News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

San Diego University Researchers Believe Bacteriophages May Be the Future of Eradicating Multi-Drug Resistant Superbugs

Clinical laboratories and microbiologists may soon have new powerful tools for fighting antimicrobial resistant bacteria that saves lives

Superbugs—microbes that have developed multidrug resistance—continue to cause problems for clinical laboratories and hospital antibiotic stewardship programs around the world. Now, scientists at San Diego State University (SDSU) believe that bacteriophages (phages) could provide a solution for dealing with multi-drug resistant superbugs.

Phages are miniscule, tripod-looking viruses that are genetically programmed to locate, attack, and eradicate a specific kind of pathogen. These microscopic creatures have saved lives and are being touted as a potential solution to superbugs, which are strains of bacteria, viruses, parasites, and fungi that are resistant to most antibiotics and other treatments utilized to counteract infections.

“These multi-drug-resistant superbugs can cause chronic infections in individuals for months to years to sometimes decades,” Dwayne Roach, PhD, Assistant Professor of Bacteriophages, Infectious Disease, and Immunology at SDSU told CNN. “It’s ridiculous just how virulent some of these bacteria get over time.”

Labs across the country are conducting research on phages in eradicating superbugs. Roach’s lab is currently probing the body’s immune response to phages and developing purification techniques to prepare phage samples for intravenous use in patients.

“There are a lot of approaches right now that are happening in parallel,” said Dwayne Roach, PhD (above), Assistant Professor of Bacteriophages, Infectious Disease, and Immunology at San Diego State University (SDSU), in a CNN interview. “Do we engineer phages? Do we make a phage cocktail, and then how big is the cocktail? Is it two phages or 12 phages? Should phages be inhaled, applied topically, or injected intravenously? There’s a lot of work underway on exactly how to best do this.” Clinical laboratories that test for bacterial infections may play a key role in diagnosis and treatment involving bacteriophages. (Photo copyright: San Diego State University.)

Building Libraries of Phages

When certain a bacterial species or its genotypes needs to be annihilated, a collection of phages can be created to attack it via methods that enter and weaken the bacterial cell. The bacteria will attempt to counter the intrusion by employing evasive actions, such as shedding outer skins to eliminate the docking ports utilized by the phages. These maneuvers can cause the bacteria to lose their antibiotic resistance, making them vulnerable to destruction. 

Some research labs are developing libraries of phages, accumulating strains found in nature in prime breeding grounds for bacteria to locate the correct phage for a particular infection. Other labs, however, are speeding up the process by producing phages in the lab.

“Rather than just sourcing new phages from the environment, we have a bioreactor that in real time creates billions upon billions of phages,” Anthony Maresso, PhD, Associate Professor at Baylor College of Medicine in Houston told CNN. “Most of those phages won’t be active against the drug-resistant bacteria, but at some point, there will be a rare variant that has been trained, so to speak, to attack the resistant bacteria, and we’ll add that to our arsenal. It’s a next-generation approach on phage libraries.”

Maresso and his team published their findings in the journal Clinical Infectious Diseases titled, “A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.”

For the Baylor study, 12 patients were treated with phages customized to each individual’s unique bacterial profile. The antibiotic-resistant bacteria were exterminated in five of the patients, while several others showed improvement.

Clinical trials are currently being executed to test the effectiveness of phages against a variety of chronic health conditions, including:

Using a phage cocktail could be used to treat a superbug outbreak in real time, while preventing a patient from a future infection of the same superbug. 

“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” Maroya Walters, PhD, epidemiologist at the federal Centers for Disease Control and Prevention (CDC) told CNN.

“They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people,” she added.

The colorized transmission electron micrograph above shows numerous phages attached to a bacterial cell wall. Phages are known for their unique structures, which resemble a cross between NASA’s Apollo lunar lander and an arthropod. (Caption and photo copyright: Berkeley Lab.)

