Outcomes of ceftriaxone 2 g versus 1 g daily in hospitalized patients with pneumonia: a nationwide retrospective cohort study.

Objectives: Ceftriaxone is widely used for hospitalized patients with community-acquired pneumonia, but its optimal dosage remains unclear.

Methods: We retrospectively identified patients diagnosed with pneumonia between July 2010 and March 2022 from the Diagnosis Procedure Combination inpatient database in Japan. They were categorized into those receiving 2 or 1 g/day of ceftriaxone within the first 2 days of hospitalization. The primary outcome was 30-day in-hospital mortality. The secondary outcomes included overall adverse events (composite of biliary tract infection, Clostridioides difficile infection and allergic reactions) and each adverse event. A subgroup analysis was conducted for patients requiring mechanical ventilation. Propensity-score overlap-weighting analysis was used for comparisons.

Results: Among the 471 694 eligible patients, 63.3% received 2 g/day and 36.7% received 1 g/day of ceftriaxone. Propensity-score analysis showed no significant difference in 30-day in-hospital mortality between the two groups [4.5% versus 4.6%; risk difference (RD), -0.1%; 95% confidence interval (CI), -0.3% to 0.1%; P = 0.219]. Overall adverse events were slightly higher in the 2 g/day group (1.9% versus 1.8%; RD, 0.1%; 95% CI, 0.0%-0.2%; P = 0.007), particularly the proportion of C. difficile infection. In the subgroup analysis of patients requiring mechanical ventilation, the 2 g/day regimen was associated with lower 30-day mortality (17.2% versus 20.4%; RD, -3.2%; 95% CI, -5.6% to -0.9%; P = 0.006).

Conclusions: While a ceftriaxone dose exceeding 1 g/day may not be necessary for routine pneumonia treatment, a 2 g/day regimen may be considered for patients with severe pneumonia requiring mechanical ventilation.