Antibiotic Resistance: The End of Eras Versus the Death of Silver Bullets

The type of antibiotic resistance you typically hear about in popular treatments is of the ‘ZOMG UR GONNA DIE11!!11’ type. In other, more grammatical words, we’re often discussing the evolution of organisms that are untreatable, such as carbapenem-resistant enterobacteriaceae (‘CRE’). Needless to say, these are real problems: if you get an infection with one of these organisms, all we can really do is support the patient, attempt to mitigate the symptoms, and hope for the best (I’ve had more than one conversation where, after being told that these infections can’t really been treated, someone says, “So how do you treat it?” Erm…).

So things we can not treat are one obviously very scary type of resistance–it often leads to morose, if accurate, phrases like ‘the end of the antibiotic era’. But there’s another way resistance can do a lot of harm: the destruction of silver bullets.

Scary Disease Woman, aka ‘Maryn McKenna’, describes a disturbing development regarding Shigella* infections (boldface mine):

the CDC describes the discovery of Shigella sonnei resistant to ciprofloxacin or Cipro, which was until now the go-to drug for treating it. Until very recently, almost all Shigella was susceptible to Cipro, but since last May, this newly resistant strain has caused 243 cases of illness in 32 states and also in Puerto Rico.

It [Shigella] causes fever and bloody diarrhea, and though people who contract it often get better on their own, it is so unpleasant and so very contagious that antibiotics are often used to end the episode faster and reduce the chances of spreading the disease. “There’s a very small infectious dose—10 bacteria are sufficient to cause infection,” Dr. Anna Bowen of the CDC told me by phone. “It’s easy to get that infectious dose onto surfaces.” (For comparison, the infectious dose of the foodborne disease Campylobacter is about 500 organisms, and Salmonella infection can require more than 1,000.)

If the bacteria don’t respond to the antibiotic given to cure a person’s case, then that person stays infectious longer, and the chances of outbreaks grows—and those outbreaks can become a significant hazard to public health. For instance: While investigating this new strain, the CDC identified a cluster of 95 cases among homeless people in San Francisco, who because of their living conditions have both obvious challenges maintaining good hygiene, and no choice about spending time in public places where they might pass the bacteria to others. “Other Shigella outbreaks we have followed over the years can reach to the multiple hundreds of people involved and can last for months and into years,” Bowen said.

Widespread outbreaks are problematic because Shigella can be a very serious illness, especially for anyone with a compromised immune system: the elderly, the very young, anyone living with HIV or undergoing cancer chemotherapy. And the changes in this strain make treatment more difficult; it has significant resistance to streptomycin, sulfa drugs, tetracycline and the drug combo known as Bactrim or Septra (trimethoprim/sulfamethoxazole or TMP-SMX) as well. “In this particular outbreak, 22 percent of patients were hospitalized,” Bowen said.

The problem with ciprofloxacin-resistant Shigella isn’t that we can’t treat it. According to the CDC report, most isolates could be treated with either amoxicillin or azithromycin. These are not difficult to administer or expensive drugs. There are other treatment options for that patient.

The problem is that, rather than making a diagnosis of shigellosis and administering ciprofloxacin with a high success rate and rapid recovery**, it will take longer to treat, as the doctor now needs to find out from the clinical lab what antibiotics should work. That’s more suffering for the patient (shitting bloody diarrhea is nobody’s idea of a good time) and a longer hospital stay (and longer absenteeism from work, etc.). From a public health perspective, we really don’t want to use other drugs: every time we use even an older beta-lactam antibiotic like amoxicillin, we are selecting for bacteria that have resistance to beta-lactam antibiotics, including newer versions of these antibiotics. Ditto for azithromycin: azithromycin resistance genes often travel with genes that confer resistance to other classes of antibiotics.

The disappearance of antibiotic ‘silver bullets’ in many ways is the public health analog of diabetes–it typically won’t kill you, but it can make everything else worse. And unlike diabetes, antibiotic resistance spreads from person to person (that’s why it’s called infectious disease).

Which brings us to another sunny point in ‘McKenna’s’ article:

The final unsettling piece of this story is that molecular evidence gathered by the CDC and its state research partners (through a nationwide data-sharing network called PulseNet that I hope to talk about sometime) demonstrates that this resistant strain exists outside the US and was carried across borders repeatedly by travelers returning home…

This is an unsolvable vulnerability in public health: Gut carriage of organisms such as NDM, which originated in India several years ago, has allowed antibiotic resistance to spread internationally in a way that is difficult to detect or prevent. (Some hospitals in Europe check patients before admitting them, by conducting rectal swabs, but that’s not really going to work at Passport Control.) It’s a reminder that antibiotic resistance arising anywhere is a threat to people everywhere…

One thing we–and by “we” I mean certain members of the Tribe Econ–could do is stop promoting medical tourism as a solution to the U.S.’s inability to provide affordable healthcare.

*From an evolutionary perspective, Shigella are E. coli, but they have some unique phenotypic characteristics, so they remain a separate genus.

**If you’ve had an infection while being otherwise healthy, the recovery when antibiotics are effective is usually nothing short of miraculous.

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1 Response to Antibiotic Resistance: The End of Eras Versus the Death of Silver Bullets

  1. NotMarkT says:

    Infectious dose > 1 is a misnomer. There is no “safe” non-zero ingested dose for pathogens.

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