What are the indications, dosing, contraindications, precautions, and adverse effects of cefdinir?

Cefdinir (Ceftanire)

Indications

Cefdinir is an oral third-generation cephalosporin indicated for mild-to-moderate bacterial respiratory tract infections and uncomplicated skin infections, positioned as an alternative when amoxicillin cannot be used. 1

Respiratory Tract Infections

• Acute bacterial sinusitis: Cefdinir is appropriate first-line therapy for adults with mild disease who have not received antibiotics in the previous 4–6 weeks, or as second-line therapy when initial amoxicillin fails after 72 hours. 2, 1
• Community-acquired pneumonia: Cefdinir is an alternative oral cephalosporin option, though not preferred over amoxicillin for penicillin-susceptible Streptococcus pneumoniae. 3
• Acute bacterial exacerbations of chronic bronchitis: Approved indication with demonstrated clinical efficacy equivalent to comparators. 4
• Streptococcal pharyngitis/tonsillitis: Cefdinir administered for 5 or 10 days provides efficacy equivalent to penicillin V. 1
• Acute otitis media (children ≥6 months): Recommended as an alternative when amoxicillin cannot be used. 1

Skin Infections

• Uncomplicated skin and skin-structure infections: Approved for adults, adolescents, and pediatric patients. 4

Penicillin Allergy

• Cefdinir is preferred among cephalosporins for patients with non-Type I penicillin hypersensitivity (e.g., rash) based on high patient acceptance, particularly in children. 2, 3

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Dosing

Adults and Adolescents

• Standard dose: 300 mg orally twice daily or 600 mg orally once daily. 5, 4
• Treatment duration: 5–10 days depending on the infection; for acute bacterial sinusitis, continue for 10 days or until symptom-free for 7 consecutive days. 2, 4

Pediatric Patients (≥6 months)

• Standard dose: 14 mg/kg/day administered as a single daily dose or divided into two doses. 1, 5
• Maximum daily dose: Do not exceed adult dosing. 4

Renal Impairment

• Creatinine clearance <30 mL/min: Reduce dose to 300 mg once daily (adults) or 7 mg/kg once daily (pediatric patients). 4
• Hemodialysis: Administer 300 mg (or 7 mg/kg) at the end of each dialysis session. 4

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Microbiologic Activity

Cefdinir provides good coverage against the three major respiratory pathogens but has important limitations against drug-resistant organisms. 2, 3

Spectrum of Activity

• Excellent activity against Haemophilus influenzae: Cefdinir demonstrates 97.1–99.0% susceptibility rates, the highest among oral cephalosporins, and is stable against 13 common β-lactamases including those produced by H. influenzae. 6, 7
• Good activity against Moraxella catarrhalis: Complete or near-complete activity (90–100% of isolates). 2, 6
• Moderate activity against Streptococcus pneumoniae: Comparable to second-generation cephalosporins (cefuroxime axetil, cefpodoxime proxetil) against penicillin-susceptible strains, with susceptibility rates of 78.5–79.4%. 2, 6

Critical Limitations

• No activity against drug-resistant S. pneumoniae (DRSP): Cefdinir has limited efficacy against highly penicillin-resistant pneumococci. 2, 1
• No activity against staphylococci: Cefdinir should not be used when Staphylococcus aureus is suspected. 2, 1
• Predicted clinical efficacy: 83–88% in adults with acute bacterial sinusitis, lower than respiratory fluoroquinolones or high-dose amoxicillin-clavulanate (90–92%). 2, 3

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Clinical Efficacy

Cefdinir demonstrates clinical and bacteriological efficacy equivalent to comparator agents in randomized controlled trials across multiple respiratory tract infections. 4

• Acute bacterial sinusitis: Equivalent efficacy to amoxicillin-clavulanate in clinical and bacteriological responses. 4
• Community-acquired pneumonia: Equivalent efficacy to cefuroxime axetil, cefaclor, and loracarbef. 4
• Streptococcal pharyngitis: At least as effective as penicillin V when administered for 5 or 10 days. 4
• Acute otitis media (pediatric): Similar efficacy to amoxicillin-clavulanate or cefprozil. 4

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Contraindications

• Known hypersensitivity to cefdinir, any component of the formulation, or other cephalosporins. 4
• History of cephalosporin-associated hemolytic anemia. 4

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Precautions and Warnings

Cross-Reactivity with Penicillin Allergy

• Patients with Type I (anaphylactic) penicillin allergy: Cefdinir carries a 1–10% cross-reactivity risk and should be avoided; respiratory fluoroquinolones are preferred. 2
• Patients with non-severe penicillin allergy (rash): Cefdinir is safe and preferred due to negligible cross-reactivity. 2, 3

