Does cumulative topical antibiotic powder use increase the risk of drug induced acute kidney injury in fracture patients?

Abstract

Aims There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients. Methods This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin. Results Of the 782 included patients (mean age 48 years (SD 20); 59% male), 83% (n = 648) received at least one vancomycin dose (cumulative range 1 to 12 g). Overall, 45% of the sample received at least one tobramycin dose (cumulative range 1.2 to 9.6 g). Drug-induced AKI occurred in ten patients (1.2%). No association was found between the cumulative dose of vancomycin and drug-induced AKI (odds ratio (OR) 1.08 (95% credible interval (CrI) 0.52 to 2.14)). Additional doses of tobramycin were associated with a three-fold increase in the adjusted odds of drug-induced AKI (OR 3.66 (95% CrI 1.71 to 8.49)). Specifically, the risk of drug-induced AKI rose substantially after 4.8 g of tobramycin powder (7.5% (95% CrI 1.0 to 35.3)). Conclusion Cumulative doses of vancomycin were not associated with an increased risk of drug-induced AKI among fracture patients. While the risk of drug-induced AKI remains less than 4% with three or fewer 1.2 g tobramycin doses, the estimated risk increases substantially to 8% after four cumulative doses. Level of evidence: Therapeutic Level III Cite this article: Bone Jt Open 2022;3(4):284–290.

Orthopaedic infections: what have we learned?

“…55,58 While a recent secondary analysis of a RCT found no increase in nephrotoxicity with cumulative dosing of topical vancomycin, there was a substantially increased risk of acute kidney injury (8%) after more than 3 doses of 1.2g tobramycin. 61 A second concern is the potential for selecting out antibioticresistant organisms. This issue is of course a theoretical concern with the use of any antibiotics but is more of a possibility with long duration of low doses of antibiotics below the MIC.…”

“… 55 , 58 While a recent secondary analysis of a RCT found no increase in nephrotoxicity with cumulative dosing of topical vancomycin, there was a substantially increased risk of acute kidney injury (8%) after more than 3 doses of 1.2 g tobramycin. 61 …”