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

Abstract

Background: A trough concentration (Cmin) ≥20 μg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging.Methods: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72–96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose.Results: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20–40 μg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥20 μg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25–12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥20 μg/mL.Conclusion: A target Cmin ≥20 μg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.

Optimal trough concentration of teicoplanin for the treatment of methicillin‐resistant Staphylococcus aureus infection: A systematic review and meta‐analysis

“…Ninety‐three articles, including studies that did not assess the target trough concentration range of 15–30 μg/ml (cut‐off value of 13 [1] or 20 μg/ml [3]). We finally included four articles ( n = 299) that assessed clinical efficacy 31‐34 and three articles ( n = 546) 32‐34 that assessed adverse effects in the meta‐analysis. No RCTs have assessed the associations of the target trough concentration of teicoplanin with efficacy and safety.…”

“…13 Byrne et al found that although their hospital adopted higher than conventional doses for patients with haematological malignancy with the aim of achieving a trough concentration approximately 50 kg) using a regimen of five doses of 600 mg every 12 h. 33 They also reported that five doses of 12 mg/kg teicoplanin delivered at 12-h intervals were required to achieve a target trough concentration of ≥20 μg/ml in patients with difficult MRSA infections. 34 Ramos-Martin et al reported that an AUC/MIC ratio of 610.4…”

“…Ueda et al demonstrated that a trough concentration of 15–30 μg/ml was obtained in 68% of patients (mean body weight, approximately 50 kg) using a regimen of five doses of 600 mg every 12 h 33 . They also reported that five doses of 12 mg/kg teicoplanin delivered at 12‐h intervals were required to achieve a target trough concentration of ≥20 μg/ml in patients with difficult MRSA infections 34 …”

“…We finally included four articles (n = 299) that assessed clinical efficacy [31][32][33][34] and three articles (n = 546) [32][33][34] that assessed adverse effects in the meta-analysis. No RCTs have assessed the associations of the target trough concentration of teicoplanin with efficacy and safety.…”