate concentration to suppress growth of methicillin-susceptible staphylococci in bone. A sensitivity analysis with values of 1 and 4 mg/L was included.

Potentially subtherapeutic concentrations (≤2 mg/L) at the end of surgery were found in 31 cases (15%). The corresponding numbers for 1 and 4 mg/L were 3 and 88 (1% and 43%). In multivariable logistic regression analysis, an ASA (American Association of Anesthesiologists physical status) score of I (relatively healthy patients), estimated glomerular filtration rate >90 mL/min/1.73 m2, body weight >100 kg and long duration of surgery significantly predicted suboptimal concentrations.

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.