More Studies are Needed

According to CDC data, more than 2.8 million antimicrobial-resistant (AMR) infections occur annually in the United States. More than 35,000 people in the country will die as a result of these infections.

In addition, AMR infections are a huge global threat, associated with nearly five million deaths worldwide in 2019. Resistant infections can be extremely difficult and sometimes impossible to treat.

“It’s estimated that by 2050, 10 million people per year—that’s one person every three seconds—is going to be dying from a superbug infection,” epidemiologist Steffanie Strathdee, PhD, Associate Dean of Global Health Services and co-director at the Center for Innovative Phage Applications and Therapeutics (IPATH) at the UC San Diego School of Medicine, told CNN.

The CDC’s 2019 report on bacteria and fungi antimicrobial resistant threats named five pathogens as urgent threats:

More research is needed before phages can be used clinically to treat superbugs. But if phages prove to be useful in fighting antibiotic-resistant bacteria, microbiologists and their clinical laboratories may soon have new tools to help protect patients from these deadly pathogens.

—JP Schlingman

Related Information:

Superbug Crisis Threatens to Kill 10 Million Per Year by 2050. Scientists May Have a Solution

About Antimicrobial Resistance

2019 AR Threats Report

Bacteriophage

Why Antibiotics Fail, and How We Can Do Better

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes

Cataloging Nature’s Hidden Arsenal: Viruses That Infect Bacteria

UCSB Researchers Discover Superior Culture Medium for Bacterial Testing, along with New Insights into Antimicrobial Resistance

German Researchers Create Non-invasive Lab-on-a-Chip Biosensor That Detects Antibiotic Levels from Breath Samples

Should the device prove effective, it could replace invasive point-of-care blood draws for clinical laboratory testing during patient drug therapy monitoring

What if it were possible to perform therapeutic drug monitoring (TDM) without invasive blood draws using breath alone? Patients fighting infections in hospitals certainly would benefit. Traditional TDM can be a painful process for patients, one that also brings risk of bloodline infections. Nevertheless, regular blood draws have been the only reliable method for obtaining viable samples for testing.

One area of critical TDM is in antibiotic therapy, also known as personalized antibiotherapy. However, for antibiotic therapy to be successful it typically requires close monitoring using point-of-care clinical laboratory testing.

Now, a team of engineers and biotechnologists from the University of Freiburg in Germany have developed a biosensor that can use breath samples to measure antibiotic concentrations present in blood, according to a University of Freiburg press release.

The team’s non-invasive collection method requires no needle sticks and can allow for frequent specimen collections to closely monitor the levels of an antibiotic prescribed for a patient. The biosensor also provides physicians the ability to tailor antibiotic regimens specific to individual patients, a core element of precision medicine.

The researchers published their findings in the journal Advanced Materials, titled, “Biosensor-Enabled Multiplexed On-Site Therapeutic Drug Monitoring of Antibiotics.”

Can Dincer, PhD
 
“Until now researchers could only detect traces of antibiotics in the breath,” said Can Dincer, PhD (above), Junior Research Group Leader at the University of Freiburg, and one of the authors of the study, in the press release. “With our synthetic proteins on a microfluid chip, we can determine the smallest concentrations in the breath condensate and [how] they correlate with the blood values.” Should the breath biosensor prove effective in clinical settings, painful blood draws for clinical laboratory testing at the point of care could become obsolete. (Photo copyright: Conny Ehm/University of Freiburg.)

Can a Breath Biosensor Be as Accurate as Clinical Laboratory Testing?

The University of Freiburg’s biosensor is a multiplex, microfluid lab-on-a-chip based on synthetic proteins that react to antibiotics. It allows the simultaneous measurement of several breath samples and test substances to determine the levels of therapeutic antibiotics in the blood stream.

To perform their research, the University of Freiburg team tested their biosensor on blood, plasma, urine, saliva, and breath samples of pigs that had been given antibiotics. The results the researchers achieved with their device using breath samples were as accurate as standard clinical laboratory testing, according to the press release.

