Nav: Home

How best to treat infections and tumors

February 09, 2017

In cases where drug resistance can lead to treatment failure, new research shows that therapies tailored to contain an infection or a tumor at tolerable levels can, in some cases, extend the effective life of the treatment and improve patient outcomes. In other cases, aggressive treatments aimed at eliminating as much of the infection or tumor as possible -- the traditional approach -- might be best. But how can we know which stands the better chance of working?

A new mathematical analysis by researchers at Penn State University and the University of Michigan, publishing February 9, 2017, in the open-access journal PLOS Biology, identifies the factors that determine which of the two approaches will perform best, providing physicians and patients with new information to help them make difficult treatment decisions.

"People die when their infections or tumors become drug resistant," said Andrew Read, Evan Pugh Professor of Biology and Entomology and Eberly Professor of Biotechnology at Penn State and an author of the study. "We analyzed when it might be better to use drugs to contain rather than try to eliminate the infection or tumor. We find there are situations where containment would keep the patient alive longer, but also situations where it would make a dire situation even worse. That means using (and testing) the containment strategy needs to be done very carefully, but if done right, it could help patients with life-threatening infections and tumors live longer."

The researchers compared the two treatment strategies with the goal of maximizing the amount of time until the treatment failed due to the development of drug resistance. For most infections and tumors, people can tolerate a certain amount of the pathogen without ill effects. For the analysis, a patient was considered healthy and the infection or tumor was considered to be managed if it was maintained at or below this level of "acceptable burden." Treatment failed if the pathogen level rose above this level. The analysis showed that the treatment leading to the longest time until treatment failure will depend on the specific characteristics of the disease, or even of the patient being treated, but it provides a framework that doctors and patients can use to make more-informed decisions about treatments.

"There are situations where we can be relatively sure that treatment will completely eliminate the infection or tumor, so aggressive treatment is the obvious choice" said Elsa Hansen, a research associate at Penn State and an author of the paper. "On the opposite end of the spectrum, there are low-level situations like urinary-tract or ear infections where a doctor may decide not to treat at all. The majority of cases, however, are somewhere in between and require hard choices that balance the damage caused by the infection or tumor and the risk of mutation with the damage caused by the treatment itself and the risk of developing uncontrollable resistance. Our analysis provides guidance for making these decisions from a standpoint of maximizing patient well-being."

The researchers focused on two main factors that influence whether or not an infection or tumor will develop drug resistance. The first is the rate at which cells that are initially sensitive to a particular treatment become resistant. The second factor is called "competitive suppression" and refers to the fact that the spread of resistance, once it appears, can be slowed through competition for resources with cells that are sensitive to treatment. More cells that still respond to treatment leads to more competition to prevent the spread of resistant cells, but it also means a greater risk of the sensitive cells developing resistance.

"The standard practice has been to treat infections and tumors as aggressively as possible to minimize the risk of cells becoming resistant," said Read, "but our analysis shows that, in many situations, containing the infection or tumor to allow for competitive suppression of resistant cells can increase the time to treatment failure. Of course, the opposite can also be true, so determining which approach will be best has to be done carefully and on a case-by-case basis".
-end-
In addition to Read and Hansen, the research team includes Robert J. Woods at the University of Michigan. The research was funded by the National Institute of General Medical Science of the U. S. National Institutes of Health and the Penn State Eberly Family Professorship in Biotechnology.

CONTACT

Andrew Read: a.read@psu.edu, 814-321-5004

IMAGE

An image with caption and credit is available at https://psu.box.com/v/Read2-2017

CAPTION

Methicillin-resistant Staphylococcus aureus (top, purple), cancer cells (bottom). Treatment designed to contain, rather than eliminate, chronic infections or tumors where drug resistance can emerge may delay treatment failure. Credit: NIAID (MRSA), Dr Cecil Fox (Photographer), via Wikimedia Commons (cancer cells).

ARCHIVE

-- After the embargo lifts, this information will be archived at http://science.psu.edu/news-and-events/2017-news/Read2-2017

Penn State

Related Drug Resistance Articles:

Drug overcomes chemotherapy resistance in ovarian cancer
In an international preclinical study, researchers found they could overcome chemotherapy resistance in clear cell ovarian cancer cell models using low doses of the drug 2-deoxy-D-glucose.
Engineers model mutations causing drug resistance
Whether it is a drug-resistant strain of bacteria, or cancer cells that no longer react to the drugs intended to kill them, diverse mutations make cells resistant to chemicals, and 'second generation' approaches are needed.
Double success for University drug resistance research
Swansea University research into the threat posed by antifungal drug resistance has been highlighted in two prestigious international journals.
What fuels a 'domino effect' in cancer drug resistance?
KAIST researchers have identified mechanisms that relay prior acquired resistance to the first-line chemotherapy to the second-line targeted therapy, fueling a 'domino effect' in cancer drug resistance.
New flu drug drives drug resistance in influenza viruses
University of Wisconsin-Madison researchers examined the effects of baloxavir treatment on influenza virus samples collected from patients before and after treatment.
Resistance to last resort drug arose in patient over 3 weeks
French investigators have described development of resistance to one of the last resort therapies used to treat extremely drug-resistant Pseudomonas aeruginosa.
Cause of drug resistance in a drug resistance in intestinal tumors identified
Researchers clarify mechanisms that allow hard-to-treat cancers to develop, and have identified strategies that could lead to new therapies.
Engineered viruses could fight drug resistance
MIT biological engineers can program bacteriophages to kill different strains of E. coli by making mutations in the protein that the viruses use to bind to host cells.
Origin of resistance to lung-cancer drug discovered
Researchers at Kanazawa University report in Nature Communications what causes some lung-cancer patients to have an intrinsic resistance to the drug osimertinib: AXL, a protein belonging to the class of receptor tyrosine kinases.
New drug resistance process found in bacteria
Researchers at the UAB and the UMBC have described a new process capable of generating resistance to synthetic antibacterial drugs within bacterial populations long before their invention and without the existence of any similar substance in nature.
More Drug Resistance News and Drug Resistance Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.