Environmental Determinants of Community-Acquired Antibiotic Resistance in Low- and Middle-Income Countries

An estimated 1.27 million deaths in 2019 were attributable to bacterial antibiotic-resistant infections, 89% of which occurred in low- and middle-income countries (LMICs) (Murray et al. 2022). Extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) are resistant to a broad spectrum of beta-lactam antibiotics, including a variety of penicillin and cephalosporin drugs. With limited treatment options, third-generation cephalosporin-resistant and ESBL-producing Enterobacterales infections result in longer and more costly hospital stays, increased severity of illness, and increased risk of mortality. Though appropriate use of antibiotics is critical for maintaining their effectiveness in treating life-threatening infections, antibiotics are available over-the-counter in LMICs and the majority of antibiotics are used in food animals, increasing the selection for antibiotic-resistant bacteria (ARB). Multidrug-resistant- (MDR) and ESBL-E in humans have been directly linked to food animals, and food animal waste is a known reservoir of antibiotic resistance (AR). Resistant microbes and genetic elements that confer resistance are transported via environmental pathways as manure is applied to crops, runs off into waterways, and seeps into soil. In LMICs, small-scale or “backyard” food animal production is often promoted for its economic and nutritional benefits. However, due to poor water, sanitation, and hygiene (WASH) in these settings, household environments in LMICs often have high levels of animal fecal contamination, which may increase the risk of ARB spillover to humans. Commercial food animal production is also expanding, and antibiotic use in livestock is projected to increase by upwards of 200% from 2010 to 2030 in LMICs. Antibiotic use and waste management are unregulated in commercial food animal production, compounding the risk of environmental and community spread of ARB. Though WASH may play an important role in the spread of community-acquired ARB infections, epidemiological evidence to support WASH interventions to reduce ARB carriage seems limited. Additionally, the relative impact of backyard versus commercial food animal production on ARB carriage remains unclear. Importantly, the Coronavirus 2019 (COVID-19) pandemic resulted in strict infection control and prevention measures, especially in LMICs affected by severe outbreaks in the context of under-resourced healthcare systems. The public health response to the pandemic may have impacted community transmission of other infectious pathogens, including ARB, though no studies to date have assessed these impacts in a LMIC. This dissertation has three aims: (1) evaluate existing evidence on the association between WASH factors and ARB in LMIC communities; (2) estimate associations between exposures to commercial and household food animals and ESBL-E carriage in a LMIC; and (3) quantify changes in antibiotic use and ESBL-E carriage in a LMIC before versus after the beginning of the COVID-19 pandemic. This work applies concepts and methods in environmental, spatial, and molecular epidemiology to inform evidence-based One Health policies and practices that will prevent the spread of ARB in under-resourced settings.

Advisor: Graham, Jay P