Linezolid Antimicrobial Spectrum
Linezolid is an oxazolidinone antibiotic with potent activity against aerobic Gram-positive bacteria, including multidrug-resistant strains, but lacks clinically useful activity against Gram-negative organisms and atypical pathogens. 1
Primary Gram-Positive Coverage
Linezolid demonstrates excellent activity against the following organisms:
Staphylococcus aureus
- Methicillin-resistant S. aureus (MRSA), including both nosocomial and community-acquired strains 1
- Vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) 1
- Methicillin-susceptible S. aureus (MSSA) 2
Enterococcus Species
- Vancomycin-resistant Enterococcus faecium (VRE) 3, 1
- Vancomycin-resistant Enterococcus faecalis 2, 4
- Vancomycin-susceptible enterococci 2
Streptococcus Species
- All strains of Streptococcus pneumoniae, including multidrug-resistant isolates (MDRSP) resistant to penicillin, second-generation cephalosporins, macrolides, tetracycline, and trimethoprim/sulfamethoxazole 1
- Streptococcus pyogenes (Group A Streptococcus) 5
- Streptococcus agalactiae (Group B Streptococcus) 5
Anaerobic Coverage
- Clostridium perfringens 2, 6
- Clostridium difficile 2
- Peptostreptococcus species 2, 6
- Bacteroides fragilis 2
- Prevotella species 6
Critical Limitations in Spectrum
Linezolid has NO clinically useful activity against:
- Aerobic Gram-negative organisms including Pseudomonas aeruginosa, Enterobacteriaceae, and Haemophilus influenzae 1
- Atypical pathogens including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species 1
This is a critical pitfall: linezolid should never be used as monotherapy for infections where Gram-negative or atypical pathogens are suspected. 1
Mechanism of Action and Resistance
- Linezolid inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit, preventing formation of the 70S initiation complex 5
- This unique mechanism means cross-resistance with other antibiotic classes is unlikely 5, 6
- Linezolid is bacteriostatic against most organisms (enterococci and staphylococci) but bactericidal against most streptococci 5, 6
- Resistance develops through point mutations in 23S rRNA (substitution of thymine for guanine at position 2576) 5
- Resistance has been reported in Enterococcus faecium and rarely in S. aureus during clinical use, particularly in patients with unremoved prosthetic devices or undrained abscesses 5
Clinical Advantages in Specific Populations
Renal Insufficiency
Linezolid is particularly advantageous in patients with impaired renal function because:
- It does not require dose adjustment based on renal function 7
- It does not require therapeutic drug monitoring 7
- Renal insufficiency is a significant predictor of vancomycin failure, making linezolid preferable in this population 7
Tissue Penetration
- Excellent tissue penetration, often exceeding plasma levels, making it effective for deep-seated infections 7
- Achieves excellent penetration into biofilms and poorly vascularized tissues such as the prostate 1, 8
- Superior penetration into lung epithelial lining fluid compared to vancomycin 7
Oral Bioavailability
- 100% oral bioavailability, allowing seamless IV-to-oral transition when patients can tolerate oral medications 1
- This allows for shorter hospital stays and earlier discharge compared to vancomycin 3, 7
Guideline-Recommended Indications
The Infectious Diseases Society of America recommends linezolid for:
- MRSA skin and soft tissue infections (Grade 1A recommendation) 1
- Nosocomial pneumonia caused by MRSA as an alternative to vancomycin 1
- Necrotizing fasciitis (in combination with broad-spectrum agents) 3
The American Thoracic Society recommends linezolid as:
- First-line agent for MRSA pneumonia, particularly hospital-acquired or ventilator-associated pneumonia 7