Daptomycin Does Not Cover Gram-Negative Bacteria
Daptomycin has no activity against gram-negative bacteria and is only effective against gram-positive organisms. 1, 2
Antimicrobial Spectrum of Daptomycin
- Daptomycin is a cyclic lipopeptide antimicrobial with bactericidal activity specifically against gram-positive bacteria, including resistant strains 1
- It has excellent activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and other difficult-to-treat gram-positive pathogens 2
- Daptomycin demonstrates no clinically relevant activity against gram-negative bacteria, which is a significant limitation in its spectrum 1
- In vitro studies consistently show that daptomycin has only minimal activity against anaerobic bacteria and no activity against gram-negative organisms 1, 2
Clinical Applications Based on Spectrum
- Daptomycin is FDA-approved for complicated skin and soft tissue infections at a dose of 4 mg/kg/day 1
- It is also approved for right-sided infective endocarditis caused by S. aureus and bacteremia associated with complicated skin and soft tissue infections at 6 mg/kg/day 2
- Guidelines recommend daptomycin as an alternative to vancomycin for gram-positive coverage in specific clinical scenarios 3
- When treating infections where gram-negative coverage is needed, daptomycin must be combined with appropriate gram-negative active agents 3
Documented Activity Against Specific Organisms
- MIC90 values for daptomycin against staphylococci, beta-hemolytic streptococci, viridans group streptococci, and enterococci are 0.5,0.25,0.5, and 2 μg/mL, respectively 4
- Daptomycin maintains excellent activity against linezolid-resistant enterococci and S. aureus 5
- Studies show that 99.9% of S. aureus, 100.0% of E. faecalis, and 99.5% of E. faecium isolates remain susceptible to daptomycin 4
- Daptomycin has shown activity against unusual gram-positive bacteria including Listeria monocytogenes and Corynebacterium species, but no activity against any gram-negative species 6
Clinical Implications and Appropriate Use
- For infections potentially involving both gram-positive and gram-negative organisms, daptomycin must be combined with agents that provide gram-negative coverage 3
- In neutropenic patients with fever, if gram-positive coverage is needed, daptomycin can be used as an alternative to vancomycin but must be combined with appropriate gram-negative active antibiotics 3
- For empiric therapy in settings where both gram-positive and gram-negative coverage is required, combination therapy is necessary when daptomycin is selected for the gram-positive component 3
- In hospital-acquired or ventilator-associated pneumonia where gram-negative coverage is critical, daptomycin should not be used as monotherapy due to its lack of gram-negative activity 3
Potential Pitfalls and Caveats
- Using daptomycin as monotherapy for mixed infections will leave gram-negative organisms untreated, potentially leading to treatment failure and increased morbidity/mortality 1
- Daptomycin is inactivated by pulmonary surfactant, making it ineffective for pneumonia regardless of the causative organism 2
- When treating empirically before culture results are available, clinicians must ensure adequate gram-negative coverage is included if daptomycin is selected 3
- For severe infections in immunocompromised patients, broad-spectrum coverage including specific agents for gram-negative bacteria must accompany daptomycin 3