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

Abstract

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.

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

“…Previous findings implied that a high C min might be associated with better outcomes. 15 , 16 , 18 , 21 , 30 In this study, the mean teicoplanin C min of the 75 patients who had a successful response (clinical cure; 18.92±5.12 mg/L) was significantly higher than that of the 38 patients who got a failed response (10.01±2.37mg/L; P <0.001). C min was significantly associated with an improved clinical response to teicoplanin using binary logistic regression ( P <0.001).…”

“…The target C min was set to 15–30 mg/L. 15 , 18 Cl cr values for males and females were calculated as follows: Renal function was assessed by Cl cr levels as normal (> 60 mL/min), mildly impaired (40–60 mL/min), or impaired (<40 mL/min).…”

“…Recent research found that teicoplanin C min was strongly influenced by loading dosage and creatinine clearance (Cl cr ) rate. 16 , 18 – 20 A teicoplanin C min range of 10–30 mg/L was identified as the therapeutic target with optimal clinical efficacy and safety. 15 – 20 An individualized initial loading dose followed by therapeutic drug monitoring was recommended to achieve the target C min .…”

Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days

“…Traditionally, a C min ≥ 10 μg/mL is considered appropriate for MRSA infections [6]. Recently, it was reported that a teicoplanin C min ≥ 15 μg/mL was required for the successful clinical treatment of MRSA infection [7,8], whereas a C min ≥ 20 μg/mL was recommended for other serious infections such as bone and joint infections and infective endocarditis [9,10]. Wilson et al [9] showed that treatment in 6/10 staphylococcal infective endocarditis patients failed if the C min was < 20 μg/mL compared with 1/11 where the C min was ≥20 μg/mL.…”

Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 μg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days

“…Traditionally, a C min ≥10 μg/mL is considered appropriate for MRSA infections [4]. Recently, it was reported that a teicoplanin C min ≥15 μg/mL was required for the successful clinical treatment of MRSA infection [5,6], whereas a C min ≥20 μg/mL was recommended for other serious infections such as bone and joint infections and infective endocarditis [7,8]. Wilson et al [7] showed that treatment in 6/10 staphylococcal infective endocarditis patients failed if the C min was <20 μg/mL compared with 1/11 where the C min was ≥20 μg/mL.…”