title: Change of teicoplanin loading dose requirement for incremental increases of systemic inflammatory response syndrome score in the setting of sepsis.
abstract: Background Target trough concentrations are recommended for teicoplanin (TEIC) to minimize its adverse effects and to maximize efficacy in sepsis caused by grampositive cocci, including methicillin-resistant Staphylococcus aureus infection. However, optimal doses to attain proper trough values in patients with sepsis have not yet been well established for TEIC. Objective This study investigated whether the systemic inflammatory response syndrome (SIRS) score could predict the pharmacokinetics of TEIC in patients with sepsis. Setting This study was conducted at Fukuoka University Hospital in Japan. Methods We retrospectively reviewed the records of patients using TEIC between April 2012 and March 2015. SIRS positive was defined as infection with a SIRS score ≥2. Estimates of pharmacokinetic parameters were calculated using a Bayesian method. Creatinine clearance rates were estimated by the Cockcroft-Gault formula (eCcr). Main outcome measure Change of TEIC loading dose requirement for incremental increases of SIRS score. Results In total, 133 patients were enrolled: 50 non-SIRS patients and 83 patients with SIRS. The TEIC plasma trough concentration was significantly lower in SIRS than non-SIRS patients (15.7 ± 7.1 vs. 20.1 ± 8.6 μg/mL; P < 0.01), although there was no significant difference in the loading dose administered. Moreover, SIRS scores were increasingly predictive of eCcr and TEIC clearance in a stepwise manner. To achieve the target trough concentration (15-30 μg/mL), the optimal doses required in non-SIRS versus SIRS patients were 12-24 versus 18-30 mg/kg/day, respectively, during the first 48 h. Conclusions These findings suggest that the pharmacokinetics of TEIC are altered in SIRS patients, who required higher doses than non-SIRS patients to achieve the target trough concentration. We suggest that the SIRS score can become a new modality to determine the initial TEIC loading dose.
authors.affiliation: Department of Pharmacy, Fukuoka University Hospital, Nanakuma 7-45-1, Jyonan-Ku, Fukuoka, 814-0180, Japan. naka0625@fukuoka-u.ac.jp.|Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. naka0625@fukuoka-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Oncology, Hematology, and Infectious Diseases, Fukuoka University, Fukuoka, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Takata
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Irie
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Pharmacy, Fukuoka University Hospital, Nanakuma 7-45-1, Jyonan-Ku, Fukuoka, 814-0180, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Imakyure
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Pharmacy, Fukuoka University Hospital, Nanakuma 7-45-1, Jyonan-Ku, Fukuoka, 814-0180, Japan.
authors.forename: Koujiro
authors.initials: K
authors.lastname: Futagami
mesh_terms: D000368:Aged; D001499:Bayes Theorem; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D017334:Teicoplanin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D017334:Teicoplanin
keywords: Inflammatory response; Pharmacokinetics; Severe sepsis; Systemic inflammatory response syndrome; Teicoplanin