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Researchers Find That Antibiotic-Resistant Bacteria Can Persist in the Body for Years

Study results from Switzerland come as clinical laboratory scientists seek new ways to tackle the problem of antimicrobial resistance in hospitals

Microbiologists and clinical laboratory scientists engaged in the fight against antibiotic-resistant (aka, antimicrobial resistant) bacteria will be interested in a recent study conducted at the University of Basel and University Hospital Basel in Switzerland. The epidemiologists involved in the study discovered that some of these so-called “superbugs” can remain in the body for as long as nine years continuing to infect the host and others.

The researchers wanted to see how two species of drug-resistant bacteria—K. pneumoniae and E. coli—changed over time in the body, according to a press release from the university. They analyzed samples of the bacteria collected from patients who were admitted to the hospital over a 10-year period, focusing on older individuals with pre-existing conditions. They found that K. pneumoniae persisted for up to 4.5 years (1,704 days) and E. coli persisted for up to nine years (3,376 days).

“These patients not only repeatedly become ill themselves, but they also act as a source of infection for other people—a reservoir for these pathogens,” said Lisandra Aguilar-Bultet, PhD, the study’s lead author, in the press release.

“This is crucial information for choosing a treatment,” explained Sarah Tschudin Sutter, MD, Head of the Division of Infectious Diseases and Hospital Epidemiology, and of the Division of Hospital Epidemiology, who specializes in hospital-acquired infections and drug-resistant pathogens. Sutter led the Basel University study.

The researchers published their findings in the journal Nature Communications titled, “Within-Host Genetic Diversity of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales in Long-Term Colonized Patients.”

“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,” said epidemiologist Maroya Spalding Walters, MD (above), who leads the Antimicrobial Resistance Team in the Division of Healthcare Quality Promotion at the federal Centers for Disease Control and Prevention (CDC). “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.” Clinical laboratories working with microbiologists on antibiotic resistance will want to follow the research conducted into these deadly pathogens. (Photo copyright: Centers for Disease Control and Prevention.)

COVID-19 Pandemic Increased Antibiotic Resistance

The Basel researchers looked at 76 K. pneumoniae isolates recovered from 19 patients and 284 E. coli isolates taken from 61 patients, all between 2008 and 2018. The study was limited to patients in which the bacterial strains were detected from at least two consecutive screenings on admission to the hospital.

“DNA analysis indicates that the bacteria initially adapt quite quickly to the conditions in the colonized parts of the body, but undergo few genetic changes thereafter,” the Basel University press release states.

The researchers also discovered that some of the samples, including those from different species, had identical mechanisms of drug resistance, suggesting that the bacteria transmitted mobile genetic elements such as plasmids to each other.

One limitation of the study, the authors acknowledged, was that they could not assess the patients’ exposure to antibiotics.

Meanwhile, recent data from the World Health Organization (WHO) suggests that the COVID-19 pandemic might have exacerbated the challenges of antibiotic resistance. Even though COVID-19 is a viral infection, WHO scientists found that high percentages of patients hospitalized with the disease between 2020 and 2023 received antibiotics.

“While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, three out of four or some 75% of patients have been treated with antibiotics ‘just in case’ they help,” the WHO stated in a press release.

WHO uses an antibiotic categorization system known as AWaRe (Access, Watch, Reserve) to classify antibiotics based on risk of resistance. The most frequently prescribed antibiotics were in the “Watch” group, indicating that they are “more prone to be a target of antibiotic resistance and thus prioritized as targets of stewardship programs and monitoring.”

“When a patient requires antibiotics, the benefits often outweigh the risks associated with side effects or antibiotic resistance,” said Silvia Bertagnolio, MD, Unit Head in the Antimicrobial resistance (AMR) Division at the WHO in the press release. “However, when they are unnecessary, they offer no benefit while posing risks, and their use contributes to the emergence and spread of antimicrobial resistance.”

Citing research from the National Institutes of Health (NIH), NPR reported that in the US, hospital-acquired antibiotic-resistant infections increased 32% during the pandemic compared with data from just before the outbreak.

“While that number has dropped, it still hasn’t returned to pre-pandemic levels,” NPR noted.

Search for Better Antimicrobials

In “Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons,” Vox reported that scientists around the world are researching innovative ways to speed development of new antimicrobial treatments.

One such scientist is César de la Fuente, PhD, Presidential Assistant Professor at University of Pennsylvania, whose research team developed an artificial intelligence (AI) system that can look at molecules from the natural world and predict which ones have therapeutic potential.

The UPenn researchers have already developed an antimicrobial treatment derived from guava plants that has proved effective in mice, Vox reported. They’ve also trained an AI model to scan the proteomes of extinct organisms.

“The AI identified peptides from the woolly mammoth and the ancient sea cow, among other ancient animals, as promising candidates,” Vox noted. These, too, showed antimicrobial properties in tests on mice.

These findings can be used by clinical laboratories and microbiologists in their work with hospital infection control teams to better identify patients with antibiotic resistant strains of bacteria who, after discharge, may show up at the hospital months or years later.

—Stephen Beale

Related Information:

Resistant Bacteria Can Remain in The Body for Years

‘Superbugs’ Can Linger in the Body for Years, Potentially Spreading Antibiotic Resistance

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

Drug-Resistant Bacteria Are Killing More and More Humans. We Need New Weapons.

