When patients are likely to develop immunity to infection, the duration of antibiotic treatments can be shortened without harm, thus delaying the spread of drug resistance and its concomitant public health impacts, according to this model-based analysis.
With attention focused on reducing overprescription, there has been little examination of whether drug resistance in the population can be slowed by reducing the dosage and duration of antibiotic treatments. This study relies on ecological theory and mathematical models to predict the behavior of bacteria in different situations in order to develop a theory of when antibiotic treatments can be shortened, and a framework for continued study of treatment design.
In response to antibiotics, all bacteria genetically select for resistance, no matter the dose. The impact of antibiotics on both the bacteria causing the infection, and on other bacteria present, is important to the spread of resistance.
When a patient is symptomatic because an infection does not prompt an immune response or because the infection and immune response oscillate, high doses of antibiotics for typical, long durations are required.
But in many common cases, where an infection is self-limiting or opportunistic, resistance is most likely to occur with intermediate dosing. Thus, therapy should be short and aggressive to keep bacteria populations low until a patient’s immune response can overwhelm the infection. Unfortunately, with this shorter therapy, the patient will experience symptoms longer.
The mode of administering antibiotics—topical, intravenously or focal delivery—matters to the development of drug resistance because it determines drug concentration throughout the body.
The study suggests the current "one-size-fits-all" view of antibiotic dosing is too simple. Noting the public health impacts of drug resistance, the authors call for the development of a functional taxonomy of pathogens and a complex, dynamic understanding of drug dosing.
This study was funded by Robert Wood Johnson Foundation support to Extending the Cure, a research and consultative effort that examines incentive-based policy solutions to curb antibiotic resistance based on the understanding that antibiotics are a shared resource that must be conserved. The project is based at the Center for Disease Dynamics, Economics & Policy in Washington, D.C.