Antibiotic Resistance: What’s Happening?

Doc Gumshoe checks up on the superbugs...

By Michael Jorrin, "Doc Gumshoe", April 25, 2017

[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]

Since the Doc Gumshoe piece in October 2013, it has only gotten worse, or at least, a lot more worrisome.   Just at the end of February, the World Health Organization issued yet another dire warning about “superbugs” – pathogens which appear to be resistant to all known antibiotics.

Is this a major threat to you, the denizens of Gumshoeland, most of whom reside in North America?   Doc Gumshoe tries to steer a careful course between sounding alarms when alarms need to be sounded and his native optimism, for which he was regularly chided by his clear-eyed mother.   In this case, I tend to agree with WHO.   The situation is serious, and likely to get worse unless there are aggressive initiatives, few signs of which appear to be on the horizon.

Whether these superbugs are a menace to non-hospitalized people in okay health as they are going about their daily activities is the question to which most of us would like a reliable answer.   But here’s a statistic as provided by the Centers for Disease Control: infections due to resistant pathogens have been the cause of death for 23,000 Americans in the last year for which data are available, and the number is predicted to hold steady or increase slightly.   Considering the numbers that die of heart disease and cancer – about 600,000 of each disease – the 23,000 that will die from superbugs may seem like a relatively minor menace.   However, for the sake of comparison, it’s estimated that 38,000 Americans will die in automobile accidents this year, and we as a nation do not view car crash mortality as a minor menace.

And, by the way, that 23,000 is likely to be an underestimate.   In attributing causes of death, the CDC eliminates any deaths that could be attributed to other causes.   If the patient had a resistant infection that led to pneumonia, but died of heart failure, the cause of death is heart failure.   No matter that if the patient had not become infected with pneumonia, he/she would not have succumbed to heart failure.

Multidrug-resistant (MDR) pathogens in the Enterobacter class, including E. coli, have increasingly been identified in children with a range of diseases, especially urinary tract infections.   A study published this February (Meropol S. J Pediatric Infec Dis 2017) investigated 107,610 discharge records from 48 pediatric hospitals, and found that a small but rapidly increasing percentage of these infections were caused by MDR bacteria.   In January 2007, just 0.2% of those infections were due to MDR bacteria, but the proportion increased to 1.5% by March 2015, an increase of 750%.   These pediatric infections did not lead to an increase in fatalities, but they did cause significant increases in the time children remained hospitalized.

About three-quarters of these MDR infections were acquired in the community.   The authors of the study observed that this fact was an additional cause for concern.   It is understood that in spite of stringent precautions, hospital-acquired (nosocomial) infections are a threat.   But the presence of MDR pathogens in the community means, in the words of the authors, that “they will spread – we can catch them anywhere.”   They urged more controlled use of drugs such as third and fourth generation cephalosporins and carbapenems.

The particular development that has most recently pushed the superbugs into the spotlight is that some of the antimicrobials that have been considered to be drugs of last resort for treatment of resistant infections have just in the past few years been found to be ineffective against some resistant pathogens.   The drugs in question are carbapenems and a member of the polymyxin group called colistin.   Resistance to carbapenems is still somewhat rare, but carbapenem- resistant Enterobacter species have been found in 44 states in the US.

Colistin is a seldom-used drug in humans because it is associated with severe kidney damage, but it has been held in reserve for use in severe infections with pathogens that resist all other available agents.   Obviously, clinicians would not routinely use a drug that might cause kidney damage if there were a more benign antibiotic available.   For example, a pathogen that causes severe lower respiratory and urinary tract infections, Klebsiella pneumoniae, causes life-threatening infections particularly in hospitalized patients.   Klebsiella is routinely treated with drugs in classes such as fluoroquinolones and third- and fourth-generation cephalosporins.   If those don’t work, the next option would likely be a carbapenem.   But some resistance to carbapenems began to be noted in 2008.   Colistin would then be the drug of last resort.   However, the first patient with a colistin-resistant pathogen was identified in the US in 2016.   After colistin, there are no other options.

How did this come to be?

With regard to colistin, the likely culprit is China, where pig farmers annually feed about 12,000 tons to their pigs to accelerate their growth.   Bacteria resistant to colistin were found in 2015, and at present more than 20% of pigs in China are colonized with this drug-resistant bacterial strain.   Of more concern is the report that about 1% of hospitalized humans have that drug-resistant strain.   And of greater concern still is the mechanism through which these pathogens become resistant.   The gene that conveys resistance is not part of the bacteria’s own DNA, but is part of a plasmid, which is a DNA ring independent of the bacterial DNA and can transfer genetic material between different cells.   In other words, resistance in one bacterial species can be transferred to another.

Chinese pig farmers are by no means the only culprits in the spread of antibiotic resistance.   It’s estimated that somewhere around 80% of all the antibiotics used in the US are fed to animals.   There has been a lot of squabbling about this issue between the livestock and poultry industries and organizations focused on human health.   The former claim that putting antibiotics in the feed means that their animals will be healthier and safer to eat, and will pass fewer diseases along to humans.   But the health authorities push in the other direction.   It’s one thing to keep disease at bay among the pigs and chickens.   It’s entirely another thing to pump them full of antibiotics so as to bring them to market more quickly.   And those antibiotics are also present in the pork chops and chicken cutlets that we eat, as well as in the animal waste.   Tiny amounts, no doubt, but capable of engendering microbial resistance.   How does this happen?

Why do microbes develop resistance to antibiotics?

The short answer is, to survive!   Micro-organisms, like all organisms, evolve in nature.   Every organism is constantly under threat from other organisms, and every species of organism constantly undergoes mutations, some of which are beneficial, and some of which turn out to be the opposite of beneficial.   So a beneficial mutation tends to spread, while a mutation that increases risk tends to die out.   The same thing is true for micro-organisms,