Temporal changes and associated factors for elevated serum gentamicin levels in continuous local antibiotic perfusion (CLAP) therapy: A multicenter analysis.

INTRODUCTION

Fracture-related, periprosthetic joint, and surgical site infections are difficult to eradicate once biofilm develops. Continuous local antibiotic perfusion (CLAP) delivers sustained high local gentamicin levels with low systemic exposure, but unexpected serum gentamicin elevation has been reported. This study aimed to describe temporal changes in serum gentamicin during CLAP and identify factors associated with levels ≥2 μg/mL.

METHODS

We conducted a multicenter study within the Trauma Research Group of Nagoya. Among 205 patients treated with CLAP, 131 met the inclusion criteria after the exclusion of patients with chronic dialysis, short follow-up periods, missing gentamicin data, and baseline aspartate aminotransferase or alanine aminotransferase >80 U/L. CLAP routes, tube configurations, drainage methods, and serum gentamicin levels (baseline, days 3, 1 week, 2 weeks) were recorded. Acute kidney injury (AKI) and hepatotoxicity were defined using standard thresholds. Missing data were handled by multiple imputation.

RESULTS

The median serum gentamicin level remained < 2 μg/mL at all time points, with correlations between day 3 and later levels. Drug-related adverse events occurred in 26.0% of patients. AKI developed in 5.3% (N = 7), 6 patients were with hypertension, and 5 were with knee or lower leg infections, and was associated with significantly higher serum gentamicin concentrations at early time points (day 3 and 1 week) compared with those without AKI. Hepatic dysfunction occurred in 4.6% (N = 6), which all used iSAP, but no significant association with serum gentamicin concentrations was observed. All renal and hepatic events resolved after treatment modification.

CONCLUSIONS

In our cohort, most patients who developed AKI had hypertension and exhibited higher gentamicin concentrations on day 3 and at 1 week than those without AKI. Early monitoring of serum gentamicin concentrations on day 3 may therefore be warranted in all patients undergoing CLAP, particularly in those with hypertension, to assess AKI risk.