Comprehensive Guide to Cephalosporins for Treating Infections
Cephalosporins should be selected based on generation class, with each generation offering specific coverage patterns for different pathogens and clinical scenarios. The appropriate selection depends on the suspected pathogen, infection site, local resistance patterns, and patient factors.
Cephalosporin Classification and Coverage
First-Generation Cephalosporins
- Examples: Cefazolin (IV), Cephalexin (oral)
- Coverage: Excellent activity against gram-positive organisms (Staphylococcus aureus including beta-lactamase producing strains, Streptococcus species) 1
- Limited coverage: Modest activity against some gram-negative organisms (E. coli, Proteus mirabilis)
- Best uses: Skin/soft tissue infections, surgical prophylaxis, uncomplicated UTIs
Second-Generation Cephalosporins
- Examples: Cefuroxime, Cefoxitin, Cefprozil
- Coverage: Maintained gram-positive activity with improved gram-negative coverage
- Special notes: Cefoxitin has anaerobic coverage 2
- Best uses: Respiratory infections, sinusitis, otitis media, community-acquired pneumonia
Third-Generation Cephalosporins
- Examples: Ceftriaxone, Cefotaxime, Ceftazidime, Cefixime, Cefpodoxime
- Coverage: Enhanced gram-negative activity including many Enterobacteriaceae
- Special notes:
- Best uses: Serious community-acquired and hospital-acquired infections, meningitis
Fourth-Generation Cephalosporins
- Examples: Cefepime
- Coverage: Broad spectrum with enhanced activity against both gram-positive and gram-negative bacteria, including Pseudomonas 3
- Best uses: Serious infections, especially when resistance is a concern, hospital-acquired pneumonia
Clinical Application by Infection Type
Respiratory Tract Infections
- Community-acquired pneumonia:
Meningitis
- First choice: Ceftriaxone or cefotaxime 2
- Age considerations:
Skin and Soft Tissue Infections
- Uncomplicated: First-generation (cefazolin IV or cephalexin oral) 1
- Diabetic foot infections:
- Mild: Cephalexin
- Moderate/severe: Cefoxitin, ceftriaxone 2
Urinary Tract Infections
- Uncomplicated: First-generation oral cephalosporins (cephalexin)
- Complicated/pyelonephritis: Third-generation (ceftriaxone) 4
- Pseudomonas suspected: Ceftazidime or cefepime 2
Multi-Drug Resistant Infections
- ESBL-producing organisms: Generally avoid cephalosporins; carbapenems preferred 3
- Carbapenem-resistant Pseudomonas: Ceftolozane/tazobactam or ceftazidime/avibactam 2
Dosing Considerations
Renal Adjustment
- Most cephalosporins require dose adjustment in renal impairment
- Exceptions: Ceftriaxone has significant biliary excretion and requires less adjustment 4
Duration of Therapy
- Community-acquired pneumonia: Generally not exceeding 8 days in responding patients 2
- Meningitis: 7-14 days depending on pathogen 2
- Skin infections: 5-10 days for uncomplicated cases 2
Common Pitfalls and Caveats
Cross-reactivity with penicillin allergy: Approximately 10% cross-reactivity; use with caution in patients with severe immediate hypersensitivity reactions to penicillins
Inadequate coverage: First and second-generation cephalosporins should not be used for suspected Pseudomonas infections
Resistance development: Use judiciously to prevent emergence of resistance; consider local resistance patterns 3
CNS penetration: Only certain cephalosporins (ceftriaxone, cefotaxime) adequately penetrate the blood-brain barrier for treating meningitis 2
C. difficile risk: All cephalosporins carry risk of C. difficile infection, particularly with prolonged use
MRSA coverage: Standard cephalosporins lack MRSA coverage; ceftaroline is the only cephalosporin with MRSA activity 2
By selecting the appropriate cephalosporin based on suspected pathogens, site of infection, and patient factors, clinicians can optimize treatment outcomes while minimizing adverse effects and resistance development.