Another study in the United Kingdom that also used genomic analysis to understand drug-resistant Shigella produced findings that may be useful for microbiologists and medical laboratory scientists
From the onset of an infectious disease outbreak, public health officials, microbiologists, and clinical laboratory managers find it valuable to trace the origin of the spread back to the “index case” or “patient zero”—the first documented patient in the disease epidemic. Given the decreased cost of genomic analysis and improved accuracy of gene sequencing, infectious disease researchers are finding that task easier and faster than ever.
One recent example is a genomic study conducted at University of Washington (UW) in Seattle that enabled researchers to “retrace” the origin and spread of a “multidrug-resistant Shigellosis outbreak” from 2017 to 2022. “The aim of the study was to better understand the community transmission of Shigella and spread of antimicrobial resistance in our population, and to treat these multi-drug resistant infections more effectively,” the UW scientists stated in a new release.
Shigellosis (aka, bacillary dysentery) is a highly contagious disease of the intestines that can lead to hospitalization. Symptoms include fever, stomach cramps, diarrhea, dysentery, and dehydration.
“Additional analysis of the gut pathogen and its transmission patterns helped direct approaches to testing, treatment, and public health responses,” the UW news release states.
Usually prevalent in countries with public health and sanitation limitations, the “opportunistic” Shigella pathogen is now being seen in high-income countries as well, UW reported.
“You can’t really expect an infectious disease to remain confined to a specific at-risk population. [Shigella infections are] very much an emerging threat and something where our public health tools and therapeutic tools have significant limitations,” infectious disease specialist Ferric Fang, MD (above) told CIDRAP News. Fang is a UW professor of Microbiology and Clinical Laboratory Medicine and a corresponding author of the UW study. (Photo copyright: University of Washington.)
Generally, Shigella infects children, travelers, and men who have sex with men (MSM), the CDC noted.
The UW researchers were motivated to study Shigella when they noticed an uptick in drug-resistant shigellosis cases in Seattle’s homeless population in 2020 at the beginning of the COVID-19 pandemic, Center for Infectious Disease Research and Policy News (CIDRAP News) reported.
“Especially during the pandemic, a lot of public facilities were closed that homeless people were used to using,” infectious disease specialist Ferric Fang, MD, told CIDRAP News. Fang is Professor of Microbiology and Laboratory Medicine at University of Washington and corresponding author of the UW study.
The researchers studied 171 cases of Shigella identified from 2017 to 2022 by clinical laboratories at Harborview Medical Center and UW Medical Center in Seattle. According to CIDRAP News, the UW researchers found that:
46% were men who have sex with men (MSM).
51% were people experiencing homelessness (PEH).
Fifty-six patients were admitted to the hospital, with eight to an intensive care unit.
51% of isolates were multi-drug resistant (MDR).
Whole-Genome Sequencing Reveals Origin
The UW scientists characterized the stool samples of Shigella isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing, according to their Lancet Infectious Diseases paper. The paper also noted that 143 patients received antimicrobial therapy, and 70% of them benefited from the treatment for the Shigella infection.
Whole-genome sequencing revealed that two strains of Shigella (S. flexneri and S. sonnei) appeared first in Seattle’s MSM population before infecting the PEM population.
The genomic analysis found the outbreak of drug-resistant Shigella had international links as well, according to CIDRAP News:
One S. flexneri isolate was associated with a multi-drug resistant (MDR) strain from China, and
S. sonnei isolates resembled a strain characteristic of a current outbreak of MDR Shigella in England.
“The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups,” the researchers wrote.
“Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection,” they continued.
UK Shigella Study Also Uses Genomics
Another study based in the United Kingdom (UK) used genomic analysis to investigate a Shigella outbreak as well.
Motivated by a UK Health Security Agency report of an increase in drug-resistance to common strains since 2021, the UK researchers studied Shigella cases from September 2015 to June 2022.
According to a paper they published in Lancet Infectious Diseases, the UK researchers “reported an increase in cases of sexually transmitted S. flexneri harboring blaCTX-M-27 (an antibiotic-resistant gene) in England, which is known to confer resistance to third-generation cephalosporins (antibiotics),” the researchers wrote.
Their analysis of plasmids (DNA with genes having antibiotic resistance) revealed a link in two drug-resistant Shigella strains at the same time, CIDRAP News explained.
