Even as the nation’s hospitals embark on efforts to implement effective antimicrobial stewardship programs, researchers continue to seek solutions to the same problem. They are following several paths to combat the growing resistance certain pathogens have to antibiotics. In particular, two approaches are interesting for pathologists and medical laboratory personnel. One involves understanding the processes that lead to antibiotic resistance. The other is to identify useful biomarkers associated with specific strains of pathogens. (more…)
Lab-on-a-chip technology could reduce the time needed to identify infection-causing bacteria and for physicians to prescribe correct antibiotics
Pathology groups and medical laboratories may see their role in the patient-care process grow if researchers succeed in developing culture-independent diagnostic tools that quickly identify bacterial infections as well as pinpoint the antibiotics needed to treat them.
In the battle against antibiotic-resistant infections (AKA “super bugs”) the National Institutes of Health (NIH) is funding nine research projects aimed at thwarting the growing problem of life-threatening infections that no longer are controlled or killed by today’s arsenal of drugs.
Common Practices in Hospitals Leading to Super Bugs
Currently, when infections are suspected in hospitals or other settings where illness can quickly spread, samples are sent to a central medical laboratory where it may take up to three days to determine what germ is causing the infection. Because of that delay, physicians often prescribe broad-spectrum antibiotics based on a patient’s symptoms rather than lab test results, a practice that can lead to the growth of antibiotic-resistant microbes. (more…)
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.”
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.
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.
Clinical laboratory leaders may be aware that many hospitals still do not have capabilities to make a timely diagnosis of sepsis
Despite the fact that “one in three people who dies in a hospital had sepsis during that hospitalization,” recent data from the Centers for Disease Control and Prevention (CDC) show that many hospitals in the US lack the resources to identify sepsis and begin treatment as soon as possible, CNN reported.
According to the CDC, 1.7 million Americans develop sepsis annually. And of that group, at least 350,000 adults die in hospitals or hospice care centers. Clinical laboratories tasked with performing the plethora of tests needed to diagnose sepsis will agree that it is one of the gravest healthcare dangers patients face.
To address this potentially deadly threat, the CDC developed the “Hospital Sepsis Program Core Elements: 2023” to support the implementation of sepsis protocols at all hospitals, to optimize any existing sepsis programs, and to organize staff and identify resources to lower sepsis rates and raise survivability.
“Modeled after CDC’s Core Elements of Antibiotic Stewardship, which has proven to be an impactful resource to protect patients from the harms caused by unnecessary antibiotic use and to combat antimicrobial resistance, the Sepsis Core Elements were created with the expectation that all hospitals, regardless of size and location, would benefit from this resource,” a CDC press release noted.
“CDC’s Hospital Sepsis Program Core Elements are a guide for structuring sepsis programs that put your healthcare providers in the best position to rapidly identify and provide effective care for all types of patients with sepsis,” said Raymund Dantes, MD (above), Medical Advisor, National Healthcare Safety Network, CDC, and Associate Professor, Emory University School of Medicine, in a CDC press release. Hospital medical laboratories will play a key role in the success of the CDC’s sepsis program. (Photo copyright: Emory School of Medicine.)
Seven Elements to Improve Sepsis Diagnosis
Sepsis can occur when chemicals released into the bloodstream to fight off an infection produce massive inflammation throughout the body. This potentially fatal reaction can cause a deluge of changes within the body that damage multiple organs, leading them to fail.
The CDC designed its hospital sepsis program to improve and monitor the management and outcomes of patients with sepsis. The core elements of the program include seven main points:
Hospital Leadership Commitment: Management must dedicate the necessary staff, financial, and information technology resources.
Accountability: Appoint a team responsible for program goals and outcomes.
Multi-professional Expertise: Make sure key personnel throughout the healthcare system are engaged in the program.
Action: Implement structures and processes to improve the identification of the illness and patient outcomes.
Tracking: Develop initiatives to measure sepsis epidemiology, management, overall outcomes, and progress towards established goals.
Reporting: Provide information on sepsis management and outcomes to relevant partners.
Education: Provide healthcare professionals, patients, and family/caregivers with information on sepsis.
