Treatment Approach for Linezolid and Erythromycin Resistant Culture
For a culture showing resistance to both linezolid and erythromycin, the specific treatment depends critically on the organism identified and the infection site, but vancomycin remains first-line for MRSA, while daptomycin (8-12 mg/kg/day) is preferred for linezolid-resistant enterococcal infections.
Organism-Specific Treatment Recommendations
If Enterococcus faecalis or faecium (Linezolid-Resistant)
Daptomycin at high doses (10-12 mg/kg/day) is the preferred agent for linezolid-resistant enterococcal infections, particularly bloodstream infections 1.
- For vancomycin-resistant, linezolid-resistant E. faecalis, daptomycin 8-12 mg/kg/day represents the most appropriate alternative 1
- Tigecycline may be considered for intra-abdominal infections when both vancomycin and linezolid resistance are present 1
- For endocarditis caused by multidrug-resistant enterococci, doses of 10-12 mg/kg per 24 hours should be used, potentially in combination with ampicillin or ceftaroline 2
- Management should involve specialists in infectious diseases, cardiology, and cardiac surgery for serious infections 2
If Methicillin-Resistant Staphylococcus aureus (MRSA)
Vancomycin remains the recommended treatment for MRSA infections despite erythromycin resistance, as erythromycin resistance does not predict vancomycin failure 2.
- For MRSA with linezolid resistance (rare but reported), vancomycin 30 mg/kg/day in 2 divided doses targeting trough levels of 15-20 μg/mL is recommended 2
- Daptomycin is an acceptable alternative to vancomycin for MRSA skin and soft tissue infections 2
- For isolates with vancomycin MIC >2 μg/mL, alternative agents must be used 2
If Nontuberculous Mycobacteria (NTM)
For NTM pulmonary disease with macrolide resistance (erythromycin/clarithromycin), linezolid may be included as part of a multidrug regimen, but alternative agents should be prioritized if linezolid resistance is also present 2.
- For macrolide-resistant MAC, consider regimens including moxifloxacin, clofazimine, and amikacin 2
- Linezolid (600 mg twice daily) can be considered for refractory MAC when susceptibility testing supports its use 2
- For M. abscessus with inducible macrolide resistance, treatment should include amikacin, imipenem or cefoxitin, and clofazimine 2
Critical Pitfalls to Avoid
- Do not use linezolid monotherapy for enterococcal endocarditis or other endovascular infections, as it is bacteriostatic 2
- Erythromycin resistance does not automatically indicate resistance to all macrolides—clarithromycin and azithromycin may retain activity depending on resistance mechanism 2
- For MRSA, perform D-zone testing if considering clindamycin, as inducible resistance may be present despite apparent susceptibility 3
- Linezolid resistance in enterococci typically develops in patients with retained prosthetic devices or undrained abscesses—source control is essential 4
Combination Therapy Considerations
- Synergistic combinations exist for linezolid-resistant staphylococci: linezolid plus imipenem shows synergy against both S. aureus and S. epidermidis 5
- Linezolid plus plazomicin demonstrates synergistic or partially synergistic activity against linezolid-resistant staphylococcal strains 5
- For enterococcal infections, combination therapy with daptomycin plus ampicillin or ceftaroline may be considered, especially with persistent bacteremia 2
Duration and Monitoring
- For complicated infections with resistant organisms, treatment duration typically extends 7-14 days minimum, with longer courses (>6 weeks) required for endocarditis 2, 6
- Monitor for clinical improvement within 72 hours; lack of response warrants source control evaluation and potential regimen modification 6
- Obtain repeat cultures to document clearance, particularly for bloodstream infections 2