The fluoroquinolone antibiotics are important drugs indeed – ciprofloxacin is probably the most famous of the bunch, but there’s a whole series of them, and they’re widely used for serious bacterial infections. (I last wrote about them here, with the various arguments about how they were developed in the first place).
But for many years now, it’s been increasingly clear that this class of drugs can have some very unwelcome effects in some patients. The most prominent of these is tendon damage, which often showing up as problems with the Achilles tendon, up to outright rupture even months after drug treatment. Other muscle and connective tissue effects have been seen, as well as CNS effects and others. Over the years, the drugs have picked up black-box warnings for these effects, which seems entirely appropriate.
How do these things happen, though? Any theory has to take into account the fact that the great majority of patients seem tolerate the drugs pretty well, but that suggests that a better knowledge of the mechanism might let you pick out which people shouldn’t take them in the first place. This article at Nature is a good summary of current research in the area. An intriguing possibility is that the effects are (at least partially) due to mitochondrial damage, likely oxidative stress, and that this might be correlated with patients who do not metabolize the fluoroquinolone scaffold as well as the general population. This might allow levels of the drugs to build up intracellularly, and since mitochondria are always dealing with the effects of their metabolic role, they’re vulnerable to being overloaded. It’s worth remembering that mitochondria have bacteria-like ancestry, so they’re certainly not guaranteed against large antibiotic concentrations. Indeed, bactericidal antibiotics in general have been associated with oxidative damage, an effect that has not gone unnoticed in drug development efforts.
There’s a disturbing part of the Nature article, though, where some researchers in the field talk about their worries about publishing results that could affect the commercial prospects of widely used drugs. I understand companies wanting to protect themselves against unfounded accusations, and there’s an endless supply of those. This blog allows me a personal look at many of them, and they just keep on coming. But not all reports of trouble with marketed drugs are unfounded – far from it. It’s a black eye for the industry to go after honest researchers reporting their honest results. Every big organization is vulnerable to falling into this sort of overdefensive behavior under pressure, but that means that the effect is well-known enough that it should be guarded against more effectively. We should be better; we should do better.