Cephalosporin Medication: Appropriate Use and Dosing
Direct Recommendation
Cephalosporins should be selected based on infection site and suspected pathogens: use first-generation agents (cephalexin) for uncomplicated skin/soft tissue infections and streptococcal pharyngitis; third-generation agents (ceftriaxone, cefotaxime) for serious infections including meningitis, pneumonia, and intra-abdominal infections; and adjust dosing for renal impairment while avoiding use in patients with severe β-lactam allergies. 1
Infection-Specific Cephalosporin Selection
Central Nervous System Infections
- For bacterial meningitis, use ceftriaxone 2 g IV every 12 hours or cefotaxime 2 g IV every 6 hours as empiric therapy. 1, 2
- For confirmed Neisseria meningitidis, continue ceftriaxone/cefotaxime for 5 days if recovered. 1, 2
- For Streptococcus pneumoniae, treat for 10 days if stable, extending to 14 days if slow to respond. 1, 2
- For Haemophilus influenzae, continue for 10 days. 1, 2
- For Enterobacteriaceae or Listeria monocytogenes, extend treatment to 21 days. 1, 2
- Add vancomycin 15-20 mg/kg IV every 12 hours if penicillin-resistant pneumococcus is suspected. 1, 2
Respiratory Tract Infections
- For community-acquired pneumonia requiring hospitalization (CURB-65 ≥2), use ceftriaxone 2 g IV daily or cefotaxime 2 g IV every 8 hours combined with a macrolide. 1
- For Haemophilus influenzae pneumonia with β-lactamase production, use ceftriaxone 2 g IV daily or other third-generation cephalosporins. 1
- Treatment duration is typically 7-10 days for pneumonia, extending to 14 days if bacteremia is present. 1
Uncomplicated Infections
- For streptococcal pharyngitis, use cephalexin 500 mg PO every 12 hours for 10 days. 3
- For uncomplicated cystitis in patients >15 years, use cephalexin 500 mg PO every 12 hours for 7-14 days. 3, 4
- For skin and skin structure infections, use cephalexin 500 mg PO every 12 hours. 3
Dosing by Generation and Indication
First-Generation Cephalosporins
- Cephalexin (oral): Adults receive 250 mg every 6 hours for mild infections, or 500 mg every 12 hours for streptococcal pharyngitis and uncomplicated cystitis. 3
- Pediatric dosing: 25-50 mg/kg/day divided into doses every 6-12 hours. 3
- For severe infections, doses may be doubled but should not exceed 4 g daily. 3
Third-Generation Cephalosporins
- Ceftriaxone: 2 g IV every 12-24 hours depending on infection severity. 1, 5
- Cefotaxime: 2 g IV every 6-8 hours for serious infections. 1
- Ceftazidime: 1-2 g IV every 8-12 hours for Pseudomonas aeruginosa infections. 1
Fourth-Generation Cephalosporins
- Cefepime: 2 g IV every 8 hours for hospital-acquired pneumonia or serious gram-negative infections. 1
Renal Dose Adjustments
Critical Considerations
- Most cephalosporins require dose reduction in renal impairment, with the notable exceptions of ceftriaxone and cefoperazone, which have significant biliary excretion. 4, 6
- For ceftriaxone in renal impairment: No adjustment needed unless concurrent hepatic dysfunction exists. 5, 6
- For cefotaxime and ceftazidime: Reduce frequency to every 12-24 hours when creatinine clearance <30 mL/min. 6
- Monitor for nephrotoxicity, particularly at high doses, as tubular damage is dose-related. 7
Allergy Management
Severe β-Lactam Allergy
- In patients with suspected severe, delayed-type allergy to cephalosporins (anaphylaxis, angioedema, Stevens-Johnson syndrome), avoid all β-lactam antibiotics regardless of time since reaction. 1
- Consider fluoroquinolones, aztreonam (except with ceftazidime/cefiderocol allergy <1 year), or vancomycin as alternatives. 1
Non-Severe Allergy
- Cephalosporins with dissimilar side chains can be used in patients with non-severe, delayed-type allergy to a different cephalosporin, regardless of timing. 1
- Avoid cephalosporins with similar/identical side chains if reaction occurred <1 year ago. 1
- After >1 year, cephalosporins with similar side chains may be cautiously used. 1
Cross-Reactivity
- Carbapenems can be used in patients with non-severe, delayed-type cephalosporin allergy. 1
- Aztreonam is safe except in ceftazidime/cefiderocol allergy <1 year old. 1
Local Resistance Patterns
Key Resistance Concerns
- Third-generation cephalosporins maintain excellent activity against E. coli, Klebsiella, Proteus, Haemophilus, and Neisseria, but resistance via plasmid-mediated β-lactamases (ESBLs) is emerging. 6
- Enterobacter species constitutively produce β-lactamases that hydrolyze cephalosporins; consider carbapenems for serious Enterobacter infections. 6
- Cephalosporins have poor activity against enterococci, Listeria, methicillin-resistant staphylococci, and Corynebacterium jekeium. 6, 8
- For ESBL-producing organisms, use meropenem 2 g IV every 8 hours rather than cephalosporins. 1, 9
Pseudomonas Coverage
- Only ceftazidime and cefoperazone have reliable anti-pseudomonal activity among cephalosporins. 1, 10
- For Pseudomonas aeruginosa infections, combine ceftazidime with an aminoglycoside or fluoroquinolone. 1
Common Pitfalls to Avoid
Dosing Errors
- Never use cephalexin for serious infections requiring parenteral therapy; it achieves inadequate serum concentrations. 3, 4
- Do not use once-daily ceftriaxone for meningitis; twice-daily dosing (every 12 hours) is required for CNS infections. 1, 5
- Avoid underdosing third-generation cephalosporins in critically ill patients; use cefotaxime every 6 hours, not every 8 hours. 1, 6
Spectrum Gaps
- Never rely on cephalosporins alone for suspected Listeria meningitis; add ampicillin. 1
- Do not use cephalosporins for enterococcal endocarditis; use ampicillin or vancomycin with gentamicin. 1
- Avoid cephalosporins for methicillin-resistant S. aureus; use vancomycin or linezolid. 6, 8
Duration Mistakes
- Do not stop meningitis treatment prematurely: 5 days for meningococcus, 10-14 days for pneumococcus, 21 days for gram-negatives and Listeria. 1, 2
- For streptococcal pharyngitis, complete the full 10-day course to prevent rheumatic fever. 3