Sepsis is a primary cause of mortality in newborns, particularly in low- and middle-income countries (LMICs). Despite the fact that neonatal sepsis is a significant public health issue in LMICs, it is still unknown how, when, and where newborn infants acquire infections that could be fatal. Additionally, it is still unclear what variables led to the occurrence of AMR in these individuals.

A new study decided to look at the presence of antibiotic resistance genes (ARGs) in the gut microbiota – the collection of microbes that are present in the human gut – of mothers and their babies from 7 LMICs in Africa and South Asia. As part of the BARNARDS study, they recruited 35,040 mothers and 36,285 neonates. From there, they collected 18,148 rectal swabs (15,217 from mothers and 2,931 from neonates, including 626 with sepsis), which were used to grow the bacteria in these samples and assess their presence of clinically important ARGs in the microbiota of mothers and their babies.

The authors discovered that several samples included genes associated with antibiotic resistance, which suggests that AMR is much more prevalent in these settings than previously thought. For instance, 18.5 percent of samples from newborns tested positive for blaNDM. This gene produces the enzyme New Delhi Metallo-beta-lactamase, which may break down ß-lactam antibiotics like the frequently used carbapenems and make bacteria resistant to them.

Notably, the researchers discovered that ARGs were present in neonates within hours of birth, indicating that the infants were initially colonized with antibiotic-resistant bacteria at birth or shortly after, either through contact with the mother or the hospital environment.

The samples collected from mothers and neonates were also used to identify the bacteria resistant to antibiotics. In total, the authors isolated 1,072 gram-negative bacteria, mostly K. pneumonia, E. coli, and E. cloacae. Whole genome sequencing revealed that while these bacteria are quite diverse across different locations, there are clear clusters associated with specific countries and hospitals.

The BARNARDS team found certain instances when distinct neonates attending the same clinical facility had the same bacterial isolate, indicating that in some instances, the transmission of resistant germs from the hospital environment or between newborns may have happened. Additionally, according to the genomic analysis, some E. coli isolates could not be distinguished from mothers or newborns, supporting the idea that mother-to-child transmission could occur during or after childbirth.

Finally, the researchers looked at aspects of water, sanitation, and hygiene (WASH) and previous infections to identify risk variables related to carrying ARGs. The scientists discovered that women who frequently washed their hands (as opposed to moms who only occasionally did so) had a lower likelihood of having resistance genes. In contrast, mothers who reported infection or took antibiotics during the previous three months had a higher risk. Mothers carrying such ARGs were also more likely to experience unfavorable delivery outcomes and neonatal sepsis.

These results show that antibiotic resistance is highly prevalent in the microbiome of women and their newborns in LMICs, even just hours after birth. The study also emphasizes how preventing neonatal sepsis requires a better understanding of how ARG is transmitted, including mother-to-child transmission and transmission within the healthcare setting. Finally, the findings highlight the significance of having access to clean water, proper sanitation, and excellent hygiene in LMICs to lessen neonatal sepsis and mortality rates and AMR.

Professor Tim Walsh, who supervised the study, stressed the novelty of the findings: “This article demonstrates two novel observations. The first is that the incidence of AMR carriage, including carbapenem resistance, is extremely worrying, not only in South Asia but also in some parts of Africa. The second is that the incidence of carbapenem resistance is high in newborn babies, demonstrating that AMR carriage occurs within a few days of life. This research poses many questions about transmission and how the acquisition of these drug-resistant strains might impact on the growth of the baby – questions we are currently working to address within the IOI and with our collaborators.”

Dr. Kirsty Sands, who co-led the study, highlighted how it starts to elucidate the factors governing the spread of AMR: “The BARNARDS group worked together for over seven years to produce one of the largest studies that analyses gut bacteria of women and their neonates. This study shows that transmission dynamics can be very complex, as we found links between carriage, infection, sanitation, and hygiene. We need to continue our research to fully understand these transmission dynamics, which could help to guide better infection prevention and control measures.”

Dr. Maria Carvalho, who co-led the research, the study also promoted capacity building in local sites. It explained: “BARNARDS developed and implemented a standardized methodology to attain the common objective of minimizing the impact of morbidity and mortality in neonates from African and South Asian countries. We also looked at the specific needs of each site. For example, BERNARDS set up an additional maternity ward (20 beds) and a Microbiology Lab in the Murtala Muhammad Specialist Hospital in Kano, Nigeria. Capacity building throughout the network at different levels (clinical, research, and outreach) was a big achievement of BERNARDS.”

Dr. Rabaab Zahra, who led the study in Islamabad, Pakistan, stressed the importance of these findings for understanding and controlling the spread of AMR said: “Based on our knowledge of AMR prevalence, we had speculated certain levels of resistance in neonates but didn’t think this started so early on in life. This raises concerns about our antibiotics use policies and hygiene and infection control practices in healthcare facilities.”

Journal Reference:

  1. Carvalho, M.J., Sands, K., Thomson, K. et al. Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries. Nat Microbiol (2022). DOI: 10.1038/s41564-022-01184-y