antibiotic resistance genes in newborns!!

 A news release last week published an oral presentation from the European Society of Clinical Microbiology and Infectious Diseases at the ESCMID Global 2026 meeting in Munich: https://www.eurekalert.org/news-releases/1124038 . thanks again to Paul Susman for bringing this to my attention.

Summary of the presentation:

-- meconium samples of 105 infants admitted to a neonatal ICU within the first 72 hours of life, based on data from July 2024 to July 2025

-- studies done 2 decades ago have documented that meconium is not sterile, contrary to prior belief, which suggests that the neonatal gut may well be exposed to maternal bacteria during pregnancy

    -- the concern was that early microbial exposure could spread antibiotic resistance through maternal transmission, delivery mode, and very early hospital exposures

-- the researchers screened meconium samples from these infants for 56 different resistance genes associated with commonly used antibiotics

-- the most common antibiotic resistance genes (ARGs) detected were oqxA (in 98% of the samples!!!) and qnrS (96% of the samples!!)

    -- oqxA is associated with ARG for K. pneumoniae

    -- qnrS is associated with ARG for K. pneumoniae and E. coli

-- they also found several genes encoding beta-lactamases, the most prevalent being blaCTXM (55% of the samples), blaCMY (51%), and blaSHV (39%)

-- also found were genes linked to resistance to carbapenems in 21%

-- each meconium sample contained a median of 8 resistance genes

-- though it is not really so surprising that maternal genes distorted by prior antibiotic use are passed onto the neonates, this study also found that the msrA gene (macrolide-streptogramin resistance gene) was linked to maternal hospitalization during the pregnancy (and therefore after the initial maternal genetic material was passed onto the embryo).

-- and a higher number of resistance genes were associated with central venous catheter placement within the first 24 hours of the neonate's life (suggesting that the neonate was able to generate their own antibiotic resistance pretty easily, since these catheters were likely involved with antibiotic infusion, or perhaps there was just exposure to healthcare-associated microbes soon after birth)

    -- though a countervailing finding was that resuscitation after the neonate's birth was associated with fewer resistance genes.

-- so, their conclusion: "Overall, the findings suggest that both maternal transmissions and early exposure to the hospital environment may contribute to the establishment of ARGs in the neonatal gut", with the caveat that there needs to be further research to understand the future of these changes: how does the carriage of these resistance genes translate into future microbiome development and infection risk as the infants grow?

    -- it is well-known that the microbiome is a labile entity, subject to changes in diet, exercise, medication use, environmental exposures, psychological stress, nicotine exposure, etc: https://pmc.ncbi.nlm.nih.gov/articles/PMC8218903/

    -- and, the Mediterranean diet is associated with a healthier microbiome: https://pmc.ncbi.nlm.nih.gov/articles/PMC7822000/

    -- if interested in a slew of prior blogs on the microbiome, see https://gmodestmedblogs.blogspot.com/2024/07/microbiome-in-cardiovascular-disease.html which points to many different blogs on the microbiome as well as many on antibiotic overuse in humans and livestock and the association with antibiotic resistance

        -- for example, a really scary report by the WHO twelve years ago about the global spread of many common highly antibiotic-resistant microbes: https://gmodestmedblogs.blogspot.com/2014/05/who-report-on-antimicrobial-resistance.html

---

there was also a small Spanish study 10 years ago confirming the high rate of antibiotic-resistant genes in infants' meconium and early fecal samples: see resistant antibiotics in newborns JDevOriginsHealthDisease2016 in dropbox, or doi: 10.1017/S2040174415001506

-- this study assessed the meconium from 20 children in Valencia and followed up until 9 years of age (though the report below is up to 1 year)

    -- this study found:

        -- 14 of the meconium samples (70%) had ARGs

            -- 10 had BL^r  (associated with beta-lactam antibiotic resistance, though also to other staphylococci and streptococci species; this resistance was conferred by 2 of the 6 gene types analyzed for this resistance, mecA (associated with methicillin-resistant Staph aureus) and blaCTX-M  (encodes extended-spectrum b-lactamases that confer high-level resistance to cefotaxime and other extended-spectrum cephalosporins)

                -- though this was a 9-year study, this report focused on the first year. There was a comment that this mecA resistance was still present after 6 years, though that was the only reference to a later time period

                -- none of the six 1-week old infants carrying mecA had been treated with antibiotics, and only 4 of the mothers had received antibiotics during pregnancy (3 had received antibiotics before the 12^th week of gestation)

                -- the other BL^r-conferring gene detected in meconium encoding the extended-spectrum b-lactamase CTX-M was found only in vaginally delivered infants

            -- 8 neonates had Tc^r (associated with tetracycline resistance); this resistance was conferred by a variety of different genes, finding tet(C), tet(K), tet(Q), tet(A), tet(B), tet(L), tet(O), and tet(X). the tet(Q) is associated with Bacteroides abundance

              -- all fecal samples from 1-week-old infants had at least one ARG; 4 had BL^r (mecA most prevalent) and 10 Tc^r genes. the specific ARGs in the 1-week-olds did not necessarily reflect the distribution in the mothers

        -- assessment of Tc^r in maternal and infant samples from birth to 1 year:

            -- a single maternal-infant pair had 5 fecal samples tested in the infant's first year of life, along with the meconium, colostrum, and maternal fecal samples

                -- the mother had five of the Tc^r strains 1 year later (ie, stable)

                -- all of these genes were recovered in the meconium or colostrum; at week 1 and 1 month after childbirth, the infant did not carry any Tc^r gene

                -- however, the 3-month sample in the infant did have 2 of the Tc^r genes and at 7 months had 4 of the Tc^r genes. at 1-year-old the infant had as many ARGs as the mother. these ARGs are typically found for Bacteroides, which is scarcely represented in the neonate's meconium despite its becoming the dominant genus in the adult microbiome. perhaps these ARGs were not present initially because these bacteria did not thrive until later?