“Our study reveals a worsening outlook regarding antimicrobial-resistant Shigella strains among MSM and highlights the value of continued integration of genomic analysis into surveillance and research,” the UK-based scientists wrote.
Current challenges associated with Shigella, especially as it evades treatment, may continue to demand attention from microbiologists, clinical laboratory scientists, and infectious disease specialists. Fortunately, use of genomic analysis—due to its ongoing improvements that have lowered cost and improved accuracy—has made it possible for public health researchers to better track the origins of disease outbreak and spread.
How one PCR laboratory optimized workflows, reduced costs, and pivoted operations for improving profitability post-COVID
As variants of SARS-CoV-2 continue to confront physicians, PCR (polymerase chain reaction) instruments purchased for COVID-19 testing may still stand idle more often than not at reference and hospital laboratories. To make matters worse, clinical laboratory administrators must still deal with fluctuating demand for COVID testing, improving the profitability of COVID testing, and maximizing their investment in PCR instruments.
Despite the challenges, Birmingham, Alabama-based Streamline Scientific, formerly Assurance Scientific Laboratories, rallied last year to improve profitability of their now limited COVID testing and, at the same time, expanded lab operations instead of cutting back.
Laboratory Creativity Led to Value-Added Process Improvements for COVID-19 PCR Testing
In a recent interview with Dark Daily, Streamline Scientific’s Chief Scientific Officer Greer Massey, PhD, explained how the lab discovered ways to adjust operations to improve profitability after the drop in COVID-19 testing demand. They started with the testing process.
Optimizing workflows has been instrumental in the profitability of continued COVID PCR testing, according to Greer Massey, PhD (pictured), of Birmingham, Alabama-based Streamline Scientific, a reference lab that pivoted during the COVID-19 pandemic to make value-added process improvements and expand testing. (Photo copyright: Streamline Scientific.)
“Some COVID testing processes are labor intensive,” Massey said. “They require an initial step to extract and purify RNA from the collected specimen. Once the genetic material is separated from the specimen, it can then be amplified to look for the presence of the virus. The extraction process requires additional materials, time, and advanced training of medical technologists conducting the work.”
The Streamline team sought to simplify the COVID testing process and, ultimately, adopted an extractionless PCR method that improved efficiency in three ways:
Shorter turnaround times with faster delivery of test results;
A reduction in staff time needed for the extractionless COVID testing workflow; and
Optimized use of consumables, such as buffers, magnetic beads, plastics, and other supplies required for COVID and other testing.
The process improvements have reduced the cost per test by as much as 25%, reducing supply chain issues and improving overall profitability in the now struggling COVID test category.
In addition, Massey said, the benefits of the extractionless PCR process have inspired the lab to further optimize its reagent use. Working with its local supplier and their research and development unit, Molecular Designs, the reference lab now keeps an inventory of preplated PCR assays in sealed and barcode-labeled 384-well plates, as well as 96-well plates developed with a “breakaway” feature to accommodate variable testing volumes and support custom test panels. Plates are customizable from one to 94 targets, Massey said.
The unique breakaway feature of sealed, preplated PCR assays optimizes and customizes test runs not only for COVID-19 but for other infectious disease assays. (Photo copyright: Molecular Designs.)
“Being able to optimize workflows with items like extractionless and breakaway plates was instrumental in our profitability during COVID peaks and valleys, and it was also instrumental in managing expected TAT,” Massey added. “It also allowed us to release other panels such as COVID/Flu/RSV and larger respiratory panels when the importance of COVID-only diagnosis shifted to other important respiratory infections.”
Operationalizing a COVID-Pivot Experience: Consulting and Reagent Supply
Building on its success, Streamline Scientific now provides end-to-end consulting services for reference and hospital laboratories, as well as physician offices that manage in-house PCR testing.
“Streamline Scientific consults with reference, hospital, and physician office labs throughout the nation to share best practices and help identify the equipment, assays, or processes that improve workflow and profitability,” said Todd Speranzo, the company’s vice president of marketing.
“What we have learned from our customers is how important it is to understand reagent pricing and how that translates into operational profitability,” Speranza said. “We’re also looking for ways to deliver cost-effective infectious disease PCR assays that laboratories can use to expand their testing services while maintaining profitability. Molecular Designs’ preplated Simplicity Panels provide convenience, reducing the complexity, time, and costs associated.”
