In a 129‑lb (≈58 kg) adult with community‑acquired pneumonia and no renal or hepatic impairment, should ceftriaxone be dosed at 1 g IV once daily or 2 g IV once daily?

Ceftriaxone Dosing for Community-Acquired Pneumonia in a 129-lb (58 kg) Adult

For a 129-lb adult with community-acquired pneumonia and no renal or hepatic impairment, use ceftriaxone 1 g IV once daily combined with azithromycin 500 mg daily; the 2 g dose is reserved exclusively for ICU-level severe pneumonia or when high-level penicillin-resistant Streptococcus pneumoniae is documented. 1, 2

Evidence-Based Dosing Algorithm

Non-ICU Hospitalized Patients (Standard Severity)

• Ceftriaxone 1 g IV once daily is the recommended dose for hospitalized adults with moderate-severity CAP who do not require ICU admission. 1, 2
• This regimen achieves equivalent clinical cure rates, mortality outcomes, and microbiologic eradication compared to 2 g daily in regions with low prevalence of drug-resistant S. pneumoniae. 3, 4
• A 2023 Israeli retrospective cohort of 3,989 patients demonstrated identical 30-day mortality between 1 g/day (14.7%) and 2 g/day (16.0%) groups (p=0.24), with the 1 g dose associated with significantly lower Clostridioides difficile infection rates (0.2% vs 0.6%, p=0.03) and shorter hospital stays (median 4 vs 5 days, p=0.02). 4
• A 2025 Japanese nationwide study of 471,694 pneumonia patients confirmed no mortality difference between 1 g and 2 g daily regimens (4.5% vs 4.6%, p=0.219) in the general hospitalized population. 5

ICU Patients (Severe Pneumonia)

• Escalate to ceftriaxone 2 g IV once daily for patients meeting ICU admission criteria (septic shock requiring vasopressors, respiratory failure requiring mechanical ventilation, or ≥3 minor severity criteria). 1, 2
• The 2025 Japanese study demonstrated that among patients requiring mechanical ventilation, the 2 g regimen reduced 30-day mortality compared to 1 g (17.2% vs 20.4%; risk difference -3.2%, 95% CI -5.6% to -0.9%, p=0.006). 5
• Combination therapy is mandatory for all ICU patients: ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily (or a respiratory fluoroquinolone). 1, 2

Mandatory Macrolide Combination

• Never use ceftriaxone monotherapy—always combine with azithromycin 500 mg daily (or clarithromycin 500 mg twice daily) to cover atypical pathogens (Mycoplasma, Chlamydophila, Legionella), which account for 10–40% of CAP cases. 1, 2
• Ceftriaxone lacks activity against atypical organisms; β-lactam monotherapy in hospitalized patients is associated with treatment failure and higher mortality. 1, 2

Duration and Transition to Oral Therapy

• Treat for a minimum of 5 days and continue until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1, 2
• Typical total duration for uncomplicated CAP is 5–7 days. 1, 2
• Switch from IV to oral therapy when the patient is hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm), clinically improving, afebrile 48–72 h, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, and able to take oral medication—usually by hospital day 2–3. 1, 2

Renal and Hepatic Considerations

• No dose adjustment is required for ceftriaxone in patients with renal or hepatic impairment, as it undergoes dual hepatic-renal elimination. 6, 1
• The FDA label confirms that "no dosage adjustment is necessary for patients with impairment of renal or hepatic function." 6

Critical Pitfalls to Avoid

• Do not automatically use 2 g daily for all hospitalized patients—reserve this dose for ICU-level severity or documented high-level penicillin resistance (MIC ≥4 mg/L). 1, 5
• Do not delay the first antibiotic dose—administration beyond 8 hours after diagnosis increases 30-day mortality by 20–30%. 1, 2
• Do not use ceftriaxone alone—macrolide combination is mandatory to prevent treatment failure from atypical pathogens. 1, 2
• Obtain blood and sputum cultures before starting antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1, 2

Comparative Safety Profile

• The 1 g daily regimen demonstrates a superior safety profile with lower rates of C. difficile infection (0.2% vs 0.6%, p=0.03) and shorter hospital stays compared to 2 g daily in non-ICU patients. 4
• Overall adverse events (composite of biliary tract infection, C. difficile infection, and allergic reactions) were slightly higher in the 2 g/day group (1.9% vs 1.8%, p=0.007) in the Japanese nationwide study. 5

Summary Algorithm

1. Non-ICU hospitalized CAP: Ceftriaxone 1 g IV once daily + azithromycin 500 mg daily 1, 2, 4
2. ICU-level severe CAP: Ceftriaxone 2 g IV once daily + azithromycin 500 mg IV daily 1, 2, 5
3. Minimum duration: 5 days and until afebrile 48–72 h with clinical stability 1, 2
4. Transition to oral: When hemodynamically stable, typically day 2–3 1, 2
5. No renal/hepatic adjustment needed 6, 1