Shortage could disrupt the ability of clinical laboratories in hospitals and health systems to run certain tests for bloodstream infections
US clinical laboratories may soon experience a “disruption of availability” of BACTEC blood culture media bottles distributed by Becton Dickinson (BD). That’s according to the federal Centers for Disease Control and Prevention (CDC) which issued a Health Alert Network (HAN) Health Advisory to all clinical laboratory professionals, healthcare providers and facility administrators, and other stakeholders warning of the potential shortfall of critical testing supplies.
“This shortage has the potential to disrupt patient care by leading to delays in diagnosis, misdiagnosis, or other challenges in the clinical management of patients with certain infectious diseases,” the CDC stated in the health advisory.
The CDC advises healthcare providers and health departments that use the bottles to “immediately begin to assess their situations and develop plans and options to mitigate the potential impact of the shortage on patient care.”
The advisory notes that the bottles are a key component in continuous-monitoring blood culture systems used to diagnose bloodstream infections and related conditions, such as endocarditis, sepsis, and catheter-related infections. About half of all US laboratories use the BD blood culture system, which is compatible only with the BACTEC bottles, the CDC advisory states.
Infectious disease specialist Krutika Kuppalli, MD (above), Chair of the Infectious Diseases Society of America (IDSA) and a Medical Officer for COVID-19 Health Operations at the World Health Organization, outlined the potential impact of the shortage on healthcare providers and clinical laboratories. “Without the ability to identify pathogens or [their susceptibility to specific antibiotics], patients may remain on broad antibiotics, increasing the risk of antibiotic resistance and Clostridium difficile-associated diarrhea,” she told STAT. “Shortages may also discourage ordering blood cultures, leading to missed infections that need treatment.” (Photo copyright: Loyola University Health System.)
FDA Advises Conservation of Existing BACTEC Supplies
The CDC advisory followed a July 10 notice from the US Food and Drug Administration (FDA) that also warned healthcare providers of “interruptions in the supply” of the bottles. The supply disruption “is expected to impact patient diagnosis, follow up patient management, and antimicrobial stewardship efforts,” the FDA’s letter states. “The FDA recommends laboratories and healthcare providers consider conservation strategies to prioritize the use of blood culture media bottles, preserving the supply for patients at highest risk.”
Hospitals have been warned that the bottle shortage could last until September, STAT reported.
BD issued a press release in which BD Worldwide Diagnostic Solutions President Nikos Pavlidis cast blame for the shortage on an unnamed supplier.
“We understand the critical role that blood culture testing plays in diagnosing and treating infections and are taking all available measures to address this important issue, including providing the supplier our manufacturing expertise, using air shipments, modifying BD manufacturing schedules for rapid production, and collaborating with the US Food and Drug Administration to review all potential options to mitigate delays in supply,” Pavlidis said. “As an additional stopgap measure, our former supplier of glass vials will restart production to help fill the intermittent gap in supply.”
Steps Clinical Laboratories Can Take
The CDC and FDA both suggested steps that clinical laboratories and other providers can take to conserve their supplies of the bottles.
Laboratories should strive to prevent contamination of blood cultures, which “can negatively affect patient care and may require the collection of more blood cultures to help determine whether contamination has occurred,” the CDC advised.
In addition, providers should “ensure that the appropriate volume is collected when collecting blood for culture,” the advisory states. “Underfilling bottles decreases the sensitivity to detect bacteremia/fungemia and may require additional blood cultures to be drawn to diagnose an infection.”
Laboratories should also explore alternative options, such as “sending samples out to a laboratory not affected by the shortage.”
The FDA advised providers to collect blood cultures “when medically necessary” in compliance with clinical guidelines, giving priority to patients exhibiting signs of a bloodstream infection.
In an email to STAT, Andrew T. Pavia, MD, Professor of Internal Medicine and Pediatrics at the University of Utah, offered examples of situations where blood culture tests are unnecessary according to clinical guidelines.
“There are conditions like uncomplicated community acquired pneumonia or skin infections where blood cultures are often obtained but add very little,” he told STAT. “It will be critical though that blood cultures are obtained from patients with sepsis, those likely to have bloodstream infections, and very vulnerable patients.”
Hospitals Already Addressing Shortage
STAT reported that some hospitals have already taken measures to reduce the number of tests they run. And some are looking into whether they can safely use bottles past their expiration dates.
Sarah Turbett, MD, Associate Director of Clinical Microbiology Laboratories at Massachusetts General Hospital in Boston, told STAT that her team tested bottles “that were about 100 days past their expiration date to see if they were still able to detect pathogens with the same efficacy as bottles that had not yet expired. They saw no difference in the time to bacterial growth—needed to detect the cause of an infection—in the expired bottles when compared to bottles that had not expired.”
