Rapidly identifying antibiotic-resistant “superbugs”

Chopping up antibiotics
Many common early-generation antibiotics, including penicillin, amoxicillin and ampicillin, are based around a molecular structure called beta-lactam, which blocks bacteria from building cell walls, making it impossible for microbes to grow and reproduce.

However, as use of these antibiotics has soared over the past 80 years, certain infectious bacteria, including strains of E. coli, Salmonella and Shigella, have evolved to produce enzymes called beta-lactamases that chop up these antibiotics and render them useless.

DETECT works by identifying the presence of beta-lactamases in urine samples. “What our technology does is detect the molecules that are actually breaking down the antibiotics,” deBoer said.

While the basic technique for detecting beta-lactamases has already been developed, it is not sensitive enough to spot the relatively small concentrations of beta-lactamases in patient samples. For this technique to work, bacteria from a patient sample must first be cultured in a lab, which can take two to three days — long enough for a simple bacterial infection like a urinary tract infection to invade the kidneys or the blood.

The DETECT technique uses an enzymatic chain reaction to boost the signal from beta-lactamases by a factor of 40,000, high enough to allow detection of the presence of these enzymes in urine samples. With DETECT, a patient who tests positive for an infection that is resistant to early-generation antibiotics can immediately be treated with a more powerful antibiotic or alternative agent.

The team tested DETECT on 40 urine samples collected from patients suspected of having a urinary tract infection, and found that approximately one-quarter of them had antibiotic-resistant infections.

“DETECT tells you not only who has antibiotic-resistant infections but also tells you who could be treated by early-generation antibiotics, allowing you to spare higher-end antibiotics and slow the spread of drug resistance,” Murthy said.

From the lab to the doctor’s office
DeBoer is now collaborating with doctors and clinical lab specialists in hospitals to design easy-to-use DETECT-based devices catering to specific medical settings.

“Everybody has different needs in the hospital,” deBoer said. “Right now we have a lot of designs, but what we are doing is allowing the intended use to define what the design is going to look like.”

For example, diagnostic tools that work well in an out-patient clinic may not be as convenient for doctors working in an emergency department, deBoer said.

With the help of UC Berkeley’s start-up incubator CITRIS Foundry, deBoer has co-founded a company, BioAmp Diagnostics, which is working to commercialize the technology into a rapid diagnostic device.

The team is continuing to perfect its enzyme signal-amplification technique in hopes of soon being able to apply it to detect specific strains of bacteria as well as bacteria in the blood.

“I think we are on the verge of having this applicable in a hospital setting,” Riley said.