Unasyn (Ampicillin-Sulbactam) Has Superior Coverage for Skin Flora
For skin and soft tissue infections, Unasyn (ampicillin-sulbactam) provides better coverage of typical skin flora compared to cefepime, particularly for methicillin-susceptible Staphylococcus aureus (MSSA) and streptococcal species that dominate community-acquired skin infections. 1
Microbiologic Coverage Comparison
Unasyn's Skin Flora Coverage
Ampicillin-sulbactam is FDA-indicated specifically for skin and skin structure infections caused by beta-lactamase producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella spp., Proteus mirabilis, Bacteroides fragilis, Enterobacter spp., and Acinetobacter calcoaceticus 1
The drug covers both beta-lactamase producing and non-beta-lactamase producing strains of staphylococci (S. aureus, S. epidermidis, S. saprophyticus) and streptococci (S. pyogenes, S. pneumoniae, S. viridans), which are the predominant pathogens in community-acquired skin infections 1
Ampicillin-sulbactam has proven clinical efficacy in adults and children for skin and soft tissue infections, including diabetic foot infections, with a broad range of activity against both aerobic and anaerobic bacteria 2
Cefepime's Limitations for Skin Flora
While cefepime maintains activity against methicillin-susceptible S. aureus and streptococci, it has lower intrinsic activity against gram-positive organisms compared to ampicillin-sulbactam 3, 4
Cefepime's spectrum is optimized for nosocomial gram-negative infections, febrile neutropenia, and complicated urinary tract infections—not primarily for community-acquired skin flora 5
Cefepime requires combination with metronidazole for anaerobic coverage in mixed infections, whereas ampicillin-sulbactam provides inherent anaerobic activity through its coverage of Bacteroides species 5, 1
Clinical Context and Practical Considerations
When to Choose Unasyn
Community-acquired skin and soft tissue infections where MSSA, streptococci, and mixed aerobic-anaerobic flora are expected 6, 1
Infections involving potential anaerobic organisms (diabetic foot infections, bite wounds, infections near mucosal surfaces) 1, 2
Mild-to-moderate severity infections where narrower spectrum therapy is appropriate and cost-effective 6
When Cefepime May Be Preferred
Nosocomial or hospital-acquired skin infections where Pseudomonas aeruginosa, Enterobacter spp., or other resistant gram-negative organisms are suspected 6
Immunocompromised patients requiring very broad empirical coverage for resistant gram-negative bacteria 6
Higher-risk patients where multidrug-resistant pathogens are likely based on prior antimicrobial exposure or local resistance patterns 6
Important Caveats
Neither agent covers MRSA, which requires vancomycin, linezolid, daptomycin, or other anti-MRSA therapy 6
Local resistance patterns must guide final selection, as ampicillin-sulbactam is not active against extended-spectrum beta-lactamase (ESBL) producers, while cefepime-sulbactam combinations may be needed for ESBL coverage 5, 2
Cefepime has no activity against enterococci, which may be relevant in nosocomial surgical site infections 4