title: Impact of pH on bacterial growth and activity of recent fluoroquinolones in pooled urine.
abstract: Acidification of urine is widely recommended for prevention and treatment of urinary tract infections. We set out to describe the effect of modification of pH on bacterial growth of relevant bacteria as well as on activity of modern fluoroquinolones in urine in vitro. Bacterial growth of Escherichia coli ATCC 25922 and Klebsiella oxytoca ATCC 700324 was determined in pooled human urine adjusted to pH levels between 5.0 and 8.0. Minimal inhibitory concentrations (MICs) and time-kill curves were performed for ciprofloxacin, levofloxacin and moxifloxacin in pH-adjusted urine and Mueller-Hinton Broth (MHB). Uptake of radioactive labeled [C(14)]-ciprofloxacin into bacterial cells was investigated at different pHs. While no difference in bacterial growth of E. coli and K. oxytoca was observed at pH values between 5.0 and 8.0, acidification of urine led to major impairment of antimicrobial activity of all tested fluoroquinolones, indicated by an up to 40-fold increase in MIC compared to MHB and nearly total neutralization of activity in time-kill experiments. The most probable mechanism behind this observation may have been reduced uptake of fluoroquinolones into bacterial cells, as indicated by bacterial uptake of [C(14)]-ciprofloxacin and a reversibility of the effect. The observed reduction in activity of modern fluoroquinolones confirms previous observations from older compounds.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. zeynep.e.yildirim@gmail.com
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Erdogan-Yildirim
authors.forename: Angela
authors.initials: A
authors.lastname: Burian
authors.forename: Mohammad
authors.initials: M
authors.lastname: Manafi
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000900:Anti-Bacterial Agents / Q000032:analysis / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D024841:Fluoroquinolones / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D041121:Klebsiella oxytoca / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D014556:Urine / Q000737:chemistry / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D003470:Culture Media; D024841:Fluoroquinolones