The mode of action of quinolones: the paradox in activity of low and high concentrations and activity in the anaerobic environment.
All 4-quinolones that have been examined display rapid bactericidal activity which is biphasic. At concentrations above the MIC, the lethality of the drugs increases until a concentration known as the optimum bactericidal concentration (OBC) beyond which the bactericidal activity then declines. The biphasic response appears to be due to the inhibition of RNA synthesis at concentrations above the OBC, as RNA synthesis is required for the full bactericidal activity of the 4-quinolones. However, differences in the biphasic response are observed as some fluoroquinolones are still able to kill bacteria in the absence of bacterial protein or RNA synthesis, thus reducing the inhibition of bactericidal activity at concentrations above the OBC. It has been proposed that this ability to kill bacteria in the absence of protein or RNA synthesis is due to the possession of an additional bactericidal mechanism by these fluoroquinolones. Oxygen also appears to be essential for the lethality of the clinically available 4-quinolones although it is not required for the drugs to inhibit bacterial multiplication. Therefore these drugs are not bactericidal under anaerobic conditions.
Lewin
C S
CS
Bacteriology Department, University of Edinburgh Medical School, UK.
Morrissey
I
I
Smith
J T
JT
D042462:4-Quinolones; D000693:Anaerobiosis; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D012329:RNA, Bacterial / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
D042462:4-Quinolones; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D012329:RNA, Bacterial