“Sepsis is taking too many lives. One in three people who dies in a hospital has sepsis during that hospitalization. Rapid diagnosis and immediate appropriate treatment, including antibiotics, are essential to saving lives, yet the challenges of awareness about and recognition of sepsis are enormous,” said CDC Director Mandy Cohen, MD, in the CDC press release. “That’s why CDC is calling on all US hospitals to have a sepsis program and raise the bar on sepsis care by incorporating these seven core elements.”
Early Diagnosis Presents Challenges
Sepsis care is complex. The condition requires urgent medical intervention to prevent organ damage and death. But the symptoms, which include fever or low temperature, shivering, confusion, breathing difficulties, extreme body pain or discomfort, high heart rate, weak pulse or low blood pressure, and low urine output, can be general and indicative of other illnesses.
The diagnosis of sepsis usually requires the collection of a blood culture specimen that is then incubated until there is enough bacterial growth to identify the specific strains of bacteria in a particular patient. This process can take several days, which can delay the administering of the most effective treatment for the condition. Treatment usually includes antibiotics and intravenous fluids.
A recent CDC survey of 5,221 US hospitals showed that in 2022, only 73% of hospitals reported having a sepsis program, ranging from 53% among hospitals with less than 25 beds to 95% among hospitals with over 500 beds.
That survey, released in the CDC’s August Morbidity and Mortality Weekly Report (MMWR), also discovered that only 55% of all hospitals had personnel with dedicated time to manage and conduct necessary daily activities for a sepsis program.
Raymund Dantes, MD, Medical Advisor, National Healthcare Safety Network, CDC, and Associate Professor, Emory University School of Medicine, told CNN that as many as 1,400 hospitals have no sepsis program in place at all. Therefore, he added, the CDC’s Hospital Sepsis Program Core Elements documents also include a “getting started guide” to help those hospitals create the needed committees.
“For those hospitals that already have sepsis programs underway and have available resources, we have a lot more details and best practices that we’ve collected from hospitals about how to better improve your sepsis programs,” he said. “The seven elements complement clinical guidelines by describing the leadership, expertise, tracking, education, and other elements that can be implemented in a wide variety of hospitals to improve the quality of sepsis care.”
Hospital Laboratories Play a Key Role in Reducing Sepsis
According to the CDC, anyone can get an infection and almost any infection can lead to sepsis. However, some populations are more vulnerable to sepsis than others. They include:
Older persons
Pregnant or recently pregnant women
Neonates
Hospitalized Patients
Patients in Intensive Care Units
People with weakened immune systems
People with chronic medical conditions
According to the World Health Organization (WHO), there were 48.9 million sepsis cases and 11 million sepsis-related deaths worldwide in 2017. This number accounted for almost 20% of all global deaths. Almost half of all the global sepsis cases occurred in children, resulting in 2.9 million deaths in children under the age of five.
“Sepsis is complex, often difficult to identify, and takes a tremendous societal toll in the United States,” said Steven Simpson, MD, Professor of Medicine at the University of Kansas and Chair, Board of Directors, Sepsis Alliance, a non-profit organization dedicated to raising awareness and reducing suffering from sepsis, in a press release. “To tackle the number one killer in American hospitals, we need a comprehensive National Action Plan to find cures, get them in the hands of professionals, and educate the public and professionals alike.”
Hospital medical laboratories can help reduce sepsis by finding ways to support their physicians’ diagnoses of this infection that has taken so many lives.
CDC’s findings are a setback for the national effort to encourage hospitals and their clinical laboratories to reduce the number of nosocomial infections and practice better antimicrobial stewardship
Nosocomial infections—also known as hospital-acquired infections—increased during the COVID-19 pandemic. That’s according to a Centers for Disease Control and Prevention (CDC) report that showed increases in several HAIs, including a 14% jump in Methicillin-resistant Staphylococcus aureus (MRSA) from 2020 to 2021.
Clinical laboratory testing is part of a concerted effort in the US to reduce HAIs in acute care hospitals. Additionally, diagnostic testing is vital to antimicrobial stewardship, which is designed to help physicians prescribe to patients only those antibiotics that are appropriate and reduce the chance for antimicrobial resistance (AMR).
