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More Caution Needed When Prescribing Antibiotics to Newborns

More caution should be used in the use of antibiotics say researchers who found a decrease in healthy gut bacteria and an increase in antimicrobial resistance in babies treated with antibiotics in the first week of life.

In their study, published in Nature Communications , researchers from the Universities of Edinburgh and Birmingham, and the Spaarne Hospital and University Medical Centre Utrecht, The Netherlands analysed how antibiotics affect the gut microbiome of a newborn.

They explained how increasingly it is becoming clear how the gut microbiome influences future health and disease. For example, they said “disturbances of the gut microbial community composition after birth are associated with a broad scale of health problems in early infancy and later in life, such as infantile colic, wheezing, allergies, functional gastrointestinal disorders, obesity and generally an altered immune development.”

The authors explained how under current guidelines broad-spectrum antibiotics are prescribed to up to 10% of all newborns for suspected infections, with this ‘over-prescription’ aiming to ensure early treatment for those who are ultimately found to have an infection, as any delay may quickly become life-threatening. Experts argue though that, in most cases, the antibiotics are prescribed unnecessarily, as only a small proportion of those who receive the drugs are eventually diagnosed with an infection.

Balance Shifts in Favour of More Potentially Harmful Microbes

For their study, the researchers performed a randomised controlled trial involving 227 infants. Of these, 147 infants born at or over 36 weeks of gestational age and with suspected sepsis, received one of three standard antibiotic treatments, penicillin and gentamicin, co-amoxiclav and gentamicin, or amoxicillin and cefotaxime, in their first week of life, for an average of 48 hours. The 147 participants were recruited from three different Dutch hospitals and compared with 80 age-matched term-born infants with no suspected infections, and who were not prescribed an antibiotic, recruited from a previous healthy birth cohort study conducted in two of the same hospitals.

All babies had a rectal or faecal sample taken before and after treatment, and at age 1, 4, and 12 months. The samples were analysed for the microbes that made up their newly forming microbiome and for bacterial genes related to antimicrobial resistance.

The researchers found reduced levels of different Bifidobacterium species – known to aid in the digestion of breast milk, promote gut health, and support the immune system – in those newborns prescribed antibiotics, compared with those babies who had no antibiotic treatment. In addition, levels of potentially disease-causing bacteria were increased in the group that received antibiotics, as were the number and abundance of genes related to antimicrobial resistance.

The authors commented how “a change in 251 of 695 different bacteria investigated was observed after treatment, changing the balance between good and bad bacteria in favour of more potentially harmful microbes”.

Prof Willem van Schaik, professor of Microbiology and Infection at the University of Birmingham, said: “It is particularly troubling that following antibiotic therapy in newborns we observed a strong increase in Klebsiella and Enterococcus species which are both important multidrug-resistant pathogens.”

The authors pointed out that, despite antibiotics being stopped after 48 hours, and although the changes seen in the microbiome and antimicrobial resistance genes gradually recovered over time, these changes “persisted for at least 12 months and did not improve with breastfeeding, which is known to help a baby’s immune system”.

Start Time not Duration of Antibiotics the Key

Prof Debby Bogaert, chair of Paediatric Medicine at the University of Edinburgh and study lead, expressed how they were “surprised with the magnitude and duration of the effects of broad spectrum antibiotics on the infants’ microbiome when compared to effects of those same antibiotics on adults’ microbiota”. She suggested how timing of the antibiotics may be responsible since “infants have just received their first microbes from their mother and have not yet developed a resilient microbiome”.

The combination of penicillin and gentamicin was found to have the least detrimental effect on a baby’s gut microbiome and the number of antimicrobial resistance genes that emerge, such that the researchers suggested that when treating suspected infections in newborns, it is this combination of antibiotics that should be preferred.

Dr Marlies van Houten, general paediatrician at the Spaarne Hospital, the Netherlands, and co-principal investigator of the study, added: “The fact that start of antibiotic treatment rather than duration seems to be responsible for the damage to the microbiome underlines we need better biomarkers or biological predictors to more accurately determine which infant will develop an infection and thus require antibiotics, and which will not.”

Prof Willem van Schaik said: “This underlines the importance of further studies into balancing the need and effectiveness of these antibiotics and the risk of the emergence of genes linked with resistance.” He added how “there may also be scope to develop new interventions, like live biotherapeutics, to effectively restore the composition of the infant gut microbiome after antibiotic therapy”.

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