What is the recommended dosing regimen for cephalosporins (e.g. ceftriaxone, cephalexin) in patients with serious or less severe infections and varying degrees of renal function?

Cephalosporin Dosing in Serious and Less Severe Infections

For serious infections requiring parenteral cephalosporins, ceftriaxone 1-2 grams IV once daily is appropriate for most adult patients regardless of renal function, with dose escalation to 2 grams every 12 hours (4 grams total daily) specifically for meningitis. 1, 2

Adult Dosing by Infection Severity

Serious Infections (Non-Meningeal)

• Standard dose: 1-2 grams IV once daily for most serious infections including pneumonia, bacteremia, complicated skin/soft tissue infections, and complicated urinary tract infections 1, 2
• Maximum daily dose: 4 grams should not be exceeded 2
• Duration typically 4-14 days depending on infection type; continue at least 2 days after clinical resolution 2

Meningitis

• Dose: 2 grams IV every 12 hours (4 grams total daily) regardless of renal function 1, 2
• This higher dosing achieves adequate CSF penetration for CNS infections 3

Endocarditis

• Dose: 2 grams IV/IM once daily for 4 weeks (or 2 weeks when combined with gentamicin) for highly penicillin-susceptible viridans streptococci 3, 1

Less Severe Infections

• Uncomplicated gonorrhea: 250 mg IM single dose 2
• Surgical prophylaxis: 1 gram IV single dose administered 0.5-2 hours preoperatively 2

Pediatric Dosing

Standard Infections

• Skin/soft tissue infections: 50-75 mg/kg once daily (maximum 2 grams) 2
• Serious miscellaneous infections: 50-75 mg/kg/day divided every 12 hours (maximum 2 grams daily) 2
• Acute otitis media: 50 mg/kg IM single dose (maximum 1 gram) 2

Serious Infections in Infants and Children

• Febrile infants 8-21 days old with UTI or bacteremia: Ampicillin 150 mg/kg/day divided every 8 hours PLUS either ceftazidime 150 mg/kg/day divided every 8 hours OR gentamicin 4 mg/kg every 24 hours 3
• Febrile infants 22-60 days old with UTI: Ceftriaxone 50 mg/kg once daily 3
• Oral step-down for infants >28 days with UTI: Cephalexin 50-100 mg/kg/day in 4 divided doses 3

Meningitis in Children

• Initial dose: 100 mg/kg (maximum 4 grams) 2
• Maintenance: 100 mg/kg/day once daily or divided every 12 hours (maximum 4 grams daily) 2
• Neonates: Administer over 60 minutes to reduce risk of bilirubin encephalopathy 2

Renal Function Considerations

Key Principle

No dosage adjustment is necessary for isolated renal impairment when administering usual doses of ceftriaxone up to 2 grams daily. 1, 2

Rationale

• Ceftriaxone has dual elimination via both renal (33-67%) and biliary excretion 2
• Elimination half-life increases only modestly even in severe renal impairment (from 5.8-8.7 hours to 15.7 hours) 2
• Not removed by hemodialysis or peritoneal dialysis; no supplemental dosing needed post-dialysis 2

Important Caveats

• Combined hepatic and renal dysfunction: Maximum 2 grams daily with close clinical monitoring 2
• Elderly patients with normal hepatic function require no dose adjustment up to 2 grams daily 2

Oral Cephalosporin Dosing

First-Generation (Cephalexin)

• Standard dose: 500 mg orally 3-4 times daily 3
• Pediatric UTI step-down: 50-100 mg/kg/day in 4 divided doses 3
• Good activity against staphylococci and streptococci; misses Pasteurella multocida and anaerobes 3

Second-Generation (Cefuroxime)

• Dose: 500 mg orally twice daily 3
• Good activity against P. multocida; misses anaerobes 3

Critical Safety Considerations

Neonatal Contraindications

• Absolute contraindication: Premature neonates and neonates ≤28 days requiring calcium-containing IV solutions due to risk of fatal ceftriaxone-calcium precipitation 2
• Hyperbilirubinemic neonates should not receive ceftriaxone due to displacement of bilirubin from albumin 2

Monitoring Requirements

• Prothrombin time monitoring in patients with impaired vitamin K synthesis, chronic liver disease, or malnutrition 2
• Consider vitamin K supplementation (10 mg weekly) if PT prolonged 2

Gallbladder and Urinary Complications

• Ceftriaxone-calcium precipitates can form in gallbladder (pseudolithiasis) and urinary tract (urolithiasis), appearing on ultrasound 2
• Higher risk in pediatric patients 2
• Ensure adequate hydration and discontinue if symptomatic urolithiasis or oliguria develops 2

Administration Specifics

IV Administration

• Infusion time: 30 minutes for adults and children; 60 minutes for neonates 2
• Recommended concentration: 10-40 mg/mL 2
• Never use calcium-containing diluents (Ringer's, Hartmann's) due to precipitation risk 2

IM Administration

• Reconstitute to 250 mg/mL or 350 mg/mL concentration 2
• Inject into large muscle mass with aspiration to avoid vascular injection 2