The microfluidic chip contains synthetic proteins affixed to a polymer film via dry film photoresist (DFR) technology. These proteins are similar to proteins used by drug-resistant bacteria to sense the presence of antibiotics in their environment. Each biosensor contains an immobilization area and an electrochemical cell which are separated by a hydrophobic stopping barrier. The antibiotic in a breath sample binds to the synthetic proteins which generates a change in an electrical current. 

“You could say we are beating the bacteria at their own game,” said Wilfried Weber, PhD, Professor of Biology at the University of Freiburg and one of the authors of the research paper, in the press release.

Rapid Monitoring at Point-of-Care Using Breath Alone

The biosensor could prove to be a useful tool in keeping antibiotic levels stable in severely ill patients who are dealing with serious infections and facing the risk of sepsis, organ failure, or even death. Frequent monitoring of therapeutic antibiotics also could prevent bacteria from mutating and causing the body to become resistant to the medications.

“Rapid monitoring of antibiotic levels would be a huge advantage in hospital,” said H. Ceren Ates, PhD, scientific researcher at the University of Freiburg and one of the authors of the study in the press release. “It might be possible to fit the method into a conventional face mask.”

Along those lines, the researchers are also working on a project to create wearable paper sensors for the continuous measurement of biomarkers of diseases from exhaled breath. Although still in the development stages, this lightweight, small, inexpensive paper sensor can fit into conventional respiratory masks, according to a University of Freiburg press release.

Other Breath Analysis Devices Under Development

Devices that sample breath to detect biomarkers are not new. Dark Daily has regularly reported on similar developments worldwide.

In “NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers,” we reported on research conducted at JILA, a research center jointly operated by the National Institutes of Standards and Technology (NIST) and the University of Colorado Boulder, that could pave the way for real-time, noninvasive breath analysis to detect and monitor diseases, and potentially eliminate the need for many blood-based clinical laboratory tests.

And in “Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test,” Dark Daily covered the FDA’s first ever emergency use authorization (EUA) for a portable breath test device designed to screen for SARS-CoV-2 infection. Developed by InspectIR Systems, the COVID-19 Breathalyzer identifies a chemical signature associated with SARS-CoV-2 in about three minutes with 91.2% sensitivity and 99.3% specificity.

Thus, University of Freiburg’s non-invasive lab-on-a-chip biosensor is worth watching. More research is needed to validate the effectiveness of the biosensor before it could be employed in hospital settings, however, monitoring and managing antibiotic levels in the body via breath samples could prove to be an effective, non-invasive method of providing personalized antibiotic therapy to patients.

Clinical trials on human breath samples are being planned by the University of Freiburg team. This type of precision medicine service may give medical professionals the ability to maintain proper medication levels within an optimal therapeutic window.

JP Schlingman

Related Information:

Antibiotic Levels Measurable in Breath for the First Time

Biosensor-Enabled Multiplexed On-Site Therapeutic Drug Monitoring of Antibiotics

A Breath of Fresh Information

NIST Scientists Enhance Frequency Comb Breathalyzer Enabling It to Detect Multiple Disease Biomarkers

Will Blowing in a Device Be Useful in Screening for COVID-19? FDA Grants Its First EUA for a Breathalyzer SARS-CoV-2 Screening Test

CDC Issues Warning on Candida Auris, a Highly Drug Resistant and Dangerous Yeast Infection

CDC advises clinical laboratories and microbiologists encountering C. auris to follow their own protocols before adopting federal agency guidelines

In July, the Centers for Disease Control and Prevention (CDC) warned healthcare facilities and clinical laboratories to be on the alert for Candida auris (C. auris) infections in their patients. An outbreak of the drug resistant and potentially deadly fungus had appeared in two Dallas hospitals and a Washington D.C. nursing home.

