Clinical efficacy of cotrimoxazole versus amoxicillin in the treatment of community acquired pneumonia in children aged 2-59 months attending Mulago hospital: A randomized clinical trial

Abstract

BACKGROUND: Acute lower respiratory infections (ALRIs), peincipally community acquired pneumonia, account for appropriately 1.9 million (95% confidence arrival (C1) 1.6-2.2 million) deaths globally in children under 5 years of age each year, 90% of which occur in developing countires. World Health Organization (WHO) recommended oral cotrimoxazole as first line drug for treatment of non-severe pneumonia at first level health services. Uganda, like most sub Saharan countries has also adopted the WHO guidelines and uses cotrimoxazole for treatment of non severe pneumonia as first line therapy in children. However, the emergence of cotrimoxazole resistance among both S. pneumonia and H. Influenza isolates from children with ARI is cause for concern. Studies have suggested that in areas where resistance to cotrimoxazole if high, amoxillin could be used as an alternative or as the first choice. We compared clinical efficacy of cotrimoxazole versus amoxicillin in the treatment of community acquired non severe pneumonia in children aged 2-59 months attending mulago hospital. METHODS: A double blind randomized controlled trial was conducted in the assessment centre of mulago hospital. Children with non severe pneumonia were randomized to receive either oral amoxillin (25mg/kg/dose) or co-trimoxazole (trimethprim 8mg/kg/dose and sulphamethoxazole 40mg/kg/dose) and followed up on day 3 and 5 of treatment. The purpose of the study was explained to the caretakers and informed conscent obtained for participation in the study before recruitment, then baseline data was collected. The primary outcome measures were normalization of respiratory rate by day 3 of treatment. Secondary outcome measures were antimicrobial susceptibility to cotrimoxazole and amoxicillin. Data was entered into Epi-info 6.4 software and analysed using SPSS package. The chi-square test for categorical variables with corresponding odds ratio and 95% confidence intervals were used. The independent t test was used for comparing continuous data, which was summarized using means, median and standard deviation. Logistic regression was done to look for factors that were associated with treatment failure. RESULTS: Between july 2007 and January 2008, 505 children with non severe pneumonia were enrolled from Assessment centre of mulago hospital. Two hundred and fifty one were randomised to receive amoxicillin and 254 to receive cotrimoxazole. There were 53(23.1%) treatment failure in amoxicillin group and 57(24.9%) in the cotrimoxazole group (Risk difference 1.10%; 95%C1-0.72 to 1.69) BY DAY 3. Multivariate analysis showed that treatment failure was more likely in children who had history of difficult breathing or those with a temperature >_37.5 0 C Streptococci pneumonia was the commonest bacterial organism isolated on sputum and blood culture in up to (48.4%) and (66.7%) respectively. Most organisms isolated in the sputum showed high in vivo resistance to cotrimoxazole; S. pneumonia (92.3%), M.catarrhalis (100%), and H. influenza (97.5%). S. pnuemoniae was also highly resistant to oxacillin (81.5%). Also a high level of in vitro resistance of S. pneumonia to cotrixazole (100%) and amoxicillin (81.8%) in the blood specimen has been reported in this study. CONCLUSIONS: Treatment outcome with oral amoxicillin (25mg/kg/dose) was not different from that with co-trimoxazole (8mg/kg trimethoprime, 40mg/kg sulphamethoxazole/dose) when used for the treatment of non severe pneumonia in children 2-59 months old in mulago hospital. Commonest bacterial organisms isolated in the sputum of children with non severe pneumonia sputum were S. pneumonia 195(48.4%), moraxella caterallis 113(28.0%) and H, influenza 81(20.1%). RECOMMENDATIONS: 1. Co-trimoxazole should be maintained as first line treatment of non severe pneumonia in children less than 5 years in mulago hospital. 2. An equivalent study should be carried out to document the clinical efficacy of co-trimoxazole versus amoxicillin in Uganda.