What are the implications of continuous infusion of linezolid (oxazolidinone antibiotic)?

From the Guidelines

Continuous infusion of linezolid is not recommended as a standard practice, and intermittent dosing is preferred, with a dose of 600 mg IV or PO every 12 hours, as recommended by recent guidelines 1. This approach is based on the most recent and highest quality studies available, which prioritize intermittent dosing for the treatment of infections due to multidrug-resistant organisms. The recommended dosing for linezolid is 600 mg IV or PO every 12 hours, with the treatment duration dependent on the site of infection and clinical response 1. Some key points to consider when using linezolid include:

• Monitoring for adverse effects, including myelosuppression and lactic acidosis, is essential regardless of administration method.
• Therapeutic drug monitoring may be useful when available, aiming for steady-state concentrations between 2-8 mg/L.
• Linezolid use may be associated with potentially severe bone marrow suppression, neuropathy, and numerous drug interactions, and patients should be treated by a care team including specialists in infectious diseases, cardiology, cardiac surgery, clinical pharmacy, and pediatrics 1. It's also important to note that linezolid is recommended for enterococcal infections, and the treatment duration is dependent on the site of infection and clinical response 1. In terms of specific patient populations, children with multidrug-resistant tuberculosis may require different dosing, with recommendations including 10 mg/kg once daily for children >12 years and 10 mg/kg twice daily for children <12 years of age 1. However, these recommendations are specific to the treatment of multidrug-resistant tuberculosis and may not be applicable to other infections. Overall, the use of linezolid should be guided by the most recent and highest quality evidence available, and treatment decisions should be made on a case-by-case basis, taking into account the specific needs and circumstances of each patient.

From the FDA Drug Label

DOSAGE FORMS AND STRENGTHS Tablet: 600 mg linezolid. Nosocomial pneumonia 10 mg/kg intravenous or oral every 8 hours 600 mg intravenous or oral every 12 hours 10 to 14

The FDA drug label does not answer the question.

From the Research

Continuous Infusion of Linezolid

• The continuous infusion of linezolid has been proposed to optimize antimicrobial exposure, although pharmacokinetic data from large patient cohorts are lacking 2.
• A study found that linezolid pharmacokinetics were highly variable, with an interindividual variability of clearance of 52.8% coefficient of variation, and non-linear clearance was quantified, which decreased from 6.82 to 3.82 L/h within 3-6 days in the population 2.
• The model predicted Grade 2,3, or 4 thrombocytopenia in 21.7%, 10.4%, and 2.5% of patients at day 14, respectively, and patients with impaired renal function displayed a higher risk 2.
• Another study found that continuous infusion of linezolid showed a higher clinical cure rate than the intermittent infusion group, and the incidence of thrombocytopenia was significantly lower in the continuous infusion group than in the intermittent infusion group 3.
• The study also found that efficacy was proven by greater improvement of P/F ratio, a lower incidence of developing sepsis after beginning treatment, and a shorter time to reach clinical cure 3.

Optimization of Linezolid Therapy

• A study found that insufficient linezolid levels are often observed in ICU patients who receive standard dosing, and strategies to overcome these insufficient levels have been discussed, but appropriate alternative dosing regimens remain to be identified 4.
• The study found that best target attainment according to T >MIC was observed for continuous infusions, followed by q6h, q8h, and q12h, and a substantially reduced target attainment was observed in patients with acute respiratory distress syndrome (ARDS) 4.
• The study also found that 1200 mg/day was insufficient irrespective of the regimen, while a dose of 1400 mg/day administered q6h or by continuous infusions provided an acceptable target attainment 4.

Therapeutic Drug Monitoring (TDM)

• A study found that linezolid exhibits potent therapeutic effects on pneumonia, but the appearance of adverse reactions is indicated as a problem, and there was a dose-dependent decrease in the platelet count 5.
• The study found that the target trough concentration (Ctrough) was estimated to be 4-6 or 2-7 µg/mL in accordance with the patient's condition, and the efficacy of linezolid may be obtained while minimizing the appearance of adverse reactions by performing TDM 5.
• Another study found that tedizolid displays potent activity against Gram-positive pathogens, and tedizolid MICs demonstrate activity against isolates with decreased susceptibility to alternative agents, including linezolid 6.