Molecular Designs is a team of doctors and scientists working to advance molecular diagnostics, Speranzo pointed out. “Their founding physicians entered the molecular diagnostics market focused on the most common pathogens that impact the population—making products that are cost-effective, reduce waste, and are easy-to-use.” The supplier has grown to offer numerous panels, including combination COVID 19-Flu-RSV and respiratory panels, UTI panels, wound/derm panels, sexually transmitted infection panels, gastrointestinal panels, fungal panels, and vaginitis panels; eight antimicrobial resistance classes are available as panel add-ons; and multiple other panels are in development.
Laboratory Outlook: Full Utilization of PCR Capacity and Ability to Respond to Changing Testing Needs
While the implementation of COVID-19 PCR testing has had a positive impact on patient care—and led to growth for reference laboratories and hospital labs—those who invested in PCR molecular testing equipment may face challenges with capacity and meeting changing needs.
Speranzo offers these tips for lab leaders sourcing PCR instruments.
Compare costs; prices have reduced from COVID peak.
Look beyond COGS for improved profitability; consider preplated options, extractionless, and breakaway plates, amongst other opportunities to improve efficiency and reduce waste.
Plan for the future; seek a partner with a robust research and development division that considers reimbursement and demand beyond COVID.
As lab leaders have experienced firsthand, nimble and adaptable operations were a critical success factor during the COVID pandemic. With the post-COVID pivot at hand, regional reference and hospital laboratory leaders will benefit from not only scrutinizing their PCR testing menus and costs but deciding what new assays will support opportunities in the year ahead.
—Liz Carey
This article was produced in collaboration with Streamline Scientific, a national reference lab and consulting organization. All products are for research use only. For more information, visit www.streamlinesci.com.
Clinical laboratory data was key in identifying antibiotic-resistant bacteria responsible for surge in BSIs in hospitals and other healthcare facilities in 2020 and 2021
Clinical laboratory data compiled by the European Antimicrobial Resistance Surveillance Network (EARS-Net) shows that a massive increase in bloodstream infections (BSIs) occurred among EU nations during the first two years of the COVID-19 pandemic. The study found that BSIs caused by certain antimicrobial-resistant (AMR) pathogens, known as superbugs, more than doubled in EU hospitals and healthcare facilities in 2020 and 2021.
Microbiologists and clinical laboratory managers in the US may find it valuable to examine this peer-reviewed study into AMR involved in blood stream infections. It could contain useful insights for diagnosing patients suspected of BSIs in US hospitals where sepsis prevention and antibiotic stewardship programs are major priorities.
“Antimicrobial resistance undermines modern medicine and puts millions of lives at risk,” said Tedros Adhanom Ghebreyesus, PhD, Director-General, World Health Organization, in a WHO press release. “To truly understand the extent of the global threat and mount an effective public health response to [antimicrobial resistance], we must scale up microbiology testing and provide quality-assured data across all countries, not just wealthier ones.” Clinical laboratories in the US may be called upon to submit data on bloodstream infections in this country. (Photo copyright: WHO.)
Clinical Laboratories in EU Report Huge Increase in Carbapenem Resistance
To perform their study, researchers measured the increase in Acinetobacter BSIs between 2020 and 2021, the first two years of the COVID-19 pandemic. Their data originated from qualitative regular antimicrobial susceptibility testing (AST) from blood samples collected by local clinical laboratories in the European Union/European economic area (EU/EEA) nations.
The researchers limited their dataset to Acinetobacter BSI information from the European medical laboratories that documented results of carbapenem susceptibility testing for the bacterial species.
Carbapenems are a class of very powerful antibiotics that are typically used to treat severe bacterial infections. A total of 255 EU/EEA clinical laboratories reported their data for the study. The scientists found that the percentages of Acinetobacter resistance varied considerably between EU/EEA nations, so they separated the countries into three different groups:
Nations in Group One—The Netherlands, Belgium, Austria, Estonia, Denmark, Germany, Iceland, Finland, Luxembourg, Ireland, Norway, Sweden, and Malta—experienced less than 10% resistance to carbapenems.
Nations in Group Two—Slovenia, Czech Republic, and Portugal—had carbapenem resistance between 10% and 50%.
