Can cefoperazone be used to treat skin and soft‑tissue infections and osteomyelitis?

Cefoperazone for Skin and Bone Infections: Not Recommended as First-Line Therapy

Cefoperazone should not be used as a first-line agent for skin and soft tissue infections or osteomyelitis, as it is not included in any major guideline recommendations for these indications and superior alternatives with better staphylococcal and streptococcal coverage are available. 1

Why Cefoperazone Is Not Guideline-Recommended

For Skin and Soft Tissue Infections

The 2024 WHO Essential Medicines guidelines and 2014 IDSA guidelines provide comprehensive recommendations for skin and soft tissue infections, and cefoperazone is conspicuously absent from all treatment algorithms 1:

• First-line agents for mild infections: Amoxicillin-clavulanic acid, cloxacillin, or cefalexin 1
• For purulent infections (likely S. aureus): Dicloxacillin, cefazolin, clindamycin, cefalexin 1
• For non-purulent infections: Benzylpenicillin, phenoxymethylpenicillin, clindamycin, nafcillin, or cefazolin 1
• For necrotizing fasciitis: Clindamycin plus piperacillin-tazobactam or ceftriaxone plus metronidazole (with or without vancomycin) 1

For Osteomyelitis

No major guideline recommends cefoperazone for osteomyelitis. The typical duration for bone infections is 6 weeks following adequate debridement 1, and agents with proven bone penetration and activity against common pathogens (S. aureus, streptococci, gram-negative bacilli) are preferred.

Critical Limitations of Cefoperazone

Inadequate Staphylococcal Coverage

While historical data from the 1980s showed cefoperazone achieved 90% clinical efficacy in skin infections including some staphylococcal cases 2, 3, this does not translate to modern clinical practice where:

• MRSA prevalence is substantially higher than in the 1980s 1
• Cefoperazone has no activity against MRSA 4
• First-generation cephalosporins (cefazolin, cefalexin) provide superior anti-staphylococcal activity for MSSA 1, 5

Suboptimal for Common Pathogens

Cefoperazone lacks adequate coverage for the most common skin and bone infection pathogens:

• Staphylococcus aureus (the predominant pathogen in 77% of bone infections from pressure injuries) 1
• Streptococcus pyogenes (group A streptococcus) 1
• Anaerobes including Peptostreptococcus spp. (48.6% of polymicrobial bone infections) and Bacteroides spp. (40%) 1

When Cefoperazone Might Be Considered (Rare Scenarios)

Pseudomonas Infections with Limited Options

Cefoperazone has activity against Pseudomonas aeruginosa 2, 3, but ciprofloxacin is preferred for Pseudomonas skin infections (e.g., hot tub folliculitis) as it offers oral administration 5.

Multidrug-Resistant Gram-Negative Infections

Cefoperazone-sulbactam (not cefoperazone alone) may be considered for:

• Carbapenem-resistant Acinetobacter baumannii (CRAB) infections at doses of 3g/3g IV every 8 hours 4
• However, this is a weak recommendation with low-quality evidence 4
• Sulbactam-containing regimens show lower nephrotoxicity than colistin 4

Practical Algorithm: Choosing Antibiotics for Skin and Bone Infections

Step 1: Identify Infection Type and Severity

Mild skin infections (cellulitis, simple abscesses):

• Use cefalexin, cloxacillin, or amoxicillin-clavulanic acid 1
• Duration: 5-10 days 1

Purulent infections with suspected MRSA:

• Oral: TMP-SMX, doxycycline, or linezolid 1
• IV: Vancomycin, daptomycin, linezolid, or ceftaroline 1

Necrotizing infections:

• Clindamycin plus piperacillin-tazobactam or ceftriaxone plus metronidazole 1
• Add vancomycin if MRSA suspected 1

Step 2: For Osteomyelitis

Following surgical debridement and flap reconstruction:

• Duration: 6 weeks 1
• Agent selection based on bone culture results
• Common regimens include nafcillin/cefazolin for MSSA, vancomycin for MRSA 1

Step 3: Adjust Based on Culture Results

• Never use cefoperazone empirically for skin or bone infections 1
• Consider cefoperazone-sulbactam only if cultures demonstrate susceptible Pseudomonas or Acinetobacter with limited alternatives 4

Common Pitfalls to Avoid

Using cefoperazone for empiric therapy: This provides inadequate coverage for the most common pathogens (S. aureus, streptococci) and is not supported by any guideline 1.

Confusing cefoperazone with cefoperazone-sulbactam: The sulbactam component provides critical β-lactamase inhibition and intrinsic activity against Acinetobacter, but this combination is still not first-line for skin/bone infections 4.

Ignoring local resistance patterns: In settings with high MRSA prevalence (>10-15%), empiric coverage with vancomycin or alternatives is mandatory 1.

Inadequate surgical management: For osteomyelitis, antibiotics alone are insufficient—adequate debridement is essential for cure 1.