Comparison of Measured Trough Values after Deriving the Initial Dose Setting of Vancomycin with a Conventional Computer Software and a Nomogram Based on the Revised Japanese 2016 Therapeutic Drug Monitoring Guidelines for Antimicrobial Agents

Abstract

Background: Due to the relatively high renal toxicity of vancomycin injection (VCM), setting an initial dose that achieves a trough that ranges between 10 and 20 μg/mL on day 3 is important to ensure safety and minimize side-effects, especially for patients with low renal function. To address these issues, the revised 2016 Therapeutic Drug Monitoring (TDM) Guidelines for Antimicrobial Agents (GL2016) proposed the use of a renal function-based, estimate glomerular filtration rate (eGFR) nomogram for setting the dose of VCM in Japan. Methods: Our hospital introduced the use of the GL2016 in September 2016 for the patients administered VCM. After setting the initial VCM dose using 1) a conventional VCM analysis software and 2) the GL2016 eGFR nomogram, the measured trough values on day 3 were compared and evaluated in this study. Results: With the VCM analysis software, the mean measured trough value in the a-total group (n = 53) was 12.8 ± 4.7 μg/mL. With the eGFR nomogram, the mean measured trough value in the b-total group (n = 13) was 9.6 ± 4.6 μg/mL. However, when the different severities of renal function were compared, the mean measured trough value was more significantly lower in the b-1 group than in the a-1 group among subjects with G2 and above (eGFR ≥ 60 mL/min/1.73 m 2), but it was similar between the a-2 group and the b-2 group among subjects with G3 and below

Analysis of Risk Factors Associated with Reduced Trough Concentrations of Vancomycin in Relation to Renal Function in a Tertiary Hospital in Japan

“…5,6 We previously reported that mean measured VCM trough values in the patients treated according to established guidelines were generally lower compared with the patients treated not according to established guidelines. 11 In other words, although using the GL2016 nomogram is associated with enhanced safety, it might reduce clinical efficacy. In order to correct this issue, the GL2016 added an amendment that recommended an initial loading dose of VCM that is slightly higher than that typically given on the first day, in order to enhance clinical efficacy on day 1.…”

“…12 In our previous study, when patients with different severities of renal dysfunction were compared, groups with low renal function had trough VCM levels within the range of adequate blood concentrations when we performed the nomogram-guided monitoring recommended by the GL2016. 11 Masuda et al retrospectively calculated the eGFR of patients after establishing the initial VCM dose using the computer software for calculation of VCM trough concentration evaluated the efficacy and safety of the dosage recommended by the nomogram, and suggested that an eGFR of between 30 and 80 mL/min/1.73 m 2 might prevent achievement of an adequate blood concentration of VCM. 17 Suzuki et al retrospectively examined the proportion of patients who achieved the recommended trough levels in the GL2016 group and found that 27.9% of the subjects in the TDM implementation group achieved a trough level ranging between 10 and 15 μg/mL, although 11.6% of the subjects had trough levels that exceeded 20 μg/mL, similar to the results of our previous study (31%).…”

“…17 Suzuki et al retrospectively examined the proportion of patients who achieved the recommended trough levels in the GL2016 group and found that 27.9% of the subjects in the TDM implementation group achieved a trough level ranging between 10 and 15 μg/mL, although 11.6% of the subjects had trough levels that exceeded 20 μg/mL, similar to the results of our previous study (31%). 11,18 The reasons for these variable results might be due to differences in the patients' background characteristics, including age and inflammation status, as is reflected by ARC, which might frequently lead to the underestimation of renal function and the VCM doses that should be given. Therefore, AUC-guided monitoring is usually recommended over trough-guided monitoring, although both VCM trough concentrations and AUC values correlate with its efficacy and safety.…”

“…The probability of achieving the PD target of AUC24/MIC ≥400 in patients treated with VCM was assessed using AUC24/MIC model and parameters estimated from the PK analysis using by the VCM analysis computer software (VCM-soft). 11…”

“…However, low trough concentrations of VCM were frequently observed in patients with deterioration of renal function in whom relatively lose doses of VCM might have been administered. 11 Additionally, the clinical risk factors associated with low VCM trough concentrations in patients stratified according to renal function are unclear. In this study, we analyzed patients who received VCM intravenously in order to determine the risk factors of lower VCM trough concentration and insufficient clinical effect by comparing patients with normal renal function, with an eGFR of ≧60 mL/min/1.73 m 2 , with patients with renal dysfunction, with an eGFR of <60 mL/min/1.73 m 2 , and found C-reactive protein (CRP) levels were significantly higher in lower VCM concentration than appropriate VCM concentration subgroups.…”