Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind studyBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7554.1355 (Published 08 June 2006) Cite this as: BMJ 2006;332:1355
- Rachida el Moussaoui, clinical research fellow1,
- Corianne A J M de Borgie, clinical epidemiologist2,
- Peterhans van den Broek, professor of infectious diseases3,
- Willem N Hustinx, internist in infectious diseases4,
- Paul Bresser, pulmonologist5,
- Guido E L van den Berk, resident6,
- Jan-Werner Poley, resident7,
- Bob van den Berg, pulmonologist8,
- Frans H Krouwels, pulmonologist9,
- Marc J M Bonten, professor of infectious diseases10,
- Carla Weenink, pulmonologist11,
- Patrick M M Bossuyt, professor of clinical epidemiology2,
- Peter Speelman, professor of infectious diseases1,
- Brent C Opmeer, clinical epidemiologist2,
- Jan M Prins, internist in infectious diseases ()1
- 1 Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands,
- 2 Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam,
- 3 Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands
- 4 Department of Internal Medicine, Diaconessenhuis, Utrecht, Netherlands,
- 5 Department of Pulmonology, Academic Medical Center, Amsterdam,
- 6 Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam,
- 7 Department of Internal Medicine, Sint Lucas-Andreas Hospital, Amsterdam,
- 8 Department of Pulmonology, Sint Lucas-Andreas Hospital,
- 9 Department of Pulmonology, Onze Lieve Vrouwe Gasthuis,
- 10 Department of Internal Medicine, University Medical Center Utrecht,
- 11 Department of Pulmonology, Kennemer Gasthuis, Haarlem, Netherlands
- Correspondence to: J M Prins
- Accepted 16 March 2006
Objective To compare the effectiveness of discontinuing treatment with amoxicillin after three days or eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment.
Design Randomised, double blind, placebo controlled non-inferiority trial.
Setting Nine secondary and tertiary care hospitals in the Netherlands.
Participants Adults with mild to moderate-severe community acquired pneumonia (pneumonia severity index score ≤ 110).
Interventions Patients who had substantially improved after three days' treatment with intravenous amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days.
Main outcome measures The primary outcome measure was the clinical success rate at day 10. Secondary outcome measures were the clinical success rate at day 28, symptom resolution, radiological success rates at days 10 and 28, and adverse events.
Results Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three day treatment group. In the three day and eight day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval − 9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%, − 9% to 15%). Both groups had similar resolution of symptoms. Radiological success rates were 86% compared with 83% at day 10 (difference 3%, − 10% to 16%) and 86% compared with 79% at day 28 (difference 6%, − 7% to 20%). Six patients (11%) in the placebo group and 13 patients (21%) in the active treatment group reported adverse events (P = 0.1).
Conclusions Discontinuing amoxicillin treatment after three days is not inferior to discontinuing it after eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment.
Members of the study group are on bmj.com
We thank GlaxoSmithKline for providing the amoxicillin and placebo capsules; the patients and investigators who participated in this trial; the medical and nursing staff of the participating centres; and M F Peeters, Tilburg, for determination of antibodies against Legionella pneumophila.
Contributors ReM coordinated the execution of the study, supervised patients' enrolment and follow-up, analysed and interpreted the data, and wrote the first draft of the paper. JMP, PS, and PMMB designed the study protocol and supervised patients' enrolment and follow-up, interpreted the data, and prepared the paper. JMP is guarantor. CAJMdB and BCO supervised the statistical analysis, interpreted the data, and prepared the paper. PvdB contributed to the study design and coordination. PvdB, WNH, PB, GELvdB, J-WP, BvdB, FHK, MJMB, and CW contributed to patients' enrolment and follow-up and the final version of the manuscript.
Funding Healthcare insurance board, Amstelveen, Netherlands (grant OG99-038).
Competing interests None declared.
Ethical approval This study was approved by the ethics committees of the participating institutions.