Cristina Monica Popescu 1, Adriana Hristea 2, Mihaela Rădulescu 2, Victoria Aramă 2, Daniela Nicolae 2, Daniela Munteanu 2, Ruxandra Moroti 2, Raluca Mihăilescu 2
1 Spitalul Judeţean Slatina, Secţia Boli Infecţioase
2 Institutul de Boli Infecţioase „Prof. Dr. Matei Balş”
Abstract
Fluoroquinolones are antibacterials with a broad activity, which is not identical for all the molecules in this class. The first fluoroquinolones are active mostly on gram negative aerobian bacilli and less on gram positive germs, while new generations of fluoroquinolones (starting with levofloxacine) are highly active on gram positive and atypical germs. Fourth generation fluoroquinolones are also active on anaerobic bacteria. Fluoroquinolones inhibit DNA synthesis, by interacting with DNA and DNA-gyrase and topoisomerase IV complexes, leading to bacterial death. There are three mechanisms of fluoroquinolone resistance: chromosomal mutations affecting the genes which encode the two target enzymes – DNA-gyrase and topoisomerase IV (this tipe of resistance is step installed); diminution of intracellular penetration; active efflux. Lowering of intracytoplasmatic antibiotic level is due to reduction of porines (the penetration route of antibacterial through bacterial membrane) and also over-expression of efflux pumps. Fluoroquinolones are well absorbed in the upper digestive tract, the new fluoroquinolones having a higher biodisponibility. In addition, new fluoroquinolones have Cmax and AUC significantly higher as compared to ciprofloxacine, and longer half time allows administration once daily. Binding to serum proteines is low, fluoroquinolones usualy reach higher concentrations in tissue and fluids comparing to serum. Fluoroquinolones have concentration dependent bactericid activity, so the AUC/MIC can be improved by increase the dose, with better bactericidal activity. Knowledge of the farmacokinetic and the farmacodynamic properties of fluoroquinolones allows a better clinical use, considering that in high bacterian inoculum infections there are populations of resistant bateria which are not detected by susceptibility standardised tests. The concept of mutant prevention concentration gives an explanation for selecting and amplifying resistance, at the same time offering important data for a preventing strategy against amplifying of resistant subpopulations.