1. In this randomized, open-label, equivalence trial, simplified antibiotic regimens were as effective as reference treatment for young infants with clinical signs of serious infection for which referral to a hospital was not possible.
Evidence Rating Level: 1 (Excellent)
Study Rundown: The World Health Organization recommends young infants (aged 0-59 days) be referred to a hospital when serious bacterial infection is suspected. This study assessed whether 3 simplified antibiotic regimens for treatment of infants with clinical signs of serious bacterial infection were as effective as standard treatment when referral to a hospital was not possible. At sites in DR Congo, Kenya, and Nigeria young infants with clinical signs of serious infection were allocated to 4 treatment groups- group A (reference group) was treated with injectable gentamicin and procaine benzylpenicillin for 7 days. The reference group was compared to 3 simplified regimens: injectable gentamicin and oral amoxicillin for 7 days (group B), injectable procaine benzylpenicillin-gentamicin for 2 days and then oral amoxicillin for 5 days (group C), and injectable gentamicin once per day for 2 days and oral amoxicillin for 7 days (group D). The 3 simplified outpatient regimens were as effective as the reference treatment for treatment of young infants with clinical signs of serious infection. Referral to a hospital is not always possible in some settings and effective outpatient treatment regimens hold potential to reduce neonatal mortality rates. A major strength of this study was its high rate of follow-up. It was limited by incomplete blinding due to the unethical nature of providing placebo injections to young infants.
The study was funded by Bill & Melinda Gates Foundation grant to WHO.
Relevant Reading: Scientific Rationale for Study Design of Community-based Simplified Antibiotic Therapy Trials in Newborns and Young Infants With Clinically Diagnosed Severe Infections or Fast Breathing in South Asia and sub-Saharan Africa
In-Depth [randomized controlled trial]: This randomized, open-label, equivalence trial sought to analyze the efficacy of simplified antibiotic regimens in infants with clinical signs of serious infection when referral was not possible. From April 2011 to June 2013, 3,364 young infants were included in analysis to compare efficacy of the 4 antibiotic regimens at 5 sites in DC Congo, Kenya, and Nigeria. To be included, young infants needed to have predefined clinical signs of serious infection but were excluded if predetermined signs of critical illness were present. Primary outcome was treatment failure by day 8 of treatment defined as clinical deterioration, development of a serious adverse event (including death), no improvement by day 4, or not cured by day 8.
67 (8%) infants failed treatment in group A compared with 51 (6%) infants in group B (risk difference -1.9%, 95% CI -4.4 to 0.1), 65 (8%) in group C (-0.6%, -3.1 to 2.0), and 46 (5%) in group D (-2.7%, -5.1 to 0.3). For treatment of infants with clinical signs of serious infection, the simplified regimens were found to be as effective as reference treatment with injectable procaine benzylpenicillin-gentamicin when referral to a hospital was not possible.
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