Pefloxacin - Mode of Action

Mode of Action

Pefloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which is an enzyme necessary to separate, replicated DNA, thereby inhibiting cell division.

• Mechanism of action:

The bactericidal action of pefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.

The fluoroquinolones interfere with DNA replication by inhibiting an enzyme complex called DNA gyrase. This can also affect mammalian cell replication. In particular, some congeners of this drug family display high activity not only against bacterial topoisomerases, but also against eukaryotic topoisomerases and are toxic to cultured mammalian cells and in vivo tumor models. Although the quinolone is highly toxic to mammalian cells in culture, its mechanism of cytotoxic action is not known. Quinolone induced DNA damage was first reported in 1986 (Hussy et al.)

Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of micronuclei. As such some fluoroquinolones may cause injury to the chromosome of eukaryotic cells.

There continues to be considerable debate as to whether or not this DNA damage is to be considered one of the mechanisms of action concerning the severe and non abating adverse reactions experienced by some patients following fluoroquinolone therapy.