Abstract
BackgroundStreptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. In some Scandinavian countries, this infection is treated with penicillin V since the resistances of pneumococci to this antibiotic are low. Four reasons justify the undertaking of this study; firstly, the cut-off points which determine whether a pneumococcus is susceptible or resistant to penicillin have changed in 2008 and according to some studies published recently the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (minimum inhibitory concentration>2 μg/ml); secondly, there is no correlation between pneumococcal infection by a strain resistant to penicillin and therapeutic failure in pneumonia; thirdly, the use of narrow-spectrum antibiotics is urgently needed because of the dearth of new antimicrobials and the link observed between consumption of broad-spectrum antibiotics and emergence and spread of antibacterial resistance; and fourthly, no clinical study comparing amoxicillin and penicillin V in pneumonia in adults has been published. Our aim is to determine whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of uncomplicated community-acquired pneumonia.MethodsWe will perform a parallel group, randomised, double-blind, trial in primary healthcare centres in Spain. Patients aged 18 to 65 without significant associated comorbidity attending the physician with signs and symptoms of lower respiratory tract infection and radiological confirmation of the diagnosis of pneumonia will be randomly assigned to either penicillin V 1.6 million units thrice-daily during 10 days or amoxicillin 1,000 mg thrice-daily during 10 days. The main outcome will be clinical cure at 14 days, defined as absence of fever, resolution or improvement of cough, improvement of general wellbeing and resolution or reduction of crackles indicating that no other antimicrobial treatment will be necessary. Any clinical result other than the anterior will be considered as treatment failure. A total of 210 patients will be recruited to detect a non-inferiority margin of 15% between the two treatments with a minimum power of 80% considering an alpha error of 2.5% for a unilateral hypothesis and maximum possible losses of 15%.DiscussionThis pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic (penicillin V) in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin (treatment currently recommended) in patients under the age of 65 years.Trial registrationEudraCT number 2012-003511-63.
Highlights
Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia
This pragmatic trial addresses the long-standing hypothesis that the administration of high doses of a narrow-spectrum antibiotic in patients with non-severe pneumonia attended in the community is not less effective than high doses of amoxicillin in patients under the age of 65 years
In some European countries, mainly those located in Northern Europe, pneumonia is treated with penicillin V since the resistances of these pneumococci to this antibiotic are low [1]
Summary
Streptococcus pneumoniae is the bacterial agent which most frequently causes pneumonia. After re-evaluation taking new clinical studies into account, in January 2008 the Clinical and Laboratory Standards Institute published new cutoffs for penicillin [4] These new cut-off points were determined on the basis of a series of criteria: first, by the pharmacokinetic and pharmacodynamic properties of the antimicrobial agents and second, by the data published relating MICs to the clinical outcome of the patients with pneumococcal infections. According to the results of the SAUCE 4 study published in 2010, the pneumococcal resistances to penicillin in Spain have fallen drastically, with only 0.9% of the strains being resistant to oral penicillin (MIC>2 μg/ml) [5] In view of these results pneumonia could be treated with penicillin in Spain. In US the American Society of Infectious Diseases recommends that patients with pneumonia be treated with penicillin if the causative strain of the infection is susceptible to this antibiotic [6]
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