Elsevier

The Lancet

Volume 360, Issue 9336, 14 September 2002, Pages 835-841
The Lancet

Articles
Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial*

https://doi.org/10.1016/S0140-6736(02)09994-4Get rights and content

Summary

Background

For most infections, especially acute respiratory infections (ARIs), the recommended duration of therapy is not based on strong scientific or clinical criteria. Shorter courses of antibiotics for non-severe pneumonia would result in lower costs, enhance patient compliance, and might help to contain antimicrobial resistance. We aimed to compare the clinical efficacy of 3-day and 5-day courses of amoxicillin in children with non-severe pneumonia.

Methods

We recruited 2000 children, aged 2–59 months, with non-severe pneumonia (WHO criteria) diagnosed in the outpatient departments of seven hospitals. Patients were randomly assigned to 3 days or 5 days of treatment with oral amoxicillin. The primary outcome was treatment failure. Analyses were by intention to treat.

Findings

We allocated 1000 children to 3 days of treatment and 1000 to 5 days. Treatment failed in 209 (21%) patients in the 3-day group, and in 202 (20%) in the 5-day group (difference 0·7%; 95% Cl−1·8 to 3·2). In 12 (1%) children in the 3-day group and in 13 (1%) in the 5-day group the disease relapsed (difference 0·1%; −0·6 to 0·8). Treatment was more likely to fail in children who did not adhere to treatment (p<0·0001), in those younger than 12 months (p<0·0001), in those whose illness lasted for 3 days or longer (p=0·004), in those whose respiratory rate was more than 10 breaths/min above the age-specific cut-off (p=0·004), and in those with vomiting (p=0·009). Non-adherence was also associated with failure of treatment in the 5-day group (p<0·0001).

Interpretation

Treatment with oral amoxicillin for 3-days was equally as effective as treatment for 5 days in children with non-severe pneumonia. The most important risk factor for treatment failure was non-compliance, which was also associated with longer duration of therapy.

Published online July 23, 2002 http://image.thelancet.com/extras/01art7461web.pdf

Introduction

Pneumonia is one of the major causes of death in children aged younger than 5 years in less-developed countries.1 To reduce the number of people dying from pneumonia, WHO developed standard guidelines2 for management of patients with this disease. These guidelines have been used widely in several less-developed countries for many years and recommend 5 days of oral co-trimoxazole or amoxicillin for treatment of non-severe pneumonia. This recommendation is based on data from less-developed countries, which show that Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial pneumonia.3 These guidelines have effectively reduced death from pneumonia in less-developed countries.4

Conventionally, antibiotics are continued until the patient no longer has a fever or laboratory measurements of infection are normal. Clinicians recognise that patients tend to stop treatment once they are better, and that treatment for any longer than this results in non-adherence.5, 6 Clinicians also acknowledge that the recommended duration of treatment for most infections, especially acute respiratory infections (ARIs), is not based on strong scientific or clinical rationale.5 For otitis media, sinusitis, and tonsillopharyngitis, shorter courses of antibiotics have been shown to be effective in children.6, 7, 8

Results from a community-based study in Bangladesh9 showed that children with non-severe pneumonia who did not complete the recommended 5-day course of antibiotics did not develop more severe disease or have more frequent relapses than those who completed the course. New macrolides have been successfully used for fewer than 5 days for treatment of lower respiratory infections in children.10

If a shorter course of antibiotic were effective for treatment of pneumonia without an increase in morbidity and mortality, the cost of treatment would fall, patient adherence would improve, antimicrobial resistance would probably decrease, and tolerability of the drug would improve. These are important policy implications. Therefore, we did a randomised controlled trial to compare clinical efficacy of a 3-day course of amoxicillin with the standard 5-day course in treatment of children aged 2–59 months who had non-severe pneumonia as defined by WHO recommendations.

Section snippets

Study design

We did a double-blind, randomised, placebo-controlled trial in seven sites in five cities of Pakistan (Gilgit, Islamabad, Lahore, Multan, and Rawalpindi). The randomisation scheme was generated by a computer programme at WHO, Geneva, with uneven blocks of four, six, and eight. Self-adhesive sticking labels with unique identification numbers were prepared in Geneva. A copy of the randomisation list with unique identification numbers was given to a health professional not associated with the

Results

Between October, 1999, and April, 2001, 2000 children were enrolled at seven sites. The sites were the Children's Hospital and Federal Government Services Hospital, Islamabad; District Headquarters Hospital, Gilgit; Nishtar Hospital, Multan; Rawalpindi General Hospital, Rawalpindi; Sheikh Zayed Hospital and the Children's Hospital, Lahore. We randomly allocated 1000 children to 3-days of treatment with amoxicillin and 1000 to 5-days of treatment. The number of children who reached the primary

Discussion

Our results show that 3-days' treatment with amoxicillin for WHO defined non-severe pneumonia is as effective as treatment for 5 days as the presently recommended duration of 5 days. Rates of treatment failure and relapse were close in both treatment groups, and in children with radiological evidence of pneumonia.

Although short-courses of antibiotics have been successful in otitis media, sinusitis, and tonsillopharyngitis in children,6, 7, 8 evidence for the best duration of treatment for lower

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