Research Article: Emergence of antibiotic resistance in immunocompromised host populations: A case study of emerging antibiotic resistant tuberculosis in AIDS patients

Date Published: February 28, 2019

Publisher: Public Library of Science

Author(s): Ashley A. DeNegre, Martial L. Ndeffo Mbah, Kellen Myers, Nina H. Fefferman, Yi Luo.


The evolution of antibiotic resistance is far outpacing the development of new antibiotics, causing global public health concern about infections that will increasingly be unresponsive to antimicrobials. This risk of emerging antibiotic resistance may be meaningfully altered in highly AIDS-immunocompromised populations. Such populations fundamentally alter the bacterial evolutionary landscape in two ways, which we seek to model and analyze. First, widespread, population-level immunoincompetence creates a novel host environment with disrupted selective pressures. Second, within AIDS-prevalent populations, the recommendation that antibiotics be taken to treat and prevent opportunistic infection raises the risk of selection for drug-resistant pathogens.

To determine the impact of HIV/AIDS on the emergence of antibiotic resistance–specifically in the developing world where high prevalence and economic challenges complicate disease management.

We present an SEIR epidemiological model of bacterial infection, and parametrize it to capture HIV/AIDS-attributable emergence of resistance under conditions of both high and low HIV/AIDS prevalence.

We demonstrate that HIV/AIDS-immunocompromised hosts can be responsible for a disproportionately greater contribution to emergence of resistance than would be expected based on population-wide HIV/AIDS prevalence alone.

As such, the AIDS-immunocompromised have the potential become wellsprings of novel, resistant, opportunistic pathogen strains that can propagate into the broader global community. We discuss how public health policies for HIV/AIDS management can shape the evolutionary environment for opportunistic bacterial infections.

Partial Text

The rapid emergence of antibiotic resistant microbes represents a worldwide health risk since development of antibiotics is being outpaced by the evolution of resistance. [1] Factors contributing to resistance include prescribing habits of health professionals, antibiotic policy-making decisions, drug availability, and sociocultural beliefs regarding the necessity of antibiotics. [2] Regardless of the drivers of emergence, the result is the same: antibiotic-resistant infections. We have seen the dangers of drug resistance exemplified in bacterial pathogens such as Escherichia coli, Streptococcus pneumoniae, Mycobacterium tuberculosis, Clostridium difficile, and Staphylococcus aureus, each of which includes strains unresponsive to at least one antimicrobial agent. [2, 3]

Fully and functionally immunocompetent hosts can still contribute to antibiotic resistance. Thus, we use our model to quantify the relative contribution to the emergence of resistance from both fully immunocompetent and HIV/AIDS patients (HIV/AIDS+) receiving highly active antiretroviral treatment (HAART+). We also compare the actual contribution to emergence attributable to AIDS-immunocompromised hosts to that which would be expected based on AIDS prevalence alone. We do so by computationally reducing HIV/AIDS prevalence to zero in both countries and then measuring the magnitude of the corresponding decreases in infection prevalence and total emergence. Finally, holding antibiotic adherence constant among infectives, we calculate total emergence as a function of gradually increasing HIV/AIDS prevalence.

Highly AIDS-prevalent populations represent a novel pathogen environment due to the combination of widespread immunoincompetence and antibiotic use. In such populations, antibiotics are used more frequently, and for longer periods of time, to treat and guard against opportunistic infections affecting the AIDS-immunocompromised. [28] This treatment scenario raises the risk of a global public health threat as these populations, following standard antibiotic protocols, may become wellsprings of novel resistant pathogen strains that can propagate into the broader global community. (Note that, while this work is focused specifically upon TB as a particular bacterial pathogen, many bacterial pathogens of accrue antibiotic resistance, and viral and parasitic infections can also be treatment-resistant, presenting additional health concerns to already at-risk populations [29]).

We demonstrated that a significant proportion of antibiotic resistance is attributable to AIDS-immunocompromised hosts. Therefore, we must also consider the associated impact–and potential tradeoff between individual and public health–that arises in the context of antibiotic regulation and policy recommendations for treating infection in the developing world. Even discounting the health behavioral choices made by AIDS-immunocompromised individuals, limited and/or excessive access to antibiotics, coupled with the potential for distribution by medical professionals unfamiliar with optimal administration protocols, [13, 26] ensures the continuing risk of rapid emergence of antibiotic resistance. To foster best medical practices, it is necessary that antibiotic cycling recommendations balance the ethical considerations associated with both personal medicine and public health, such that an active, purposeful, consideration of public health is inherent in antibiotic policy decisions. That said, changes to dosing regulations that may involve the withholding of antibiotics from those unlikely to adhere to prescribing instructions are not without their own set of ethical considerations. The ethical questions surrounding the withholding of potentially life-sustaining treatments–especially among those whose access to antibiotics is already limited by economic constraints–are equally complex, and remain the subject of considerable debate. [33] However, considering the disproportionate increase in drug-resistance that accompanies the presence of HIV/AIDS-affected hosts in an otherwise healthy population, a greater population-level health risk than that imposed by AIDS may occur in the presence of strong selection for antibiotic-resistant microbes.




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