Innovative in-office test, when integrated with UTI microbiology testing performed by clinical laboratories, could contribute to better patient outcomes
Treatments for certain bacterial infections are becoming less effective due to antimicrobial resistance (AMR). Now, after a 10-year-long worldwide competition, the first multi-million euro prize for an accurate, rapid, and cost effective clinical laboratory test for diagnosing and treating urinary tract infections (UTIs) went to Sysmex Corporation’s subsidiary Astrego. This milestone event could benefit tens of millions of people who suffer from UTIs annually.
Astrego, of Uppsala, Sweden, won the €8 million (US$8.19 million) Longitude Prize on AMR for its PA-100 AST System. The new diagnostic technology will “transform treatment of urinary tract infections and brings the power of clinical laboratory testing into a doctor’s office,” according to a news release from Challenges Works, the United Kingdom-based organization that organized and awarded the prize.
The Astrego system is, according to Challenge Works’ website, a “game-changing solution” in “a novel point-of-care diagnostic test that rapidly and accurately identifies the presence of a bacterial infection and the right antibiotic to prescribe.”
“We launched the Longitude Prize on AMR (in 2014) to create the urgent ‘pull’ needed to get innovators working on one of the biggest life-and-death challenges facing humanity. Hundreds of teams [that] competed with multiple solutions [are] now close to market thanks to the prize,” said Tris Dyson, Managing Director, Challenge Works, in a news release.
The new diagnostic technology “could herald a ‘sea change’ in antibiotic use” according to the judges of the competition, The Guardian reported.
“The PA-100 AST System (above) creates a future where patients can quickly and accurately get a diagnosis and the correct treatment when they visit the doctor,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Accurate, rapid diagnosis of bacterial infections that help doctors and health workers to manage and target antibiotics, will slow the development and spread of antibiotic resistant infections, improve healthcare and save potentially millions of lives,” she added. In-office point-of-care systems like the PA-100 may reduce the number of doctor orders for UTI tests to clinical laboratories while contributing to better patient outcomes. (Photo copyright: Sysmex.)
How the Test Works
In the UK, people are treated for UTIs more than any other infection. It takes about three days for doctors to receive the results from traditional microbiology testing. They then prescribe an antibiotic to treat the infection. But about half of “infection-causing bacteria are resistant to at least one antibiotic,” according to a news release from the Geneva, Switzerland-based NESTA Foundation which funded the Longitude Prize on AMR.
“It’s impossible to overstate how critical it is to address AMR [antimicrobial resistance]. By 2050, it is predicted to cause 10 million deaths a year—matching those caused by cancer—and cost $1 trillion in additional health costs,” the news release states.
UTI are more common in women and the reason for eight million healthcare appointments annually in the US, according to Medscape.
The PA-100 AST system makes it possible for patients to provide a small urine sample during their appointments with doctors, find out if they have a bacterial infection in 15 minutes, and receive the “right antibiotic to treat it within 45 minutes,” NESTA said. Sysmex describes the PA-100 AST as an “automated phenotypic analyzer, based on EUCAST standards,” that combines “phase-contrast microscopy and nanofluidics to make available antibiograms at point of care.” It enables healthcare providers to perform antimicrobial susceptibility testing (AST) in-office rather than sending out urine samples to microbiology laboratories.
The systems works as follows, according to the Sysmex website:
As a urine sample passes through the chip, “single bacterial cells are trapped in individual channels.”
Meanwhile, “larger cellular components” are filtered and kept out of the nanofluidic chip.
Contrast-phase microscopy enables real-time monitoring of cell growth. “Resistant bacteria keep a higher growth rate during incubation, while susceptible ones grow slowly or lyse.”
Expert computer software identifies that bacterial strain, delivers an “easy to interpret antibiogram after assay completion” and provides an “informed prescription decision” on which antibiotic is expected to fight the infection.
“The PA-100 AST System challenges bacteria present in a patient’s urine with microscopic quantities of antibiotics in tiny channels embedded in a cartridge the size of a smartphone,” said Mikael Olsson, CEO and co-founder of Sysmex Astrego, in The Microbiologist.
“We rapidly pinpoint whether a bacterial infection is present and identify which antibiotic will actually kill the bugs, guiding doctors only to prescribe antibiotics that will be effective,” he added.
