[Mutant Prevention Concentration: is it significant in the clinical practice?].
Fluoroquinolones therapeutic efficacy is closely related to the achievement of the highest concentration (concentration-dependent drugs). However, following exposure to antibiotics, along with a decrease in the overall bacterial population, a selection of resistant bacterial population can also occur. In such a scenario, the Mutant Prevention Concentration (MPC) has to be considered, the antibiotic concentration that approximatively allows to obtain inhibition of fully susceptible as well as low resistant strains. In the range between MPC and MIC values, the Mutant Selection Window (MSW) is delineated, a range of antibiotic concentrations within a selection of mutant strains could possibly take place. The clinical impact of these microbiological observations can be found in the importance that the drug concentration a patient will be exposed to, consequently assumes: a concentration that doesn't reach MIC, although doesn't alter the resistance pattern, will not guarantee the recovery; increasing concentration up to values comprised within the MSW, leads to killing of susceptible bacteria and to a successful clinical response; on the other hand, the possibility does exist that less susceptible microorganisms are selected. Finally, a third higher concentration profile subsists, corresponding to the MPC, above the MSW, which permits to obtain both the results. Such an approach has been extensively studied with fluoroquinolones. A number of studies suggests that different fluoroquinolones are contradistinguished by a diverse MPC value. Multiple factors can influence the risk of selecting bacterial resistance: mutagenicity of the fluoroquinolone utilized, size of microbial population to treat, antibiotic concentration attainable at the site infection, pathophysiologic features of the patient, and lastly the prescribing behaviour, not always appropriate.
Istituto di Farmacologia Clinica e Tossicologia, Dipartimento di Patologia e Medicaina Sperimentale e Clinica, Università di Udine, Italy.
Federico
F
Pea
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis / Q000187:drug effects*; D012641:Selection, Genetic; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; D027081:DNA Gyrase
Mutant Prevention Concentration: è un parametro significativo nella pratica clinica?