One topic that I don’t discuss enough is the role that the agricultural use of antibiotics plays in the evolution (and ecology) of antibiotic resistance. A recent review in Clinical Microbiology and Infection describes how the illegal use of nitrofuran antibiotics in Portugese agriculture led to an increase in highly virulent Salmonella.

What are nitrofurans? There are several different nitrofuran antibiotics (furazolidone, nitrofurazone, and nitrofurantoin), but the one drug some readers might have heard of (or taken) is nitrofurantoin, which is used to treat urinary tract infections, in part, because these strains have evolved resistance to other antibiotics. Nitrofurantoin typically is not the first drug used to treat urinary tract infections because there can be complications from long-term nitrofurantoin use. It also makes your pee orange–this, in and of itself, has no health consequences other than upsetting the Mighty Pee Gods.

By 1995, the European Union had banned the use of nitrofuran antibiotics in agriculture because they can elevate the risk of cancer (these antibiotics kill bacteria by damaging bacterial DNA once the bacterium inadvertently changed these antibiotics into DNA damaging forms). Because these antibiotics don’t break down very quickly, they are deemed a health hazard. In 2002, the U.S. banned all uses of nitrofuran antibiotics in agriculture.

In 2002-2003, there was an ‘outbreak’ of illegal nitrofuran antibiotic use in Portugese poultry farming. Decreased susceptibility of Salmonella to nitrofurantoin skyrocketed to 65% of all Salmonella isolates, and the prevalence in food animals of S. Enteriditis serogroup D* isolates also increased (these particular salmonellae are very effective at causing disease in humans). Also, the frequency of nitrofurantoin resistance was indistinguishable between hospital isolates and poultry, while Samonella from other sources had much lower frequencies of resistance.

There was an added ‘bonus’: nitrofurantoin resistant Salmonella were more likely to be resistant to other antibiotics too. One thing to keep in mind is that Salmonella are the tip of the iceberg. Just like cefquinome use, the real concern should be the evolution of resistant–in this case, nitrofurantoin resistant–E. coli. Think of it all microbial ‘collateral damage.’

For those of you keeping score at home, E. coli results in about 70% of all urinary tract infections, and, in the U.S., kills around 9,000 people/year due to urinary tract infections gone horribly wrong. Remember what I said the primary use of nitrofurantoin in human medicine is: treating urinary tract infections.

This is one more reason why using these antibiotics responsibly is so critical in preserving the power of these literally life-saving drugs.

*No, I didn’t screw up the italicizing or capitalization. Salmonella taxonomy is a pandimensional clusterfuck.