Validation of Vancomycin Area under the Concentration-Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections.

Takashi Ueda,Shingo Takubo,Toshie Tsuchida,Yoshiko Takahashi,Kazutaka Oda,Motoi Uchino,Kaori Ishikawa,Kumiko Yamada,Naruhito Otani,Toshimi Kimura,Kazuaki Matsumoto,Kazuhiko Nakajima,Kaoru Ichiki,Mika Ishihara,Hiroki Ikeuchi,Takeshi Kimura,Yoshio Takesue

doi:10.3390/antibiotics11010096

Abstract

Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections.

Highlights

Vancomycin remains a first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections [1]
Among 444 patients with MRSA infections, 312 patients met the inclusion criteria (reasons for exclusion: less than 18 years (33), intermittent hemodialysis (71), and continuous renal replacement therapy (28)), but 52 of these patients were excluded for the following reasons: pregnancy (6), the previous use of antimicrobial agents with anti-MRSA activity (31), and MRSA infections with a vancomycin minimum inhibitory concentration (MIC) = 2 mg/L (15)
Vancomycin was administered with q12h in 202 patients and Antibiotics 2022, 11, 96

Summary

Introduction

Vancomycin remains a first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections [1]. The ratio of the area under the concentration–time curve (AUC). Over 24 h to the minimum inhibitory concentration (MIC) has been demonstrated to reflect the maximal clinical effects of vancomycin [2,3,4,5]. The trough concentration (Cmin ) has been used as a surrogate marker of the AUC. Et al [6] found that among patients with an AUC of ≥400 μg·h/mL and an organism vancomycin MIC of 1 μg/mL, approximately 60% were expected to have a Cmin < 15 μg/mL. Cmin -guided dosing targeting a Cmin ≥ 15 μg/mL may lead to excessive vancomycin exposure.

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