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.

Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C‐Reactive Protein in Hospitalized Patients With Gram‐Positive Infections

“…5, 6 Matsumoto et al suggested a target AUC 24 /MIC ratio of ࣙ900. [14][15][16][17] Therefore, an optimal loading dose is necessary to promptly achieve the target C min (>15 mg/L), 8,9,18,19 but the standard dose (400 mg of teicoplanin twice a day as a loading dose at day 1 and 400 mg once a day as the maintenance dose) is insufficient to obtain the target concentration. [8][9][10][11][12][13] Teicoplanin has a long elimination half-life (>30 hours), which leads to prolongation of the time needed to achieve a steady state.…”

“…[8][9][10][11][12][13] Teicoplanin has a long elimination half-life (>30 hours), which leads to prolongation of the time needed to achieve a steady state. [14][15][16][17] Therefore, an optimal loading dose is necessary to promptly achieve the target C min (>15 mg/L), 8,9,18,19 but the standard dose (400 mg of teicoplanin twice a day as a loading dose at day 1 and 400 mg once a day as the maintenance dose) is insufficient to obtain the target concentration. 9,20 Recently, a higher loading dose (ࣙ600 mg) and dose adjustment based on the total body weight (ࣙ10 mg/kg) have been recommended to quickly achieve the target C min .…”

Hospital Pharmacometrics for Optimal Individual Administration of Antimicrobial Agents for Anti-methicillin-resistant <i>Staphylococcus aureus</i> Infected Patients

“…28,32) We simulated the probability of achieving the target concentration range at steady-state using a Monte Carlo simulation to investigate the optimal loading and maintenance dose. 30) The result of the simulation suggested that a 1200 mg/d loading dose and 600 mg maintenance dose might be necessary to maintain > 15 mg/L of C min (at a probability of > 80%). In patients with severe infection, a loading dose of 1600 mg/d and a maintenance dose of 800 mg might be necessary to maintain > 20 mg/L of C min (at a probability of 80%).…”

“…22) TEIC has a long elimination half-life (> 30 h), and it takes a long time to reach steady-state. [24][25][26][27] Therefore, a loading dose is recommended to achieve the target concentration promptly in the initial administration, [28][29][30][31] but it has been reported that the standard loading dose (i.e., 400 mg of TEIC twice a day) is insufficient. 28,32) We simulated the probability of achieving the target concentration range at steady-state using a Monte Carlo simulation to investigate the optimal loading and maintenance dose.…”