Turbett pointed to a letter in the Journal of Clinical Microbiology and Infection in which European researchers found that bottles from a different brand “were stable for between four and seven months after their expiration dates,” STAT reported.
During a Zoom call hosted by the CDC and the IDSA, hospital representatives asked if the FDA would permit use of expired bottles. However, “a representative of the agency was not able to provide an immediate answer,” STAT reported.
With sepsis being the leading cause of death in hospitals, these specimen bottles for blood culture testing are essential in diagnosing patients with relevant symptoms. This is a new example of how the supply chain for clinical laboratory instruments, tests, and consumables—which was a problem during the SARS-CoV-2 pandemic—continues to be problematic in unexpected ways.
Taking a wider view of supply chain issues that can be disruptive to normal operations of clinical laboratories and anatomic pathology groups, the market concentration of in vitro diagnostics (IVD) manufacturers means fewer vendors offering the same types of products. Consequently, if a lab’s prime vendor has a supply chain issue, there are few options available to swiftly purchase comparable products.
A separate but related issue in the supply chain involves “just in time” (JIT) inventory management—made famous by Taiichi Ohno of Toyota back in the 1980s. This management approach was designed to deliver components and products to the user hourly, daily, and weekly, as appropriate. The goal was to eliminate the cost of carrying large amounts of inventory. This concept evolved into what today is called the “Lean Manufacturing” method.
However, as was demonstrated during the SARS-CoV-2 pandemic, manufacturers and medical laboratories that had adopted JIT found themselves with inadequate numbers of components and finished products.
In the case of the current shortage of BD blood culture media bottles, this is a real-world example of how market concentration limited the number of vendors offering comparable products. At the same time, if this particular manufacturer was operating with the JIT inventory management approach, it found itself with minimal inventories of these media bottles to ship to lab clients while it addressed the manufacturing problems that caused this shortage.
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.
As infectious bacteria become even more resistant to antibiotics, chronic disease patients with weakened immune systems are in particular danger
Microbiologists
and clinical
laboratory managers in the United States may find it useful to learn that
exceptionally virulent strains of bacteria are causing increasing numbers of cancer
patient deaths in India. Given the speed with which infectious diseases spread
throughout the world, it’s not surprising that deaths due to similar hospital-acquired
infections (HAIs) are increasing in the US as well.
Recent news reporting indicates that an ever-growing number
of cancer patients in the world’s second most populous nation are struggling to
survive these infections while undergoing chemotherapy and other treatments for
their cancers.
In some ways, this situation is the result of more powerful antibiotics. Today’s modern antibiotics help physicians, pathologists, and clinical laboratories protect patients from infectious disease. However, it’s a tragic fact that those same powerful drugs are making patients with chronic diseases, such as cancer, more susceptible to death from HAIs caused by bacteria that are becoming increasingly resistant to those same antibiotics.
India is a prime example of that devastating dichotomy. Bloomberg
reported that a study conducted by Abdul
Ghafur, MD, an infectious disease physician with Apollo Hospitals in Chennai, India,
et al, concluded that “Almost two-thirds of cancer patients with a
carbapenem-resistant infection are dead within four weeks, vs. a 28-day
mortality rate of 38% in patients whose infections are curable.”
This news should serve as an alert to pathologists, microbiologists,
and clinical laboratory leaders in the US as these same superbugs—which resist
not only antibiotics but other drugs as well—may become more prevalent in this
country.
‘We Don’t Know
What to Do’
The dire challenge facing India’s cancer patients is due to escalating
bloodstream infections associated with carbapenem-resistant
enterobacteriaceae (CRE), a particularly deadly bacteria that has become
resistant to even the most potent carbapenem antibiotics, generally
considered drugs of last resort for dealing with life-threatening infections.
Lately, the problem has only escalated. “We are facing a
difficult scenario—to give chemotherapy and cure the cancer and get a
drug-resistant infection and the patient dying of infections.” Ghafur told Bloomberg.
“We don’t know what to do. The world doesn’t know what to do in this scenario.”
Ghafur added, “However wonderful the developments in the
field of oncology, they are not going to be useful, because we know cancer
patients die of infections.”
Abdul Ghafur, MD (above), an infectious disease physician with Apollo Hospitals in Chennai, India, told The Better India that, “Indians, are obsessed with antibiotics and believe that they can cure almost all infections, including viral infections! Moreover, at least half of the prescriptions by Indian doctors include an antibiotic. Sadly, the public believes that whenever we get cold and cough, we need to swallow antibiotics for three days along with paracetamol [acetaminophen]! This is a myth that urgently needs to disappear!” (Photo copyright: Longitude Prize.)
