First-Generation Cephalosporin Oral Options
Cephalexin is the most commonly recommended first-generation oral cephalosporin due to its wide availability, established efficacy, and reasonable cost. 1
Primary First-Generation Oral Cephalosporin Options
Cephalexin
- Standard adult dosing: 250-500 mg every 6 hours or 500 mg every 12 hours 2
- Total daily dose ranges from 1-4 g divided throughout the day 2
- Widely available as a generic medication and relatively inexpensive 1
- Recommended in multiple guidelines for skin and soft tissue infections, urinary tract infections, and as alternative therapy for streptococcal pharyngitis 1
- Included in American Heart Association guidelines as an alternative for endocarditis prophylaxis in penicillin-allergic patients 1
Cefadroxil
- Standard adult dosing: 500 mg every 12 hours or 1 g daily 3
- Longer half-life allows for less frequent dosing (once or twice daily) compared to cephalexin 3, 4
- Similar antimicrobial spectrum to cephalexin 4
- Particularly useful for urinary tract infections, pharyngitis/tonsillitis, and skin infections 3
Comparative Efficacy
- Both cephalexin and cefadroxil have similar in vitro activity against methicillin-susceptible Staphylococcus aureus (MSSA), with identical MIC50 values of 2 μg/mL and MIC90 values of 4 μg/mL 4
- Cefadroxil's longer half-life allows for twice-daily dosing, which may improve medication adherence compared to cephalexin's traditional four-times-daily regimen 4, 5
- For streptococcal pharyngitis, cephalexin is recommended as an alternative to penicillin in penicillin-allergic patients 1
Clinical Applications
- First-generation cephalosporins are particularly effective against gram-positive organisms including Staphylococcus and Streptococcus species 5
- Commonly used for:
Important Considerations and Caveats
- Cephalosporins should not be used in patients with history of anaphylaxis, angioedema, or urticaria with penicillins or ampicillin due to potential cross-reactivity (approximately 10%) 1
- First-generation cephalosporins have limited activity against gram-negative organisms compared to second and third-generation agents 5
- Resistance concerns: Studies have shown high resistance rates (96%) of viridans group streptococci to cephalexin 1
- When treating serious infections, parenteral agents may be more appropriate than oral options 2
- For pediatric patients, cephalexin suspension is dosed at 25-50 mg/kg/day divided into four doses 2
Comparison with Other Generation Cephalosporins
- First-generation cephalosporins (cephalexin, cefadroxil) have better gram-positive coverage but less gram-negative activity compared to later generations 5
- Third-generation oral cephalosporins like cefdinir offer broader spectrum activity against respiratory pathogens but should be reserved for specific indications to prevent resistance 7, 8
- When treating sensitive organisms, first-generation agents are preferred to prevent resistance development to newer cephalosporins and to minimize cost 5