“New antimicrobial resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases, resulting in prolonged illness, disability, and death…More than one-third of the estimated four million newborn deaths around the world each year are caused by severe infections, and a quarter – around one million deaths – are due to neonatal sepsis/pneumonia alone.” – World Health Organization (WHO)

The level of antibiotic resistance in neonatal infections and its impact on mortality in low-middle income countries (LMICs) is unacceptably high. The study, entitled the Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS), will provide the means, support, network and tools to understand the impact of antibiotic resistance on neonatal morbidity and mortality in addition to identifying possible solutions to minimize its impact.

Antimicrobial resistance (AMR) is now recognised as one of the most serious global threats to human health in the 21st century. There is evidence of political traction through endorsements of statements by the UK and US governments, WHO and CDC describe a global crisis and an impending catastrophe of moving into a post-antibiotic era. These serious concerns have been catalysed by the rapid increase in Multi-Drug Resistant (MDR) Gram-negative bacteria (GNB), particularly Enterobacteriaceae.

Developing countries bear the burden of 99% of neonatal mortality worldwide (WHO) with infections such as tetanus, pneumonia and sepsis acting as a leading causes of neonatal mortality. Increased antibiotic resistance in bacteria, including MDR pathogens, render infections increasingly difficult to treat, with resistance arising against last resort treatments.

The study will be the first of its kind in the world to blend clinical and molecular epidemiology from low-middle income countries with respect to neonatal Gram-negative infections. The data generated will be used to inform local, national and international health bodies. The BARNARDS group will focus on monitoring and improving mother and infant wellbeing by exploring the impact of infection control interventions. In addition to assessing the burden of antibiotic resistance, we will also determine the prevalence of multi-drug resistant Gram-negative bacteria (MDR_GNB) carried as normal flora  that causes neonatal sepsis and identify contributing demographic indices such as population size, overcrowding, access to clean water, sanitation conditions, family size, poverty level and antibiotic usage impact on MDR_GNB.

BARNARDS is currently active in 12 different sites, across seven different countries; Bangladesh (Chittagong and Dhaka), Ethiopia (Addis Ababa), India (Kolkata), Nigeria (Kano, Abuja (National Hospital) and Abuja (Wuse), Pakistan (Islamabad and Bhara Kahu), Rwanda, (Kigali and Kabgayi) and South Africa (Cape Town). Bangladesh, Nigeria, Pakistan, Rwanda and South Africa joined the study in 2015 and Nigeria (Kano), Ethiopia and India joined in 2016 (Fig. 1).

Figure 1- BARNARDS across the globe.
1. Boston Children’s Hospital, 2. Cardiff University, 3. Chittagong Ma o Shishu Hospital, 4. University Central Hospital of Kigali, 5. Gates Foundation, 6. Kabgayi, 7. Kumudini, 8. Murtala Mohammed Specialist Hospital, 9. National Hospital Abuja, 10. National Institute of Cholera and Enteric Diseases, 11. Pakistan Institute of Medical Sciences, 12. St. Paul’s Hospital Millennium Medical College, 13. Tygerberg Hospital, 14. WUSE District Hospital.

The local clinical epidemiology is supported with state-of-the-art molecular genetics by performing the characterisation of the microbiota of the samples in study, particularly of the MDR GNB. In addition, the prevalence of MDR-GNB carried as normal microbiota in pregnant women that can be identified as aetiological agents of MDR-GNB neonatal sepsis was assessed. BARNARDS also identified socio-demographic traits such as education, overcrowding, access to clean water, sanitation conditions, living conditions, socioeconomic status and antibiotic usage which may have a role on the development of neonatal sepsis. In addition, hospital environmental samples were collected, including from medical devices and surfaces, to understand if a link between the microbiota of the hospital environment and the late onset of sepsis could be established. Furthermore, BARNARDS produced an extensive dataset of resistance profiles of isolates causing neonatal sepsis and challenged the current paradigm of ampicillin and gentamicin for prophylactic coverage of neonatal sepsis.

The BARNARDS group has established a genomics platform, incorporating a bespoke bioinformatics pipeline which is dedicated to extract key epidemiological information on a large scale. BARNARDS aims to extend this platform by incorporating a metagenomics branch in attempt to track the sepsis-causing isolate within the mother’s microbiome, a novel and unique approach. Our genomics platform can be utilised by our international partners as part of our education and training program. With the aim of sequencing over 2000 isolates, BARNARDS is establishing a comprehensive international database of bacterial isolates causing neonatal sepsis. Although not an initial focal point, Gram-positive pathogens are also being scrutinised due to its relevance in neonatal sepsis in the countries involved. In addition to producing this critical data, BARNARDS group carries a strong educational aspect, supporting the international partners in uniform and excellent microbiology practices and providing study periods in an established molecular / genomics laboratory based in the UK. On publication, data captured during BARNARDS and related findings will be released to the public in the form of publications in high impact scientific peer reviewed journals.

This research has been funded by the Bill and Melinda Gates Foundation.