"Why do we give broad spectrum antibiotics like Benzylpeniciilin, Gentamicin and Metronidazole to babies with necrotising enterocolitis [NEC] when their gut is sterile?" asked the Neonatal Unit [NNU] Registrar.
It was the middle of the NNU multidisciplinary ward round.
"Pardon?" said the Microbiologist, caught red-handed reaching for a second chocolate biscuit and suddenly feeling self-conscious as everyone turned to stare at him.
"Babies are born with a sterile gut so when they develop NEC why do they need antibiotics; surely there are no bacteria to cause a problem". The Registrar restated his question again but with more clarity.
The Microbiologist recognised the question was being rephrased; he obviously looked like he did not understand what was being asked! It was actually a very good observation of the Microbiologist! But it was an even better question thought the Microbiologist…so it needed a good answer…
Fortunately the Microbiologist was on the ball, and in fact was armed with the latest research provided by the NNU Pharmacist only a few weeks earlier.
Hopefully everyone knows where babies come from... but do you know where babies gut bacteria come from? Read on...
It was the middle of the NNU multidisciplinary ward round.
"Pardon?" said the Microbiologist, caught red-handed reaching for a second chocolate biscuit and suddenly feeling self-conscious as everyone turned to stare at him.
"Babies are born with a sterile gut so when they develop NEC why do they need antibiotics; surely there are no bacteria to cause a problem". The Registrar restated his question again but with more clarity.
The Microbiologist recognised the question was being rephrased; he obviously looked like he did not understand what was being asked! It was actually a very good observation of the Microbiologist! But it was an even better question thought the Microbiologist…so it needed a good answer…
Fortunately the Microbiologist was on the ball, and in fact was armed with the latest research provided by the NNU Pharmacist only a few weeks earlier.
Hopefully everyone knows where babies come from... but do you know where babies gut bacteria come from? Read on...
In utero (inside the uterus or womb) babies are sterile. They have to be, bacteria in the uterus will cause a nasty infection making both the mother and baby very unwell. And yet the human body is full of bacteria; there are up to a trillion (1,000,000,000,000) bacteria per gram of stool in the large bowel. So where did they come from?
As soon as babies are born they start to swallow. They swallow secretions from the maternal genital tract as well as their own saliva shortly after. They are given milk (either breast or formula) to feed on and they swallow that. They suck their fingers, their parents’ fingers and anything else they can put in their mouths, all of which are covered in bacteria from their environment. Every time babies swallow they take microorganisms down into their little guts and start the process of intestinal colonisation.
Now it perhaps sounds a bit gross to say that babies swallow maternal genital secretions during birth and that might sound like a bad thing, but is it?
As soon as babies are born they start to swallow. They swallow secretions from the maternal genital tract as well as their own saliva shortly after. They are given milk (either breast or formula) to feed on and they swallow that. They suck their fingers, their parents’ fingers and anything else they can put in their mouths, all of which are covered in bacteria from their environment. Every time babies swallow they take microorganisms down into their little guts and start the process of intestinal colonisation.
Now it perhaps sounds a bit gross to say that babies swallow maternal genital secretions during birth and that might sound like a bad thing, but is it?
Difference between normal vaginal delivery (NVD) compared to caesarean-section (CS)
Exposure to normal maternal flora helps to promote a healthy gut flora in a newborn baby. That might not be much of a surprise to you, but it’s actually very hard to prove.
A recent study from the UK published in Nature has looked at the difference between gut flora between babies born by NVD and those born by CS. They called this the Baby Biome Study. The team looked at the gut flora of 596 term babies by studying faecal samples, and in 178 cases they compared this flora to the baby’s mother. They used broad molecular techniques including whole-genome sequencing to look at the microbial diversity in the samples.
One of the main features the study found is that the babies gut flora changes frequently during the neonatal period (1st month of life); presumably because they initially have no flora and as new microorganisms are added the levels keep changing until they reach equilibrium. This suggests that the neonatal gut flora might be particularly vulnerable to selective pressure such as exposure to antibiotics or acquisition of more rapidly dividing bacteria such as E. coli or Staphylococcus spp. If you stick these rapidly dividing bacteria in with slow growing bacteria they will out compete and prevent the slow bacteria surviving or the use of antibiotics will kill off any sensitive bacteria allowing resistant bacteria to overgrow.
The study also found that the amount of maternal Bacteroides spp. and Bifidobacterium spp. (considered to be markers of a healthy gut flora) were considerably lower in babies born by CS. In addition CS babies were heavily colonised with environmental bacteria that were not found in such quantities in the baby’s mother, such as Enterococcus spp., Staphylococcus epidermidis, Klebsiella spp. and Enterobacter spp. These bacteria have the potential to become pathogens and make the newborn baby ill (e.g. neonatal sepsis).