Since those outbreaks, researchers have studied with urgency the “superbug’s” emergence in various types of healthcare facilities around the nation, not just hospitals. Their goal was to discover how it was successfully identified and contained.

One such recently released study involved researchers from the Orange County Health Department (OCHD) working with the California Department of Public Health and the CDC to track C. auris in long-term acute care hospitals (LTACHs) and ventilator-capable skilled-nursing facilities (vSNFs), Medscape reported.

The researchers published their findings in Annals of Internal Medicine, titled, “Rapid Assessment and Containment of Candida auris Transmission in Post-acute Care Settings—Orange County, California, 2019.”

“Seeing what was happening in New York, New Jersey, and Illinois [was] pretty alarming for a lot of the health officials in California [who] know that LTACHs are high-risk facilities because they take care of [very] sick people. Some of those people are there for a very long time,” the study’s lead author Ellora Karmarkar, MD, MSc, told Medscape. Karmarkar is an infectious disease fellow with the University of Washington and formerly an epidemic intelligence service officer with the CDC.

“One of the challenges was that people were so focused on COVID that they forgot about the MDROs (multi-drug resistant organisms] … Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care,” she added.

According to Medscape, “The OCHD researchers screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%–10% of colonized patients later develop invasive infections, and 30%–60% die.

Medscape also reported that the first bloodstream infection was detected in May 2019, and that, according to the Annals of Internal Medicine study, as of January 1, 2020, of 182 patients:

  • 22 (12%) died within 30 days of C. auris identification,
  • 47 (26%) died within 90 days,
  • One of 47 deaths was attributed to C. auris,
  • Whole-genome sequencing showed that the isolates were all closely related in clade III.

“This is really the first time we’ve seen clustering of resistance in which patients seemed to be getting the infections from each other,” Meghan Lyman, MD, Medical Officer in the Mycotic Diseases Branch of the CDC, told Fox News.

Candida auris graphic

The graphic above illustrates how Candida auris is “spanning the globe,” The New York Times reported. Clinical laboratories that encounter this potentially deadly fungus are advised to contact the CDC immediately for guidance and to take proactive steps to prepare for the “superbug’s” arrival. (Graphic copyright: The Scottish Sun.)

Be More Proactive than Reactive in Identifying C. Auris, CDC Says

C. auris is a type of yeast infection that can enter the bloodstream, spread throughout the body, and cause serious complications. People who appear to have the highest risk of contracting the infection are those:

  • Who have had a lengthy stay in a healthcare facility,
  • Individuals connected to a central venous catheter or other medical tubes, such as breathing or feeding tubes, or
  • Have previously received antibiotics or antifungal medications.

The CDC is concerned about C. auris for three primary reasons:

  • It tends to be resistant to the antifungal drugs that are commonly used to treat Candida infections.
  • It can be difficult to identify via standard laboratory testing and is easily misidentified in labs without specific technology.
  • It can quickly lead to outbreaks in healthcare settings.

“With all this spread that we’ve been seeing across the country we’re really encouraging health departments and facilities to be more proactive instead of reactive to identifying Candida auris in general,” Lyman told STAT. “Because we’ve found that controlling the situation and containing spread is really easiest when it’s identified early before there’s widespread transmission.”

Dan Diekema, MD

There continues to be concerns over this highly drug-resistant infection among hospital physicians and medical laboratories. “Acute care hospitals really ought to be moving toward doing species identification of Candida from nonsterile sites if they really want to have a better chance of detecting this early,” Dan Diekema, MD (above), an epidemiologist and clinical microbiologist at the University of Iowa, told Medscape. (Photo copyright: University of Iowa.)

Candia Auris versus Other Candida Infections

C. auris can cause dangerous infections in the bloodstream and spread to the central nervous system, kidneys, liver, spleen, bones, muscles, and joints. It spreads mostly in long-term healthcare facilities among patients with other medical conditions.

