New vaccine could give clinical laboratories and antimicrobial stewardship programs the tool they need to dramatically reduce hospital-acquired infections
The innovative approach focuses on bolstering the patient’s immune system itself, rather than relying on proteins to fight infections, according to a USC Today article.
Developed by senior study author Brad Spellberg, MD, Chief Medical Officer at the Los Angeles General Medical Center, and colleagues, “The experimental vaccine takes an entirely different approach: It gooses the body’s preexisting supply of pathogen-gobbling immune cells called macrophages, which engulf and digest bacteria, fungi, and other bad actors. These activated fighters, found in all tissues, quickly neutralize incoming invaders which might otherwise multiply rapidly and overwhelm the body’s defenses,” USC Today reported.
“This is very different from developing new antibiotics,” Jun Yan, a doctoral student at Keck School of Medicine and the study’s first author, told USC Today. “This is using our own immune system to fight against different superbugs, which is a different approach than everybody else.”
To develop the vaccine [the USC researchers] formed a biotechnology startup called ExBaq LLC in Bethesda, Md.
“The pandemic stimulated unprecedented innovation in vaccine development, where federal funding and university-industry partnerships were game changers for translating promising discoveries from academic labs for the good of all,” said Ishwar K. Puri, PhD (above), senior vice president of research and innovation at USC. “We are both pleased and proud of the critical support the USC Stevens Center provided to enable the development of ExBaq’s experimental vaccine that protects vulnerable populations from serious infections.” Clinical laboratories that work with hospitals in the fight against hospital-acquired infections understand the importance of this discovery. (Photo copyright: University of Southern California.)
USC Vaccine Details
The USC team developed a “protein-free vaccine, composed of aluminum hydroxide, monophosphoryl lipid A, and fungal mannan, that stimulates the innate immune system and confers protection,” the researchers wrote in Science Translational Medicine.
“Tested in two independent labs, the vaccine works within 24 hours and lasts for up to 28 days. In lab models, the number of pathogen-eating immune cells in the blood increased dramatically, and survival time of invasive blood and lung infections improved. Early data suggest that a second dose could extend the window to prevent infection,” USC Today reported.
Unlike anything currently available, the new vaccine focuses on boosting the body itself instead of creating antibodies against certain pathogens. A mere dose of the vaccine is described to “provide rapid protection against nine different bacteria and fungi species,” USC Today noted.
“It’s an early warning system. It’s like Homeland Security putting out a terror alert. Everybody, keep your eyes open. Keep an eye out for suspicious packages. You’re alerting the soldiers and tanks of your immune system. The vaccine activates them,” Spellberg told USC Today.
“The vaccine acted through stimulation of the innate, rather than the adaptive, immune system, as demonstrated by efficacy in the absence of lymphocytes that were abrogated by macrophage depletion. A role for macrophages was further supported by the finding that vaccination induced macrophage epigenetic alterations that modulated phagocytosis and the inflammatory response to infection. Together, these data show that this protein-free vaccine is a promising strategy to prevent deadly antimicrobial-resistant healthcare-associated infections,” the researchers wrote in Science Translational Medicine.
“Patients who acquire infections from surgery spend, on average, an additional 6.5 days in the hospital, are five times more likely to be readmitted after discharge and twice as likely to die. Moreover, surgical patients who develop infections are 60% more likely to require admission to a hospital’s intensive care unit. Surgical infections are believed to account for up to 10 billion dollars annually in healthcare expenditures,” the CDC reports.
“All hospitalized patients are susceptible to contracting a [hospital-acquired] infection. Some patients are at greater risk than others: young children, the elderly, and persons with compromised immune systems are more likely to get an infection. Other risk factors are long hospital stays, the use of indwelling catheters, failure of healthcare workers to wash their hands, and overuse of antibiotics,” the CDC notes.
Therefore, USC’s new vaccine may be just what the doctor ordered to protect patients in hospitals and other healthcare settings from deadly HAIs.
Looking Ahead
There are currently no vaccines that are FDA-approved that treat “the most serious antibiotic resistant infections,” USC Today reported.
“Even if there were such vaccines, multiple vaccines would have to be deployed simultaneously to protect against the full slate of antibiotic-resistant microbes that cause healthcare-acquired infections,” Brian Luna, PhD, assistant professor of molecular microbiology and immunology at USC’s Keck School of Medicine, told USC Today.
Thus, USC’s new vaccine could be a boon to hospital antimicrobial stewardship programs. But so far, it has only been tested on mice.
“The next step is getting guidance from the US Food and Drug Administration (FDA) on the design of a clinical trial. The first such trial would be done in healthy volunteers to find the right dose of vaccine that is safe and triggers the same kind of immune response in people as seen in the mice,” USC Today reported.
ExBaq LLC has begun talking with potential larger partners who might be willing to help develop the vaccine into clinical testing.
For years hospitals and other healthcare settings—such as long-term care facilities, urgent care clinics, and clinical laboratories—have fought an uphill battle against superbugs. So, for a vaccine to be on the horizon that can prevent life-threatening hospital-acquired infections would be a game changer.
With antimicrobial stewardships being a requirement in all hospitals, medical laboratory managers and microbiologists may celebrate this new development and its potential to be a useful tool in fighting antimicrobial resistant bacteria in their facilities.
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.
Clinical laboratories and microbiologists will want to be on the alert for this deadly infectious agent that has killed patients through blood infections
Healthcare continues to struggle with the issue of how much to disclose to the public when new and deadly infectious agents are identified in a limited number of patients. Timely disclosure of new pathogens is a matter of great concern to clinical laboratory scientists, microbiologists, and clinical pathologists because their laboratories get specimens from infected patients and they must correctly identify rare or emerging pathogens to help minimize the spread of disease.
