International health officials recently warned of a “catastrophic threat” to human health, given one of the last remaining antibiotics capable of defeating superbugs – carbapenem antibiotics – is succumbing to the deadly bacteria.
The group of bacteria in question is called enterobacteriaceae. These organisms cause a range of serious infections which, if left untreated, can kill. With the growing resistance to carbapenems, and limited options available to treat these infections, patients are increasingly succumbing to the infection.
So, what exactly is enterobacteriaceae? And how did we get ourselves into this situation?
The rise of superbugs
Once in a while, a special drug comes along that seems to revolutionise medicine. Take penicillin: derived from the mould penicillium, it was first used in the 1940s, and subsequently became the most heavily used antibiotic of all time.
Unfortunately, with time it became clear that some bugs were able to outsmart penicillin, as well as other subsequently developed antibiotics, to become resistant. This occurs as bacteria evolve and develop spontaneous mutations in their genome, providing them with mechanisms of protection against the antibiotic. The result? The antibiotic is no longer able to work.
To complicate things, these resistant suberbugs are also able to share these genes between other bacteria, resulting in the spread of antibiotic resistance.
To fight back, scientists developed a number of derivatives of penicillin and similar drugs, which combat resistant organisms. The molecular structure of these drugs shares a common beta-lactam ring and thus they became known as beta-lactams. They all work to stop the bacteria from being able to create its cell wall, resulting in its death.
The heroes of this class of antibiotic are known as carbapenems. They comprise a number of drugs that have a broad spectrum of activity and mostly differ in dosing, tolerance and degree of effectiveness, including doripenem, meropenem, imipenem and ertapenem. For a short while, these drugs seemed to revolutionise medicine yet again.
To an infectious diseases physician, carbapenems were the antibiotics at the end of a short line, to be used only in situtations where other drugs don’t work. Unfortunately, their use has now become common, leading to a growing number of carbapenem-resistant bacteria, called enterobacteiacea.
Enterobacteriacea are organisms that mostly live in the gastrointestinal tract of humans and animals, water and soil. They include common pathogens such as Klebsiella pneumoniae, E. coli, Proteus mirabilis and Enterobacter cloacae, all of which are important causes of hospital and community-acquired infections including urinary tract infections, intra-abdominal and respiratory tract infections.
Losing the battle
Resistance to antibiotics has been present since their conception. But while we were once able to combat superbugs with new antibiotics, over the past two decades we’ve seen little development of new drugs to target them, and growing resistance.
Bacteria, despite being single-cell organisms, are capable of acquiring a number of different mechanisms to combat antibiotics. It is essentially a war between bug and drug, where only the bug is acquiring new ammunition.
As part of its artillery, carbapenem-resistant enterobacteriaceae have gained a number of mechanisms of resistance to drugs in this class, including being able to produce enzymes that reduce the activity of the drug. New Delhi metallo-beta-lactamase 1, or NDM-1 bacteria as they’re commonly known, are perhaps the most well-known and dangerous enzymes to emerge in recent years.
Unfortunately, carbapenem-resistant enterobacteriaceae are, in a sense, family oriented and are able to pass on genes that encode for resistance mechanisms onto their relatives. With the ease of travel in this era, resistance genes are traversing the world. Along with genes encoding for resistance against carbapenems, these organisms also carry genes that confer resistance to other classes of antibiotics.
Infectious diseases physicians have a very small repertoire of drugs to kill resistant enterobacteriaceae and have to resort to new ways of using older drugs, such as polymyxins and fosfomycin, and using a combination of antibiotics.
Tigecycline is a newer drug, which works in the laboratory, but has not been trialled extensively for enterobacteriaceae; there are already growing reports of resistance.
Resistance is an ever-growing problem for which the answer lies in more than just the next revolutionary drug. Drug development and active research in novel ways of targeting these bacteria is very important.
But the biggest battle in the war against antibiotic resistance is the policing of their use, be it in the clinical or industrial setting. We need to stop inappropriate prescribing of antibiotics, in instances where they are unlikely to help, such as viral infections, and target antibiotic use according to culture and resistance testing.
Smart use of these valuable drugs is essential.