Background Linezolid is an antibiotic with a broad spectrum of activity against all clinically important Gram +bacteria, including methicillin-resistant staphylococcus aureus and vancomycin-resistant enterococci. Standard dosing is prescribed for critical patients, regardless of their pharmacokinetic variability.
Purpose To describe the plasma concentrations of linezolid in critical patients and its relationship with antibiotic discontinuation.
Material and methods A prospective, observational study was carried out in a university hospital ICU during June 2017. Patients with linezolid treatment >48 hours that signed the informed consent were included. Two blood samples, Cmin and Cmax, were taken per patient. They were analysed by validated high-performance liquid chromatography assay. General, clinical data and analytic parameters of interest were recorded. Results were expressed in median, interquartile range and percentages. Fischer exact test for dichotomic variables was employed.
Results Twelve patients were included, 11 males, age 66 (12) years, weight 82.50 (21) kg, body mass index 26.85 (2.88) kg/m2, APACHE II score 22 (11) at admission.
Analytical parameters: leukocytes 11.80 (10.80) cells x109/mL, neutrophils 89.10 (19.05)%, creatinine 0.95 (0.73) mg/mL, and PCR 6.77 (28.49) mg/dL.
All patients received intravenous linezolid 600 mg b. i. d. Duration of treatment: 7 (5.5) days. Respiratory tract infections were the most prevalent (50%). 91.67% of patients received combination therapy, mostly linezolid +meropenem (66.67%). In 10 cases, linezolid was the empirical antibiotic regimen, only two as targeted therapy.
A total of 24 serum samples were obtained at steady state (between 5th and 11th dose). Cmax were 10.49 (range 6.50–19.80) µg/mL and Cmin were 0.7 (0.02–6.10) µg/mL. Eight patients (67%) presented with plasma levels<1 mcg/mL, and two (17%) presented with plasma levels>18 mcg/mL.
Factors that might influence linezolid pharmacokinetics: 83.3% patients presented overweight or obese, 72.73% were mechanically ventilated, 58.33% received parenteral nutrition, 50% vasoactive drugs and 33.33% had postsurgical drains. Reasons for therapeutic discontinuation (1_Empirical treatment recommendations 2_Ineffectiveness 3_Toxicity) could be related with Cmin concentrations (p=0.045).
Conclusion A high interindividual pharmacokinetic variability of linezolid was observed and it could be related to the discontinuation of this antibiotic.
Frequently, pharmacokinetic/pharmacodynamic targets are not achieved with standard dosing (600 mg b. i. d). TDM should be considered for individualised linezolid dosing in ICU patients.
No conflict of interest
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