Outpatient treatment for neonates and young infants with clinically suspected severe infection
Authors: Maharaj K Bhan, Vinod K Paul
Journal: The Lancet Global Health (2015)

The reduction in mortality in children younger than 5 years over recent decades has been impressive, but shortfalls still exist in achievement of the MDG4 targets.1Requejo JH Bryce J Aluisio JDB et al.Countdown to 2015 and beyond: fulfilling the health agenda for women and children.Lancet. 2015; 385: 466-476Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar Acceleration of progress for child survival would need increased emphasis on quality care at and around birth, and timely and efficacious treatment for neonatal infections, diarrhoea, and pneumonia in regions where these causes contribute substantially to mortality in children younger than 5 years. The challenge in provision of standard care is increased wherever health systems are weak, socioeconomic conditions are suboptimum, and settings are remote and inaccessible. Innovative implementation research is being widely promoted to provide solutions that improve equitable delivery of established interventions without compromising safety or effectiveness. This type of research is challenging and often complex. In The Lancet Global Health, Abdullah Baqui and colleagues2Baqui AH Saha SK Ahmed ASMNU et al.for the Projahnmo Study Group in BangladeshSafety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.Lancet Glob Health. 2015; (published online April 2.)http://dx.doi.org/10.1016/S2214-109X(14)70347-XGoogle Scholar report their findings from a large equivalence trial in Bangladesh, in which two antibiotic regimens were compared with the standard regimen (intramuscular injections of procaine benzylpenicillin and gentamicin once per day for 7 days) for treatment of clinically suspected serious infection in young infants (aged 0–59 days) who were treated in an outpatient setting after their parents sought help but refused hospital admission. The two alternative regimens assessed were: intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days; and intramuscular procaine benzylpenicillin and intramuscular gentamicin once per day for 2 days, followed by oral amoxicillin twice per day for 5 days. Thus, compared with the 14 injections in the reference treatment, these regimens had reduced numbers of injections (seven and four, respectively). The primary outcome was a composite measure of treatment failure by day 8 of enrolment based on several individual indicators, and deaths were also carefully recorded. The risk of treatment failure was 8% in each of the two alternative regimens, compared with 10% in the standard treatment group.2Baqui AH Saha SK Ahmed ASMNU et al.for the Projahnmo Study Group in BangladeshSafety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.Lancet Glob Health. 2015; (published online April 2.)http://dx.doi.org/10.1016/S2214-109X(14)70347-XGoogle Scholar Risk of death by day 15 of follow-up was 2% in all treatment groups. This result was similar to the number of deaths in infants who opted for hospital admission (2% in hospital and another 1% within one week of discharge). We believe that the equivalence of these regimens for the primary outcome was satisfactorily established in the type of patients enrolled. The case fatality rates were low overall and consistent with the similar failure rates across treatment arms. What are the implications of these findings for child health programmes? In an ideal world, serious infections in neonates and young infants would be treated in medical facilities. However, the barriers to such care are overwhelming for millions of families in Asia and Africa. Facilities can be far away, often the services provided are of poor quality, and families might not be able to afford the related direct and indirect costs of care. Therefore, simplified outpatient treatment regimens in settings close to home make for a strong programmatic rationale for treatment of serious infections in young infants whose caregivers are unwilling or unable to accept hospital admission. Widespread acceptance of such a strategy needs rigorous and conclusive evidence for its feasibility, efficacy, and safety. In this respect, Baqui and colleagues should be complimented for designing and undertaking a high quality study that paves the way for adoption of this approach in health programmes. Some limitations of the study, however, should be noted. The trial was not masked for practical reasons. The trial enrolled fewer infants younger than 7 days than older infants, and this subgroup might differ in terms of causes and outcomes. The study individuals were young infants whose families sought care but did not accept admission to hospital; the infants in the study might therefore represent a group with milder disease than that of those who accepted hospital admission. In this efficacy trial, high compliance was achieved for all regimens, which were delivered at home through regular physician visits. Regardless of the regimen, compliance with treatment and monitoring might be better in hospitals than at home in real-life programmes. Our view is that referral and hospital admission should be promoted for sick neonates and young infants. The study results do, however, provide good evidence that when hospital admission is not feasible, and if simplified regimens can be delivered in outpatient settings, complications rates would be low and similar to those in hospitals. Community-based management of infections in young infants that includes intramuscular injections every day for 7 or more days, given by trained health workers, has been studied and reported to be effective.3Bang AT Bang RA Baitule SB Reddy MH Deshmukh MD Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India.Lancet. 1999; 354: 1955-1961Summary Full Text Full Text PDF PubMed Scopus (591) Google Scholar, 4Baqui AH Arifeen SE Williams EK et al.Effectiveness of home-based management of newborn infections by community health workers in rural Bangladesh.Pediatr Infect Dis J. 2009; 28: 304-310Crossref PubMed Scopus (97) Google Scholar, 5Khanal S Sharma J Gc VS et al.Community health workers can identify and manage possible infections in neonates and young infants: MINI—a model from Nepal.J Health Popul Nutr. 2011; 29: 255-264Crossref PubMed Scopus (59) Google Scholar Regimens with reduced numbers of injections could be easier to deliver and have a substantial effect on young infant mortality. However, in many countries or subregions, even these simplified regimens might be challenging. The questions of who should give injections in primary care and outpatient settings, and at what level in the health-care system, remain unsettled in many developing countries. Growing realisation exists that primary health centres need to be upgraded to become effective treatment facilities. The health-care providers deployed to them should be able to assess young infants whose parents seek care, arrange referral for hospital admission for those with possible serious infections, and when that is not acceptable to the families, they could offer ambulatory treatment using one of the study regimens in Baqui and colleagues' study.2Baqui AH Saha SK Ahmed ASMNU et al.for the Projahnmo Study Group in BangladeshSafety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.Lancet Glob Health. 2015; (published online April 2.)http://dx.doi.org/10.1016/S2214-109X(14)70347-XGoogle Scholar The treatment provider could be a doctor (as in the study, but often not feasible), or an effectively trained health assistant, nurse, or auxiliary nurse midwife. This approach could particularly help female infants whose care-seeking is differentially undermined in many societies. 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. Safety margins in care can be enhanced further through mobile phone communication wherever possible. Overall, the innovative findings of the trial2Baqui AH Saha SK Ahmed ASMNU et al.for the Projahnmo Study Group in BangladeshSafety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial.Lancet Glob Health. 2015; (published online April 2.)http://dx.doi.org/10.1016/S2214-109X(14)70347-XGoogle Scholar are a valuable contribution, and a vital part of a whole solution in which other components must fall into place to have a noticeable effect on mortality in neonates and young infants. Studies such as these should motivate reflection and action. VKP was a member of the data safety monitoring board in Baqui and colleague's study. MKB declares no competing interests. Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trialOur results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable. Full-Text PDF Open Access