Teicoplanin in Patients with Acute Leukaemia and Febrile Neutropenia

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Abstract
To define the optimal dosage regimen of teicoplanin that ensures early therapeutically relevant trough concentrations (Cmin) [>10 mg/L at 24 hours and possibly close to 20 mg/L at 48 hours] in patients with acute leukaemia who develop febrile neutropenia after chemotherapy. Prospective observational pharmacokinetic study. Adult patients (n = 33) with normal renal function previously treated with antineoplastic chemotherapy because of acute lymphocytic or acute nonlymphocytic leukaemia, and subsequently developing febrile neutropenia treated with empirical antimicrobial therapy. First, the standard dosage group (n= 11) was administered standard loading and maintenance doses of teicoplanin (400mg every 12 hours for three doses followed by 400mg once daily). Blood samples were collected at defined times as part of routine monitoring and assessed for teicoplanin plasma concentration by fluorescence polarisation immunoassay. Secondly, the high dosage group (n = 22) received a high loading regimen (800 + 400mg 12 hours apart on day 1, 600 + 400mg 12 hours apart on day 2) followed by a high maintenance regimen (400mg every 12 hours) from day 3 on. In the standard dosage group, no patient had the recommended teicoplanin Cmin of ≥10 mg/L within the first 72 hours, and only five of the 11 patients (45%) had a Cmin of ≥10 mg/L after 120 hours. No patient had a Cmin of ≥20 mg/L. In the high dosage group, teicoplanin Cmin averaged ≥10 mg/L within 24 hours, and this value was achieved within 48 hours in all but one patient. Of note, Cmin at 72 hours exceeded 20 mg/L in ten of the 22 patients (45%). No patient experienced significant impairment of renal function. In this patient group, therapeutically relevant Cmin may be achieved very early in the treatment period with loading doses of 12 mg/kg and 6 mg/kg 12 hours apart on day 1, and 9 mg/kg and 6 mg/kg 12 hours apart on day 2, regardless of renal function. Subsequently, in patients with normal renal function a maintenance dosage of 6 mg/kg every 12 hours may be helpful in ensuring Cmin close to 20 mg/L. Assessment of Cmin after 48–72 hours may be useful to individualise teicoplanin therapy. Factors increasing volume of distribution and/or renal clearance of teicoplanin (fluid load, hypoalbuminaemia, leukaemic status) may explain the need for higher dosages.