Newborns and young infants with possible severe bacterial infections (PSBI), such as pneumonia and sepsis, whose families do not accept or cannot access hospital care, can be safely and effectively treated with simplified antibiotic regimens outside hospital, according to the results of three large trials from Africa and Bangladesh published in The Lancet and The Lancet Global Health journals.
In light of these findings, WHO guidelines on the management of newborns and young infants with PSBIs should be modified, say the authors.
About 1 in 5 babies worldwide develop severe bacterial infections during the first month of life. These infections are responsible for around 700,000 deaths in newborns every year. Current WHO guidelines recommend that newborns and young infants with PSBI be hospitalised and treated with injectable antibiotics for at least 7-10 days. However, in resource poor settings, many children with PSBI never reach hospital for reasons such as poor transportation, cost, and distance. What is more, around 60% of parents refuse hospital treatment for young infants and many are unwilling to adhere to treatment regimens of injectable antibiotics.
"Safe, effective, simplified treatment alternatives provided on an outpatient basis could help increase the number of children receiving care, improve adherence to treatment, and reduce the burden on limited hospital resources and the risk of hospital acquired infections," explains Professor Ebunoluwa Adejuyigbe, co-lead author of one of the studies, and Dean of the School of Medicine at Obafemi Awolowo University in Nigeria.
The two African Neonatal Sepsis Trial (AFRINEST) studies, published in The Lancet, examined whether two groups of young infants with clinical signs of PSBI -- those with mild disease (fast breathing only) and those with severe but non-critical disease (eg, poor feeding, lethargy, temperature ≥38°C or <35.5°C, severe chest indrawing) -- from diverse settings in the Democratic Republic of Congo, Kenya, and Nigeria could be effectively treated in outpatient settings with simplified antibiotic regimens.
In the first trial, Professor Adejuyigbe and colleagues randomly assigned 2333 young infants aged 0-59 days with fast breathing, whose parents did not accept referral to hospital, to either oral amoxicillin syrup twice daily (1163) or injectable antibiotics once daily (1170; procaine benzylpenicillin and gentamicin) for 7 days. Oral antibiotics were as effective as injectable therapy with 221 treatment failures in the oral antibiotics group and 235 in the injectable antibiotics group by day 8 (19.5% vs 22.1%). Moreover, there were very few deaths in either group, and adherence to oral antibiotics was better than adherence to injectable therapy.
In the second trial, Fabian Esamai, Professor of Child Health and Paediatrics and Principal of the College of Health Sciences at Moi University in Kenya, and colleagues, randomly assigned 3564 children aged 0-59 months with clinical signs of severe infection, whose parents did not accept referral to hospital, to one of three simplified treatment regimens (fewer injections combined with oral antibiotics) or to a course of injectable antibiotics (daily procaine benzylpenicillin and gentamicin) for 7 days. Similar rates of treatment failure were recorded in all four groups by day 8. Moreover, there was better adherence to the simpler regimens.
According to Professor Esamai, "For the first time we show that young infants with signs of suspected severe infection whose parents do not accept referral or cannot access hospital can be managed with simplified antibiotic treatment in clinics under the supervision of a skilled health worker. This could improve access to care for millions of families in Africa and substantially reduce costs and deaths from possible severe bacterial infections."
In another trial from Bangladesh, published in The Lancet Global Health journal, Professor Abdullah H. Baqui from Johns Hopkins Bloomberg School of Public Health, Baltimore, USA, and colleagues, compared two simplified antibiotic regimens involving a reduced number of injections combined with oral antibiotics with the standard regimen (once daily injections of procaine benzylpenicillin and gentamicin) for 7 days. They enrolled 2490 infants aged 0-59 days old with one or more clinical signs of severe but not critical illness (the same as the second AFRINEST trial) whose parents refused hospital admission. The risk of treatment failure was 8% in each of the two simplified regimens compared with 10% in the recommended regimen. The risk of death was low and similar in all three groups, and much the same as infants whose families opted for hospital admission.
According to Professor Baqui, "These alternative treatment regimens could be easier to deliver and would provide treatment options for many more infants with suspected severe bacterial infections. However, safe delivery of these new treatment options will need substantial input into training and strengthening of primary health-care systems."*
Writing in a linked Comment in The Lancet, Dr Harish Nair and Professor Harry Campbell from the Centre for Global Health Research at the University of Edinburgh in the UK say, "An increasing proportion of child mortality is in the first few months of life. Large-scale trials to identify interventions that are effective for reduction of mortality from serious bacterial infections and other major causes of disease in young infants will continue to be of high priority. These trials will need a similar carefully coordinated, high-quality, multicenter approach supported by substantial donor commitment of funds, as shown by the AFRINEST studies."
Writing in a linked Comment in The Lancet Global Health journal, Professor Maharaj Bhan from the Government of India and Dr Vinod Paul from the All India Institute of Medical Sciences in New Delhi, India say, "For outpatient treatment to be effective, frontline treatment centres need to be predictably open and accessible to families, and have adequate supplies. The interface between home and the treating health centre, and between the treatment provider and the hospital doctor, will need to be optimised and supported."
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