The symptoms of having a Candida auris infection include:

  • Fever
  • Chills
  • Pain
  • Redness and swelling
  • Fluid drainage (if an incision or wound is present)
  • General feeling of tiredness and malaise

C. auris infections are typically diagnosed via cultures of blood or other bodily fluids, but they are difficult to distinguish from more common types of Candida infections, and special clinical laboratory tests are needed to definitively diagnose C. auris.

Whole-genome Sequencing of C. Auris and Drug Resistance

The CDC conducted whole-genome sequencing of C. auris specimens gathered in Asia, Africa, and South America and discovered four different strains of the potentially life-threatening Candida species. All four detected strains have been found in the United States.

There are only three classes of antifungal drugs used to treat Candida auris infections:

However, 85% of the infections in the US have proven to be resistant to azoles and 38% are resistant to polyenes. Patients respond well to echinocandins, but more effective therapies are needed especially as some isolates may become resistant while a patient is on drug therapy, STAT reported.

“Even while it might be susceptible upfront, after a week or two of therapy, we may find that the patient has an infection now caused by an isolate of the same Candida auris that has become resistant to the echinocandins and we are really left with nothing else,” Jeffrey Rybak, PhD, PharmD, Instructor, Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, told Infection Control Today.

Although relatively rare, C. auris infections are on the rise. The good news is that there may be further pharmaceutical help available soon. New antifungal agents, such as Ibrexafungerp (Brexafemme) show promise in fighting C. auris infections, but more research is needed to prove their efficacy.

What Should Clinical Laboratories Do?

The CDC stresses that clinical laboratories and microbiologists working with known or suspected cases of Candida auris should first adhere to their own safety procedures. The CDC issued guidelines, but they are not meant to supersede the policies of individual labs.

The CDC also recommends that healthcare facilities and clinical laboratories that suspect they have a patient with a Candida auris infection immediately contact the CDC and state or local public health authorities for guidance.  

JP Schlingman

Related Information

U.S. Sees First Cases of Dangerous Fungus Resistant to all Drugs in Untreated People

‘Superbug’ Fungus Spread in Two Cities, Health Officials Say           

CDC: Candida auris

CDC: Drug-resistant Candida auris   

CDC Reports Two Outbreaks of Pan-resistant Candida auris

Notes from the Field: Transmission of Pan-Resistant and Echinocandin-Resistant Candida auris in Health Care Facilities―Texas and the District of Columbia, January–April 2021

Drugs in Development Might Help Fight Deadly Candida Auris

During Pandemic, Clinical Laboratories Should Be Alert for Drug Resistant Infections That Pose High Risk to COVID-19 Patients

Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed

Pew Charitable Trusts and CDC Find Hospitals Are Overusing Antibiotics, Set New Targets for Antibiotic Prescribing and Avoiding Antimicrobial Resistance

Clinical laboratories and microbiology tests provide key tools for physicians engaged in antibiotic stewardship programs

One important and continuing trend in healthcare is the need for hospitals, nursing homes, and other medical providers to introduce effective antibiotic stewardship programs (ASPs). The findings of a recent study on antibiotic stewardship emphasize the need for improvement and suggest guidelines that will involve and engage clinical laboratories.

Antibiotic-resistant infections kill at least 35,000 people in hospitals each year, according to the Centers for Disease Control and Prevention (CDC). And that, the CDC notes, is out of 2.8 million drug-resistant infections that occur annually.

In a recent brief of a study The Pew Charitable Trusts (Pew) conducted with the CDC and various public health and medical experts, Pew wrote, “Minimizing inappropriate antibiotic use in hospitals is a vital element in the fight against antibiotic resistance because more than half of patients admitted to hospitals will receive these drugs. Determining how much antibiotic prescribing is inappropriate and setting national targets to reduce such use are necessary steps for guiding clinical efforts and policies that promote improved antibiotic use.”

To do this, and Pew and the CDC are suggesting “widespread adoption of effective antibiotic stewardship programs, which promote responsible antibiotic prescribing, in order to minimize the harmful effects of inappropriate or unnecessary antibiotic use for patients and slow the spread of resistance.”

