Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate–severe Gram-positive infections

Abstract

ObjectivesTeicoplanin, an antibiotic, has poor clinical efficacy when using the current drug label’s recommended regimen, which is approved by the China Food and Drug Administration. This study explores the appropriate loading and maintenance doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough concentration (minimum concentration [Cmin]).Subjects and methodsAll patients treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central Hospital were screened for enrollment. A total of 113 subjects were included and then divided into four groups: A (received three to six doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B (received three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D (received one to three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were detected with high-performance liquid chromatography on day 4, 30 minutes before maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were compared among the four groups.ResultsMean Cmin differed significantly among the four groups (A, 18.11±6.37 mg/L; B, 15.91±4.94 mg/L; C, 17.06±5.66 mg/L; D, 11.97±3.76 mg/L) (P<0.001), with creatinine clearance of 89.62 (53.72–162.48), 49.66 (40.69–59.64), 27.17 (9.7–39.45), and 96.6 (17.63–394.73) mL/min, respectively. The ratio of loading dose for 3 days to creatinine clearance and serum Cmin were significantly correlated (R=0.59, P<0.001). The correlation between the estimated probability of success and teicoplanin Cmin was assessed using binary logistic regression (OR 2.049, P<0.001). Hepatotoxicity- and nephrotoxicity-incidence rates did not significantly differ among the four groups (P=0.859 and P=0.949, respectively).ConclusionA loading dose of 400 mg at 12-hour intervals three to six times is needed to achieve the early target range (15–20 mg/L) and improve the clinical efficacy rate for normal-renal-function patients. It is urgently necessary to amend the drug label for the recommended regimen.

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

“…Therefore, several loading dose regimens have been proposed to quickly obtain the target teicoplanin C min (15-30 mg/L). [8][9][10][11][12][13] These regimens were compared by simulating the probabilities of reaching the target C min at days 1, 3, and 7 using the final population PK model from this study. Although only 13% to 15% of patients with the standard loading regimen (400 mg every 12 hours) attained the target C min on day 1 (after 2 administrations of the loading dose), 56% to 59% of .…”

“…4 The clinical benefit of teicoplanin is associated with the ratio of the area under the drug concentrationtime curve (AUC) to the minimum inhibitory concentration (MIC). [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. 6 The use of therapeutic drug monitoring has been recommended with a target minimum concentration (C min ) range of 15-30 mg/L, 7 but the optimal dosing regimen is not yet known.…”

“…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 .…”

Effectiveness of Teicoplanin Versus β-lactam for Bacteremia Due to Methicillin-Susceptible Staphylococcus Aureus: A Propensity Score-Based Study

“…Adequate dosage was de ned as dosage based on the manufacturer's instructions (Sano -Aventis, Taiwan). Teicoplanin was prescribed at a loading dose of 6 mg/kg (three loading doses 12 hours apart) followed by a maintenance dose of 6 mg/kg every 12 hours or adjusted equivalent doses for patients with impaired renal function [20,21].…”