Therapeutic Dose Monitoring for Linezolid in a Pat

Authors: Yoshihiko Nakamura Masanobu Uchiyama Shuuji Hara Mariko Mizunuma Takafumi Nakano Hiroyasu Ishikura Kota Hoshino Yasumasa Kawano Tohru Takata

Publish Date: 2015/12/19

Volume: 5, Issue: 1, Pages: 81-87

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Abstract

Few studies have investigated the effect of increased creatinine clearance CrCl on linezolid LZD concentration Herein we report the pharmacokinetic/pharmacodynamic PK/PD profile of LZD used in the management of methicillinresistant Staphylococcus aureus MRSA pneumonia with concomitant bacteremia in a patient with high CrCl caused by diabetes insipidus DIA 19yearold man was admitted to the intensive care unit following a traumatic brain injury After admission he underwent a craniotomy for the severe brain injury However he developed DI after the operation Despite treatment with vasopressin his urine output reached 5–6 L/day as a result of the DI and his CrCl increased to 180–278 mL/min We were required to administer 6–7 L of fluid a day to compensate for the high urinary fluid output On day 55 MRSA pneumonia with sepsis was suspected and consequently LZD was administrated intravenously 600 mg every 12 h He was treated with LZD for 14 days The patient has since successfully recovered from MRSA pneumonia with concomitant bacteremia and was transferred to the general ward on day 82 Blood LZD levels from days 60–68 which were measured after the patient’s transfer to the general ward showed that the trough levels were lower than the threshold level of detection The blood 24h area under the plasma LZD concentration–time curve AUC24/minimum inhibitory concentration MIC was 693Linezolid LZD is an oxazolidinone antibiotic characterized by a wide spectrum of activity against Grampositive pathogens resistant to βlactams and glycopeptides and its use has progressively increased in recent years 1 2 LZD clearance is mainly nonrenal approximately 65 through the formation of two major inactive metabolites the hydroxyethyl glycine metabolite PNU142586 and the aminoethoxyacetic acid metabolite PNU142300 which account for 40–50 and 9–10 of the total dose respectively Renal clearance of the unchanged parent drug accounts for the remaining 30–40 3 More recent reports have suggested that the influence of renal dysfunction on high LZD blood concentration may lead to hematological side effects such as thrombocytopenia 8 9However the influence of low LZD blood concentration in conjunction with high creatinine clearance CrCl still remains unknown Additionally the pharmacokinetic/pharmacodynamic PK/PD index for the efficacy of LZD was previously shown to be a 24h area under the plasma LZD concentration–time curve/minimum inhibitory concentration AUC24/MIC ratio of ≥100 4 5 6 Herein we report the PK/PD profile of a patient with methicillinresistant Staphylococcus aureus MRSA pneumonia and bacteremia who developed diabetes insipidus DI with a high level of CrCl Despite the low AUC24/MIC of LZD in comparison with the efficacy level of AUC24/MIC ≥100 4 5 6 the patient was successfully treated for the MRSA infectionBlood samples for the quantification of LZD in plasma were collected through an indwelling arterial catheter both before and after the morning dosing which was administered through an intermittent intravenous infusion of 600 mg over the course of 1 h LZD was administrated twice a day morning and night Blood samples were taken in the morning before dosing trough and after the morning’s 1hlong LZD administration After centrifugation plasma samples were separated and stored at −80 °C until assayed Blood LZD concentration was measured after the patient’s transfer to the general ward

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