Nations in Group Three—Croatia, Bulgaria, Greece, Cyprus, Italy, Hungary, Lithuania, Latvia, Romania, Poland, Spain, and Slovakia—demonstrated carbapenem resistance equal or greater than 50%.
The study also found that Acinetobacter BSIs rose by 57% and case counts increased by 114% in 2020 and 2021 when compared to 2018 and 2019. The percentage of resistance to carbapenems rose to 66% in 2020 and 2021, up from 48% in 2018 and 2019.
Antimicrobial Resistance Especially High in Hospital Settings
The researchers further arranged the data into three hospital ward types: intensive care unit (ICU), non-ICU, and unknown. The increase in BSIs caused by Acinetobacter species resistant to carbapenems was greater in ICU-admitted individuals (144%) than non-ICU-admitted individuals (41%).
There are more than 50 species of Acinetobacter bacteria and various strains are often resistant to many types of commonly-used antibiotics. Symptoms of an Acinetobacter infection usually appear within 12 days after a person comes into contact with the bacteria. These symptoms may include:
Blood infections,
Urinary tract infections,
Pneumonia, and
Wound infections.
Healthy people have a low risk of contracting an Acinetobacter infection with the highest number of these infections occurring in hospitals and other healthcare settings. Acinetobacter bacteria can survive for a long time on surfaces and equipment, and those working in healthcare or receiving treatment are in the highest risk category.
The prevalence of this type of bacteria increases in relation to the use of medical equipment, such as ventilators and catheters, as well as antibiotic treatments.
WHO Report Validates EARS-Net Research
In December of 2022, the World Health Organization (WHO) issued a Global Antimicrobial Resistance and Use Surveillance System (GLASS) report that revealed the presence of an increasing resistance to antibiotics in some bacterial infections. That report showed high levels (above 50%) of resistance in bacteria that frequently caused bloodstream infections in hospitals, such as Klebsiella pneumonia and Acinetobacter.
The WHO report examined data collected during 2020 from 87 different countries and found that common bacterial infections are becoming increasingly resistant to treatments. Both Klebsiella pneumoniae and Acinetobacter can be life threatening and often require treatment with strong antibiotics, such as carbapenems.
More research is needed to determine the reasons behind increases in Acinetobacter infections as reported in European hospitals and other healthcare settings, and to ascertain the extent to which they are related to hospitalizations and the upsurge in antimicrobial resistance during the COVID-19 pandemic.
Microbiologists and clinical laboratory managers in the US may want to learn more about the fIndings of this European study involving AMR and use those insights to plan accordingly for any future increase in bloodstream infections in this country.
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On top of everything else during this pandemic, drug-resistant infections are threatening the most vulnerable patients in COVID-19 ICUs
New study by researchers at the University of Minnesota highlights the continuing need for microbiologists and clinical laboratories to stay alert for COVID-19 patients with drug-resistant infections. In their study, researchers highlighted CDC statistics about the number of Candida auris (C. auris) infections reported in the United States during 2020, for example.
In a paper, titled, “Three Cases of Worrisome Pan-Resistant C Auris Found in New York,” the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota reported that “As of Dec 11, the CDC said 941 confirmed and probable C. auris cases have been reported in 13 states, and an additional 1,830 patients have been found to be colonized with the multidrug-resistant fungus. Most of the cases have been detected in the New York City area, New Jersey, and the Chicago area.”
Candida auris is a particularly nasty fungus. It spreads easily, is difficult to remove from surfaces, and can kill. Worst of all, modern drugs designed to combat this potentially deadly fungus are becoming less effective at eradicating it, and COVID-19 ICU patients appear especially vulnerable to C. auris infections.
COVID-19 and C. auris a Potentially Devastating Combination
Hospitals in many areas are at a critical capacity. Thus, hospital-acquired infections such as sepsis can be particularly dangerous for COVID-19 patients. Adding to the problem, C. auris requires special equipment to identify, and standard medical laboratory methods are not always enough. Misidentification is possible, even probable.
