One of the most commonly used fluoroquinolones, ciprofloxacin, has dramatic negative effects on the mitochondrial genome, and should thus be used with great caution, a new study published in Nucleic Acids Research suggests.
Mitochondria possess their own small circular genome, which requires topoisomerase enzymes for its maintenance.
While fluoroquinolones inhibit the bacterial topoisomerase gyrase, thus killing bacterium, they also inhibit topoisomerase 2, the study found.
“We noticed that topoisomerase 2 is especially important in the replication of the mitochondrial genome, as it regulates the winding of this small DNA molecule by removing positive twists,” study author Steffi Goffart said.
Ciprofloxacin stopped this normal maintenance and transcription of mitochondrial DNA by changing its topology, causing impaired mitochondrial energy production and blocking cellular growth and differentiation.
This dramatic impact on mitochondrial DNA is the likely cause for most negative fluoroquinolone side effects (eg, involving muscles, tendons and bones and the nervous system) experienced by patients, and fluoroquinolone antibiotics should thus be used with great caution, the study authors said.
Earlier this month, the European Medicine Agency’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended restricting the use of fluoroquinolone and quinolone antibiotics following a review of disabling and potentially long-lasting side effects reported with these medicines.