Sysmex is conducting more studies in the UK and working with regulators in Europe for clearances, according to Olsson.
Older Antibiotics May Make Comeback
It’s possible that use of the PA-100 system to identify the best antibiotic to treat infections could lead to a resurgence in the use of previously retired antibiotics.
“Roughly 25-30% of patients have infections resistant to older first-line antibiotics which have been retired as a result; this means the remaining 70-75% of patients could still benefit from those older drugs,” Pathology in Practice reported, adding, “Since the PA-100 AST System identifies which specific antibiotic can treat an infection, it will likely allow retired antibiotics to be brought back into service because the test is able to demonstrate when an infection is susceptible to their effects.”
Many people could benefit from the older antibiotics, Challenge Works noted.
Revolutionizing Healthcare
The Sysmex Astrego’s PA-100 AST System is a significant development.
“Currently, I send the urine sample off for analysis, and it usually takes around three days to come back with results,” said Sherry Taylor, MD, UK National Health Service, Temple Fortune Medical Group, London, in the Challenge Works news release. “Having a bedside test that would enable rapid diagnosis through antibiotic susceptibility testing would revolutionize general practice and patient care. It’s all about using antibiotics only when necessary and appropriate.”
Each individual test costs about €25 (US$25.72), The Guardian reported, adding that ramped up production may lower the price.
The PA-100 AST System is the latest example of a diagnostic/therapeutic solution developed in Europe rather than the US, which is often slower to award regulatory clearance.
It also is another test that will be performed outside of traditional clinical laboratory settings, demonstrating the trend to move medical laboratory tests closer to patients.
Genomic analysis of pipes and sewers leading from the National Institutes of Health Clinical Care Center in Bethesda, Md., reveals the presence of carbapenem-resistant organisms; raises concern about the presence of multi-drug-resistant bacteria previously undetected in hospital settings
If hospitals and medical laboratories are battlegrounds, then microbiologists and clinical laboratory professionals are frontline soldiers in the ongoing fight against hospital-acquired infections (HAIs) and antibiotic resistance. These warriors, armed with advanced testing and diagnostic skills, bring expertise to antimicrobial stewardship programs that help block the spread of infectious disease. In this war, however, microbiologists and medical laboratory scientists (AKA, medical technologists) also often discover and identify new and potential strains of antibiotic resistance.
Potential Source of Superbugs and Hospital-Acquired Infections
According to the mBio study, “Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections.”
Karen Frank, MD, PhD (above), is Chief of the Microbiology Service Department at the National Institutes of Health and past-president of the Academy of Clinical Laboratory Physicians and Scientists. She suggests hospitals begin tracking the spread of the bacteria. “In the big picture, the concern is the spread of these resistant organisms worldwide, and some regions of the world are not tracking the spread of the hospital isolates.” (Photo copyright: National Institutes of Health.)
Frank’s team used Illumina’s MiSeq next-generation sequencer and single-molecule real-time (SMRT) sequencing paired with genome libraries, genomics viewers, and software to analyze the genomic DNA of more than 700 samples from the plumbing and sewers. They discovered a “potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes, and increase the risk of antibiotic resistant ‘superbugs’ and difficult to treat hospital-acquired infections (HAIs).”
Genomic Sequencing Identifies Silent Threat Lurking in Sewers
Frank’s study was motivated by a 2011 outbreak of antibiotic-resistant Klebsiella pneumoniae bacteria that spread through the NIHCC via plumbing in ICU, ultimately resulting in the deaths of 11 patients. Although the hospital, like many others, had dedicated teams working to reduce environmental spread of infectious materials, overlooked sinks and pipes were eventually determined to be a disease vector.
In an NBC News report on Frank’s study, Amy Mathers, MD, Director of The Sink Lab at the University of Virginia, noted that sinks are often a locus of infection. In a study published in Applied and Environmental Microbiology, another journal of the ASM, Mathers noted that bacteria in drains form a difficult to clean biofilm that spreads to neighboring sinks through pipes. Mathers told NBC News that despite cleaning, “bacteria stayed adherent to the wall of the pipe” and even “splashed out” into the rooms with sink use.
During the 2011-2012 outbreak, David Henderson, MD, Deputy Director for Clinical Care at the NIHCC, told the LA Times of the increased need for surveillance, and predicted that clinical laboratory methods like genome sequencing “will become a critical tool for epidemiology in the future.”