                -- and, 2 ARGs were detected in the infant that were not found in the mother, meconium, or colostrum and perhaps these were acquired later

            -- for Tc^r in the overall group:

                -- 40% of meconium samples had Tc^r, but that increased to 85% in 1-week olds, and some form of Tc^r was found in all of the mothers

                -- the highest prevalence of ARGs was in the meconium and 1-week old samples in the newborns, and this was up to 6-fold higher than in the maternal samples

    -- all of the mothers in his study were born in Spain, had a non-vegetarian diet, and mostly had normal BMIs prior to pregnancy. they all had normal pregnancies without complications and delivered their infants at >37 weeks of gestation and with normal birth weights

        -- 6 of them did receive amoxicillin prior to having a C-section; 3 of them had antibiotics prior to the 12^th week of pregnancy, one between the 12^th and 32^nd week,

        -- there does seem to be active transfer of antibiotic-resistant genes to newborns, and this seems to happen even within a few days of maternal exposure to new antibiotics

    -- a study found that there were epigenetic changes in rats exposed to marijuana that were inherited by the next rat generation, suggesting that there may well be environmentally-induced chemical changes to genes that can be inherited, and not just inheritance of the genome itself. this study also found that these changes could be transferred to the rat babies even if marijuana was used before the pregnancy: https://gmodestmedblogs.blogspot.com/2015/07/marijuana-passing-through-generations.html

    -- but, the significance of this is unclear given the fluidity of the gut microbiome, as noted above. we really need more information over time. hopefully, this new provocative study will be followed by subsequent gut microbiome assessments over time to assess the evolution of the microbiome despite very high levels of antibiotic-resistant genes initially. it would be great to have assessments every 6 months or so, with granular data on antibiotic exposures, diet, stress, etc

        -- a few other issues:

            -- this was a small study, and the 1-year outcome in the study was limited to a single mother-infant pair

            -- antibiotics were given to several of the mothers (and thereby to the infants) prior to delivery, so at least some ARGs may have occurred in the infant in response to the maternal antibiotics and not through gene inheritance from the mother/father at the time of conception

        -- shockingly (and hard to explain), there was a study of the Yanomami people in the Amazon finding that BL^r-conferring genes were identified in the fecal microbiomes without any exposure to antibiotic use: https://www.science.org/doi/10.1126/sciadv.1500183 

            -- this overall suggests that the presence of large numbers of ARGs in infants is likely complex and multifactorial. some ARGs are likely from direct transfer from mother to infant as pretty clearly demonstrated above, some seem to be generated in the infants themselves as suggested above, perhaps some from being in the hospital environment and contacting bacteria from others, some perhaps just from being around other humans or animals and acquiring their ARGs: https://pmc.ncbi.nlm.nih.gov/articles/PMC9765467/. also, the infant could be exposed to microbes from other areas of the maternal microbiomes besides the GI tract (skin, vagina...), perhaps explaining the discordance in ARGs between mothers and infants.

-- as background here that informs the above:

    -- there are important changes in pregnancy that may predispose women to infections and potential microbiome changes:

        -- there are changes in the third trimester that mimic metabolic disorders: including diabetes and obesity, that could themselves enhance an inflammatory state of the intestinal epithelium and mesenteric lymph nodes and blood; some studies have found translocation of bacteria  to these lymph nodes, intestinal bacterial overgrowth, increased mucosal barrier permeability, reduction of epithelium integrity and host immune deficiencies. for example, there is altered maternal immune responsiveness necessary for the development of the fetus and placenta

        -- and, there are studies finding bacteria in amniotic fluid, fetal membranes, umbilical cords, placenta, and meconium; bacteria are also found in colostrum (specifically the gram-positive oxygen-tolerant lactic acid bacteria, including lactobacilli, lactococci, enterococci, streptococcci, leuconostoc and pediococci: https://pmc.ncbi.nlm.nih.gov/articles/PMC3417654/. these microbes may travel through the maternal circulation and go to the fetus and mammary gland

so,

-- intriguing that the infants' microbiome inherits antibiotic-resistance genes from the mother, and that even epigenetic changes are potentially inheritable

-- but it is clear from many studies that the gut microbiome is changeable and reflects many external factors beyond the female/male genetic initial input, including diet, exercise, emotional stress, etc.  And the microbiome is healthier with a healthy diet, regular exercise, and a calm and peaceful existence.

-- so, the big question is whether the microbiome in infants is able to re-establish itself as a healthier one over time. we need individual-level data on the evolution of the initial meconium derangements over many years to assess this progression

-- the next blog will address the time course of antibiotic resistance in a large Swedish cohort, with evidence that some antibiotics can lead to ARGs lasting for more than 8 years

-- and, of course, the usual concern: there are way too many antibiotics prescribed to people without clear clinical indication, and (the infected elephant in room) the really huge amount of antibiotics used for non-infectious reasons in livestock that make their way into our systems

geoff

-----------------------------------

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@bidmc.harvard.edu

to get access to all of the blogs:  go to http://gmodestmedblogs.blogspot.com/ to see the blogs in reverse chronological order

to get access to the dropbox: https://www.dropbox.com/scl/fo/pcf4vymtpo77f49wd2ljr/ANyJqB40CuBd-DMEr67XDoI?rlkey=5dsalmuhf8ekd0svsgvn93xm1&dl=0

or you can just click on the magnifying glass on top right, then type in a name in the search box and get all the blogs with that name in them