Τίτλος:
Pharmacodynamics of nitrofurantoin at different pH levels against pathogens involved in urinary tract infections
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Urinary tract infections are among the most common human infections. Due to the progressive increase in ESBL-producing bacteria and the unavailability of new antibiotics, re-evaluation of 'old' antibiotics is needed. However, the pharmacodynamics of nitrofurantoin under variable pH conditions are poorly understood. We determined the pharmacodynamic properties of nitrofurantoin at different pH levels using time-kill assays. Methods: Time-kill assays were performed at four pH levels (5.5, 6.5, 7.5 and 8.5), exposing the bacteria to 2-fold increasing concentrations from 0.125 to 32 times the MIC. Seven ESBL-positive and two ESBL-negative strains (MICs 8-32 mg/L) were used. The Δlog10 cfu/mL values at 6 and 24 h were plotted against each log10- transformed concentration and analysed with non-linear regression analysis using the sigmoid maximumeffect model with variable slope. Geometric means normalized by the MIC of the EC50, stasis and 1 and 3 log10 cfu/mL kill were calculated. Results: Minimum bactericidal effects differed significantly by species and pH level. At pH 5.5-6.5 bactericidal effects were observed at≥0.5×MIC for Escherichia coli and Enterobacter cloacae. At pH 8.5 only the two highest concentrations were considered bactericidal. Strong pH-dependent pharmacodynamic output parameters were observed in 6 h and especially 24 h modelling. At 24 h, pH 5.5-6.5 for E. coli and Klebsiella pneumoniae required significantly lower nitrofurantoin concentrations compared with pH 7.5 or 8.5. Although for E. cloacae similar strong decreasing trends were visible with decreasing pH, none of the tested pharmacodynamic parameters was significant. Conclusions: Nitrofurantoin bactericidal activity against Enterobacteriaceae significantly increases at lower pH levels. Bactericidal activity of nitrofurantoin may be overestimated or underestimated, which may have implications for therapy and the interpretation of clinical breakpoints. © The Author 2017.
Συγγραφείς:
Fransen, F.
Melchers, M.J.B.
Lagarde, C.M.C.
Meletiadis, J.
Mouton, J.W.
Περιοδικό:
The Journal of antimicrobial chemotherapy
Εκδότης:
Oxford University Press
Λέξεις-κλειδιά:
extended spectrum beta lactamase; nitrofurantoin; nitrofurantoin; urinary tract antiinfective agent, Article; bacterial growth; bacterial strain; bactericidal activity; cell viability; controlled study; EC50; Enterobacter cloacae; Escherichia coli; Klebsiella pneumoniae; minimum inhibitory concentration; nonhuman; pH; pharmacodynamic parameters; phenotype; urinary tract infection; bacterial count; drug effect; human; isolation and purification; microbial sensitivity test; microbial viability; microbiology; physiology; urinary tract infection, Anti-Infective Agents, Urinary; Colony Count, Microbial; Enterobacter cloacae; Escherichia coli; Humans; Hydrogen-Ion Concentration; Klebsiella pneumoniae; Microbial Sensitivity Tests; Microbial Viability; Nitrofurantoin; Urinary Tract Infections
