What is the antimicrobial spectrum of linezolid?

Antimicrobial Spectrum of Linezolid

Linezolid is a synthetic oxazolidinone antibiotic with excellent activity against a broad range of gram-positive bacteria, including multi-drug resistant organisms, with limited activity against certain gram-negative anaerobes but no significant activity against gram-negative aerobes. 1, 2

Mechanism of Action

• Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit, preventing the formation of a functional 70S initiation complex essential for bacterial reproduction 1
• This unique mechanism of action means cross-resistance between linezolid and other classes of antibiotics is unlikely 2
• Linezolid is primarily bacteriostatic against enterococci and staphylococci, but bactericidal against most streptococcal strains 1

Gram-Positive Coverage

FDA-Approved Indications

• Vancomycin-resistant Enterococcus faecium infections 1
• Staphylococcus aureus (including methicillin-resistant strains) 1
• Streptococcus pneumoniae (including multi-drug resistant isolates) 2
• Streptococcus agalactiae (Group B streptococci) 1
• Streptococcus pyogenes (Group A streptococci) 1

Additional Gram-Positive Organisms with Documented In Vitro Activity

• Enterococcus faecalis (including vancomycin-resistant isolates) 1
• Enterococcus faecium (vancomycin-susceptible isolates) 1
• Staphylococcus epidermidis (including methicillin-resistant isolates) 1
• Staphylococcus haemolyticus 1
• Viridans group streptococci 1

Gram-Negative Coverage

• Limited activity against gram-negative bacteria 1
• Has in vitro activity against Pasteurella multocida 1
• No significant activity against most aerobic gram-negative pathogens 3

Anaerobic Coverage

• Active against certain anaerobes including Clostridium perfringens, Clostridium difficile, Peptostreptococcus species, and Bacteroides fragilis 3

Clinical Efficacy Against Resistant Organisms

• Particularly effective against multi-drug resistant strains of Staphylococcus aureus, including MRSA and glycopeptide-intermediate S. aureus (GISA) 3
• Effective against vancomycin-resistant enterococci (VRE) 3
• Active against penicillin-resistant Streptococcus pneumoniae 3
• Linezolid has demonstrated better clinical and microbiological success rates than vancomycin in various infection types, particularly skin and soft tissue infections (Odds Ratio 4.0; 95% CI, 1.3-12.0) 4

Resistance Patterns

• Resistance to linezolid occurs in vitro at a frequency of 1 × 10⁻⁹ to 1 × 10⁻¹¹ 2
• Resistance mechanisms include point mutations in the 23S rRNA (substitution of thymine for guanine at position 2,576) 1
• Reports of vancomycin-resistant E. faecium becoming resistant to linezolid during clinical use have been documented 1
• Resistance in staphylococci mediated by the enzyme methyltransferase has been reported, which can be transferred between staphylococci via the cfr gene on a plasmid 1

Drug Interactions

• Linezolid shows additivity or indifference when combined with vancomycin, gentamicin, rifampin, imipenem-cilastatin, aztreonam, ampicillin, or streptomycin 1
• As a reversible, nonselective inhibitor of monoamine oxidase, linezolid has potential interactions with adrenergic and serotonergic agents 1

Clinical Applications

• First-line therapy for vancomycin-resistant Enterococcus faecium infections 2
• Alternative to vancomycin for MRSA infections, particularly in patients who cannot tolerate vancomycin 5
• Effective for complicated skin and soft tissue infections, nosocomial pneumonia, and community-acquired pneumonia 6
• Excellent tissue penetration properties, including into the prostate, making it valuable for treating infections in tissues with limited blood supply 7

Limitations and Considerations

• Primarily indicated for gram-positive infections; not effective against most gram-negative pathogens 3
• Risk of thrombocytopenia with prolonged use 6
• Potential for serotonin syndrome when combined with serotonergic agents 1
• The suspension formulation can be poorly tolerated in children due to its taste 8

Linezolid's unique mechanism of action and effectiveness against resistant gram-positive pathogens make it a valuable antimicrobial agent, particularly in settings where multi-drug resistant organisms are prevalent.