ArticlesOral amoxicillin versus injectable penicillin for severe pneumonia in children aged 3 to 59 months: a randomised multicentre equivalency study*
Introduction
Acute respiratory infection is one of the leading causes of morbidity and mortality in children under 5 years of age in developing countries, and is responsible for an estimated 1·9 million deaths in this age group every year.1, 2, 3 Bacterial infection has a far greater role as a cause of pneumonia in children in developing countries than it does in developed countries. One explanation for the higher mortality associated with acute respiratory infection in developing countries is the high prevalence of a bacterial cause. Researchers using lung aspiration have isolated Streptococcus pneumoniae and Haemophilus influenzae (as well as others), in up to 74% of patients with pneumonia in developing countries.4
Standard guidelines developed by WHO5 recommend that children with no lower chest wall indrawing who have fast breathing (⩾50 breaths per min in infants aged 2–11 months and ⩾40 breaths per min in those aged 12–59 months)—ie, with non-severe pneumonia—be treated at home with oral antibiotics, and those with lower chest wall indrawing (ie, severe pneumonia), be admitted and given parenteral antibiotics (benzylpenicillin or ampicillin). Application of these guidelines in developing countries has resulted in decreased mortality from acute respiratory infection.6, 7 However, admission required for administration of injectable treatment has several drawbacks. First, routine use of injectable antibiotics, either intravenously or intramuscularly, is associated with an increase in the risk of clinically significant morbidity, such as complications of abscess formation at the injection site and transmission of HIV, hepatitis, or other pathogens associated with use of contaminated needles. Second, injection needles and administration equipment are in short supply or periodically unavailable in some settings, preventing delivery of recommended treatment. Third, admission can substantially raise the cost of health care. Fourth, children who have to be referred for admission and injectable treatment might not be brought or be able to travel to hospital.
A recent trial in Pakistan showed that oral amoxicillin was effective in 82% of bacteraemic children with a clinical diagnosis of severe pneumonia.8 If oral amoxicillin proved as effective as injectable penicillin in the treatment of severe pneumonia, substantial improvements in access to appropriate care, nosocomial complications, iatrogenic infections, and costs could be achieved with its widespread use. Our aim was to do a multicentre equivalency study comparing oral amoxicillin with injectable penicillin in the treatment of WHO-defined severe pneumonia in children.
Section snippets
Patients
We undertook a randomised, non-blinded equivalency trial of oral amoxicillin and injectable penicillin in children aged 3–59 months with WHO-defined severe pneumonia,5 in the paediatric departments of tertiary-care facilities at nine international sites: Colombia, Ghana, India, Mexico, Pakistan, South Africa (two sites), Vietnam, and Zambia. Children presenting as emergencies with a history of coughing or difficulty breathing and lower chest indrawing were assessed for enrolment into the study.
Results
Participant accrual took place between May, 1999, and May, 2002. The Cape Town and Zambia centres ended recruitment in September, 1999, and July, 2000, respectively, both because of poor accrual from changes in the referral patterns. We randomly assigned 1702 participants to penicillin and amoxicillin (figure). 27 children aged between 2 and 3 months were mistakenly allocated but this protocol deviation was distributed evenly between both treatment groups, and these babies were included in the
Discussion
We have shown that oral amoxicillin and injectable penicillin are equally effective at 48 h and beyond. The 48-h treatment failure rate was similar to that of 18% Straus and colleagues reported with oral amoxicillin for the treatment of severe pneumonia.8 Although several baseline characteristics were predictive of treatment failure at 48 h, only infancy (age 3–11 months), severe tachypnoea, and hypoxaemia were predictive in the multivariable model, which is in accordance with the findings of
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Complicated pneumonia in children
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