Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial / Eficacia de dosis altas de penicilina frente a amoxicilina en el tratamiento de la neumonía no complicada adquirida en la comunidad en adultos. Ensayo clínico controlado de no inferioridad

Introduction: Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. Objectives: To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. Design: Multicentre, parallel, double-blind, controlled, randomized clinical trial. Setting: 31 primary care centers in Spain. Participants: 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. Main measurements: 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. Results: 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. Conclusions: 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

Introducción: En algunos países la neumonía adquirida en la comunidad (NAC) se trata con penicilina. Objetivo: Evaluar si penicilina V a dosis altas es igual de efectiva que amoxicilina a dosis altas en la NAC no complicada. Diseño. Ensayo clínico paralelo, doble ciego, controlado y multicéntrico. Emplazamiento: Treinta y un centros de salud en España. Participantes: Se reclutaron pacientes de 18 a 75 años de edad sin comorbilidad asociada importante, con síntomas de infección respiratoria inferior y confirmación radiológica de neumonía, que fueron asignados aleatoriamente a 1,6M unidades de penicilina V o amoxicilina 1.000 mg, 3 veces al día, durante 10 días. Mediciones principales: La variable de resultado principal fue curación clínica a los 14 días y se planteó la hipótesis de que penicilina no era inferior a amoxicilina con un margen de 15% para la diferencia de proporciones. Registro EudraCT 2012-003511-63. Resultados: Se aleatorizaron 43 personas (amoxicilina: 28; penicilina: 15). Se observó curación clínica en 10 pacientes asignados a penicilina (90,9%) y en 25 asignados a amoxicilina (100%), observándose una diferencia de -9,1% (IC 95%: -41,3 a 6,4%; p = 0,951) para no inferioridad. En el análisis por intención de tratar amoxicilina fue 28,6% superior a penicilina V (IC 95%: 7,3% a 58,1%; p = 0,009 para superioridad). El número de eventos adversos fue similar en ambos grupos. Conclusiones: Se observó una tendencia de un mayor beneficio de amoxicilina frente a penicilina en adultos con NAC no complicada. La principal limitación fue la baja potencia estadística debido al bajo número de pacientes incluidos

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

INTRODUCTION: Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. OBJECTIVES: To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. DESIGN: Multicentre, parallel, double-blind, controlled, randomized clinical trial. SETTING: 31 primary care centers in Spain. PARTICIPANTS: 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. MAIN MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Factors associated with inhaled corticosteroids prescription in primary care patients with COPD: A cross-sectional study in the Balearic Islands (Spain).

BACKGROUND: There is a worldwide over-prescription of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD), off-label prescribing, and unnecessary prescription of high doses. OBJECTIVES: Our aim was to assess the prescription rate of ICS and to identify sociodemographic and clinical factors associated with ICS prescription among patients with COPD, treated in Balearic primary healthcare. METHODS: This cross-sectional study included all patients with a clinical COPD diagnosis, who attended a primary care centre of the Balearic Islands (Spain) during 2012. Also, a sub-population with spirometry-confirmed COPD was defined. Data were obtained on patient demographics, smoking status, spirometry, ICS prescriptions, other respiratory medication, exacerbations and comorbidities. Associations with ICS and high-dose ICS prescription were assessed using multivariate regression analyses. RESULTS: In total, 15,440 patients were included (70% men, mean age 68.6 years), and 44.6% were prescribed ICS. The largest association with ICS prescription was asthma comorbidity (OR: 3.50; 95%CI: 3.12-3.92), followed by exacerbation history (OR: 2.23; 95%CI: 2.07-2.47). In addition, smoking status, spirometry, atopic dermatitis, allergic rhinitis and mean age were significantly (P < 0.001) associated with ICS treatment. In the spirometry-confirmed population, asthma (OR: 2.89; 95%CI: 2.29-3.64) and exacerbations were also the major factors (OR: 2.85; 95%CI: 2.45-3.32) followed by severe bronchial-obstruction (OR: 2.63; 95%CI: 2.24-3.08). High-dose ICS prescription was mainly associated with severe obstruction (OR: 2.27; 95%CI: 1.93-2.68). CONCLUSION: The percentage of COPD patients prescribed ICS in Balearic primary care is relatively low. Asthma comorbidity, exacerbation history, severe bronchial-obstruction, smoking status and a spirometry-confirmed COPD diagnosis were significantly associated with ICS prescription. [Box: see text].