Systemic Absorption Resulting from Tobramycin-Loaded Antibiotic Cement Spacers Used in the Treatment of Prosthetic Joint Infection.

Abstract

Antimicrobial cement spacer (ACS) placement has been a cornerstone of two-stage management of prosthetic hip and knee infection. Pharmacokinetic modelling has described peak systemic antibiotic concentrations within the first 24-48h post-operatively, followed by rapid clearance. A few studies have, however, identified detectable tobramycin levels in patients with a post-operative decline in creatinine clearance. Our study sought to determine how frequently detectable serum tobramycin levels occurred within the first 72h following ACS placement in all patients regardless of baseline or subsequent changes in renal function, whether these levels correlated with tobramycin spacer dosage, creatinine clearance, or potential nephrotoxicity risk factors, and whether any patients developed acute kidney injury within the 14-day post-operative period. We prospectively enrolled patients with prosthetic hip or knee infections and subsequent ACS placement from October 2017 to February 2020. Patient comorbidities (chronic kidney disease, diabetes mellitus, chronic liver disease, chronic obstructive pulmonary disease, and atrial fibrillation), Charleston Comorbidity Index score, risk factors for post-operative nephrotoxicity (perioperative hypotension and nephrotoxic agent receipt), total tobramycin dosage, post-operative days 1 and 3 serum tobramycin concentrations, and serum creatinine and creatinine clearance throughout a 14-day post-operative period were recorded. A total of 20 patients were enrolled, comprising 20 spacers with a median total tobramycin dosage of 4.80g with an interquartile range (IQR) of 4.13-7.20g. Thirteen patients had a median detectable post-operative day 1 serum tobramycin concentration of 0.80 (IQR 0.50-1.60) mcg/mL. Five of these 13 patients had a median detectable post-operative day 3 serum tobramycin concentration of 0.80 (IQR 0.50-1.10) mcg/mL. A correlation was not found between serum tobramycin drug levels and patient comorbidities, receipt of nephrotoxic medications, or baseline and subsequent post-operative creatinine clearance up to day 14. The majority of patients who underwent tobramycin ACS placement had detectable serum tobramycin levels in the immediate post-operative period, but most reached undetectable levels within 72h. There were no reliable perioperative predictors of detectable drug levels.