Update on Antibiotic Resistance: December 2019

Doc Gumshoe's attention turns to "Thirty-five Thousand Americans Die of Antibiotic-Resistant Infections Each Year”

By Michael Jorrin, "Doc Gumshoe", December 19, 2019

The headline that snagged my attention was this: 

Thirty-five Thousand Americans Die of Antibiotic-Resistant Infections Each Year”

This was based on the Centers for Disease Control’s Antibiotic Resistance Threats in the United States, 2019, which led off with the statement that more than 2.8 million antibiotic-resistant infections occur in the US every year, and more than 35,000 people die as a result. 

This was a pretty big uptick from the previous figures from the CDC, which Doc Gumshoe had reported in a piece back in March 2017.   At that time, the most recent tally for deaths was 23,000.   The number cited back then for antibiotic-resistant infections was just about 2 million.   The increases were quite a bit larger than one would expect – 40% over two years for infections, and nearly 50% for deaths.   And considering that antibiotic resistance has been getting a great deal of attention, those increases are alarming.   What’s happening, and what are we going to do about it?

Speaking for myself only, I was more troubled by the rise in the number of antibiotic-resistant infections than by the deaths, because “cause of death” is a somewhat fungible bit of data.   For example, if a person recovering from a traumatic injury develops an infection while hospitalized, and the infection turns out to be due to a pathogen that does not respond to any of the drugs used to try to control that infection, and the patient in question then sustains a heart attack and dies, what is the cause of death?   Answer, not the antibiotic-resistant infection.   It was the MI that carried him off.   Similarly, patients with congestive heart failure who are hospitalized may acquire a nosocomial (hospital-acquired) infection resulting in pneumonia that does not respond to whatever is used for treatment.   That patient’s cause of death will likely be reported as congestive heart failure.   This would suggest that the number of deaths related to antibiotic-resistant pathogens was, if anything, larger than the official report.

But the increase in antibiotic-resistant infections in genuinely scary, considering that infections rank fairly low among health-care concerns, at least in the “developed” world.   There are well-publicized and well-funded campaigns to end cancer, HIV, and any number of childhood diseases, but the assumption has been that, antibiotics having been invented, infections can be managed.   Well, not so fast.

It’s not as though resistance is a newly emergent phenomenon.   Microbes have been engaged in a battle against their enemies since those little organisms emerged from the primordial slime.   The process goes like this.   As one generation of microbes gives rise to another generation, there are tiny glitches in the transcription of the genetic material.   Some of those glitches are relatively meaningless.   Some are fatal – creatures with those glitches fail to reproduce and die out.   But some are valuable.   They encode survival characteristics.   Some of those survival characteristics are resistance to their natural enemies – other organisms that would, if they could, attack them and kill them.   The organisms that possess those beneficial glitches survive and multiply.

Precisely the same thing is happening now.   Bacteria, parasites, viruses, and fungi, as they reproduce, do not transcribe their genetic material with complete accuracy.   The offspring are not identical to the parents.   In some cases, the differences in genetic material encode characteristics that enable them to resist their enemies, which in this case may be the antibiotics that have been introduced into their environment specifically to kill them or at least to halt their spread.   The organisms that have those resistance characteristics are the ones that survive and reproduce; the antibiotics eliminate the unprotected remainder.

This process frequently takes place over time.   The patient is dosed with the drug daily, or twice daily, for periods sometimes of a month or even longer.   With each administration of the antibiotic, more of the susceptible pathogens get eliminated, leaving the resistant pathogens to reproduce.   Sometimes, the population of pathogens becomes mostly or entirely resistant to the antibiotic.

Clinicians try to address this problem in several ways.   A regimen of antibiotics may start with an extra heavy dose of the drug, with the intention of effecting a major reduction in the pathogen population right off the bat.   This is then followed by a treatment period which can last a considerable time, depending on the particular infection.   The objective is to reduce to pathogenic population to a level where it can no longer form a colony.   

A major impediment to this process is that a great many patients do not continue the full course of their antibiotic.   In many cases, a patient will feel considerably better after just a few days of treatment with the antibiotic, and say, “I feel just fine.   Why do I have to keep taking that pill?”

It also happens with considerable frequency that physicians prescribe antibiotics when there’s no reason to do so, as in the treatment of viruses.   A new study, published in the British Medical Journal, but conducted in the US, looked at data from more than 28,000 ambulatory clinic visits and found that only about 57% of antibiotic prescriptions were appropriate, that is, for the treatment of bacterial infections.

For example, when children catch colds that are nasty enough to keep them home from school, they are sometimes required to present proof that they were seen by a physician before being allowed back into the classroom.   And when their parents take them to the doctor, the parent wants a prescription for something.   The parent is thinking, “The kid has a cold!   For Lord’s sake, give her something to help her get over it, or at least prevent her from catching something worse.”   But then, after a couple of days, the kid’s cold vanishes, and her mother stops making her take her medicine.   So, even if the child was infected with one of those upper respiratory viruses that are hanging around, the antibiotic did have an effect, but what it did was kill off some of the population of susceptible bacteria that are present in all of our bodies.   It killed off the susceptible germs, but left unharmed the ones that had some kind of resistant mechanism.   Those remained, and reproduced.   

The child is now the carrier of a potentially dangerous source of infection, which she might pass on to a debilitated elderly relative or to another child whose immune system is temporarily compromised, or, in fact, to anyone at all.

What mechanisms do pathogens use to defend themselves against antibiotics?

For example, let’s look at Acinetobacter baumanii.   This little bug didn’t get a lot of attention until military personnel in Iraq and Afghanistan began to be infected with this particular pathogen, which got nicknamed “the Iraquibacter.”   A. baumanii  infected many soldiers who had been injured by explosive devices.   Their open wounds came into contact with the pathogen, which can survive for fairly long periods on exposed surfaces.   When the infected soldiers were admitted to hospitals, the pathogens spread, sometimes to other patients.   A. baumanii  has been identified as the cause of nearly 20% of cases of pneumonia in patients who require the assistance of a ventilator in some hospitals.   It happens to be related to Staph aureus, Klebsiella, and Pseudomonas aeruginosa  (a pathogen particularly linked with the development of pneumonia in intubated hospital patients).   All of these bugs are good at developing the mutations that combat antibiot