1551. Systemic Tobramycin Absorption Resulting from Antibiotic-Impregnated Cement Spacers for the Treatment of Prosthetic Joint Infection

Abstract

BackgroundAntibiotic-impregnated cement spacer (ACS) placement has been a cornerstone of two-stage surgical management of prosthetic hip and knee infection for decades. Utilized antibiotics have included aminoglycosides and vancomycin. Pharmacokinetic modeling studies have described peak systemic levels within the first 24–48 hours post-operatively, followed by rapid clearance. While this systemic exposure was previously felt insufficient to cause organ toxicity, a few studies have described antibiotic-induced nephrotoxicity.MethodsWe prospectively enrolled patients with prosthetic hip or knee infection, and subsequent ACS placement, containing vancomycin and tobramycin, from October 2017 to February 2019, at Allegheny General Hospital. Risk factors for post-operative nephrotoxicity, including patient comorbidities, receipt of potentially nephrotoxic medications, estimated creatinine clearance (CrCl), perioperative hypotension, total spacer tobramycin dosage, and post-operative day 1 (POD1) and 3 (POD3) serum tobramycin levels were recorded. Patients who had antibiotic cement spacer exchange, or had received systemic aminoglycoside therapy, were excluded.ResultsThirteen patients were enrolled, comprising 4 hip and 9 knee ACS, with respective median (interquartile range (IQR)) tobramycin cement dosages of 3.8 (2.86–4.58) and 4.8 (4.8–9.6) grams. Tobramycin levels were measured at a median 16.5 and 60.7 hours on POD1 and POD3, respectively. Three hip and six knee ACS had respective, detectable POD1 median serum tobramycin levels of 0.6 (0.38–1.20) and 0.8 (0–0.8) μg/mL; three knees, but no hip ACS had detectable POD3 serum tobramycin levels. Six of the nine patients with detectable POD1 serum tobramycin levels had a CrCl of less than or equal to 65 mL/minute (figure), while each patient with detectable POD3 levels had a CrCl of less than 45 mL/minute. No significant changes in baseline CrCl were identified. A relationship between tobramycin cement dosage and detectable serum tobramycin levels was not observed.ConclusionLow baseline CrCl, but not the total tobramycin dosage or other nephrotoxicity risk factors, may be the single most reliable predictor of detectable postoperative systemic tobramycin levels in patients who have received hip or knee ACS. Disclosures All authors: No reported disclosures.