By
Dina Fine Maron on September 7, 2016
Several
times a week Brad Spellberg struggles with a difficult decision. A
patient stumbles into his emergency room in southern California
suffering from familiar symptoms: pressure when she urinates, pain in
her side, fever and nausea. Based on these clues Spellberg can quickly
diagnose the problem as a kidney infection, but the trouble lies in
deciding what he should do next. He knows the patient is hurting and of
course he wants to help, but more than his patient’s health hangs in the
balance.
Like any emergency room clinician Spellberg has two disparate
options. The first is to treat the patient with a powerful antibiotic
called carbapenem, administered intravenously. It would wipe out a
variety of bacteria that might be causing the infection, but there is a
catch. Deploying this precious resource may make it less likely he can
use it to treat a future patient. The drug would kill susceptible
bacteria but it would also fuel resistance by allowing the few microbes
that are able to survive carbapenem to thrive and multiply. Spellberg’s
second option is to send the patient home with a lower-level class of
drug, a quinolone. The stakes of his decisions are high. If a relatively
mild bacterium is behind the patient’s infection, a quinolone would
neutralize it and the patient would recover. But if the infection is
caused by a drug-resistant pathogen, the patient would not recover
without carbapenem and the untreated infection may worsen.
Spellberg’s catch-22 comes down to an issue of timing. He will not
know exactly what bug is causing the patient’s infection for several
days because there are no fast, cheap diagnostic tests available. So it
will take three days for lab workers to identify the patient’s
assailant. Spellberg cannot wait that long to make his choice. His
dilemma, sadly, is not uncommon. Across the country doctors are
struggling with the same issues he faces as the chief medical officer at
the Los Angeles County + University of Southern California Medical
Center.
Such situations now represent a key front against encroaching
antibiotic resistance. And there is alarming evidence that we are
quickly losing ground. In August, for example, the World Health
Organization issued new guidance on sexually transmitted diseases. It
said that the standard drugs used to treat gonorrhea are often no longer
effective due to escalating resistance. Now WHO recommends employing
two drugs against the bacterium that causes the infection. Moreover,
earlier WHO analysis concluded that antibiotic-resistant pathogens are
now present in every part of the world—jeopardizing a century of medical
advances.
The threat of antibiotic resistance has become so dire that the
United Nations General Assembly is holding a meeting to discuss it this
month in New York City. Although WHO has been sounding the alarm on
antibiotic resistance for years, this month’s high-level U.N. meeting
represents only the fourth time in the international body’s history that
its General Assembly—a global deliberative body that primarily grapples
with issues like war and economics—has held a meeting to tackle a
health topic. (The other three were HIV, noncommunicable diseases and
Ebola.) The meeting “is a clear recognition that this is a worldwide
threat to everyone and worldwide action is what we need to address it,”
says Ezekiel Emanuel, chair of medical ethics and health policy at the
University of Pennsylvania.
The pressure to hold such a high-level meeting has grown in recent
years, even as unnecessary or incorrect antibiotic use in health care
settings and agricultural production has exacerbated the problem. For
example, when agricultural producers treat their healthy livestock or
fish with antibiotics to help speed their growth and keep them healthy
in subpar conditions, they are simultaneously fueling resistance that
can sideline the drugs for human use.
A New Urgency
The September 21 U.N. meeting will come on the heels of some
particularly bad news about superbugs. Last November an analysis
published in
The Lancet Infectious Diseases reported
that scientists had detected resistance to a last-line antibiotic
called colistin in meat animals and people in China—likely from use of
colistin in livestock to speed agricultural production. The resistant
gene was found on a plasmid, a length of DNA that can be easily
transferred between different strains of bacteria. Then, more bad news:
In recent months we have seen the spread of this colistin resistance
gene emerging rapidly in various areas around the globe.
Colistin-resistant
Escherichia coli has surfaced in more than 30 countries, including in a patient in the U.S. One strain of
E. coli
in the U.S. has actually proved resistant to both carbapenem and
colistin (but fortunately that strain appears to be susceptible to some
other antibiotics). “The fact we are so concerned about colistin
resistance is a sign of how desperate we are,” says Lance Price, a
microbiologist and director of the Antibiotic Resistance Action Center
at The George Washington University. “It’s a shitty drug. It’s toxic and
doctors don’t like to use it, but now they have to use it because it’s
the only thing that treats some of these drug-resistant infections.”
