MERCED, CA— Amid international concern about
the public health threat of drug-resistant Staphylococcus aurea
bacteria, researchers at the University of California, Merced, have
filed for a patent on a powerful new screening tool that could
someday answer widespread calls for universal staph screenings
before patients are admitted to hospitals.
“Universal screening is not possible right now,” said Professor
Miriam Barlow of UC Merced’s School of Natural Sciences. “The
standard means for identifying drug-resistant staph is a two-step
process that requires several days. Obviously hospitals can’t make
patients wait that long to be admitted.”
“Our screening method is being developed with the aim of
accomplishing a screening in six hours or less.”
M2IDF at a Glance
Barlow and her colleagues, professors Matthew Meyer of the
School of Natural Sciences and Shawn Newsam of the School of
Engineering, are developing what they call the Microcalorimetry
Microorgamism Infectious Disease Analyzer (M2IDF), a machine that
measures how bacterial cells respond to heat as a way of
identifying the bacteria and determining whether they are resistant
to antibiotics.
“We’re melting the cells, the same way ice melts,” Barlow
explained. “When compounds are melting, they absorb heat at
different rates. Chemical differences in different strains of
bacteria make them absorb different amounts of heat at different
times. These differences are the basis for identifying bacteria.”
Experiments and testing continue at UC Merced with the aim of
bringing M2IDF to the market. The professors involved are seeking
industrial partners for its development. Their patent application
was filed Jan. 3.
The Grave Threat of Resistant Staph
Barlow and her colleagues believe that resistant staph (Multiply
Resistant Staphylococcus aureus, or MRSA) is a public health threat
comparable in scope to AIDS. Antibiotic resistant pathogenic
bacteria have been increasing in frequency and global spread for
years. Hospital-acquired infections have long been a major source
of resistant bacteria, but now those hospital-acquired infections
are moving from hospitals into the community and posing an
increasingly serious public health threat.
Barlow also said that MRSA is only the first of what will be
many antibiotic resistant organisms that will spread from hospitals
to the community.
Current Screening and Treatment Procedure
The standard means for identifying MRSA and other resistant
bacteria is a two step process that requires several days.
- Material from the site of infection must be cultured for 2-3
days in order to identify the organism that is responsible for the infection. - The isolated organism must be tested for susceptibility to a
panel of antibiotics that are commonly effective against that
organism, a process that requires another 1-2 days.
During the assessment period the patient is usually treated with
an antibiotic that the physician hopes will be effective. When the
infectious organism is resistant to that antibiotic the patient
suffers as the infection often becomes more severe. With luck, in
2-5 days an effective antibiotic can be identified and administered.
Radical New Screening Tool: M2IDF Analyzer
Professors at UC Merced are developing their new staph screening
tool, the M2IDF, with the aim of reducing the time required for
identification of the organism and determining antibiotic
resistance from the current 3-5 days to a matter of six hours or
less. This rapid identification will permit early intervention with
an effective antibiotic, providing a significant savings in risk to
the patient, duration of hospital stay and cost of treatment.
Every time an ineffective antibiotic is administered, especially
in a hospital setting, the population of resistant organisms
increases and the problem of worldwide antibiotic resistance
becomes a little more severe. By reducing the use of ineffective
antibiotics the M2IDF will reduce the spread of resistance and
prolong the use of antibiotics as an effective means of infectious
disease therapy.
Future Development and Availability of M2IDF
The M2IDF is currently at an early stage of development in the
laboratories of Barlow, Meyer and Newsam at UC Merced.
The M2IDF measures bacterial metabolism to determine what
concentrations of antibiotics are lethal to microbes. It identifies
bacteria by measuring variations during heat-stimulated
denaturation of cellular components — the melting process
Barlow described.
So far, the research team has used standard microcalorimeters
and limited their experiments to known organisms grown one at a
time in separate cultures. The effectiveness of the M2IDF approach
has been demonstrated under controlled laboratory conditions.
Continued development of the M2IDF will involve four stages.
- Continued experiments with a wide variety of infectious
bacteria to determine the accuracy with which the M2IDF can
distinguish infectious organisms and determine antibiotic
susceptibility from monocultures. That will be followed by similar
experiments on mixed cultures. During this period we will assess
the limitations of the approach. How complex a mixture of organisms
can the M2IDF handle? What is the limitation of sensitivity? How
many cells are required for an accurate analysis? - Assessing the capability of the system when dealing with
clinical samples from infection sites, including a variety of
bodily materials in addition to the infectious organisms
themselves. How do those materials affect the sensitivity and
reliability of the testing? Will a brief period of culture be
required before analysis, or can the method be applied directly to
some clinical samples? During this period the team plans to develop
a library of response profiles of an increasingly wide variety of
pathogens. They also anticipate moving from being able to
distinguish Pseudomonas from Staphyloccoccus toward being able to
distinguish Pseudomonas aeruginosa (another common and dangerous
hospital-spread bacterium) from Pseudomonas florescens (a generally
harmless relative used to produce antibiotics, protect plants from
fungi and even make yogurt). - Current microcalorimeters are capable of analyzing only one
sample at a time. The team will have to design a machine to perform
high-throughput analysis, handling dozens of samples a day. This
stage will require partnering with a medical engineering and
instrumentation company. During this period an integrated
collaboration with the medical engineering firm is very likely to
result in increased sensitivity and increased resolution. - Finally, a prototype high-throughput M2IDF instrument will have
to be refined and turned into a well-designed, user-friendly,
reliable instrument that can be provided at a reasonable cost to hospitals.
Barlow, Meyer and Newsam are actively seeking industrial
partners for the continued development of the M2IDF technology.
With the right partner or partners, they hope to bring the M2IDF to
the market in about six years.
About the Researchers
All three professors are members of the founding faculty at UC
Merced. Barlow is an expert in microbial evolution and antibiotic
resistance, and Meyer is optimizing the chemical aspects of the
M2IDF process. Newsam, who is developing algorithms to analyze the
output from the instrument, recently won the Presidential Early
Career Award for Scientists and Engineers based on his highly
interdisciplinary research in computer vision.
Biomedical Research at UC Merced
The growing program in biomedical research at UC Merced is a
vital component of an innovative medical education program planned
leading to a future medical school to begin educating doctors in
Merced in 2013. For more information, please see the
Medical Education and Health
SciencesWebsite.
