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Getting a bacterial infection is no
big deal, right? Your doctor prescribes an antibiotic and you get well.
Not so fast. Some bacteria—like Acetinobacter, aka Iraqibacter—have become resistant to
commonly used antibiotics; some "superbugs" can withstand a host of
different medications. A sobering case in point is Staphylococcus
aureus. As this time line shows, strains of
Staph aureus have gotten the
better of every antibiotic we've developed, often within just a year or
two of a new agent's introduction. Follow this ongoing arms race and
learn about its unsettling implications below.—Ron
Lubelchek
Penicillin resistance reported (1942)
Only a year after an English
constable named Albert Alexander became the first patient to receive penicillin,
experts identified strains of Staph aureus
that showed resistance to the "miracle" drug. (Ironically, the
original culture dish upon which the Scottish biologist Alexander Fleming had
first observed the antibiotic properties of the penicillium mold in 1928 was
growing colonies of Staph aureus.)
Experts now know that, without controls, a single-celled bacterium like Staph
aureus can give rise to five billion
trillion new cells in a day. With such exponential growth, the chance for
natural mutations that might confer resistance is robust. Currently, over 90
percent of Staph aureus strains
are essentially immune to penicillin.
Methicillin resistance reported (1961)
As with penicillin, only a year
passed after this semi-synthetic penicillin was released before
methicillin-resistant Staph aureus
(MRSA) was reported. Initially, MRSA only appeared in hospitals and nursing
homes, but in the past decade it has become a major public health problem,
sickening otherwise healthy people in the community. Often it lurks in schools,
gyms, and other places where people come in close contact with one another.
Most cases involve only a minor skin infection, such as a boil, but some prove
deadly. A 2007 Centers for Disease Control study reported that serious Staph
aureus infections struck over 94,000 people
in the U.S. in 2005, contributing to the deaths of 18,650 of them, more than
died of AIDS that year.
Staph aureus gains vancomycin-resistant gene
from Enterococci bacteria (1992)
In the laboratory, scientists
documented Enterococci, a strep-like
bacteria, transferring a vancomycin-resistant gene known as vanA into Staph
aureus. Such "horizontal gene
transfer" has been observed in many bacterial species, including
Iraqibacter. (We humans can only do "vertical" transfer, from
parents to their offspring.) With this ability, microbes don't need to
evolve resistance themselves but simply appropriate it from other pathogens
that already have. Experts knew after this study, if not before, that it would
only be a matter of time before Staph aureus gained resistance against vancomycin in the outside
world.
Partial Vancomycin resistance was reported five years later.
Partial vancomycin resistance
reported (1997)
Vancomycin, originally derived from
a soil bacterium scooped from the rain forests of Borneo, demonstrated more
tenacity against the ever-evolving staph than any other antibiotic. But
eventually its defenses weakened. In 1997, the first strains of so-called
vancomycin-intermediate Staph aureus, or
VISA, were reported. VISA strains, by definition, require a minimum of 4 to 8
micrograms per milliliter of vancomycin to inhibit bacterial growth in a test
tube. Again, experts knew all too well that full vancomycin resistance would
eventually appear.
Full Vancomycin resistance was reported in 2002.
Quinupristin/dalfopristin
resistance reported (2000)
In the laboratory, this one-two
punch initially showed activity against methicillin-resistant Staph aureus. But like all antibiotics that came before it, it
quickly lost its immunity. In the United States, certain strains of Staph
aureus had acquired resistance within a
year after this pair was approved for use. With each weakened
antibiotic, bacterial infections are becoming more severe, require longer and
more complex treatments, and are more expensive to diagnose and treat.
Linezolid resistance reported (2001)
Linezolid, a broad-spectrum
antibiotic, fared no better than its predecessors in, well, resisting
resistance. Introduced to the market in April 2000, its standing was shaken by
the following July, when the first resistant strain was reported; other
resistant strains appeared in 2003 and 2004. To date, bacteria have discovered
resistance to all classes of antibiotics. The molecular mechanisms by which
they have done so remain diverse and complex, stymieing easy explanation.
Full vancomycin resistance
reported (2002)
In 2002, specialists reported the
first full vancomycin-resistant strain of Staph aureus. By definition, such strains require a dose of
vancomycin greater than or equal to 16 micrograms per milliliter to inhibit the microbe's growth in the test
tube. Neither raising the dose nor using vancomycin in combination with other
antibiotics has helped to any degree. As one researcher put it bluntly, "S.
aureus has evolved; vancomycin has
not." Fortunately, outright resistance to vancomycin remains vanishingly
rare, though partial resistance is becoming increasingly frequent.
Daptomycin resistance reported (2005)
Daptomycin binds to the membrane of
the Staph aureus cell, disrupting the
membrane's function. But some strains, predictably, got around this,
developing resistance to Daptomycin within two years of its release. Staph
aureus's ever-evolving resistance
casts a more ominous shadow when one considers the range of severe infections
it can cause, including pneumonia as well as bloodstream and surgical-wound
infections. Characterized by the death of tissue, hence the colloquial term
"flesh-eating bacteria," these severe infections have killed both
adults and children.
Tigecycline resistance reported (???)
Approved in 2005, Tigecycline has
shown activity against multidrug-resistant Staph aureus. Resistance to this new agent has yet to be
documented in clinical isolates—that is, strains from individual patients
studied in the lab. But judging from past history, it will happen soon enough.
And so the arms race continues, with fears of a post-antibiotic era rising with
each new hardy strain. Several things need to happen, experts say: Wanton
overuse of antibiotics in medicine and agriculture must be curbed. Hospitals
need to improve basic hygiene. Pharmaceutical companies, large universities,
and the government need to step up their currently anemic R&D of the next
generation of antibiotics. And a vaccine against Staph aureus is essential. Several vaccines are in early stages of
development, but none will be available soon. Meanwhile, Staph aureus lies in wait, ready to adapt once again.
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