Economic Evaluations of New Antibiotics: The High Potential Value of Reducing Healthcare Transmission Through Decolonization


Abstract

Background: Antibiotics designed to decolonize carriers of drug-resistant organisms could offer substantial population health benefits, particularly if they can help avert outbreaks by interrupting person-to-person transmission chains. However, cost effectiveness of an antibiotic is typically evaluated only according to its benefits to recipients, which can be difficult to demonstrate for carriers of an organism that may not pose an immediate health threat to the carrier.

Methods: We developed a mathematical transmission model to quantify the effects of 2 hypothetical antibiotics targeting carbapenem-resistant Enterobacteriaceae (CRE) among long-term acute care hospital inpatients: one assumed to decrease the death rate of patients with CRE bloodstream infections (BSIs) and the other assumed to decolonize CRE carriers after clinical detection. We quantified the effect of each antibiotic on the number of BSIs and deaths among patients receiving the drug (direct effect) and among all patients (direct and indirect effect) compared to usual care. We applied these results to a cost-effectiveness analysis with effectiveness outcome of life-years gained and assumed costs for antibiotic doses and for CRE BSI.

Results: The decolonizing antibiotic, once indirect effects were included, produced increased relative effectiveness and decreased relative costs compared to both usual care and the BSI treatment antibiotic. In fact, in most scenarios, the decolonizing drug was the dominant treatment strategy (ie, less costly and more effective).

Conclusions: Antibiotics that decolonize carriers of drug-resistant organisms can be highly cost-effective when considering indirect benefits within populations vulnerable to outbreaks. Public health could benefit from finding ways to incentivize development of decolonizing antibiotics in the US, where drugs with unclear direct benefits to recipients would pose difficulties in achieving FDA approval and financial benefit to the developer.

Keywords: antimicrobial resistance; health economics; healthcare associated infections; mathematical models.

Figures

Figure 1.
Figure 1.
Patient states and state transition rates Squares depict possible states with respect to CRE in the compartmental model. Arrows between squares depict possible state transitions during the LTACH stay and are labeled with rate parameters; arrows into squares from outside point to possible states at admission and are labeled with probabilities of each admission state. Patients in any state can be removed via death or live discharge (not depicted)—see Supplementary material for full mathematical specification.
Figure 2.
Figure 2.
Model results—deaths prevented
Figure 3.
Figure 3.
Model results—bloodstream infections prevented
Figure 4.
Figure 4.
Cost-effectiveness analysis results Note: The assumed CRE importation level for each particular model run is indicated next to each dot
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