Short Antibiotic Therapy good enough for Community-Acquired Pneumonia: Lancet

Shortening the duration of therapy could lead to fewer antibiotic side-effects, less pressure for antimicrobial resistance, reduced costs, and a reduced risk of bacterial superinfection. However, these benefits must be weighed against the potential harm from recurrent illness. Therefore, researchers of the Raymond-Poincaré University Hospital, AP-HP, Paris Saclay University, France, conducted a study to examine the need for an additional 5-day course of β-lactam therapy among patients with community-acquired pneumonia who were stable after three days of treatment.

It was a double-blind, randomised, placebo-controlled, non-inferiority trial in 16 centres in France. The researchers included a total of 310 eligible patients with severe community-acquired pneumonia. They randomly assigned the patients to receive either β-lactam treatment (n=153) (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or placebo (n=157) for 5 extra days. The major outcome assessed was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. The researchers choose a non-inferiority margin of 10 percentage points. They also assessed safety outcomes in the intention-to-treat [ITT] population.

Key findings of the study were:

• In the ITT analysis, the researchers noted that cure at day 15 occurred in 77% of participants in the placebo group and 68% of participants in the β-lactam group (between-group difference of 9·42%), indicating non-inferiority.
• Results of the per-protocol analysis also indicated non-inferiority, with 78% of patients in the placebo group and 68% of patients in the β-lactam group cured at day 15 (between-group difference, 9.44 percentage points).
• The observed similar incidence of adverse events between the treatment groups (14% in the placebo group and 19% in the β-lactam group).
• The most common adverse event was digestive disorders. Also, by day 30, they reported three deaths in the placebo group and two deaths in the beta-lactam group.

The authors concluded, "Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing β-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow a substantial reduction of antibiotic consumption."

For further information:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00313-5/fulltext