In the early 1960s, a team of researchers developed a new class of synthetic antibacterial compounds called quinolones that circumvented the limitations of existing antibiotic drugs. The team discovered that a synthetic compound called nalidixic acid worked effectively against Gram-negative bacteria present in uncomplicated urinary tract infections (UTIs). However, the drug’s use was limited because it required high concentrations and caused adverse side effects, which led researchers to continue working to improve it. (Source)
The team proceeded to synthesize analogs of the drug to find the most potent and effective compounds for clinical use. During the 1980s, there was a major breakthrough in the development of a class of synthetic broad spectrum antibiotics that became the major treatment for many commonplace infections. (Source)
Researchers attached fluorine atoms to the quinolones’ structures, creating a new type of antibiotic known as fluoroquinolones. These new antimicrobials could eliminate a broader range of bacterial infections and even penetrate tissues throughout the body, including the central nervous system. Subsequent generations of fluoroquinolones have been developed that can be used to treat even more kinds of infections.
Nowadays, fluoroquinolones are some of the most prescribed antibiotics in the US, with more than 24 million prescriptions written in 2017, making them the fourth highest-selling class of antibiotics. (Source) However, as with many antibiotics, overuse has led to the development of drug-resistant bacteria that are more difficult to treat.
Read on to learn more about fluoroquinolone toxicity, also known as the reason why even the most effective treatments can call for caution.
What Are Fluoroquinolones, and Why Should I Care?
They’re a family of antibiotics
Fluoroquinolones are a class of broad spectrum antibiotics used to treat a wide range of respiratory, urinary, skin, gastrointestinal, and sexually transmitted infections. However, they are best known for their effectiveness against serious infections, such as certain types of bacterial pneumonia. (Source)
There are more than 60 generic fluoroquinolones. Some of the FDA-approved fluoroquinolones include:
- Levofloxacin (Levaquin)
- Ciprofloxacin (Cipro)
- Ciprofloxacin extended-release tablets
- Moxifloxacin (Avelox)
- Gemifloxacin (Factive)
- Delafloxacin (Baxdela)
They’ve been linked to serious side effects
Fluoroquinolones are notorious for causing antibiotic-associated adverse events, ranging from diarrhea to a potentially permanent syndrome that the FDA has deemed “fluoroquinolone-associated disability” (FQAD). The increasing list of severe adverse effects has led the FDA to issue a black box warning about the serious risks of fluoroquinolones. (Source, Source)
They’ve been overprescribed to treat infections
Despite the FDA’s recommendations, fluoroquinolones are prescribed for common infections that occur in the upper respiratory tract, sinuses, skin, and urinary tract. Although the drugs are not intended for routine infections, they are often prescribed as first-line therapy for infections that can be effectively treated with other antibiotics. In 2018, the journal Clinical Infectious Diseases reported an estimated 20% of outpatient fluoroquinolone prescriptions were given for conditions that were more appropriately treated with less powerful antibiotics, and 5% were given for conditions that shouldn’t be treated with antibiotics at all. (Source, Source)
Fluoroquinolone resistance in humans is linked to farm use
Campylobacter food poisoning in humans — usually picked up from contact with raw or undercooked chicken — was once easily treated with fluoroquinolones, especially ciprofloxacin. After the FDA approved fluoroquinolones for use in poultry, though, Campylobacter bacteria in chickens began developing resistance to the antibiotics. These resistant bacteria are passed on to humans, with studies estimating that 19% of Campylobacter strains infecting humans in the US are now ciprofloxacin-resistant, with resistance rates exceeding 80% in Spain. Also of concern is the rise in drug-resistant E. coli infections, which may also be associated with the use of fluoroquinolones in poultry. (Source, Source, Source)
How Do Fluoroquinolones Work?
Fluoroquinolones work by damaging bacterial DNA. They inhibit two essential enzymes — gyrase, which is involved in DNA replication, and topoisomerase IV, which helps to unwind DNA so that it can be copied. By disrupting these two enzymes and causing breakage of bacterial chromosomes, fluoroquinolones prevent the synthesis of bacterial DNA, resulting in bacterial cell death. (Source)
What Does the Research Show About Fluoroquinolone Toxicity?
Fluoroquinolones have been associated with an increased risk of tendon rupture
In a study of human Achilles tendon cells, researchers found that fluoroquinolones can damage collagen in tendons, which can lead to tendon ruptures. The researchers found that the fluoroquinolones inhibit an enzyme involved in the synthesis of collagen, which is critical for the strength and structure of tendons. (Source, Source, Source)
They have a high association with aortic aneurysms
In a number of observational studies, researchers found that fluoroquinolone antibiotics were associated with an increased risk of aortic dissections and ruptured aortic aneurysms. The FDA has estimated the rate of aortic aneurysm rupture among patients to fall between nine and 300 events out of every 100,000. (Source, Source, Source)