Since I haven’t discussed antibiotic resistance for a while, I want to put that health problem in context. The CDC estimates that every year, over 60,000 U.S. residents die from a hospital-acquired bacterial infection that is resistant to one or more commonly used antibiotics. Roughly 25,000 per year die from bacterial infections resistant to three or more antibiotics (e.g., MRSA). And that’s just the infections you catch in the hospital. For a little perspective, HIV/AIDS kills under 18,000 U.S. residents per year. Antibiotic resistance is a serious, albeit neglected, problem.
Onto the post. I realize the post title has more obscure jargon than a bad Tom Clancy novel. Translated for those who don’t speak Biology, CTX-M-15 ESBL is a bacterial gene that confers resistance to most of the beta-lactam antibiotics (and all of the oral ones)–that means the antibiotics that start with “cef-” or end with “-cillin” don’t work (aztreonam also can’t kill these bacteria). This gene also makes bacteria resistant to cefepime, which is commonly used to treat serious infections in immunocompromised patients. It’s also resistant to cefquinome, an antibiotic used in European agriculture; where cefquinome is used, CTX-M-15 is often found. To make things worse, CTX-M-15 is found on plasmids; plasmids are mini-chromosomes that can be transfered between different bacteria (even those that diverged tens of millions of years ago). At this point, it’s not a speculative matter of if this plasmid–and the CTX-M-15 gene–can jump species: it’s already done so.
Scary stuff, but so far it’s been very rare in the U.S., and only very rarely observed in hospitals.
Erm, not anymore (italics mine):
Although CTX-M-producing E. coli have previously been found in the United States, clinical descriptions of community-acquired ESBL-producing E. coli infections have not been reported in this country. We describe 2 healthy young women in Pennsylvania in whom UTI with CTX-M-15-producing E. coli developed….
To our knowledge, these 2 cases represent the first cases of community-acquired ESBL-producing E. coli known to have occurred in the United States.
It’s the phrase “community-acquired” that is terrifying. What that means, without getting into the population genetics*, is that CTX-M-15 is at high enough frequencies in the existing E. coli fauna (remember that most E. coli live in mammals as harmless commensals) that we can no longer make it ‘extinct.’ It also means that the gene is common enough that widespread, uncontrolled use of antibiotics could cause this gene to increase in frequency–and remember, there’s a whole slew of antibiotics that would favor bacteria that have this gene. In other words, we are no longer in the prevention business, but now in the control business–this gene is not going away. By contrast, we have been able to prevent the evolution of vancomycin-resistant Staphylococcus aureus (VRSA). VRSA evolves, but we’ve been able to squash it before it spreads (so far….).
So what is the effect of CTX-M-15 possessing E. coli? In typical understated CDC fashion (italics mine):
These 2 patients did not appear to have substantial clinical effects from their infections. However, the potential importance of community-acquired ESBL-producing E. coli is that UTI may be associated with bloodstream infection. Empiric antimicrobial therapy of bloodstream infection presumed to be of urinary tract origin typically comprises use of fluoroquinolones, aminoglycosides, or ceftriaxone. ESBL-producing E. coli may be resistant to all of these antimicrobial agents. In the United Kingdom, 25 of the first 108 patients with documented community-onset ESBL-producing E. coli infections died. Frequent occurrence of ESBL-producing E. coli in the United States would be an important public health problem and may necessitate changes in empiric antimicrobial therapy.
Essentially, we would have to start using carbapenems to treat urinary tract infections, which would increase resistance to those drugs. So how did these CTX-M-15 bacteria evolve. Funny you should ask that….
If these infections were truly community-acquired, how and why did they arise? The CTX-M-15 ESBL has been found in many countries. We do not know the travel histories of these 2 patients. Thus, the organisms may have been acquired overseas. We assessed the genetic relatedness of these 2 strains by pulsed-field gel electrophoresis but found no evidence of clonality (data not shown). Another possibility is that food was the source of infections. CTX-M-15-producing E. coli have been detected in food-producing animals, and we have recently found CTX-M-15-producing E. coli in chicken sold at a Pittsburgh area supermarket. We are currently conducting ongoing surveillance for community-acquired ESBL producers in our region in E. coli isolates from both humans and from foodstuffs to determine the prevalence of CTX-M producers in the United States.
Between this and KPC, we might lose all of the beta-lactams in five to ten years. Not good.
*Basically, the argument is as follows. The effective population size of E. coli is roughly 1,000,000,000, give or take. For a resistance gene to be detected in the community, it would probably be present in 0.01% of isolates (or more). While that sounds small, 0.01% of a billion (or even ten million) is enough bacteria such that genetic drift will not purge the population of this gene. The awful irony of most surveillance systems that look at community samples (i.e., not stuff evolving in hospitals) is that once they detect resistance, it’s already too late to put the genie back in the bottle. That doesn’t mean, however, that interventions which keep resistance low (or lower high frequencies of resistance) aren’t important in terms of disease and economic burden. But it’s a lot cheaper to prevent something (e.g., VRSA) than to control it (e.g., CTX-M-15).
Oh, geeze, this is really not good.
And, hey, what do you know? Just at the time this gene is starting to pop up in significant frequencies, the FDA is allowing cefquinome use in agriculture. Because what we really need right now is a strong selective pressure to increase the frequency of this gene in food-borne bacterial populations.