And because clinical laboratories perform all the in-hospital testing for ASPs, they will be big part of this effort.

Pew/CDC Set New National Targets for Antibiotic Use Improvement

The Pew brief states that in 2018 the researchers began “to evaluate antibiotic use in hospitals and set national targets to improve prescribing.” The brief adds that “Because of the complexity and diversity of illnesses among hospitalized patients, and the limitations on available clinical data for all antibiotic use in hospitals, the panel focused its analysis on four categories of prescribing that account for the most common antibiotic therapies in US hospitals. Using national prescribing data, the experts examined the use of two types of antibiotics—vancomycin and fluoroquinolones—and antibiotic treatments associated with two conditions: community-acquired pneumonia (CAP) and hospital-acquired urinary tract infection (UTI).”

It their paper published in JAMA Network Open, titled, “Assessment of the Appropriateness of Antimicrobial Use in US Hospitals,” the Pew/CDC researchers wrote, “In this cross-sectional study of 1,566 patients at 192 hospitals, antimicrobial use deviated from recommended practices for 55.9% of patients who received antimicrobials for community-acquired pneumonia or urinary tract infection present at admission or who received fluoroquinolone or intravenous vancomycin treatment.”

Infection Control Today reported that the CDC and Pew set the following goals for hospitals, but did not give a deadline for improvement:

  • Decrease antibiotic inappropriate prescribing in CAP and UTI cases by 90%.
  • Decrease overprescribing of fluoroquinolones and vancomycin by 95%.

“Meeting these national reduction targets will require widespread adoption of effective antibiotic stewardship programs, which promote responsible antibiotic prescribing in order to minimize the harmful effects of inappropriate or unnecessary antibiotic use for patients and slow the spread of resistance,” noted the Pew brief, which also pointed out that hospitals should provide incentives to report antibiotic use and impact of stewardship programs to the CDC’s National Healthcare Safety Network (NHSN).

‘Ample Room for Improvement’

The Pew/CDC panel of experts analyzed hospitalized patient data from August 2017 through May 2020. Of those patients, the researchers found that:

  • 219 had CAPs,
  • 452 had UTIs,
  • 550 had received fluoroquinolones, and
  • 403 had received vancomycin.

They also found that:

  • 56% of antibiotic prescriptions were wrong in the type of antibiotic, how long it was used, or why it was chosen.
  • 79% of antibiotic prescriptions for CAP were inappropriate.
  • 77% of antibiotic prescriptions did not suit UTI patients.
  • 47% of fluoroquinolone prescriptions were unsupported.
  • 27% of vancomycin prescriptions were amiss.

The researchers concluded that providers have “ample room for improvement,” the Pew brief notes.

“A substantial percentage of CAP, UTI, fluoroquinolone, and vancomycin treatment was unsupported by medical record data collected (55.9% overall and as high as 79.5% for CAP),” the researchers wrote in their published study. 

Pew/CDC Researchers Find Many Antibiotic Prescription Errors

According to the Pew/CDC researchers, missteps in antibiotic usage include:

  • Treating inpatients too long with antibiotics.
  • Selecting antimicrobials inconsistent with guidelines.
  • Absence of signs and symptoms of infection.
  • Lack of clinical laboratory tests or microbiologic evidence of infection.

The study revealed antibiotic duration errors were most prevalent in the CAP patients, some being treated with antibiotics for more than seven days.

“Almost 60% of the inappropriate prescribing is attributed to exceeding the recommended seven days of treatment, and the use of the wrong antibiotic accounts for most of the remaining inappropriate (CAP) cases,” the Pew brief explained.

Antibiotics Prescribed without Evidence of Infection

As medical laboratory professionals know, microbiology tests identify presence and type of bacteria in urine. But the Pew/CDC researchers reported they found UTI cases that lacked evidence of infection.  

