Ceftriaxone versus chloramphenicol for the treatment of severe Pneumonia in children at Mulago Hospital: A randomized clinical trial

Abstract

Background Acute lower respiratory tract infections are a leading cause of morbidity and mortality in Sub-Saharan Africa. The World Health Organization (WHO) still recommends intravenous chloramphenicol for the treatment of severe pneumonia in children aged less than five years. However, up to 20% of children fail treatment due to the emergence of resistance by bacteria. Several centers now use ceftriaxone a third generation cephalosporin, which is reported to be efficacious in the treatment of severe pneumonia. However the high cost of ceftriaxone is too prohibitive to allow for its routine use in resource constrained countries like Uganda. We compared the efficacy of Ceftriaxone versus Chloramphenicol in the treatment of severe pneumonia in children aged 6-59 months admitted to Acute Care Unit Mulago hospital.

Methods From September 2006 to March 2007, a double- blinded randomized placebo controlled trial of 352 children with severe pneumonia and whose caretakers gave informed consent, were randomized to receive either intravenous ceftriaxone (75mg/kg/day) or intravenous chloramphenicol (100mg/kg/day) for seven days. The primary outcomes measured were: mortality, treatment success or failure (measured as time to normalization or no normalization of respiratory rate, temperature, and oxygen saturation). Secondary outcome measures were short term complications. Adverse effects associated with ceftriaxone and chloramphenicol were reported. Data was entered into Epi-info 6.4 software and analyzed using an SPSS package. The chi-square test with corresponding risk or odds ratios and 95% confidence intervals were used for categorical variables and the student’s t or other appropriate test was used for continuous variables. Kaplan- Meier survival curves measured time to the event; and logistic regression for factors predicting outcome in both treatment groups.

Results: Mortality was similar in the two groups: 8.5% in the chloramphenicol group and 7.5% in the ceftriaxone group; RR 1.15 (95% CI 0.57-3.35); p = 0.69. This difference was not statistically significant. The fever clearance time, time to normalization of respiratory rate, oxygen saturation, and disappearance of chest in drawing were similar in both treatment groups. There were minor adverse events observed in both drugs.

Conclusions: Intravenous ceftriaxone is as efficacious as intravenous chloramphenicol in the treatment of severe pneumonia in children.

Recommendations: Intravenous chloramphenicol should still be considered as the first line drug for treatment of severe pneumonia for children in Uganda.