کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5665987 | 1407780 | 2017 | 5 صفحه PDF | دانلود رایگان |
- We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3-g oral dose against Escherichia coli using an in vitro pharmacodynamic model.
- Fosfomycin urinary concentrations obtained after a single 3-g oral dose were bactericidal as early as 1Â h after dosing with complete bacterial eradication at all time-points over the 48Â h testing period against urinary isolates of E. coli (including MDR ESBL- and/or carbapenemase-producing strains).
- This study helps to explain the high (>90%) microbiological and clinical cure rates achieved with fosfomycin when used as a single 3-g oral dose to treat patients with acute uncomplicated cystitis.
We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3-g oral dose against Escherichia coli using an in vitro pharmacodynamic model. Eleven urinary isolates of E. coli were studied. Isolates were ESBL-producing or carbapenemase-producing. The in vitro pharmacodynamic model was inoculated with an inoculum of (~1 Ã 106 cfu/mL). Fosfomycin was administered to simulate maximum free (Æ) urine (U) concentrations and a t1/2 obtained after a standard single 3-g oral dose in healthy volunteers (ÆUmax, 4000 mg/L; t1/2, 6 h). Sampling was performed over 48 h to assess the rate and extent of bacterial reduction as well as resistance selection. Complete bacterial eradication from the model was defined by no regrowth over the 48 h study period. Fosfomycin MICs ranged from 1 to 4 μg/mL for ESBL producers, while all 3 carbapenemase-producing E. coli demonstrated a fosfomycin MIC of 2 μg/mL. Fosfomycin ÆT>MIC of 100% (ÆAUC0-24/MIC, â¥~7250) resulted in bacterial killing (reductions in log10 CFU assessed relative to the starting inoculum at 2, 4, 6, 12, 24, and 48 h of â¥3.0) at each time-point versus all isolates of ESBL-producing and carbapenemase-producing E. coli. We conclude that fosfomycin urinary concentrations obtained after a single 3-g oral dose were bactericidal as early as 1 h after dosing with complete bacterial eradication at all time-points over the 48 h testing period against urinary isolates of E. coli (including MDR ESBL- and/or carbapenemase-producing strains). Our data help to explain the high (>90%) microbiological and clinical cure rates achieved with fosfomycin when used as a single 3-g oral dose to treat patients with acute uncomplicated cystitis.
Journal: Diagnostic Microbiology and Infectious Disease - Volume 88, Issue 3, July 2017, Pages 271-275