Shorter antibiotic courses non-inferior for inpatient community-acquired pneumonia

1. In this target trial emulation, a shorter antibiotic course (3 to 4 days) demonstrated a similar 30-day all-cause mortality rate compared with a longer course (5 days or more) in patients hospitalized with community-acquired pneumonia (CAP).

2. The generalizability of these findings is limited due to the strict exclusion criteria used in the study.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Updated American Thoracic Society guidelines for inpatient management of community-acquired pneumonia (CAP) recommend antibiotic courses of ≤5 days for patients who achieve clinical stability. This recommendation is supported by the 2021 Pneumonia Short Treatment randomized controlled trial, although its conclusions were limited by a small sample size and lack of mortality outcomes. In this multicenter study across 67 hospitals, investigators sought to determine the proportion of patients eligible for short-course therapy using these criteria and to compare 30-day clinical outcomes between those receiving ≤5 days versus longer antibiotic courses. After applying inclusion and exclusion criteria from the Pneumonia Short Treatment trial, only 10% of patients were eligible for short-course therapy. Of these, fewer than 10% received a short course of antibiotics. The primary outcome, 30-day all-cause mortality, was similar between groups. Secondary outcomes, including readmissions and urgent care visits, were also comparable, each occurring in just under 10% of patients. Rates of C. difficile infection were equivalent and rare. Adverse events were slightly more frequent in the short-course group, most commonly diarrhea, rash, and renal dysfunction. Sensitivity analyses excluding patients who received antibiotics prior to admission showed consistent results. Although generalizability is limited by the small number of patients receiving short-course therapy, short follow-up, and potential residual confounding, these findings suggest that short-course antibiotic treatment provides similar mortality outcomes with minimal differences in benefits or harms compared with longer courses.

Click to read this study in AIM

Relevant Reading: Discontinuing β-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial

In-Depth [randomized controlled trial]: This target trial emulation evaluated 30-day clinical outcomes between patients receiving shorter versus longer antibiotic courses for community-acquired pneumonia (CAP). Data were drawn from 67 hospitals in the Hospital Medicine Safety Consortium in Michigan. Eligible patients were admitted to general care, discharged between February 23, 2017, and July 31, 2024, with CAP, and received antibiotics on hospital day 1 or 2. Inclusion required clinical and radiographic evidence of pneumonia, ≥3 days of inpatient antibiotics, and clinical stability by hospital day 3. Exclusions included severe pulmonary disease, complications, immunosuppression, specific infections, major comorbidities, β-lactam allergy, aspiration pneumonia, lack of insurance, or ≥2 days of empiric MRSA or Pseudomonas coverage. The cohort included 5620 patients, median age 68.2 years, 54.3% male, and 71.6% White. Only 4.4% (n = 249) received 3 days of antibiotics and 3.5% (n = 195) received 4 days. Short-course use ranged from 0% to 18.2% across hospitals (median 7.5%). Median antibiotic duration was 7 days (interquartile range [IQR], 5–8). The primary outcome was 30-day all-cause mortality; secondary outcomes included readmission, urgent care visits, and C. difficile infection. Data were cloned into 11,240 records. In the short-duration group, 5166 clones (91.9%) were censored for extending therapy beyond 4 days; in the longer-duration group, 444 (7.9%) were censored for stopping early. Only 20 clones (0.2%) remained uncensored in each group. Thirty-day mortality was 0.7% in both groups (3 vs 37 deaths), with median time to death 21 vs 18 days. The unadjusted mortality risk ratio was 0.92 (95% confidence interval [CI], 0.01–2.38) and adjusted 0.89 (95% CI, 0.01–2.25). Readmission occurred in 8.8% (n = 40) vs 8.1% (n = 417), urgent visits in 8.1% (n = 37) vs 8.8% (n = 458), and C. difficile infection in 0.2% (n = 1) vs 0.2% (n = 11), with adjusted risk ratios of 1.07, 0.94, and 1.01, respectively. Antibiotic-associated adverse events occurred in 2.3% overall (3.3% vs 2.2%). Sensitivity analyses excluding pre-admission antibiotics were consistent. Overall, short and longer courses showed similar 30-day outcomes with minimal differences in benefits or harms.

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