Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections

Nakamura, Atsuo; Takasu, Osamu; Sakai, Yoshiro; Sakamoto, Teruo; Yamashita, Norio; Mori, Shinjiro; Morita, Takeshi; Nabeta, Masakazu; Hirayu, Nobuhisa; Yoshiyama, Naomasa; Moroki, Mariko; Tashiro, Keita; Kannae, Mikinori

doi:10.1016/j.jiac.2015.02.002

Cited by 32 publications

(57 citation statements)

References 19 publications

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“…Several doses (loading doses 400-800 mg or 10-15 mg/kg and maintenance dose 200-800 mg or 5-15 mg/kg) were selected based on the standard dosing regimen and the recommendation in previous studies, [10][11][12][13] and the probabilities of reaching the target C min (15-30 mg/L) at days 1, 3, and 7 in 1000 virtual patients were compared. One thousand virtual patients were randomly generated by uniform random numbers based on 95% observation intervals of patients in the popPK analysis (TBW 34-90 kg, height 139-176 m, CLcr 1.1-10.4 L/h) using R 3.5.0 (Vienna, Austria).…”

Section: Population Pkpd Simulationmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…[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. [10][11][12][13] Assessment of clinical efficacy in patients with infections is usually based on the serum concentrations of C-reactive protein (CRP). 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 .…”

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confidence: 99%

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

Ogami

Tsuji

Mizoguchi

et al. 2019

Clinical Pharm in Drug Dev

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Teicoplanin is an antibiotic agent used for the treatment of Gram-positive infections. The clinical benefit of teicoplanin is associated with its blood concentrations, but the optimal dosing regimen is not yet known. To explore the optimal individual dosing regimen, we performed a population pharmacokinetic (PK) and pharmacodynamic (PD) analysis targeting a large-scale population, including patients with a wide range of ages, body weights, and renal functions. The PK of teicoplanin was described with a 2-compartment model, and the PD of C-reactive protein (CRP) concentrations was described with a turnover maximum inhibition model. The elimination half-life of teicoplanin calculated from the final estimated parameters was 169 hours, and renal function was a significant covariate of teicoplanin clearance. The teicoplanin concentration producing 50% of the maximum inhibition of CRP production was estimated to be 2.66 mg/L. The minimum concentration of teicoplanin in patients with higher loading doses (15 mg/kg) reached the target range (15-30 mg/L) with a probability of >50% in the dosing simulation. We described the influence of body size, body composition, and renal function on the PK of teicoplanin. The population PKPD model of teicoplanin and CRP in this study should provide useful information for development of a dosing strategy including the sequential clinical benefit of teicoplanin. KeywordsC-reactive protein, pharmacodynamics, pharmacokinetics, teicoplanin, therapeutic drug monitoring Teicoplanin, a glycopeptide antibiotic agent first approved in France and Italy in 1988, is currently available and used in over 60 countries for the treatment of Gram-positive infections including methicillinresistant Staphylococcus aureus. 1 Teicoplanin has a structure and a mechanism similar to those of vancomycin, another glycopeptide antibacterial agent, and exhibits bactericidal activity by inhibiting the synthesis of cell wall peptidoglycan. 2 A meta-analysis study comparing the efficacy and toxicity of teicoplanin and vancomycin revealed no significant differences in efficacy between these 2 drugs, but adverse events (eg,

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Section: Population Pkpd Simulationmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

Ogami

Tsuji

Mizoguchi

et al. 2019

Clinical Pharm in Drug Dev

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“…Although various enhanced loading dose regimens to achieve the new target C min have been reported in patients with normal Electronic supplementary material The online version of this article (doi:10.1007/s10096-016-2691-z) contains supplementary material, which is available to authorized users. renal function [9,[13][14][15][16][17][18][19][20][21][22], there are limited data in patients with renal dysfunction [19][20][21][22]. Ueda et al [13] reported that the proportion of patients achieving the target C min of 15 μg/ml was only 20.3 % with the conventional teicoplanin loading regimen in patients with renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…1Comparison of clinical success rate in patients with C min of <15 μg during therapy, who achieved initial C min of ≥15 μg, and who achieved C min of ≥15 μg with adjustment after TDM observed in the present study. Nakamura et al[22] utilized an even higher dose loading regimen (12 mg/kg every 12 h for 48 h) of teicoplanin in patients with renal dysfunction. C min on the 3rd day increased beyond the target threshold (30 μg/ml) in five of the 20 patients (25 %), and achievement of adequate C min of 15-30 μg/ml remained only 55 % in patients with a CLcr of <50 ml/min/m 2 .…”

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Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction

Takesue

Nakajima

Ichiki

et al. 2016

Eur J Clin Microbiol Infect Dis

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We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 μg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 μg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml. In conclusion, achievement of Cmin of 15-30 μg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

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UHPLC–MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy

Kai

Tanaka

Suzuki

et al. 2022

Clinical Laboratory Analysis

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Background Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC–MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti‐MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples. Methods Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate. Results The method showed good linearity over wide ranges. Within‐batch and batch‐to‐batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations. Conclusion This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.

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Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections

Cited by 32 publications

References 19 publications

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

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

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction

UHPLC–MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy

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