title: Area under the concentration-time curve to minimum inhibitory concentration ratio as a predictor of vancomycin treatment outcome in methicillin-resistant Staphylococcus aureus bacteraemia.
abstract: There have been few clinical studies on the association between the 24-h area under the concentration-time curve (AUC24) to minimum inhibitory concentration (MIC) ratio and vancomycin treatment outcomes in methicillin-resistant Staphylococcus aureus (MRSA) infections. Patients with MRSA bacteraemia between July 2009 and January 2012 were analysed retrospectively. All adult patients treated with vancomycin for ≥72 h without dialysis were included. The MIC was determined by Etest and broth microdilution (BMD). Initial steady-state AUC24 was estimated using a Bayesian model, and the AUC24/MIC cut-off value for differentiating treatment success and failure was calculated by classification and regression tree (CART) analysis. In total, 76 patients were enrolled; vancomycin treatment failure occurred in 20 patients (26.3%). Catheter-related infection was the most frequent (35.5%), followed by surgical site infection (26.3%), whilst 25 (32.9%) had complicated infections. In univariate analysis, decreased MRSA vancomycin susceptibility (MIC≥1.5 mg/L) and vancomycin trough levels (15-20 mg/L) were not associated with treatment outcomes. In the CART analysis, low initial vancomycin AUC24/MIC (<430 by Etest; <398.5 by BMD) was associated with a higher treatment failure rate (50.0% vs. 25.0%, P=0.039 by Etest; 45.0% vs. 23.2%; P=0.065 by BMD). In multivariate analysis, low initial vancomycin AUC24/MIC was a significant risk factor for treatment failure [adjusted odds ratio (aOR)=4.39, 95% confidence interval (CI), 1.26-15.35 by Etest; aOR=3.73, 95% CI 1.10-12.61 by BMD]. In MRSA bacteraemia, a low initial vancomycin AUC24/MIC is an independent risk factor for vancomycin treatment failure.
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea.
authors: Younghee
authors: Y
authors: Jung
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: khsongmd@gmail.com.
authors: Kyoung-Ho
authors: KH
authors: Song
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea.
authors: Jeong eun
authors: Je
authors: Cho
authors: Department of Pharmacy, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Hyung-sook
authors: HS
authors: Kim
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Nak-Hyun
authors: NH
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Taek Soo
authors: TS
authors: Kim
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Pyoeng Gyun
authors: PG
authors: Choe
authors: Department of Clinical Pharmacology and Therapeutics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Jae-Yong
authors: JY
authors: Chung
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Wan Beom
authors: WB
authors: Park
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Ji Hwan
authors: JH
authors: Bang
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Eu Suk
authors: ES
authors: Kim
authors: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors: Kyoung Un
authors: KU
authors: Park
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Sang-Won
authors: SW
authors: Park
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, 173 Gumi-ro, Bundang-gu, Seongnam 463-707, Republic of Korea; Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Hong Bin
authors: HB
authors: Kim
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Nam Joong
authors: NJ
authors: Kim
authors: Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Myoung-don
authors: MD
authors: Oh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Area under the concentration–time curve; Bacteraemia; Methicillin-resistant Staphylococcus aureus; Minimum inhibitory concentration; Vancomycin