“In most instances—where antibiotic use was not supported—the antibiotics were prescribed to patients who lacked symptoms or microbiology test results consistent with UTIs,” according to their report.

Antibiotics Overprescribed to COVID-19 Patients

Another study conducted by The Pew Charitable Trusts “assessed the frequency of bacterial infections and antibiotic prescribing patterns in hospitalized patients diagnosed with COVID-19 in the US.” The researchers, according to the Pew brief on that study, titled, “Could Efforts to Fight the Coronavirus Lead to Overuse of Antibiotics?” used “IBM Watson Health’s electronic health records [EHR] database to capture data about approximately 5,000 patients and nearly 6,000 hospital admissions from February through July 2020.”

The researchers of that study found potential antibiotic misuse among COVID-19 patients as well.

  • 52% received at least one antibiotic prescription.
  • 36% had multiple antibiotics.
  • 96% were treated with antibiotics within 48 hours of admission and likely before infection was confirmed. 
Rachel Zetts headshot in black sweater
“Our data shows that there was very likely a significant amount of unnecessary antibiotic prescribing among hospitalized COVID-19 patients,” Rachel Zetts, Officer, Antibiotic Resistance Project at The Pew Charitable Trusts, told Becker’s Hospital Review. “Overprescribing on this scale could negatively impact the progress we’ve made in the fight against antibiotic resistance over the years, so encouraging physicians to reduce inappropriate antibiotic use and equipping them with the tools needed to do so is critical.” Those tools include test results clinical laboratories produce in support of antibiotic stewardship programs. (Photo copyright: The Pew Charitable Trusts.)

Clinical Laboratories are Key Partners

Hospital-based clinical laboratory leaders may want to contact physicians and infection control colleagues and work toward correcting use of antibiotics in patient care. And microbiologists are advised to aggressively communicate available medical laboratory test data about UTI infections, which the Pew/CDC study suggests can be missed.

Medical laboratories provide testing to diagnose infections and to identify strains of infectious agents that may be antibiotic-resistant. Therefore, lab leaders will be key partners in hospitals’ efforts to reduce infections and prevent antibiotic resistance.

—Donna Marie Pocius

Related Information:

Health Experts Establish Targets to Improve Hospital Antibiotic Prescribing

Assessment of the Appropriateness of Antimicrobial Use in U.S. Hospitals

CDC Wants to Improve Antibiotic Overprescribing by Over 90%

National Healthcare Safety Network (NHSN)

Could Efforts to Fight the Coronavirus Lead to Overuse of Antibiotics?

Antibiotics Significantly Overprescribed During Early Months of Pandemic, Study Suggests

During Pandemic, Clinical Laboratories Should Be Alert for Drug Resistant Infections That Pose High Risk to COVID-19 Patients

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.

In “Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed,” Dark Daily reported how Candida auris’ ability to elude detection makes decontamination of hospital rooms far more complicated. And in “CDC Ranks Two More Drug-Resistant Microbes as ‘Urgent Threat’ to Americans; Clinical Laboratories Are Advised to Increase Awareness of Antimicrobial Resistance,” we covered how the federal Centers for Disease Control and Prevention (CDC) added C. auris to its “Biggest Threats and Data: Antibiotic Resistance Threats in the United States” report for 2019.

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.

—Dava Stewart

Related Information:

Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed

CDC Ranks Two More Drug-Resistant Microbes as ‘Urgent Threat to Americans; Clinical Laboratories Are Advised to Increase Awareness of Antimicrobial Resistance:

Biggest Threats and Data: Antibiotic Resistance Threats in the United States report for 2019

Three Cases of Worrisome Pan-Resistant C auris Found in New York

COVID Unleashes the ‘Lurking Scourge’ Candida Auris

The Lurking Scourge of Multidrug Resistant Candida auris in Times of COVID-19 Pandemic

CDC: Fungal Diseases and COVID-19

CDC: Candida auris

;