Frank’s research fulfilled Henderson’s prediction and proved the importance of genomic sequencing and analysis in tracking new potential sources of infection. Frank’s team used the latest tools in genomic sequencing to identify and profile microbes found in locations ranging from internal plumbing and floor drains to sink traps and even external manhole covers outside the hospital proper. It is through that analysis that they identified the vast collection of CPOs thriving in hospital wastewater.
In an article, GenomeWeb quoted Frank’s study, noting that “Over two dozen carbapenemase gene-containing plasmids were identified in the samples considered” and CPOs turned up in nearly all 700 surveillance samples, including “all seven of the wastewater samples taken from the hospital’s intensive care unit pipes.” Although the hospital environment, including “high-touch surfaces,” remained free of similar CPOs, Frank’s team noted potential associations between patient and environmental isolates. GenomeWeb noted Frank’s findings that CPO levels were in “contrast to the low positivity rate in both the patient population and the patient-accessible environment” at NIHCC, but still held the potential for transmission to vulnerable patients.
Since carbapenems are a “last resort” antibiotic for bacteria resistant to other antibiotics, the NIHCC “reservoir” of CPOs is a frightening discovery for physicians, clinical laboratory professionals, and the patients they serve.
The high CPO environment in NIHCC wastewater has the capability to spread resistance to bacteria even without the formal introduction of antibiotics. In an interview with Healthcare Finance News, Frank indicated that lateral gene transfer via plasmids was not only possible, but likely.
“The bacteria fight with each other and plasmids can carry genes that help them survive. As part of a complex bacterial community, they can transfer the plasmids carrying resistance genes to each other,” she noted. “That lateral gene transfer means bacteria can gain resistance, even without exposure to the antibiotics.”
The discovery of this new potential “reservoir” of CPOs may mean new focused genomic work for microbiologists and clinical laboratories. The knowledge gained by the discovery of CPOs in hospital waste water and sinks offers a new target for study and research that, as Frank concludes, will “benefit healthcare facilities worldwide” and “broaden our understanding of antimicrobial resistance genes in multi-drug resistant (MDR) bacteria in the environment and hospital settings.”
In studies, the automated microbial susceptibility testing device for smartphone performed with 98.2% accuracy, meeting FDA criteria
Imagine doing antimicrobial susceptibility testing outside a clinical laboratory. That’s the goal of researchers on the West Coast who are developing a smartphone-based diagnostic device with the capability of performing this type of point-of-care testing (POCT).
This new mobile POCT device is under development at the University of California-Los Angeles (UCLA). It promises to bring antimicrobial susceptibility testing—a routine procedure in the most medical laboratories—to remote, resource-limited areas of the world.
All hospital laboratories will be part of these programs, and it is an opportunity for medical laboratory professionals to deliver considerable value, as hospitals take steps to improve the utilization of antibiotics
Overuse and inappropriate use of antibiotics is now considered one of the biggest problems in medicine. “Antibiotics are lifesaving drugs, and if we continue down the road of inappropriate use we’ll lose the most powerful tool we have to fight life-threatening infections,” stated Tom Frieden, MD, MPH, Director, Centers for Disease Control and Prevention (CDC) and Administrator, Agency for Toxic Substances and Disease Registry (ATSDR), in a press release issued by the CDC last May. “Losing these antibiotics would undermine our ability to treat patients [who have] deadly infections, cancer, provide organ transplants, and save victims of burns and trauma.”
Much publicity is devoted to the rise of the increase of antibiotic-resistant organisms. In recognition of this problem, the Centers for Medicare and Medicaid Services (CMS), and The Joint Commission (TJC), took steps to add antimicrobial stewardship program requirements to their respective hospital accreditation programs. (more…)
Early results are promising and this technology could lead to a clinical laboratory test that would give microbiologists and pathologists a new tool for helping diagnose infections
These findings are timely because, starting on January 1, 2017, hospitals and health systems will need to implement more rigorous antimicrobial stewardship programs to comply with new requirements of the Centers for Medicare & Medicaid Services (CMS) and The Joint Commission (TJC). A clinical laboratory test that makes it easier to determine whether the cause of an infection is bacterial or viral would be a welcome tool for physicians, pharmacists, pathologists, and microbiologists involved in a hospital’s infection control program. (more…)
