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.
The UE study sheds light on the types of bacteria in
wastewater that goes down hospital pipes to sewage treatment plants. The study
also revealed that not all infectious agents are killed after passing through
waste treatment plants. Some bacteria with antimicrobial (or antibiotic)
resistance survive to enter local food sources.
The scientists concluded that the amount of AMR genes found
in hospital wastewater was linked to patients’ length-of-stays and consumption
of antimicrobial resistant bacteria while in the hospital.
In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”
Additionally, they wrote, “Using metagenomics to identify
the full range of AMR genes in hospital wastewater could represent a useful
surveillance tool to monitor hospital AMR gene outflow and guide environmental
policy on AMR.”
Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]
Don’t Waste the Wastewater
Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.
Wastewater, the UE scientists suggest, should not go to
waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial
resistance, as well as to boost environment antimicrobial-resistance polices.
They used metagenomics (the study of genetic material
relative to environmental samples) to compare the antimicrobial-resistance
genes in hospital wastewater against wastewater from community sewage
points.
The UE researchers:
First collected samples over a 24-hour period from various areas in a tertiary hospital;
They then obtained community sewage samples from various locations around Seafield, Scotland;
Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted.
Fey suggests that further research into using sequencing
technology to monitor patients is warranted.
“I think that monitoring each patient and sequencing their
bowel flora is more likely where we’ll be able to see if there’s a significant
carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In
five years or so, sequencing could become so cheap that we could monitor every
patient like that.”
Fey was not involved in the University of Edinburgh
research.
Given the rate at which AMR bacteria spreads, finding antibiotic-resistance
genes in hospital wastewater may not be all that surprising. Still, the University
of Edinburgh study could lead to cost-effective ways to test the genes of
bacteria, which then could enable researchers to explore different sources of
infection and determine how bacteria move through the environment.
And, perhaps most important, the study suggests clinical
laboratories have many opportunities to help eliminate infections and slow
antibiotic resistance. Microbiologists can help move their organizations forward
too, along with infection control colleagues.
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.”
