Quantifying where human acquisition of antibiotic resistance occurs: a mathematical modelling study

Abstract

BackgroundAntibiotic-resistant bacteria (ARB) are selected by the use of antibiotics. The rational design of interventions to reduce levels of antibiotic resistance requires a greater understanding of how and where ARB are acquired. Our aim was to determine whether acquisition of ARB occurs more often in the community or hospital setting.MethodsWe used a mathematical model of the natural history of ARB to estimate how many ARB were acquired in each of these two environments, as well as to determine key parameters for further investigation. To do this, we explored a range of realistic parameter combinations and considered a case study of parameters for an important subset of resistant strains in England.ResultsIf we consider all people with ARB in the total population (community and hospital), the majority, under most clinically derived parameter combinations, acquired their resistance in the community, despite higher levels of antibiotic use and transmission of ARB in the hospital. However, if we focus on just the hospital population, under most parameter combinations a greater proportion of this population acquired ARB in the hospital.ConclusionsIt is likely that the majority of ARB are being acquired in the community, suggesting that efforts to reduce overall ARB carriage should focus on reducing antibiotic usage and transmission in the community setting. However, our framework highlights the need for better pathogen-specific data on antibiotic exposure, ARB clearance and transmission parameters, as well as the link between carriage of ARB and health impact. This is important to determine whether interventions should target total ARB carriage or hospital-acquired ARB carriage, as the latter often dominated in hospital populations.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1121-8) contains supplementary material, which is available to authorized users.

Outpatient prescribing of four major antibiotic classes and prevalence of antimicrobial resistance in US adults

“…While prevalence of resistance in bacteria in CAUTI samples is affected by the use of antibiotics and the prevalence of resistance in the community [24], it may also be affected by antibiotic administration in the hospital setting and practices related to urinary catheterization. While we tried to adjust for that by considering random effects for the US HSS regions, our results would benefit from independent analyses based on resistance data for bacterial specimens obtained in other settings.…”

“…Previous work suggests that outpatient prescribing of antibiotics plays a key role in the propagation of antibiotic resistance [24]. In this paper, we examine the relationship between outpatient prescribing for different antibiotic classes and prevalence of antibiotic resistance for certain combinations of antibiotics/bacteria in the US.…”

The relation between prescribing of different antibiotics and rates of mortality with sepsis in US adults

“…One potential important source of confounding is the in-hospital antibiotic use. While there is evidence that community prescribing of antibiotics plays a bigger role than in-hospital prescribing in the acquisition of antibiotic resistance [29,30], various synergistic effects between community and inhospital antibiotic prescribing take place, both in terms of promoting the prevalence of resistance as well as the progression to sepsis, with some infections not cleared by the community use of antibiotics leading to hospitalizations, and the subsequent hospital use of antibiotics leading to sepsis and lethal outcomes. To adjust for potential effects of unmeasured confounding (including inhospital antibiotic use) and residual confounding, we included random effects for the ten US Health and Human Services regions, which led to an improvement in the model fits.…”

“…Correspondingly, the use of different antibiotics is expected to affect the rates of sepsis and sepsis-associated mortality by both propagating antibiotic resistance, and leading to sepsis and associated deaths when antibiotics are used against infections resistant to those antibiotics. Modeling studies suggest that community use of antibiotics plays a bigger role in the acquisition of resistant infections than the in-hospital use of antibiotics [29,30], though in-hospital antibiotic prescribing may also be an important contributor to the propagation of resistant infections and the associated severe outcomes [14,15]. At the same time, there is limited information in the literature about the relation between the use of different antibiotics, particularly antibiotic prescribing in the community, and the risk/rates of sepsis and the associated mortality.…”

The role of “spillover” in antibiotic resistance

“…This effect of resistance “spilling over” can be so strong that, for example, an individual in the hospital who has no recent antibiotic use may have a higher risk of antibiotic resistance than an individual in the community with a high antibiotic use rate (21). The same spillover phenomenon occurs at the level of populations, such that resistance in a hospital can be affected by resistance in nearby hospitals or by antibiotic use in the surrounding community (22–24).…”