Drug Interactions

• Antacids containing aluminum or magnesium: Coadministration impairs cefdinir absorption; separate administration by at least 2 hours. 3, 4
• Iron supplements and iron-fortified foods: May reduce cefdinir absorption; separate administration by at least 2 hours. 4

Renal Impairment

• Dose adjustment required: Reduce dose in patients with creatinine clearance <30 mL/min to prevent drug accumulation. 4

Clostridium difficile-Associated Diarrhea

• Risk of pseudomembranous colitis: Consider C. difficile infection in patients who develop diarrhea during or after cefdinir therapy. 4

Superinfection

• Prolonged use may result in overgrowth of non-susceptible organisms: Monitor for fungal or bacterial superinfection. 4

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Adverse Effects

Cefdinir is generally well tolerated, with a safety profile similar to comparator agents. 4

Common Adverse Events

• Diarrhea: Most common adverse event across all age groups; incidence generally higher than comparators (40–43% in some studies), though discontinuation rates are similar. 4, 7
• Nausea: Reported in clinical trials but generally mild. 4
• Abdominal pain: Occurs in a minority of patients. 4
• Rash: Mild cutaneous reactions reported. 4

Pediatric-Specific Considerations

• Superior taste and palatability: The oral suspension formulation is very well accepted among children, with superior taste compared to other oral antimicrobials. 2, 5, 4

Serious Adverse Events (Rare)

• Hypersensitivity reactions: Including anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. 4
• Hemolytic anemia: Rare but serious; discontinue cefdinir immediately if hemolysis occurs. 4
• Hepatotoxicity: Elevated liver enzymes reported rarely. 4

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Position in Treatment Algorithms

Acute Bacterial Sinusitis

• First-line for mild disease (no recent antibiotics): Cefdinir is an appropriate alternative to amoxicillin or amoxicillin-clavulanate in adults and children. 2, 1
• Second-line after amoxicillin failure: Switch to cefdinir if no improvement after 72 hours of amoxicillin monotherapy. 2
• Preferred for penicillin-allergic patients: Cefdinir is the cephalosporin of choice for non-Type I penicillin allergy due to high patient acceptance. 2, 3
• Avoid in moderate disease with recent antibiotic use: Prefer respiratory fluoroquinolones or high-dose amoxicillin-clavulanate instead. 3

Streptococcal Pharyngitis

• Alternative to penicillin V: Cefdinir 5- or 10-day courses provide equivalent efficacy. 1, 4

Acute Otitis Media (Pediatric)

• Alternative when amoxicillin cannot be used: Cefdinir is recommended for children ≥6 months with documented penicillin allergy. 1

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Common Pitfalls

• Do not use cefdinir as first-line therapy when amoxicillin or amoxicillin-clavulanate is appropriate: This contradicts guideline recommendations and exposes patients to unnecessary risk. 2, 3
• Cefdinir has no activity against DRSP: Use high-dose amoxicillin-clavulanate or respiratory fluoroquinolones for suspected resistant pneumococci. 2, 1
• Avoid coadministration with antacids or iron: Separate administration by at least 2 hours to prevent impaired absorption. 3, 4
• Ensure adequate treatment duration: Minimum 10 days for acute bacterial sinusitis to prevent relapse. 2
• Reassess at 72 hours (pediatrics) or 3–5 days (adults): Switch to alternative therapy if no improvement to avoid treatment failure. 2

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Pharmacokinetics

• Absorption: Rapidly absorbed from the gastrointestinal tract; mean time to peak plasma concentration is 3 hours. 7
• Distribution: Distributes well into respiratory tract tissues (sinus, tonsil) and fluids (middle ear, skin blisters). 5, 4
• Metabolism: Not appreciably metabolized. 2
• Elimination: Primarily eliminated via renal excretion of unchanged drug. 2, 7
• Half-life: Approximately 1.5 hours, allowing once- or twice-daily dosing. 7, 8

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Key Advantages

• Convenient dosing: Once- or twice-daily administration improves adherence. 5, 4
• Excellent taste: Superior palatability in pediatric suspension formulations enhances patient acceptance. 2, 5, 4
• Broad β-lactamase stability: Stable against 13 common β-lactamases, including those produced by H. influenzae and M. catarrhalis. 4, 7
• Well tolerated: Generally similar adverse event profile to comparators, with low discontinuation rates. 4