In addition to mode of delivery the team also found less maternal flora and more environmental flora in baby’s whose mothers had been given antibiotics in labour. This perhaps isn’t surprising as the antibiotics will damage the maternal normal flora which will be replaced with other bacteria (home or hospital environmental flora) which can then be passed onto their baby.
Hospital environments are known to be colonised with antimicrobial resistant bacteria, presumed to be because of the use of antibiotics in patients who develop flora resistant to those antimicrobials and then spread those bacteria back into the hospital environment. The increase in environmental bacteria in babies born by CS, or to mothers given antimicrobials, suggests there is a higher risk of acquisition of antibiotic resistant bacteria.
Pathological potential of swallowed, or inhaled, bacteria
Not all bacteria the baby comes into contact with are good for them. The two most common causes of neonatal sepsis, Streptococcus agalactiae (Group B beta-haemolytic Streptococcus) and Escherichia coli, are usually acquired at the time of delivery from maternal secretions. It is also possible for babies to become unwell after acquiring Streptococcus agalactiae from maternal breast milk which can contain this bacterium without causing any symptoms in the mother.
More uncommon bacterial causes of neonatal sepsis are acquired from the mother if she has gastrointestinal infection or colonisation e.g. Listeria monocytogenes, Salmonella spp. and antibiotic-resistant Gram-negative bacteria. Although the baby can get antibiotic-resistant bacteria from their mother; it’s actually more likely that they will be exposed to antibiotic-resistance from the hospital environment.
In addition to bacteria, maternal secretions can be a source of viral infections for newborn babies.
Antibiotic-resistant Gram-negative bacteria such as E. coli, Klebsiella spp. and Enterobacter spp. can be a real problem for neonatal units. The normal first line antibiotics for septic babies are Benzylpenicillin PLUS Gentamicin, with second line being Cefotaxime PLUS Gentamicin. However antibiotic-resistant Gram-negative bacteria are often resistant to BOTH these first and second line antibiotics. Therefore babies can potentially come to harm in the time it takes to discover that they have one of these difficult to treat infections. Clinical suspicion is the key; if the baby isn’t responding to treatment think “resistance!”
So how does this latest study affect medical practice?
At the moment it is unclear what impact this study will have on neonatal medicine; further studies are required to look at whether these results translate into a clinical effect on the health of babies.
From my perspective it confirms my view that babies should be exposed to normal healthy maternal flora. We should be very careful about the hospital environment and take steps to try and reduce the exposure of babies to potential pathogens and antibiotic resistance. This includes:
And before anyone asks, no I don’t think probiotics are a good idea for neonates, not until someone knows exactly what is safe and healthy for good gut development. Most probiotics are not physiologically balanced and we have no idea what impact they have on gut development. Better to let “Nature” do what she has been doing for millions of years and try to meddle as little as possible… that’s what I think anyway… I just think the more we tinker the more of a mess we are likely to cause… okay, rant over… now where’s my glass of milk…
Having explained to the team where babies gut bacteria come from, the Microbiologist reached out again for a biscuit only to find the box snatched away at the last minute.
"Huh" said the Microbiologist.
The NNU Registrar smiled sweetly.
"No offence, but if babies get their bacteria from the environment and you work in a lab handling antibiotic resistant bacteria perhaps we should quarantine these biscuits so there is less opportunity to put your flora into our environment... oh and it's your turn to buy the biscuits next week!"
Reference
Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Shao, Forster, Tsaliki, et al. Nature September 2019: 574; 117-121
Thanks to my pharmacy friend who drew my attention to the Nature paper… you know who you are
Oh and please don’t tell my wife that I was eating chocolate biscuits!!
Exposure to normal maternal flora helps to promote a healthy gut flora in a newborn baby. That might not be much of a surprise to you, but it’s actually very hard to prove.
A recent study from the UK published in Nature has looked at the difference between gut flora between babies born by NVD and those born by CS. They called this the Baby Biome Study. The team looked at the gut flora of 596 term babies by studying faecal samples, and in 178 cases they compared this flora to the baby’s mother. They used broad molecular techniques including whole-genome sequencing to look at the microbial diversity in the samples.
One of the main features the study found is that the babies gut flora changes frequently during the neonatal period (1st month of life); presumably because they initially have no flora and as new microorganisms are added the levels keep changing until they reach equilibrium. This suggests that the neonatal gut flora might be particularly vulnerable to selective pressure such as exposure to antibiotics or acquisition of more rapidly dividing bacteria such as E. coli or Staphylococcus spp. If you stick these rapidly dividing bacteria in with slow growing bacteria they will out compete and prevent the slow bacteria surviving or the use of antibiotics will kill off any sensitive bacteria allowing resistant bacteria to overgrow.
