October 6, 2015
Written by Bina Valsangkar
This post originally appeared on the Healthy Newborn Network’s website here. Reposted with permission.
On April 2, the Lancet and the Lancet Global Health released results of randomized, open-label equivalence trials conducted in Bangladesh, the Democratic Republic of Congo, Kenya, and Nigeria evaluating the effectiveness of simplified antibiotic regimens administered in the outpatient setting, when hospital referral is not possible, for treatment of possible serious bacterial infection (PSBI) in neonates.1,2 The simplified regimens, which consist of combinations of intramuscular injections of gentamicin and penicillin and oral amoxicillin, give treatment access to families that might not otherwise have access to the WHO standard of care for PSBI in neonates (7–10 days of inpatient admission and parenteral antibiotics). Following publication of these studies, the World Health Organization has released a guideline, Managing possible serious bacterial infection in young infants when referral is not possible.
The intention of the simplified regimens was not to challenge the appropriateness of hospitalization for PSBI, but to provide safe, alternative outpatient regimens for managing PSBI when hospitalization is not possible. In the Bangladesh and African study sites, the simplified regimens of 2, 4, or 7 injections were found to be as efficacious as the reference regimen of 14 injections of daily penicillin and gentamicin, delivered on an outpatient basis.
As a global health professional, I found these studies exciting, intriguing, and robust. Accessing hospital care for PSBI can be overwhelmingly difficult for poor families—transport, cost, access to quality services, and sociocultural barriers are just some obstacles to seeking advanced care for PSBI, to the point that families stay home as their ill neonate deteriorates, and in some cases, dies a preventable death.
On the other hand, as a general pediatrician, I felt uneasy with the idea of managing PSBI in an outpatient or community setting. From my experience, neonates with sepsis can present nonspecifically and deteriorate rapidly. They should be treated with inpatient admission, laboratory and clinical monitoring, parenteral antibiotics, and supportive care. The thought of detecting PSBI, administering intramuscular injections, and completing treatment and monitoring for clinical deterioration on an outpatient basis or in the home sounded like delivery of substandard care.
Although the evidence from the Bangladesh and African trials is clear – that the simplified regimens are as efficacious as the reference regimen – the studies are complex, and need to be applied carefully. But it is also important to appreciate what they do tell us, so we do not miss the opportunity to reach newborns that are dying needlessly from preventable causes. Understanding some key features of the trials can help clinical professionals interpret and apply this important evidence appropriately:
The trials are not without weaknesses and limitations, and significant implementation challenges exist, including ensuring the training and quality of health workers, ensuring simplified regimens are used only when hospital referral is not possible, maintaining skills and adherence to protocols, establishing adequate monitoring and evaluation, setting up surveillance systems for antibiotic resistance, and ensuring antibiotic supply. But outpatient regimens are now an evidence-based option when hospitalization is not possible.
Engagement from professional associations of pediatric and neonatal professionals around the world is needed to ensure proper use of this evidence in the programmatic setting, ask the tough questions, and help us deliver much-needed care to the world’s most vulnerable newborns.