ABSTRACT
Title
Linezolid tailored therapy through therapeutic drug monitoring in a patient with nocardiosis assuming p-glycoprotein (P-gp) inhibitors
Authors
PG. Cojutti1, F. Pea1, A. Pagotto2, F. Cristini3, P. Viale3, M. Furlanut1
1 Institute of Clinical Pharmacology and Toxicology, Dpt. of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy
2 Clinic of Infectious Diseases, Dpt. of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy
3 Clinic of Infectious Diseases, Dpt. of Internal Medicine, Geriatrics and Nephrologic Diseases, University of Bologna, Bologna, Italy
1 Institute of Clinical Pharmacology and Toxicology, Dpt. of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy
2 Clinic of Infectious Diseases, Dpt. of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy
3 Clinic of Infectious Diseases, Dpt. of Internal Medicine, Geriatrics and Nephrologic Diseases, University of Bologna, Bologna, Italy
Abstract
A 67 years old woman with a diagnosis of pulmonary nocardiosis and presenting with a cerebral temporo-parietal abscess positive for Nocardia asteroides at biopsy, started an antibiotic therapy with linezolid at the standard regimen of 600 mg q12h. Co-medications she was currently assuming included: omeprazole, carvedilole, barnidipine, doxazosine, nortriptiline/flufenazine and oxcarbazepine. After 41 days of therapy red blood cells (RBC), platelet (PLT) and haemoglobin (Hb) concentrations gradually dropped at 2.3*106/mm3, 280*103/mm3 and 7.82 g/dL respectively. Therapeutic drug monitoring (TDM) of linezolid revealed a trough concentration (Cmin) of 23.49 mg/L (Cmin therapeutic range: 2-7 mg/L) and the dose was promptly reduced to 600 mg q24h.
During the following 120 days, linezolid regimen varied between 600 mg q24/36h and Cmin remained far above the therapeutic range (18.9±5.4 mg/L) with high level of lactic acid (up to 4.5 mmol/L) owing to poor patient’s compliance in following clinical pharmacologist’s suggestions of further reducing the dose.
At day 161 after a complete re-assessment of therapeutic drugs, linezolid dose was set at 600 mg q72h. From then till to the end of therapy (day 273) mean Cmin was 2.56±0.4 mg/L and RBC, Hb, PLT, lactic acid values normalized. Complete patient recovery was confirmed at imaging at 6 months and 1 year of follow-up.
Pharmacological interactions of linezolid with well-recognized P-gp inhibitors often used in clinical practice (omeprazole, carvedilole, barnidipine) probably caused an excessive plasmatic exposition to this antibiotic, and should foster the implementation of TDM in tailoring therapies for critical infections.
During the following 120 days, linezolid regimen varied between 600 mg q24/36h and Cmin remained far above the therapeutic range (18.9±5.4 mg/L) with high level of lactic acid (up to 4.5 mmol/L) owing to poor patient’s compliance in following clinical pharmacologist’s suggestions of further reducing the dose.
At day 161 after a complete re-assessment of therapeutic drugs, linezolid dose was set at 600 mg q72h. From then till to the end of therapy (day 273) mean Cmin was 2.56±0.4 mg/L and RBC, Hb, PLT, lactic acid values normalized. Complete patient recovery was confirmed at imaging at 6 months and 1 year of follow-up.
Pharmacological interactions of linezolid with well-recognized P-gp inhibitors often used in clinical practice (omeprazole, carvedilole, barnidipine) probably caused an excessive plasmatic exposition to this antibiotic, and should foster the implementation of TDM in tailoring therapies for critical infections.