The study also found that the amount of maternal Bacteroides spp. and Bifidobacterium spp. (considered to be markers of a healthy gut flora) were considerably lower in babies born by CS. In addition CS babies were heavily colonised with environmental bacteria that were not found in such quantities in the baby’s mother, such as Enterococcus spp., Staphylococcus epidermidis, Klebsiella spp. and Enterobacter spp. These bacteria have the potential to become pathogens and make the newborn baby ill (e.g. neonatal sepsis).
In addition to mode of delivery the team also found less maternal flora and more environmental flora in baby’s whose mothers had been given antibiotics in labour. This perhaps isn’t surprising as the antibiotics will damage the maternal normal flora which will be replaced with other bacteria (home or hospital environmental flora) which can then be passed onto their baby.
Hospital environments are known to be colonised with antimicrobial resistant bacteria, presumed to be because of the use of antibiotics in patients who develop flora resistant to those antimicrobials and then spread those bacteria back into the hospital environment. The increase in environmental bacteria in babies born by CS, or to mothers given antimicrobials, suggests there is a higher risk of acquisition of antibiotic resistant bacteria.
Pathological potential of swallowed, or inhaled, bacteria
Not all bacteria the baby comes into contact with are good for them. The two most common causes of neonatal sepsis, Streptococcus agalactiae (Group B beta-haemolytic Streptococcus) and Escherichia coli, are usually acquired at the time of delivery from maternal secretions. It is also possible for babies to become unwell after acquiring Streptococcus agalactiae from maternal breast milk which can contain this bacterium without causing any symptoms in the mother.
More uncommon bacterial causes of neonatal sepsis are acquired from the mother if she has gastrointestinal infection or colonisation e.g. Listeria monocytogenes, Salmonella spp. and antibiotic-resistant Gram-negative bacteria. Although the baby can get antibiotic-resistant bacteria from their mother; it’s actually more likely that they will be exposed to antibiotic-resistance from the hospital environment.
In addition to bacteria, maternal secretions can be a source of viral infections for newborn babies.
Antibiotic-resistant Gram-negative bacteria such as E. coli, Klebsiella spp. and Enterobacter spp. can be a real problem for neonatal units. The normal first line antibiotics for septic babies are Benzylpenicillin PLUS Gentamicin, with second line being Cefotaxime PLUS Gentamicin. However antibiotic-resistant Gram-negative bacteria are often resistant to BOTH these first and second line antibiotics. Therefore babies can potentially come to harm in the time it takes to discover that they have one of these difficult to treat infections. Clinical suspicion is the key; if the baby isn’t responding to treatment think “resistance!”
So how does this latest study affect medical practice?
At the moment it is unclear what impact this study will have on neonatal medicine; further studies are required to look at whether these results translate into a clinical effect on the health of babies.
From my perspective it confirms my view that babies should be exposed to normal healthy maternal flora. We should be very careful about the hospital environment and take steps to try and reduce the exposure of babies to potential pathogens and antibiotic resistance. This includes:
- Strict attention to hand hygiene whilst in hospital; from parents and relatives as well as staff
- Careful environmental cleaning
- Isolation of babies known to already be colonised with antibiotic-resistant bacteria
- Careful use of antibiotics and attention to antimicrobial stewardship
- Surveillance of antibiotic-resistance rates in maternal and neonatal areas
- Adequate staffing to ensure the above can be done
And before anyone asks, no I don’t think probiotics are a good idea for neonates, not until someone knows exactly what is safe and healthy for good gut development. Most probiotics are not physiologically balanced and we have no idea what impact they have on gut development. Better to let “Nature” do what she has been doing for millions of years and try to meddle as little as possible… that’s what I think anyway… I just think the more we tinker the more of a mess we are likely to cause… okay, rant over… now where’s my glass of milk…
Having explained to the team where babies gut bacteria come from, the Microbiologist reached out again for a biscuit only to find the box snatched away at the last minute.
"Huh" said the Microbiologist.
The NNU Registrar smiled sweetly.
"No offence, but if babies get their bacteria from the environment and you work in a lab handling antibiotic resistant bacteria perhaps we should quarantine these biscuits so there is less opportunity to put your flora into our environment... oh and it's your turn to buy the biscuits next week!"
Reference
Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Shao, Forster, Tsaliki, et al. Nature September 2019: 574; 117-121
Thanks to my pharmacy friend who drew my attention to the Nature paper… you know who you are
Oh and please don’t tell my wife that I was eating chocolate biscuits!!
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