For an adult patient with a ceftriaxone‑sensitive organism and normal renal and hepatic function, what is the appropriate ceftriaxone dose, duration of therapy, and alternative agents if a severe β‑lactam allergy is present?

Ceftriaxone Dosing and Management for Ceftriaxone‑Sensitive Organisms

Standard Adult Dosing for Ceftriaxone‑Sensitive Infections

For an adult with normal renal and hepatic function infected by a ceftriaxone‑sensitive organism, administer ceftriaxone 1–2 g IV or IM once daily, with the specific dose and duration determined by the infection site and severity. 12

Dosing by Infection Type

• Meningococcal meningitis: Ceftriaxone 2 g IV every 12 hours for 5 days provides optimal CSF penetration and bactericidal activity against Neisseria meningitidis. 1
• Pneumococcal meningitis (cephalosporin‑sensitive): Ceftriaxone 2 g IV every 12 hours for 10–14 days (extend to 14 days if clinical response is delayed). 1
• Haemophilus influenzae meningitis: Ceftriaxone 2 g IV every 12 hours for 10 days. 1
• Enterobacteriaceae meningitis: Ceftriaxone 2 g IV every 12 hours for 21 days; seek specialist advice regarding local resistance patterns. 1
• Meningococcal sepsis (no lumbar puncture): Ceftriaxone 2 g IV every 12 hours; discontinue at day 5 if recovered. 1
• Acute bacterial sinusitis (second‑line or intolerance to oral therapy): Ceftriaxone 1–2 g IM or IV once daily for 5 days in adults; 50 mg/kg once daily for 5 days in children. 3
• Uncomplicated gonorrhea (cervix, urethra, rectum): Ceftriaxone 250 mg IM as a single dose PLUS azithromycin 1 g orally or doxycycline 100 mg twice daily for 7 days. 1
• Pharyngeal gonorrhea: Ceftriaxone 250 mg IM as a single dose PLUS azithromycin 1 g orally or doxycycline 100 mg twice daily for 7 days. 1

Pharmacokinetic Rationale

• Ceftriaxone achieves a plasma half‑life of 6.5–8.7 hours in healthy adults, permitting once‑daily dosing for most infections. 45
• A single 1 g dose maintains plasma concentrations exceeding the MIC of most staphylococci, streptococci, and Enterobacteriaceae for 12–24 hours. 5
• Peak plasma concentrations after 1 g IV infusion reach 168 mcg/mL; after 1 g IM injection, 81 mcg/mL. 5
• CSF penetration in the presence of meningeal inflammation is excellent, supporting twice‑daily dosing (2 g every 12 hours) for CNS infections. 16

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Treatment Duration by Infection

• Meningococcal disease: 5 days if clinically recovered. 1
• Pneumococcal meningitis: 10 days if stable; extend to 14 days if response is delayed. 1
• Haemophilus influenzae meningitis: 10 days. 1
• Enterobacteriaceae CNS infection: 21 days. 1
• Acute bacterial sinusitis (parenteral therapy): 5 days. 3
• Uncomplicated gonorrhea: Single dose. 1

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Alternative Agents for Severe β‑Lactam Allergy

For patients with documented severe (Type I/anaphylactic) β‑lactam allergy, ceftriaxone is contraindicated due to 1–10 % cross‑reactivity risk; use the following alternatives based on infection type. 3

Meningitis in Severe β‑Lactam Allergy

• Pneumococcal meningitis (penicillin and cephalosporin non‑susceptible): Chloramphenicol 25 mg/kg IV every 6 hours for 14 days. 1
• Meningococcal meningitis: Chloramphenicol 25 mg/kg IV every 6 hours for 5 days. 1
• Haemophilus influenzae meningitis: Moxifloxacin 400 mg IV once daily for 10 days. 1

Gonorrhea in Severe β‑Lactam Allergy

• Uncomplicated gonorrhea (all sites): Azithromycin 2 g orally as a single dose PLUS test‑of‑cure in 1 week. 1
• This regimen is reserved for patients who cannot receive ceftriaxone due to severe allergy; it is not first‑line due to emerging azithromycin resistance. 1

Acute Bacterial Sinusitis in Severe β‑Lactam Allergy

• Respiratory fluoroquinolones are the preferred alternative: Levofloxacin 500 mg orally once daily for 10–14 days OR moxifloxacin 400 mg orally once daily for 10 days, providing 90–92 % predicted clinical efficacy against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 3
• Doxycycline 100 mg orally once daily for 10 days is an acceptable but suboptimal alternative (predicted efficacy 77–81 % with a 20–25 % bacteriologic failure rate) when fluoroquinolones are contraindicated. 3

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Monitoring and Reassessment

• Meningitis: Continue definitive therapy based on organism identification and susceptibility; adjust duration if clinical response is delayed. 1
• Gonorrhea: Perform test‑of‑cure at 1 week if treated with alternative regimens (cefixime or azithromycin monotherapy); ideally use culture or NAAT. 1
• Acute bacterial sinusitis: Reassess at 3–5 days; if no improvement, switch to high‑dose amoxicillin‑clavulanate or a respiratory fluoroquinolone. 3

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Critical Pitfalls to Avoid

• Do not use ceftriaxone as sole therapy for pseudomonal infections; it has limited activity against Pseudomonas aeruginosa. 72
• Ceftriaxone carries a 1–10 % cross‑reactivity risk in patients with severe penicillin allergy; confirm allergy type before prescribing. 3
• For gonorrhea, never use ceftriaxone monotherapy; always combine with azithromycin or doxycycline to prevent resistance. 1
• Ensure adequate treatment duration (minimum 5 days for sinusitis, 10 days for meningitis) to prevent relapse. 13
• Chloramphenicol is no longer recommended for routine use in meningitis due to toxicity concerns; reserve for severe β‑lactam allergy when fluoroquinolones are unsuitable. 1

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Adjunctive Therapies (Sinusitis Only)

• Intranasal corticosteroids (mometasone, fluticasone, budesonide) twice daily reduce mucosal inflammation and accelerate symptom resolution; supported by strong evidence from multiple randomized controlled trials. 3
• Saline nasal irrigation 2–3 times daily provides symptomatic relief and aids mucus clearance. 3
• Analgesics (acetaminophen or ibuprofen) for pain and fever control. 3