A method to detect heteroresistance to antibiotics in bacteria.
- Significantly faster than commercially available options.
- Aside from the interferometer itself, no specialized reagents are required.
- Inexpensive to use.
Antibiotic resistance is a significant threat to public health. One estimate predicts there will be 10 million deaths per year worldwide by 2050 unless significant action is taken. Rapid and sensitive diagnostics would significantly help in the fight against drug-resistant bacteria. Heteroresistance is a specific form of antibiotic resistance in which a subpopulation of resistant cells is present in a nonresistant bacterial culture. Upon incubation with a specific antibiotic, the resistant cells can survive and replicate, while the majority of susceptible cells are killed. If the frequency of the resistant subpopulation is very low (less than 1 in 10,000), heteroresistance is undetected by current diagnostics. This can lead to clinicians inappropriately treating patients with antibiotics that are likely to fail, without realizing this and leading to unexplained treatment failures. Conversely, antibiotic combination therapy, using two drugs to which a strain exhibits heteroresistance, can then be used to kill cultures of bacteria that have been classified as resistant to all available drugs. Most diagnostics currently on the market require long incubation times, often leading to inappropriate therapy and poor patient outcomes as clinicians are forced to treat patients while they wait for antibiotic susceptibility results. In addition, these diagnostics are marketed for the detection of antibiotic susceptibility, rather than heteroresistance in particular, making the market for antibiotic heteroresistance relatively unencumbered.
Emory researchers have found that interferometry can detect otherwise imperceptible heteroresistance. Interferometry could be used to rapidly determine which antibiotics a given strain is resistant, heteroresistant, or susceptible to, thereby guiding antibiotic therapy including effective combination therapy. White light interferometry can be used to observe the growth (or lack thereof) of a culture of bacteria with or without antibiotics. Interferometry has a nanometer resolution and can detect very small changes in bacterial density and patterns of bacterial distribution. This technique can therefore distinguish bacteria that are resistant or susceptible to a given antibiotic in a short timeframe (data available at 3 hours, but perhaps even faster). Interferometry measures biofilm surface topography rather than the index of refraction, which is also commonly described in the literature as interferometry.
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