Pharmacodynamic evaluation of vancomycin by Monte Carlo simulation against Staphylococcus spp isolated in a hospital teaching

Abstract

Background: Vancomycin is the first-choice drug for the treatment of Gram-positive infections. The pharmacokinetic (PK) and pharmacodynamic (PD) indexes of this antimicrobial are the main determinants of its in vivo efficacy. The PK/PD parameter to vancomycin is the 24-h area under the curve to minimum inhibitory concentration ratio (AUC24/MIC ≥ 400), which can be associated with improvement of treatment outcomes. The aim of this study was to evaluate the therapeutic success probability of different dosing regimens of vancomycin by Monte Carlo simulation (MCS) and compare its coverage to vancomycin MIC against staphylococci isolates from a brazilian teaching hospital over six years (2011 to 2016). Methods & Materials: In total, 1112 clinical samples were enrolled, 578 Staphylococcus aureus and 426 Staphylococcus epidermidis. The vancomycin MICs were obtained by automated Phoenix BDTM. The AUC24/MIC index of vancomycin was evaluated by MCS in the following dosing regimens: 1 g every 12 h (q12 h), 1 g q8 h, 1 g q6 h and 1.5 g q6 h. The probability of target attainment (PTA) ≥ 0.9 and AUC / MIC ≥ 400 were considered adequate. Results: During the six years of the study, no change was observed in MIC50 and MIC90 of vancomycin for Staphylococcus aureus (MIC = 1 μg/mL). In the same period we identified that MIC50 = 1 μg/mL for S. epidermidis in 2011 increased to 2 μg/mL from 2014, while MIC90 = 2 μg/mL was predominant. The PK/PD analysis of the different dosing regimens showed that vancomycin 1 g q12 h achieved adequate PTA only for MIC = 0.5 μg/mL. Vancomycin 1 g q8 h and 1 g q6 h reached the MIC target ≤ 1 μg/mL, while 1.5 g q6 h covered MIC up to 2 μg/mL. No dosing regimen proposed in this study achieved adequate PTA for MIC > 2 μg/mL. Conclusion: The results showed that vancomycin achieved pharmacodynamic coverage for MIC = 1 μg/mL in high daily doses (≥3 g); for MIC = 2 μg/mL to achieve the same therapeutic target, 6 g/day was required. Considering that high daily doses of vancomycin increase the risk of toxicity, we suggest the individual and monitored use of this antimicrobial to optimize PK/PD parameters, or when possible, the use of other antimicrobial agent with activity against these microorganisms.