The problem in India, Bloomberg reports, is
exacerbated by contaminated food and water. “Germs acquired through ingesting
contaminated food and water become part of the normal gut microbiome, but they can
turn deadly if they escape the bowel and infect the urinary tract, blood, and
other tissues.” And chemotherapy patients, who likely have weakened digestive
tracts, suffer most when the deadly germs reach the urinary tract, blood, and surrounding
tissues.
“Ten years ago, carbapenem-resistant superbug infections
were rare. Now, infections such as carbapenem-resistant klebsiella bloodstream
infection, urinary infection, pneumonia, and surgical site infections are a
day-to-day problem in our (Indian) hospitals. Even healthy adults in the
community may carry these bacteria in their gut in Indian metropolitan cities;
up to 5% of people carry these superbugs in their intestines,” Ghafur told The
Better India.
“These patients receive chemotherapy during treatment, which
lead to severe mucositis
of gastrointestinal tract and myelosuppression.
It was hypothesized that the gut colonizer translocate into blood circulation
causing [bloodstream infection],” the AIIMS paper states.
US Cases of C. auris Also Linked to CRE
Deaths in the US involving the fungus Candida auris (C. auris)
have been linked to CRE as well. And, people who were hospitalized outside the
US may be at particular risk.
The CDC reported on
a Maryland resident who was hospitalized in Kenya with a
carbapenemase-producing infection, which was later diagnosed as C. auris. The CDC
describes C. auris as “an emerging drug-resistant yeast of high public concern
… C auris frequently co-occurs with carbapenemase-producing organisms like
CRE.”
The graphic above, developed by the NYT from CDC data, shows that Candida auris is found globally and not restricted to poor or resource-strapped nations. “The fungus seems to have emerged in several locations at once, not from a single source,” the NYT reports. This means clinical laboratories can expect to be processing more tests to identify the deadly fungus. (Graphic copyright: New York Times/CDC.)
Drug-resistant germs are a public health threat that has
grown beyond overuse of antibiotics to an “explosion of resistant fungi,”
reported the New
York Times (NYT).
“It’s an enormous problem. We depend on being able to treat
those patients with antifungals,” Matthew Fisher, PhD,
Professor of Fungal Disease Epidemiology at Imperial College London, told the NYT.
The NYT article states that “Nearly half of patients
who contract C. auris die within 90 days, according to the CDC. Yet the world’s
experts have not nailed down where it came from in the first place.”
Cases of C. auris in the US are showing up in New York, New
Jersey, and Illinois and is arriving on travelers from many countries,
including India, Pakistan, South Africa, Spain, United Kingdom, and
Venezuela.
“It is a creature from the black lagoon,” Tom Chiller, MD,
Chief of the Mycotic
Diseases Branch at the CDC told the NYT. “It bubbled up and now it
is everywhere.”
Since antibiotics are used heavily in agriculture and
farming worldwide, the numbers of antibiotic-resistant infections will likely
increase. Things may get worse, before they get better.
Pathologists, microbiologists, oncologists, and clinical
laboratories involved in caring for patients with antibiotic-resistant
infections will want to fully understand the dangers involved, not just to
patients, but to healthcare workers as well.
Nanosphere’s Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) gives pathologists and clinical laboratory managers a new tool in the diagnosis of septicemia
One of the more challenging diseases to diagnose and treat is septicemia. Traditional microbiology methods typically require two or three days before an accurate diagnosis can be made. Now there is news of a rapid test for bloodstream infections that can allow a hospital clinical laboratory to deliver an answer to physicians in as little as two hours.
It was just last week when the Food and Drug Administration LINK (FDA) granted a de novo petition to allow Nanosphere, Inc., of Northbrook, Illinois, to market its Gram Positive Blood Culture Nucleic Acid Test (BC-GP). This assay is design to be run on Nanosphere’s Verigene automated system. Because the time-to-answer is as little as two hours, this diagnostic technology has the potential to trigger swift changes in the current standard of care for diagnosing and treating blood infections. (more…)
New diagnostic and treatment approach will require close interaction with Pathologists
There’s a novel diagnostic device designed to detect sepsis that also has to potential to engage the pathologist as part of the bedside care team. It is also an example of how nanotechnology and magnetism are being combined in ways that may support in vivo diagnosis and treatment.
Created by a research scientist at Children’s Hospital Boston, this new device uses magnetism to quickly pull disease pathogens out of infected blood. Experts predict it could become the first line of defense for sepsis, a disease which kills about 200,000 Americans each year.
The system works by drawing the patient’s blood and adding tiny magnetic beads, pre-coated with antibodies against specific pathogens, such as Candida albicans. The blood is run through a microfluidic system in which two liquid flow streams run side by side without mixing. One channel contains blood and the other contains a saline-based collection fluid. The beads bind to the pathogens. A magnet then pulls them, along with the pathogens, into the collection fluid. The collection fluid is ultimately discarded, and the cleansed blood reintroduced into the patient.
