Τίτλος:
Evaluation of pooled human urine and synthetic alternatives in a dynamic bladder infection in vitro model simulating oral fosfomycin therapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The impact of the bladder environment on fosfomycin activity and treatment response is uncertain. Standard laboratory media does not reflect the biomatrix of urine, where limited nutritional factors are important for growth and antimicrobial kill rates. We compared fosfomycin activity against Enterobacteriaceae in laboratory media, human urine and synthetic alternatives. Sixteen clinical isolates (8-Escherichia coli, 4-Enterobacter cloacae, 4-Klebsiella pneumoniae) were studied with broth microdilution (BMD) susceptibility, static time-kill assays and dynamic testing in a bladder infection model simulating a 3 g oral fosfomycin dose. Mueller-Hinton broth (MHB) with and without 25 mg/L glucose-6-phosphate (G6P), pooled midstream urine (MSU), pooled 24 h urine collection (24 U), artificial urine medium (AUM) and synthetic human urine (SHU) were compared. BMD susceptibility, bacterial growth and response to static fosfomycin concentrations in urine were best matched with SHU and were distinctly different when tested in MHB with G6P. Fosfomycin exposure in the bladder infection model was accurately reproduced (bias 4.7 ± 6.2%). Under all media conditions, 8 isolates (2-E. coli, 2-E. cloacae, 4-K. pneumoniae) re-grew and 4 isolates (4-E. coli) were killed. The remaining isolates (2-E. coli, 2-E. cloacae) re-grew variably in urine and synthetic media. Agar dilution MIC failed to predict re-growth, whereas BMD MIC in media without G6P performed better. Emergence of resistance was restricted in synthetic media. Overall, SHU provided the best substitute for urine for in vitro modelling of antimicrobial treatment of uropathogens, and these data have broader utility for improved preclinical testing of antimicrobials for urinary tract infections. © 2020 Elsevier B.V.
Συγγραφείς:
Abbott, I.J.
van Gorp, E.
Wijma, R.A.
Meletiadis, J.
Mouton, J.W.
Peleg, A.Y.
Περιοδικό:
Journal of Microbiological Methods
Λέξεις-κλειδιά:
fomicyt; fosfomycin; glucose 6 phosphate; antiinfective agent; fosfomycin, antibiotic sensitivity; Article; bacterial growth; bactericidal activity; bacterium isolation; bladder disease; bladder infection; broth dilution; controlled study; drug exposure; dynamics; Enterobacter cloacae; Escherichia coli; evaluation study; human; in vitro study; Klebsiella pneumoniae; minimum inhibitory concentration; nonhuman; priority journal; simulation; urine sampling; antibiotic resistance; bladder; chemistry; culture medium; drug effect; isolation and purification; microbial sensitivity test; microbiology; pathology; physiology; urinary tract infection; urine, Anti-Bacterial Agents; Culture Media; Drug Resistance, Bacterial; Enterobacter cloacae; Escherichia coli; Fosfomycin; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Urinary Bladder; Urinary Tract Infections; Urine
DOI:
10.1016/j.mimet.2020.105861
