Indications
Linezolid is prescribed for both adults and children to treat infections caused by susceptible Gram-positive bacteria. These infections include nosocomial pneumonia, community-acquired pneumonia, skin and skin structure infections, as well as infections due to vancomycin-resistant Enterococcus faecium. Linezolid is effective against bacteria such as Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae. It is important to note that Linezolid is not indicated for Gram-negative infections and is not recommended for treatment durations exceeding 28 days.
Pharmacodynamics
Linezolid belongs to the oxazolidinone class of antibacterial agents and exhibits activity against most strains of aerobic Gram-positive bacteria and mycobacteria. It generally acts as a bacteriostatic agent against staphylococci and enterococci, while demonstrating bactericidal properties against most streptococcal isolates. Although Linezolid shows some in vitro activity against Gram-negative and anaerobic bacteria, it is not considered effective for treating these microorganisms. Additionally, Linezolid acts as a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes, which may lead to serotonin syndrome when used concurrently with serotonergic drugs such as SSRIs or TCAs. It is not recommended for treating catheter-related bloodstream infections or catheter-site infections due to an unfavorable risk-benefit balance in these cases.
Absorption
Following oral administration, Linezolid is well-absorbed with an absolute bioavailability of nearly 100%. Peak plasma concentrations are typically reached within 1 to 2 hours post-dosing, with concentrations ranging from 8.1-12.9 mcg/mL after a single dose and 11.0-21.2 mcg/mL with multiple dosing. Food intake does not significantly influence the absorption of Linezolid, allowing it to be administered without regard to meals.
Metabolism
Linezolid undergoes primary metabolism to form two inactive metabolites, namely an aminoethoxyacetic acid metabolite (PNU-142300) and a hydroxyethyl glycine metabolite (PNU-142586), resulting from the oxidation of the morpholine ring. The hydroxyethyl glycine metabolite is the more prevalent of the two and is likely generated through non-enzymatic processes, though the specifics remain uncertain. While the exact enzymes responsible for Linezolid's metabolism are not definitively identified, it is not extensively metabolized by the CYP450 enzyme system nor does it significantly inhibit or induce these enzymes. However, Linezolid is a reversible and non-selective inhibitor of monoamine oxidase enzymes.
Mechanism of Action
Linezolid operates as an antibacterial agent by disrupting the bacterial protein synthesis process. It achieves this by binding to the 23S rRNA of the 50S ribosomal subunit, thereby inhibiting the formation of a functional 70S initiation complex, which is crucial for bacterial replication and division. However, point mutations in the 23S rRNA can confer resistance to linezolid, and instances of linezolid-resistant Enterococcus faecium and Staphylococcus aureus have been observed in clinical settings. Given that antimicrobial susceptibility varies by region, it is advisable to reference local antibiograms to ensure effective coverage against pertinent pathogens before commencing treatment.
