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Primary Care Corner with Geoffrey Modest MD: Antibiotic Resistant Bugs in Gut Microbiome of Kids

22 Dec, 15 | by EBM

By Dr. Geoffrey Modest

Ciprofloxacin​-resistant e. coli are increasingly found worldwide and are capable of causing extraintestinal infections, especially urinary tract infections. A report in 2006 found that 1.5% of healthy Seattle children excreted cipro-resistant e coli in their stool, without prior fluoroquinolone exposure. A new study looked at 80 healthy children and their mothers​ who were part of the St Louis twin cohort, assessing stool samples from 2010-2013 semiannually from mothers, and monthly from their twins til age 2 yo and then bimonthly, analyzing for e coli resistance (see J Infect Dis. (2015) 212 (12): 1862-1868).

Results:

  • 15 kids (19%) and 8 mothers (20%) excreted ciprofloxacin-resistant e coli at least once, and 11 of 23 colonized subjects had multiple and usually consecutive positive samples
  • Overall 33% of 40 families had at least 1 member with a positive culture for cipro-resistant e coli
  • For the kids, the median day-of-life for the first positive specimen was 341
  • Stools specimens positive for cipro resistance correlated with length of hospital stay after birth (p=0.002), where the median was 6 days longer (10 vs 4 days) than for those with no resistance, and with maternal colonization (p=0.001); antibiotic use in the first 2 months of life, acid suppression, sex, mode of delivery or maternal perinatal antibiotic use were not correlated. and only 2 of the 15 kids with a positive stool specimen received any antibiotics at all in the first 9 months of life
  • In 6 families, both kids had positive stool samples
  • Cipro-resistant e coli were often resistant to other antibiotics: of 57 cipro-resistant e coli, 1 sample was resistant to 5 other antibiotics (ampicillin/cefazolin, tmp/smx, piperacillin/tazobactam, gentamicin, doxycycline), 5 were resistant to 4 of the other antibiotics, 16 to 3 antibiotics, 21 to 2 antibiotics, 8 to 1 antibiotic, and only 6 were resistant only to cipro
  • The cipro-resistant e coli had genotypes typical of extraintestinal pathogenic e coli.

So, some points:

  • Antibiotic-resistance is pretty common and may be increasing, even without the selection pressure of prescribed antibiotics
  • The cipro-resistant e coli found have the genetic profile of potential human pathogens (not just for urinary tract infections but also for soft-tissue and bone infections)
  • In this study they used a very small stool sample for inoculation, raising the issue of underestimating the actual presence of cipro-resistant e coli​ (and 1/2 the kids had only one positive stool sample, which may be because of the small inoculum and low levels of colonization)
  • Though there was a correlation between the length of hospital stays for the infants and subsequent positive stools, suggesting hospital-acquired colonizatons, the median date of the first positive culture was almost a year later​. One possible explanation is that these infants were in fact colonized in the hospital but their level of colonization was below what was detectable. Or, perhaps kids who stayed 6 days longer were more premature and there was something either developmentally or posthospitalization specific to these kids which led to more likelihood of acquiring the resistant bug. Not sure from the data.
  • So, how does this all fit together? Clearly the issue is common, probably increasing, and potentially quite profound, especially since the cipro resistance was almost always associated with resistance to other antibiotics, and we don’t have a slew of new, great antibiotics in the wings. The presence of resistance in kids without antibiotic exposure suggests, I think most likely, that there was community-acquired colonization, potentially from food (e.g. from animals or plants treated with antibiotics. Fyi, 80% of antibiotics used is for food production, and quinolones have been heavily used in agriculture and aquaculture for years). So, the canary in the mine whispers in my ear that we really try to understand the mode of spread of these resistant organisms (whether from food or community or hospital), to look at ways of restoring a healthy gut microbiome (through lifestyle interventions of diet/exercise — esp in adults, avoiding use of antibiotics or meds which put the microbiome at risk of pathologic changes), and largely to eliminate the unnecessary use of antibiotics in animals/plants and us.

For an array of prior blogs on antimicrobial resistance, see http://blogs.bmj.com/ebm/category/antimicrobial-resistance/ .

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