A paper in the Journal of Global Antimicrobial Resistance (JGAR), titled, “The Lurking Scourge of Multidrug Resistant Candida Auris in Times of COVID-19 Pandemic,” notes that “A particularly disturbing feature of COVID-19 patients is their tendency to develop acute respiratory distress syndrome that requires ICU admission, mechanical ventilation, and/or extracorporeal membrane oxygenation. … This haunting facet of COVID-19 pandemic has severely challenged even the most advanced hospital settings. Yet one potential confounder, not in the immediate attention of most healthcare professionals, is the secondary transmission of multidrug resistant organisms like the fungus Candida auris in COVID-19 ICUs. … C. auris outbreaks occur in critically ill hospitalized patients and can result in mortalities rates ranging from 30% to 72%. … Both C. auris and SARS-CoV-2 have been found on hospital surfaces including on bedrails, IV poles, beds, air conditioner ducts, windows and hospital floors. Therefore, the standard COVID-19 critical care of mechanical ventilation and protracted ventilator-assisted management makes these patients potentially susceptible to colonization and infections by C. auris.”
One study mentioned in the JGAR paper conducted in New Delhi, India, looked at 596 cases where patients were admitted to the ICU with COVID-19. Fifteen of them had infections caused by C. auris. Eight of those patients died. “Of note, four patients who died experienced persistent fungemia and despite five days of micafungin therapy, C. auris again grew in blood culture,” according to reporting on the study in Infection Control Today (ICT).
Some C. auris mortality rates are as high as 72%. And patients with weakened immune systems are at particular risk, “making it an even more serious concern when 8% to 9% of roughly 530,000 ICU patients in the United States have COVID-19,” ICT reported.
Apparently, the COVID-19 pandemic has created circumstances that are particularly suited for C. auris to spread. “Given the nosocomial transmission of SARS-CoV-2 by those infected, many hospital environments may serve as venues for C. auris transmission as it is a known environmental colonizer of ICUs,” wrote the JGAR paper authors.
CDC Reports and Recommendations
Along with being especially dangerous for people with weakened immune systems, C. auris infections also produce symptoms similar to those of COVID-19, “including fever, cough, and shortness of breath,” according to the CDC’s website. People admitted to ICUs with COVID-19 are especially vulnerable to bacterial and fungal co-infections. “These fungal co-infections are reported with increasing frequency and can be associated with severe illness and death,” says the CDC.
C. auris outbreaks in the United States have mostly been in long-term care facilities, but the pandemic seems to be changing that and more outbreaks have been detected in acute care facilities, the CDC reported. The lack of appropriate personal protective equipment (PPE), changes in infection control routines, and other factors could be to blame for the increase.
Just as community spread is an issue with COVID-19 variants, so too is it a concern with C. auris infections. “New C. auris cases without links to known cases or healthcare abroad have been identified recently in multiple states, suggesting an increase in undetected transmission,” the CDC noted.
As of January 19, 2021, according to the CDC the case count of C. auris infections in the US was 1,625, with California, Florida, Illinois, New Jersey, and New York having more than 100 cases each.
According to a CDC report, “Candida auris (C. auris) is an emerging multidrug-resistant yeast (a type of fungus). It can cause severe infections and spreads easily between hospitalized patients and nursing home residents.” The graphic above, taken from the report, illustrates how “C. auris began spreading in the United States in 2015. Reported cases increased 318% in 2018 when compared to the average number of cases reported in 2015 to 2017.” (Graphic copyright: Centers for Disease Control and Prevention.)
Using Clinical Laboratory Tests to Identify C. Auris
One of the big concerns about C. auris is that it is so difficult to detect, and that medical laboratories in some countries simply do not have the technology and resources to identify and tackle the infection.
“As C. auris diagnostics in resource-limited countries is yet another challenge, we feel that alerting the global medical community about the potential of C. auris as a confounding factor in COVID-19 is a necessity,” wrote the authors of the paper published in the Journal of Global Antimicrobial Resistance.
As if the COVID-19 pandemic has not been enough, drug resistant bacteria, viruses, and deadly fungi are threatening to wreak havoc among SARS-CoV-2 infected patients. Microbiologists and medical laboratory scientists know that testing for all types of infections is vitally important, but especially when it comes to infections caused by antibiotic-resistant bacteria (ARB) and other dangerous organisms that demonstrate antimicrobial resistance (AMR).
Microbiologists and clinical laboratory professionals will want to stay informed about the number of C. auris cases identified in the US and the locations and settings where the fungus was detected. They will want to be on the alert within their hospitals and health networks, as well as with the doctor’s offices served by their labs.
