title: Exploration of optimal teicoplanin dosage based on pharmacokinetic parameters for the treatment of intensive care unit patients infected with methicillin-resistant Staphylococcus aureus.
abstract: Severely ill intensive care unit (ICU) patients are frequently at risk of developing methicillin-resistant Staphylococcus aureus (MRSA) infections. It is generally accepted that a trough level of >10 μg/mL teicoplanin (TEC) is appropriate for most such infections. The present study was designed to determine how TEC exposure and patient characteristics affect microbiological response in the treatment of MRSA infections. All patients studied were admitted to Aichi Medical University Hospital ICU between May 2005 and April 2010. Fifty-nine patients were prescribed TEC and 33 of those patients used to treat MRSA infection. Outcome was classified as either cure or failure, and logistic regression analysis was performed to determine which covariates, including severity, significantly influenced the microbiological response. Satisfactory outcomes were obtained in 19 of the 33 patients. Although the cured and failed groups showed adequate trough concentrations, the area under the serum concentration curve (AUC(0-24)) on the third day was significantly higher for the cured group (897.6 ± 71.7) than for the failed group (652.9 ± 83.4) (p < 0.05). The results suggested that at least 800 μg h/mL TEC AUC(0-24) were required to obtain microbiological cure. The higher AUC(0-24), the better the outcome. In our study, higher initial AUC(0-24) was associated with a better microbiological outcome, which demonstrates the importance of the loading dose of TEC, especially for ICU patients. Moreover, the present findings are useful for optimizing the individual dose of TEC using AUC(0-24) in the treatment of MRSA-infected patients.
authors.affiliation: Department of Pharmacy, Aichi Medical University School of Medicine, Nagakute-cho, Aichi-gun, Aichi, 480-1195, Japan. hagimao@aichi-med-u.ac.jp
authors.forename: Mao
authors.initials: M
authors.lastname: Hagihara
authors.forename: Takumi
authors.initials: T
authors.lastname: Umemura
authors.forename: Masao
authors.initials: M
authors.lastname: Kimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Mikamo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016903:Drug Monitoring; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D017334:Teicoplanin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin