Frequency of bystander exposure to antibiotics for enteropathogenic bacteria among young children in low-resource settings

Abstract

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.

The impact of antibiotic resistance on the rampant spread of infectious diseases in Pakistan: Insights from a narrative review

“…More alarming is the bystander effect, wherein antibiotics administered to a child in a low‐resource setting may develop resistance in pathogens which were not the drug's intended target. Such exposures are termed as “subclinical.” It has been shown that Pakistan has one of the highest subclinical exposure incidences (1243.3 exposures per 100 child‐years) 47 . Should such subclinical exposures continue, resistance across various classes of bacteria may increase manyfold, exacerbating the prevalent ABR problem among children.…”

Can drinking water, sanitation, handwashing, and nutritional interventions reduce antibiotic use in young children?

“…Repeated antibiotic use within a short period persistently alters the gut microbiota into a predominantly resistant population 26 . Children in LMICs often carry enteropathogens asymptomatically in their gut; when antibiotics are used to treat symptomatic respiratory and diarrheal infections, these "bystander" pathogens that are not the target of treatment are exposed to antibiotics, increasing the risk of resistance 27 . We would expect the observed reductions in antibiotic use among children receiving interventions in our analysis to translate to reduced carriage of AMR.…”

Burden of diarrhea and antibiotic use among children in low-resource settings preventable byShigellavaccination: a simulation study

“…Furthermore, a Shigella vaccine may produce ancillary benefits that need to be quantified, specifically reductions in antibiotic exposures since diarrhea is a major cause of antibiotic use. 4,5 Previous analyses have identified Shigella as a leading contributor to antibiotic consumption among children in low-resource settings. 5 In MAL-ED, Shigella was responsible for 14.8 antibiotic courses per 100-child years.…”

“…4,5 Previous analyses have identified Shigella as a leading contributor to antibiotic consumption among children in low-resource settings. 5 In MAL-ED, Shigella was responsible for 14.8 antibiotic courses per 100-child years. 4 Furthermore, 20.9% and 16.2% of all fluoroquinolone and macrolide courses given for diarrhea, respectively, were to treat shigellosis.…”

“…There were more than 7 antibiotic exposures per child-year for bystander enteropathogenic bacteria in MAL-ED. 5 To inform the vaccine value proposition, we aimed to quantify the potential impact of a Shigella vaccine on the incidence of Shigella diarrhea (severe and non-severe), all diarrhea, and antibiotic use in the first two years of life via various potential vaccination strategies. We considered different vaccine efficacies, dosing schedules, and types, including leaky vaccines (i.e., prevention of a fraction of episodes in all children) and all-or-nothing vaccines (i.e., prevention of all episodes in a subset of children who are vaccine responders).…”