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Aten Primaria. 2019 Jan;51(1):32-39. doi: 10.1016/j.aprim.2017.08.003. Epub 2017 Oct 20.

Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial.

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Primary Care Centre Via Roma, Barcelona, Spain. Electronic address:
Primary Care Centre La Marina, Barcelona, Spain.
Primary Care Centre Son Pisà, Palma de Mallorca, Spain.
Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Barcelona, Spain.
Primary Care Centre Jaume I, Tarragona, Spain.
Pneumology Department, Hospital Universitari Vall d'Hebron, CIBER de Enfemedades Respiratorias (CIBERES), Barcelona, Spain.



Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries.


To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP.


Multicentre, parallel, double-blind, controlled, randomized clinical trial.


31 primary care centers in Spain.


Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000mg three times per day for 10 days.


The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63.


A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3-58.1%; p=.009 for superiority). The number of adverse events was similar in both groups.


There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAP. The main limitation of this trial was the low statistical power due to the low number of patients included.


Adultos; Adults; Amoxicilina; Amoxicillin; Community-acquired pneumonia; Ensayo clínico aleatorizado; Neumonía adquirida en la comunidad; Penicilina; Penicillin; Randomized controlled trial

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