Rapid Antimicrobial Susceptibility Assay

BACKGROUND: The rising incidence of infectious bacterial strains that are resistant to multiple broad-spectrum antibiotics poses serious complications to the treatment of infectious diseases. Absent knowledge of a given infectious agent's susceptibility to various antibiotics, physicians face the dilemma of prescribing an antibiotic that may prove to be ineffective, or prescribing an antibiotic capable of treating the most resistant strains but, if used unnecessarily, may accelerate the breeding of even more resistant strains.

In these circumstances, selection of the optimal antibiotic requires rapid profiling of a bacteria's susceptibility to various antibiotics. However, current methods for assaying susceptibility of a purified bacterial culture, involving observations of the strain's visibile growth in antibiotic media, can take up to a full day. Thus, there is an urgent need for more rapid methods for assaying susceptibility that are suitable for use in clinical settings.

DESCRIPTION: Researchers at the University of California, Merced (UC Merced) have developed a calorimetric technique that reduces the time need for determination of a microbe's susceptibility from 16–24 hours to as little as 2.5 hours. In situations where purified strains can be obtained quickly (especially blood-borne diseases), the entire process from taking a sample to making a diagnosis can be reduced to 6 hours. At a minimum, the UC Merced invention is likely to reduce the time required for diagnosing bacterial antibiotic susceptibility (typically 3 to 4 days at present for most diseases) by a full day.

The basis for this invention was the discovery that antibiotics can have an almost immediate measurable effect on the thermal output of a growing culture in a suitable system. Using the protocols and thermal measurement techniques of this invention, the efficacy of an antibiotic relative to a control is readily apparent long before visible colonies could be observed. There is a dramatic and unambiguous difference in the thermal signatures of normal growth versus antibiotic inhibition of non-resistant strains, as shown for E. coli in figure 1 below. The UC Merced researchers have demonstrated the utility of this invention not only with E. coli, but also with K. pneumoniae, A. baumanii and P. mirabilis, and have also shown that thermal signatures can be used to characterize the effects of different antibiotic dosages.

APPLICATIONS: The UC Merced susceptibility assay may become the preferred system for clinical determinations of microbial susceptibility to antibiotics, and might also be found useful in research and public health laboratory settings when rapid assays are desired.

ADVANTAGES: As compared to existing disk diffusion tests and minimum inhibitory concentration tests, the UC Merced thermal test for antibiotic susceptibility offers:

* Much more rapid results, often in as little as 2.5–4 hours;
* Quantifiable data that is also useful for determining dosage effects; and * Simple protocols and devices that can be automated.

FIGURE 1—Thermograms of an E. coli strain that is sensitive to both ampicillin and ciprofloxacin. Starting at time = 7200 seconds, the rate of heat output of samples exposed to either of the antibiotics shows no increase, while in less than 2 hours a 100 µW rise is detected in the H2O control.

Reference: 2007-465

Type of Offer: Licensing

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