Expanding Our Arsenal
Keiji Fukuda, special representative of the WHO Director-General for
Antimicrobial Resistance, says the coming U.N. meeting is designed to
elevate the discourse on antibiotic resistance and signal this is a high
priority. “The previous discussions have been held at the level of
ministers of health and agriculture but this meeting will take this up
to the level of prime ministers and presidents,” Fukuda explains. Yet
the actions that are hoped for as a result of the meeting remain meager.
No binding agreement is expected. What may be more realistic, Fukuda
says, is a political declaration of commitment to coordinate further on
this issue. “This may seem like a relatively easy thing, but to get that
kind of cooperation on a worldwide basis is extremely difficult,” he
says. The discussions will also hopefully include the recognition and
commitment of financing to support such plans, he says.
Encroaching antibiotic resistance will not slow to keep pace with
international diplomacy, however. It has been decades since a new class
of antibiotics has been introduced—a needed innovation as more pathogens
become resistant to existing antimicrobials. Researchers say that new
antibiotics might not be the only option. Other weapons under
development—likely to be used with antibiotics—include reintroducing
tiny bacterial parasites called bacteriophages against some pathogens.
Research teams are also looking into engineering souped-up antibodies to
beat back specific infections or developing medications that would
modulate a human’s immune response to a pathogen—because in some cases
blocking inflammation will help alleviate much of the damage from
infections. Another approach, Spellberg says, might be to employ
iron-sequestration technologies that would passively starve microbes so
they cannot grow in the body. Still other research pursued by Price and
others zeros in on the gut microbiome, in the hope of designing
probiotics that would change or help tamp down problematic bacterial
colonization. “There’s not one silver bullet for combating antibiotic
resistance,” Spellberg says. “Many things need to be explored so the
solutions that are most promising will bubble to the surface.”
Already, drug resistance risks in our daily lives—outside of health
care settings and farms—often go unrecognized but represent a growing
concern. One little-discussed issue is community-acquired
infections—situations in which people contract a superbug through food,
drink or by touching a contaminated surface and then putting their hands
in their mouths, Spellberg says. In such situations patients may
unwittingly pick up superbugs that can reside in the gut without causing
any issues for weeks or years. It is only when those superbugs go
elsewhere in the body—the urinary tract, for example—that they can
become dangerous or even deadly.
Unfortunately, this is already happening with alarming frequency. A
recent small analysis found that about a third of patients with
infections and resistance to major antibiotics (including penicillins
and cephalosporins) did not have typical resistance risk factors such as
exposure to a health care setting, prior use of antimicrobial drugs or
international travel. That suggests they contracted their superbug
infections in their own communities where the microbes apparently
circulated, undetected.
There are already things that
can be and are being done—with
mixed results—to combat the increase in antibiotic resistance. One such
measure is shortening the duration of drug treatment to the bare
minimum required to end an infection. (Longer courses put selective
pressure on the bacteria in the body, which can help resistance grow.)
The Infectious Diseases Society of America, for example, has recently
changed its guidelines for hospital- and ventilator-acquired
pneumonia—shaving the recommended treatment time down to seven days or
less based on new science showing that is long enough to treat the
patient. Yet Spellberg worries that too often such recommendations only
exist on paper, and have not yet been put into practice. He says
consumers can help ensure the best future for our existing drugs by
taking steps to protect themselves: washing their hands and vegetables,
disinfecting surfaces, asking their doctors if antibiotics are truly
necessary and getting vaccinated to prevent infections.
Yet perhaps the most intractable problem remains sparking investments
to expand the arsenal against these microbes. “The basic issue is this
research is needed but we don’t have the business models to facilitate
or encourage this,” Fukuda says. Drugmakers often say that without a
different incentive structure—perhaps government rewards for new classes
of antibiotics—it does not make good business sense to invest in
antibiotics when they could focus on projects that would command higher
profits, such as new drugs to fight cancer. In Spellberg’s emergency
room, however, patients simply cannot afford to wait.
Scientific American