Aggressive treatment, however, may not always be for the best.
Even when it initially works, antimicrobial medicines and chemotherapy
can suddenly become ineffective.
Research suggests that in some cases where drug resistance can lead to
treatment failure, containing an infection or a tumor at a tolerable level
can improve patient outcomes.
In other cases, the traditional approach of elimination might be better.
The problem is in determining which option is likely to be successful.
Researchers at Penn State University and the University of Michigan developed
a mathematical analysis to identify factors that can help in that determination.
Acceptable disease burden
The researchers compared containment to eradication.
Their goal was to lengthen the amount of time until drug resistance developed.
You can have a certain amount of infection or tumor without being sick.
It’s called an “acceptable burden.”
In their paper, the researchers wrote that the concept of an acceptable
burden is their core premise.
They acknowledge this is likely to make clinicians uneasy.
They recognize situations, such as bacterial meningitis, where there’s
no acceptable burden.
Identifying the maximum acceptable burden is a complex problem.
To determine if an infection or tumor would develop drug resistance, the
researchers looked at two key things.
One was the rate at which cells become resistant.
The other was “competitive suppression.” In cells that are
responding to treatment, there’s a competition for resources. More
competition can slow the spread of resistant cells. However, there’s
a risk that the sensitive cells will also develop resistance.
The infection or tumor was considered to be managed if it was maintained
at or below the level of acceptable burden. The treatment was considered
a failure if a pathogen rose above that level.
The researchers found that containment can sometimes double a patient’s
“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,” Elsa Hansen, a research associate at Penn
State, and an author of the paper, said in a press release.
“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,” she continued.
“The majority of cases, however, are somewhere in between,”
she added, “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.”
How long treatment can continue before failing depends on the disease and
the person. There won’t be a single solution that applies to everyone.
The researchers' goal is to provide a basic outline so doctors and
patients can make informed choices.
The growing problem of resistance
There’s no doubt that antimicrobial drugs have saved a lot of lives.
But the more we use them, the more resistant infectious organisms become.
According to the
U.S. Centers for Disease Control and Prevention (CDC), 2 million people are infected with antibiotic-resistant organisms every
year, causing 23,000 deaths.
“Drug resistance is a major problem in cancer and infection,”
said Dr. Timothy Byun, medical oncologist at the
Center for Cancer Prevention and Treatment at St. Joseph Hospital in California.
“Antimicrobial drug resistance is a major public health crisis. According
to WHO [World Health Organization], it is a major global health threat,”
Byun wrote in an email to Healthline. “Many cancers are incurable
because chemotherapy may not completely eradicate cancer cells.”
Antibiotic resistance is a consequence of evolution, said Dr. Santosh Kesari.
“We’ve had various stages of health crises over the years.
Flesh-eating bacteria, for example, is very resistant.”
Kesari is a board-certified neurologist and neuro-oncologist, and current
chair of the Department of Translational Neuro-Oncology and Neurotherapeutics at the
John Wayne Cancer Institute at Providence Saint John’s Health Center in California.
In an interview with Healthline, Kesari said that antibiotic resistance
is obvious right away when a patient doesn’t respond. Sometimes
that’s the case with chemotherapy as well.
“But here we’re talking about getting an initial response to
treatment. Then resistance develops. This can take weeks or months,” he said.
There are several reasons cancer cells become resistant to treatment.
Sometimes the cancer is heterogeneous to begin with.
You might wipe out one type, but a different type of cell starts to grow.
It takes over and creates a resistant tumor.
Kesari explained that sometimes killing a tumor with drugs can actually
promote regrowth. It may be better to just keep it stable.
“The question is, can we do better in preventing resistance by understanding
the tumor better in the beginning? Maybe giving multiple drugs rather
than one could resolve this at the start,” said Kesari.
“What you’re doing in the short term may, in the long run,
be bad because of the emergence of resistance. Rather than aggressive
treatment up front, containment might have a better long-term effect,”
“For infection, we use multiple antibiotics right away. This is to
prevent resistance from happening. In cancer, combination therapy rather
than a single agent is more complicated. It takes time to study each drug
and combine them safely.”
“It’s a significant problem,” said Kesari.
“We need to think about this more carefully. This paper describes
an approach of containment rather than elimination. That’s interesting.
But it needs to be proven in a clinical setting that this concept works
using drugs that don’t necessarily kill 100 percent of cells, but
contain the tumor, and with the same outcome. That includes different
cancer types and types of infection. That’s what ultimately needs
to be proven,” said Kesari.