PKP-002 Decreased linezolid serum levels in critically ill patients: clinical case studies of a drug-drug-interaction between linezolid and rifampicin

Background Infections caused by multiresistant Gram-positive pathogens present a special challenge, resulting in increased clinical complications. Linezolid is used as reserve antibiotic in case of resistance or contraindication to vancomycin. Lack of effective linezolid levels due to co-administration of rifampicin has been described in healthy subjects. However, the clinical significance of this drug-drug-interaction (DDI) for critically ill patients is still unclear. Purpose To report a DDI between linezolid and rifampicin resulting in linezolid levels below the minimal inhibitory concentration (MIC) in three patients. Material and methods Three patients with linezolid and rifampicin were identified through routine therapeutic drug monitoring. Linezolid serum level was measured by a validated high performance liquid chromatography assay. Results The therapeutic range of linezolid serum levels is expected to lie between 4 mg/l (2 × 600 mg IV) and 6 mg/l (2 × 600 mg p.o.). The MIC values of pathogens require trough levels between 2(4)–10 mg/l. However, the majority of observed linezolid levels in three patients were below 2 mg/l, even if rifampicin had already been stopped (Patient 1). Conclusion We observed accelerated linezolid clearance in critically ill patients as previously described in healthy subjects. Monitoring of linezolid levels and corresponding dose adjustments could ensure safe and effective antibiotic treatment in patients with rifampicin co-administration as well as with previous rifampicin treatment. Further investigation is necessary to assess the clinical value of combination treatment. References Egle H, Trittler R, Kümmerer K, et al. Linezolid and rifampicin: drug interaction contrary to expectations? Clin Pharmacol Ther 2005;77:451–3 Zyvox (Linezolid) Pfizer US Prescribing information 09/2013 No conflict of interest.