In this episode, I’ll discuss whether 3 days of beta-lactam use is enough to treat CAP in non-ICU hospitalized patients.
Presumably, if a shorter duration of antibiotic therapy can be used for patients admitted to hospital with community-acquired pneumonia, then the adverse consequences associated with antibiotic use (bacterial resistance, adverse events, and financial burden) can be lessened.
Researchers recently published in Lancet a multicenter, double-blind, randomized, placebo-controlled, non-inferiority trial looking at a 3 day course of parenteral beta-lactam therapy vs an additional 5 days of oral therapy.
Non-critically ill hospitalized patients with CAP who were clinically stable after 3 days of treatment with beta-lactam therapy were randomly assigned (1:1) to receive oral amoxicillin 1 g plus clavulanate 125 mg three times a day or placebo for an extra 5 days.
The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia, resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause.
310 patients were split between the 2 groups. Cure at day 15 occurred in 77% of patients in the placebo group and 68% in the 5 extra days of therapy group. This was numerically superior in favor of shorter duration of treatment and it met the prespecified criteria for non-inferiority. This finding was present in both the intention to treat and the per-protocol analysis.
The incidence of adverse events was numerically greater in the extra 5 day of therapy group, however this did not reach statistical significance.
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 substantial reduction of antibiotic consumption.
While this data suggests shorter treatment in appropriately selected patients is non-inferior to longer treatment, the sample size was likely too small to prove a decrease in adverse effects.
Notable exclusion criteria for the study were patients with a creatinine clearance below 30ml/min, patients with hepatic impairment, patients with risks for healthcare associated pneumonia with bacterial resistance, and the presence of complications or severity of pneumonia (abscess , significant pleural effusion, severe chronic respiratory failure , septic shock, respiratory condition requiring the passage resuscitation).
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