So, it’s disturbing to see a setback in both HAIs and antimicrobial stewardship in the wake of the COVID-19 pandemic. Burda called the CDC’s findings a “regression” that “gives new meaning to the term long COVID.”
“I think, without any proof, doctors, nurses, medical technicians, and other clinicians who provide direct patient care regressed in terms of infection control best practices,” wrote healthcare journalist David Burda in his column for 4Sight Health. Clinical laboratories that processed COVID-19 tests during the pandemic can attest to the burnout. (Photo copyright: 4Sight Health.)
CDC Report Reveals Increase in Hospital Acquired Infections
The CDC used standardized infection ratios (SIRs) in its report to detail changes in nosocomial infections. CDC calculates SIRs by dividing the number of observed infections by the number of predicted infections.
“In 2021, the nation and the world continued to experience unprecedented challenges due to the COVID-19 pandemic, which impacted surveillance for and incidence of HAIs,” the CDC explained in its report.
“Compared to pre-pandemic years, hospitals across the nation experienced higher than usual hospitalizations and shortages in healthcare personnel and equipment, which may have resulted in deterioration in multiple patient safety metrics since the beginning of the pandemic,” the CDC added.
In his 4Sight Health article, Burda noted that physicians and other care providers may have “regressed” in their infection control practices due to severe pressures during the COVID-19 pandemic. “I also think the traveling nurse and temporary staff situation had something to do with it. Who has time to learn or follow the infection control policies and protocols at every hospital when you’re moving from one hospital to the next every few weeks?” he added.
The CDC explored HAIs in acute care hospitals, critical access hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals. According to the federal agency’s report, at acute care hospitals, increases in nosocomial infections from 2020 to 2021 include the following:
27 states performed better on at least two types of infection.
30 states performed worse on at least two infection types.
In response to the CDC’s report, the American Hospital Association (AHA) wrote, “In acute care hospitals, the increases seen in some HAIs in 2021 contrast with the success in reducing these infections prior to the pandemic. Despite the challenges of the COVID-19 pandemic, acute care hospitals performed significantly better than the 2015 national baseline in preventing CLABSI, CAUTI, SSIs following colon surgeries, and C. difficile infections.”
The AHA recommended that hospitals “continue to reinforce prevention practices and review HAI surveillance data to identify areas for improvement.”
Dangers of Antimicrobial Resistance
According to CDC data, in the US there are 2.8 million antimicrobial infections each year, and more than 35,000 people die as a result. Dark Daily has reported extensively on the growing danger of antibiotic resistance and outlined the importance of clinical laboratory involvement in hospital antimicrobial stewardship programs.
In “During Pandemic, Clinical Laboratories Should Be Alert for Drug Resistant Infections That Pose High Risk to COVID-19 Patients,” we covered a study conducted at the University of Minnesota which highlighted the continuing need for microbiologists and clinical laboratories to stay alert for COVID-19 patients with drug-resistant infections following a CDC report on 941 confirmed and probable Candida auris cases that had been reported in 13 states, with an additional 1,830 patients that had been found to be colonized with the multidrug-resistant fungus.
The Joint Commission’s expansion of antibiotic stewardship standards, which went into effect on January 1, 2023, could help hospitals reduce nosocomial infections and fight antimicrobial resistance.
Pew conducted research related to the requirements and found “significant room for improvement in adoption and implementation of stewardship practices” in acute care hospitals, Hyun wrote.
Allocate financial resources for staffing and IT to support the antimicrobial stewardship program.
Implement evidence-based guidelines to improve antibiotic use for infections such as urinary tract c. diff. community-acquired pneumonia.
Evaluate the program using evidenced-based criteria.
“New antibiotic stewardship standards should help limit the emergence and spread of new drug-resistant superbugs,” Hyun noted.
Clinical Laboratories Need to Deepen Involvement
By testing patients and quickly reporting results to physicians, hospital-based and independent medical laboratories play an important role in appropriate antibiotic use and elimination of HAIs.
Heightened involvement by microbiologists and other medical laboratory professionals is key to success in light of recent setbacks in elimination of HAIs and antimicrobial resistance due to the SARS-CoV-2 outbreak.