How the Pandemic Gave Power to Superbugs

WHO Reports Widespread Overuse of Antibiotics in Patients Hospitalized with COVID-19

Swiss Researchers Develop a Multi-omic Tumor Profiler to Inform Clinical Decision Support and Guide Precision Medicine Therapy for Cancer Patients

New biomarkers for cancer therapies derived from the research could usher in superior clinical laboratory diagnostics that identify a patient’s suitability for personalized drug therapies and treatments

In another advancement toward accurate precision medicine, Swiss researchers from the University Hospitals of Zurich and Basel, ETH Zurich, the University of Zurich, and pharmaceutical company Roche have developed a multi-omic tumor profiling technology for cancer patients they hope will isolate biomarkers that allow doctors to tailor drug therapies to individual patients’ medical needs.

Once approved for clinical use, not only would these biomarkers become targets for specific cancer therapies, they also would require development of new diagnostic tests that anatomic pathologists could use to determine whether a biomarker was present in a patient.

If yes, the drug can be administered. If no, the patient is not a candidate for that drug. Thus, this research may produce both diagnostic biomarkers and therapeutic targets.

The researchers published their study in the journal Cancer Cell, titled, “The Tumor Profiler Study: Integrated, Multi-omic, Functional Tumor Profiling for Clinical Decision Support.”

Relevance of In-Depth Tumor Profiling to Support Clinical Decision-Making

In the Swiss “Tumor Profiler” (TuPro) project, the research team is examining the cellular composition and biology of tumors of 240 patients with melanoma, ovarian cancer, and acute myeloid leukemia. Recruitment for the study began in 2018. Today, the melanoma cohort is fully enrolled, and the ovarian cancer and acute myeloid leukemia cohorts are nearing complete enrollment.

“The Tumor Profiler Study is an observational clinical study combining a prospective diagnostic approach to assess the relevance of in-depth tumor profiling to support clinical decision-making (“fast diagnostic loop”) with an exploratory approach to improve the biological understanding of disease (“exploratory science loop”),” the TuPro website states.

Tumor Profiler graphic

The graphic above taken from the Tumor Profiler project paper illustrates how the TuPro study’s workflow entails patient enrollment, sample collection, analysis by different technology platforms, and data integration, creation and discussion of molecular research and summary reports, discussion of treatment options in pre-tumor boards and the final treatment decision in tumor boards. (Photo copyright: Cancer Cell.)

“For this study of melanoma, ovarian carcinoma, and acute myeloid leukemia tumors, in addition to the emerging standard diagnostic approaches of targeted NGS panel sequencing and digital pathology, extensive characterization is performed using the following exploratory technologies: single-cell genomics and transcriptomics, proteotyping, CyTOF, imaging CyTOF, pharmacoscopy, and 4i drug response profiling (4i DRP),” the TuPro website explains.

In their published paper, the Swiss researchers say these three cancers were selected for the study “based on the potential clinical benefit and availability of sufficient tumor material for simultaneous analysis across all technologies.”

Gunnar Rätsch PhD

According to a University Hospital Basel blog post, the TuPro project examination of each cancer tumor goes “much further than the limited use of molecular biological methods” used by leading hospitals. “This results in huge amounts of data per patient, which we process and analyze using data science methods,” stated data scientist Gunnar Rätsch, PhD (above), Professor for Biomedical Informatics at ETH Zurich and one of the study’s corresponding authors, in the blog post. This research could lead to new precision medicine biomarkers for clinical laboratory cancer diagnostics and therapies. (Photo copyright: ETH Zurich.)

The TuPro Project’s findings are available to doctors who analyze them at interdisciplinary tumor board meetings and generate treatment options, creating a “fast diagnostic loop” with an estimated four-week turnaround time from surgery to tumor board. “This approach has the potential to alter current diagnostics and paves the way for the translation of comprehensive molecular profiling into clinical decision-making,” the study’s authors wrote in Cancer Cell.

Could Oncologists Be Making Better Precision Medicine Decisions?

In its writeup on the TuPro Project’s research, Precision Oncology News concluded that the Swiss study “is rooted in the researchers’ notion that oncologists are not making the best personalized treatment decisions for patients by relying just on targeted DNA profiling using next-generation sequencing and digital pathology-based tests.

“The researchers within the TuPro consortium hypothesized that integrating a more comprehensive suite of omics tests could lead to a more complete understanding of patients’ tumors, including providing insights into the tumor microenvironment, heterogeneity, and ex vivo responses to certain drugs. This, in turn, could help inform the best course of treatment,” Precision Oncology News added.

“With the Tumor Profiler study, we want to show that the widespread use of molecular biological methods in cancer medicine is not only feasible, but also has specific clinical benefits,” said TuPro consortium member Viola Heinzelmann-Schwarz, MD, Head of Gynecological Oncology at University Hospital Basel, in an ET Zurich news release.

New Precision Medicine Biomarkers from TuPro’s Molecular Analysis

Researchers in the study also are investigating whether and what influence the molecular analysis had on doctors’ therapy decisions.

The University Hospital Basal blog notes the long-term benefits of the Tumor Profiler approach is to expand the personalized-medicine therapy options for patients, including determining whether patients would benefit in certain cases “if they were not treated with drugs from standard therapy, but with drugs that have been approved for other types of cancer.”

Anatomic pathologists and clinical laboratory scientists will want to take note of the TuPro project’s ultimate success or failure, since it could usher in changes in cancer treatments and bring about the need for new diagnostic tests for cancer biomarkers.

—Andrea Downing Peck

Related Information

The Tumor Profiler Study: Integrated, Multi-omic, Functional Tumor Profiling for Clinical Decision Support

The Tumor Profiler Study: Integrated, Multi-omic, Functional Tumor Profiling for Clinical Decision Support

Detailed Profile of Tumors

Swiss Study to Prospectively Assess Value of Multi-Omic, Functional Tumor Profiling

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