This is why many medical laboratory professionals were surprised to see national news headlines recently about a particularly deadly new form of a pathogen. The Centers for Disease Control and Prevention (CDC) has been dealing with one particularly nasty example of Candida auris, or C. auris. This “superbug” fungus has been appearing in hospitals and healthcare clinics across the globe and it has killed people.
The news coverage of C. auris focused on two
elements:
First, how the pathogen was recognized by such
healthcare agencies as the CDC.
Second, why CDC and others did not issue a
public alert to hospitals, physicians, and other caregivers once it was known
that C. auris was responsible for the death of several patients.
Once C. auris takes hold, it can enter a patient’s bloodstream or wounds and cause life- threatening complications like sepsis. When hospitals rooms are not properly decontaminated, life-threatening hospital-acquired infections (HAIs), also known as nosocomial infections, can occur.
Incidences of HAIs have been on the rise in the past few
years. Dark Dailyhas reported
on this disturbing trend many times.
The New York Times (NYT) reported on one such HAI that had tragic consequences. A patient admitted to Mount Sinai Hospital in New York for abdominal surgery was later discovered to have contracted C. auris. He was immediately isolated and spent 90 days in the hospital before passing away. Tests showed that Candida auris was everywhere in his room.
“Everything was positive—the walls, the bed, the doors, the curtains, the phones, the sink, the whiteboard, the poles, the pump,” Scott Lorin, MD, President and Chief Operating Officer at Mount Sinai Brooklyn Hospital, told the NYT. “The mattress, the bed rails, the canister holes, the window shades, the ceiling, everything in the room was positive,” he said.
The hospital had to use special cleaning equipment to
sterilize the room and even found it necessary to tear out some ceiling and
floor tiles to annihilate the fungus, the NYT reported.
Media News Coverage of ‘Culture of Secrecy’
When this deadly fungus first emerged in America, it was not
disclosed to the public for a lengthy period of time. Then, when details of
deaths in hospitals due to the superbug went public, the national news media
reacted but then went silent. Why?
In that article, the NYT states that “under its
agreement with states, the CDC is barred from publicly identifying hospitals
that are battling to contain the spread of dangerous pathogens.” So, the CDC is
prevented from revealing to the public the names and locations of facilities
that are dealing with C. auris. And state governments typically do not
share that information either.
The NYT article also states, “The CDC declined to
comment, but in the past officials have said their approach to confidentiality
is necessary to encourage the cooperation of hospitals and nursing homes, which
might otherwise seek to conceal infectious outbreaks.”
And that, “Those pushing for increased transparency say they
are up against powerful medical institutions eager to protect their
reputations, as well as state health officials who also shield hospitals from
public scrutiny.”
“Who’s speaking up for the baby that got the flu from the hospital worker or for the patient who got MRSA from a bedrail? The idea isn’t to embarrass or humiliate anyone, but if we don’t draw more attention to infectious disease outbreaks, nothing is going to change,” Arthur Caplan, PhD (above), told the NYT. Caplan is Drs. William F and Virginia Connolly Mitty Professor and founding head of the Division of Medical Ethics at NYU School of Medicine in New York City. (Photo copyright: NYU Langone Health.)
Common Yeast Infection or Killer Superbug? Both!
C. auris grows as a common yeast infection. However,
it can be life threatening if it enters the bloodstream.
“The average person calls Candida infections yeast infections,” William Schaffner, MD, Professor and Chair, Department of Preventative Medicine at Vanderbilt University Medical Center, told Prevention. “However, Candida auris infections are much more serious than your standard yeast infection. They’re a variety of so-called superbugs [that] can complicate the therapy of very sick people.”
The CDC reports that, as of May 31, 2019, there have been a total of 685 cases of C. auris reported in the US. The majority of those cases occurred in Illinois (180), New Jersey (124), and New York (336). Twenty more cases were reported in Florida, and eight other states—California, Connecticut, Indiana, Maryland, Massachusetts, Oklahoma, Texas, and Virginia—each had less than 10 confirmed cases of C. auris.
The CDC states the infection seems to be most prominent among populations that have had extended stays in hospitals or nursing facilities. Patients who have had lines or tubes such as breathing tubes, feeding tubes, or central venous catheters entering their body, and those who have recently been given antibiotics or antifungal medications, seem to be the most vulnerable to contracting C. auris.
The fungus typically attacks people who are already sick or have weakened immune systems, which can make it challenging to diagnose, the CDC notes. C. auris infections are typically diagnosed with special clinical laboratory testing of blood specimens or other body fluids. Infections have been found in patients of all ages, from infants to the elderly.
Data from the CDC indicates that C. auris can cause
bloodstream infections, wound infections, and ear infections. Common symptoms
that indicate a person has Candida auris include fever, chills,
weakness, low blood pressure, and general malaise that do not improve with
antibiotics.
“A patient’s temperature may go up, their blood pressure can
go down, and they have complications of a pre-existing illness because of Candida
auris,” Schaffner told Prevention.
The CDC reports that more than one in three patients with
invasive C. auris dies. Even though the mortality rates for Candida
auris are high, it is unclear whether patients are dying from the infection
or from their underlying illnesses. “Whatever the cause, having Candida
auris doesn’t help a patient in any way,” Schaffner noted.
The CDC states that it and its public health partners are
working hard to discover more about this fungus, and to devise ways to protect
people from contracting it. Average healthy people probably don’t need to worry
about becoming infected with Candida auris. However, individuals who are
at high risk, and healthcare professionals, microbiologists, and pathologists,
should be on the alert for this new superbug strain of fungus.
