Therapeutic drug monitoring of vancomycin in the real-world clinical practice of treating patients with deep suppuration after hip arthroplasty

Abstract

Relevance. Vancomycin, like other glycopeptide antibiotics, is characterized by its pharmacokinetic and pharmacodynamic profile by both time-dependent and concentration-dependent bactericidal effect. Its optimal achievement is ensured by maintaining the drug concentration several times higher than the minimum inhibitory concentration (MIC). Exceeding peak concentrations of vancomycin (> 20 µg/ml) increase the risk of nephrotoxicity, and extremely low (<9.9 µg/ml) — selection of resistant forms of Gram-positive microorganisms.Objective of this study is to evaluate the achievement of target level of vancomycin concentration in plasma of patients with deep suppuration after hip arthroplasty based on therapeutic drug monitoring.Methods. The study included patients who received infusion therapy with vancomycin in the purulent department of traumatology and orthopedics of the University Clinic of the Privolzhsky Research Medical University for deep suppuration after hip arthroplasty in the period from 01.03.2023 to 30.06.2023. The study was conducted without correction for the trade name of vancomycin. Therapeutic drug monitoring was performed on the third day after the start of therapy (after the 4th administration). Blood sampling was performed 1 hour after infusion and 1 hour before subsequent infusion. Vancomycin in blood plasma was determined by high-performance liquid chromatography using a chromatograph "LC-20 Prominance" (Shimadzu, Japan) in reverse phase mode with matrix photodiode detector of UV and visible spectra (SPD–M20A).Results. A total of 14 patients were included in the study, including 6 males and 8 females. The mean age of the patients was 60.36±12.38 years. Bacterial flora was detected in all patients included in the study. Resistant Gram-positive microorganisms were isolated: St. aureus (MRSA) — 5, in 9 patients — coagulase-negative staphylococci (St. epidermidis (MRSE) — 7, St. simulans — 2). Therapeutic concentrations of both initial and residual concentrations were achieved in 28.57% of cases. In 71.43% of cases residual concentrations had values <10 µg/ml, which corresponded to extremely low values, not sufficient for clinical effect associated with eradication of the pathogen at MPC = 1 µg/ml. At the same time initial concentrations of vancomycin were defined as extremely low in 14.29% of cases, and in 42.86% — as exceeding the therapeutic range. Vancomycin concentrations in the therapeutic range of 10 to 20 µg/ml 1 hour after infusion (initial concentrations) were determined in 42.86% of patients.Conclusion. The results of therapeutic drug monitoring of vancomycin in patients with deep suppuration after hip arthroplasty show a wide range of concentrations. A high proportion of residual concentrations at extremely low levels (<9.9 μg/ml) was observed, which is consistent with the results of other studies and confirms the need for therapeutic drug monitoring in every patient receiving vancomycin therapy.