I have a story in the April Scientific American (“The Enemy Within,” just previewed online) about a new and very troubling form of antibiotic resistance: Carbapenem resistance, spreading through Gram-negative bacteria such as Klebsiella (above, from the CDC) and E. coli.
Carbapenems are drugs of last resort for Gram-negatives, which include many of the bacteria that cause potentially deadly infections in debilitated ICU patients and frail elderly in nursing homes. Gram-negatives have been becoming ever-more resistant to antibiotics, but the carbapenems remained reliable drugs of last resort for even the most serious cases. Then, in 1996, researchers at the Centers for Disease Control and Prevention spotted the first signal that carbapenems were under threat: A single bacterial sample, found in a patient in a North Carolina hospital, that was resistant to the carbapenems and could only be treated by a few remaining drugs that were much less effective or so toxic that medicine had put them on the shelf years ago.
By 2000, that same resistance pattern surfaced in hospitals in Manhattan: first one, then another, then a third and fourth. Then it began to spread to cities where New Yorkers vacation, and then to countries where they travel. Now, more than a decade later, it has reached at least 37 states and at least a dozen countries around the world.
It is spreading much faster than drugs to combat it could be developed — if there were such drugs. One of the difficulties, indeed tragedies, of carbapenem resistance is that there are very few such drugs left — because, for reasons I’ve explored before, drug development in the United States has ground to a halt. For resistant Gram-negatives, there are almost no drugs left, and none on the immediate horizon. If that scares you, well, it should.
The end of the antibiotic miracle is not a new theme. For as long as there have been antibiotics, there has been antibiotic resistance: The first penicillin-resistant bacteria surfaced before penicillin was even released to the marketplace in the 1940s. And for almost that long, doctors have raised the alarm over running out of drugs, sparked by the global spread of penicillin-resistant organisms in the 1950s and followed by methicillin resistance in the 1980s and vancomycin resistance in the 1990s.
This time, though, the prediction of post-antibiotic doom comes from a different part of the microbial world. The genes that confer carbapenem resistance have appeared over the past decade or so in a particularly challenging grouping of bacteria called gram-negatives.
Gram-negative bacteria are promiscuous: They facilely exchange bits of DNA, so that a resistance gene that arises in Klebsiella, for example, quickly migrates to E. coli, Acinetobacter and other gram-negative species. Gram-negative germs are also harder to dispatch with antibiotics because they have a double-layered membrane that even powerful drugs struggle to penetrate, and possess certain internal cellular defenses as well. In addition, fewer options exist for treating them. Pharmaceutical firms are making few new antibiotics of any type these days. For the protean, stubborn gram-negatives, they have no new compounds in the pipeline at all.
Carbapenem resistance has already brought hospital-acquired infections to the brink of untreatable. The imagined future that keeps health authorities awake at night is the undetected dissemination of carbapenem resistance genes into organisms that cause everyday maladies—such as E. coli, which is responsible for most of the millions of urinary tract infections in the U.S. every year.