3 days of β-lactam therapy is non-inferior to 8 days of therapy among patients with community-acquired pneumonia

1. Cure at 15 days occurred in 77% of patients in the placebo (3-day therapy) group compared to 68% of patients in the β-lactam (8-day therapy) group.

2. Incidence of adverse events was similar between both groups (14% placebo vs. 19% β-lactam). 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Lower respiratory tract infections are a common indication for antibiotic treatment in community and hospital settings. In the US, treatment of community-acquired pneumonia requires at least 5 days of treatment whereas European guidelines recommend at least 8 days. Other studies have shown that fewer than 5 days could be sufficient. A shorter course could potentially reduce bacterial resistance, likelihood of adverse events, and result in many other benefits. This randomized controlled trial aimed to assess noninferiority between a 3- and 8-day course of β-lactam therapy among patients with community-acquired pneumonia who were clinically stable after 3 days of treatment. The primary outcome was cure at 15 days after start of antibiotic treatment, while key secondary outcomes were cure at day 30, all-cause mortality at day 30, and frequency and severity of adverse events. According to study results, 3-day β-lactam treatment was noninferior to the 8-day course with respect to the primary outcome of cure at 15 days. Additionally, the incidence of adverse events was similar in both groups. This study was limited by a short follow-up of 30 days. It would be interesting to assess the risk of pneumonia relapse in patients who were on β-lactam therapy for 3 days versus 8 days.

Click to read the study in The Lancet

Relevant Reading: Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source

In-depth [randomized controlled trial]: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility from 16 centers in France. Included patients were ≥ 18 years old, with moderately severe community-acquired pneumonia, treated with β-lactam monotherapy, and had a clinical response after 72 h of treatment. Patients with severe pneumonia, known immunosuppression, and other infection were excluded. Altogether, 303 patients (152 in the placebo group and 151 in the β-lactam group) were included in the intention-to-treat (ITT) population. The median patient age was 73.0 years (interquartile range [IQR] 57.0-84.0) and 57% were male.

Primary outcome of cure at day 15 was noninferior between the placebo (3-day therapy) group (117 of 152, 77%) and the β-lactam (8-day therapy) group (102 of 151, 68%, 95% confidence interval [CI] -0.38 to 20.04). This was also true for the per-protocol analysis. Additionally, in the ITT analysis, the number of patients who had been cured by day 30 was similar in the placebo group (n=109, 72%) and the β-lactam group (n=151, 72%, 95% CI -11.31 to 9.98). Furthermore, no difference was seen in the proportion of patients reporting ≥ 1 adverse event (14% for placebo vs. 19% for β-lactam), with the most common event being digestive disorders (11% for placebo vs. 19% for β-lactam). By day 30, 2% (n=3) patients had died in the placebo group (due to bacteremia from S. aureus, cardiogenic shock after acute pulmonary edema, and heart failure) and 1% (n=2) in the β-lactam group (due to pneumonia relapse and acute pulmonary edema). Overall, findings from this study suggest that discontinuation of β-lactam therapy after 3 days was non-inferior to 8 days of therapy among stable hospitalized patients with community-acquired pneumonia.

Image: PD

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