Multiple heteroresistance to guide combination antibiotic regimens

Inventors

Weiss, David • Band, Victor • Hufnagel, David

Assignees

Emory University

Abstract

This disclosure contemplates detecting antimicrobial heteroresistance to guide antibiotic or other antimicrobial therapy. In certain embodiments, this disclosure contemplates avoiding a monotherapy with antibiotics to which an individual bacterial pie isolate is heteroresistant, because this can lead to treatment failure. Thus, in certain embodiments, one uses a combination of antibiotics to which a bacterium is individually heteroresistant.

Core Innovation

The disclosure describes a method of determining whether a bacterial culture is heteroresistant to antibiotics and treating a bacterial infection using a combination of heteroresistant antibiotics. It begins by obtaining a sample from a subject diagnosed with a bacterial infection and growing bacteria from the sample to provide a purified single bacterial colony. The single colony is contacted with a plurality of individual antibiotics from an antibiotic library to generate individual contacted bacterial cultures for each antibiotic.

For each antibiotic in the library, the method determines whether the individual contacted bacterial culture is resistant, heteroresistant, or susceptible. The treatment is then carried out by administering to the subject in need of treatment an effective amount of a combination of heteroresistant antibiotics. Each antibiotic in the administered combination is selected based on the determination that the antibiotic is heteroresistant to the culture in the individual contacted bacterial cultures.

The disclosure addresses bacterial antimicrobial heteroresistance in infection treatment, including situations in which an isolate can be heteroresistant in the presence of resistant and susceptible subpopulations. It also describes diagnostic workflow elements using a purified single-colony culture and an antibiotic library to guide selection of the heteroresistant antibiotic combination for treatment.

Claims Coverage

The independent claim provides a diagnostic-to-treatment regimen with three inventive features: isolating a purified single bacterial colony from a subject sample, testing a plurality of individual antibiotics from an antibiotic library, and administering a combination composed only of antibiotics determined to be heteroresistant for the culture. Dependent claims further refine selection rules, specify representative antibiotic library contents, and narrow the diagnosed bacterial types and clinical infection syndromes.

Overall, the claim set centers on determining heteroresistance for each antibiotic using a purified single-colony culture exposed to an antibiotic library, classifying each contacted culture as resistant, heteroresistant, or susceptible, and selecting the administered treatment regimen as a combination consisting only of antibiotics identified as heteroresistant for that culture.

Stated Advantages

Documented Applications