What is the recommended treatment and dosage for infections using 1st generation cephalosporins (first-generation cephalosporins)?

First-Generation Cephalosporins: Treatment Recommendations and Dosing

First-generation cephalosporins, specifically cephalexin (oral) and cefazolin (IV), are effective for staphylococcal and streptococcal infections but have critical coverage gaps against Pasteurella multocida, Eikenella corrodens, and anaerobes that must be considered when selecting therapy. 1

Spectrum of Activity and Clinical Indications

Coverage Profile

• Excellent activity against: Staphylococcus aureus (methicillin-susceptible) and Streptococcus species 1
• Poor or no activity against: Pasteurella multocida (animal bites), Eikenella corrodens (human bites), anaerobes including Bacteroides fragilis, and gram-negative anaerobes 1
• Not active against: Methicillin-resistant S. aureus (MRSA) or enterococci 1, 2

Appropriate Clinical Uses

• Skin and soft tissue infections caused by staphylococci and streptococci in penicillin-allergic patients 1
• Surgical prophylaxis where gram-positive coverage is primary concern 1, 3
• Diabetic foot infections (mild) when MRSA is not suspected 1

Inappropriate Uses (Critical Pitfall)

• Animal bites: First-generation cephalosporins miss P. multocida and anaerobes—use amoxicillin-clavulanate instead 1
• Human bites: They miss E. corrodens and gram-negative anaerobes—use amoxicillin-clavulanate or ampicillin-sulbactam 1
• Polymicrobial infections requiring anaerobic coverage 1

Dosing Recommendations

Cephalexin (Oral)

Adults:

• Standard dosing: 250 mg every 6 hours 4
• Alternative dosing for specific infections: 500 mg every 12 hours for streptococcal pharyngitis, skin/soft tissue infections, and uncomplicated cystitis in patients >15 years 4
• Severe infections: May require up to 4 grams daily in divided doses 4
• Animal bites (when appropriate): 500 mg three times daily 1
• Human bites (when appropriate): 500 mg four times daily 1

Pediatric Patients:

• Standard dosing: 25-50 mg/kg/day in divided doses 4
• Streptococcal pharyngitis and skin infections: May divide total daily dose every 12 hours in patients >1 year 4
• Severe infections: Dosage may be doubled 4
• Otitis media: 75-100 mg/kg/day in 4 divided doses 4
• β-hemolytic streptococcal infections: Continue for at least 10 days 4

Cefazolin (Intravenous)

Adults:

• Standard infections: 1 gram every 8 hours 1
• Surgical prophylaxis (standard): 2 grams IV 30-60 minutes before incision, redose 1 gram if procedure >4 hours 3
• Cardiac surgery: 2 grams IV plus 1 gram in cardiopulmonary bypass priming solution, redose 1 gram at 4th hour 3
• Neurosurgery/spine with implants: 2 grams IV as single dose, redose 1 gram if duration >4 hours 3
• Urologic procedures: 1 gram every 8 hours 3

Pediatric Patients:

• Staphylococcal infections: 150 mg/kg/day divided every 8 hours 3
• Infective endocarditis: 100 mg/kg/day IV divided every 8 hours (maximum 12 grams daily) 3
• CNS infections: 100 mg/kg/day divided every 8 hours 3

Pharmacokinetic Considerations

• Cephalexin bioavailability: 85-90% when administered orally 5
• Serum half-life: 1-2 hours for most first-generation cephalosporins 5
• Elimination: Primarily renal with contribution from active tubular secretion (blocked by probenecid) 5
• Tissue penetration: Cefazolin demonstrates variable penetration into interstitial fluid with mean penetration ratio of 0.80 6

Pharmacodynamic Targets for Optimal Efficacy

• For MSSA at MIC 1 mg/L: Cefazolin 1 gram every 8 hours achieves 96% probability of 30% fT>MIC and 91% probability of 50% fT>MIC 6
• For organisms at MIC 2 mg/L (Enterobacteriaceae breakpoint): Requires 2 grams every 8 hours to achieve 50% fT>MIC target 6

Cross-Reactivity in Penicillin Allergy

• Cefazolin has unique side chain structure with very low cross-reactivity to penicillins despite being first-generation 1
• Reaction rate in unverified penicillin allergy: 0.7% (95% CrI: 0.1%-1.7%) 1
• Reaction rate in confirmed penicillin allergy: 0.8% (95% CI: 0.13%-4.1%) among 131 patients 1
• Cephalexin shares R1 side chain with aminopenicillins: Higher cross-reactivity risk of 16.45% (95% CI: 11.07-23.75) in proven aminopenicillin allergy 1

Key Clinical Pitfalls to Avoid

• Never use first-generation cephalosporins as monotherapy for bite wounds (animal or human) due to coverage gaps 1
• Do not use for necrotizing fasciitis where broader coverage including anaerobes is essential 1
• Avoid in suspected MRSA infections—consider alternative agents with anti-MRSA activity 1
• Do not exceed 4 grams daily oral cephalexin—if higher doses needed, switch to parenteral cephalosporins 4
• Recognize that activity against gram-negative organisms is limited compared to later-generation cephalosporins 2