title: Impact of pH on activity of trimethoprim, fosfomycin, amikacin, colistin and ertapenem in human urine.
abstract: OBJECTIVE
  Although major impairment of activity at lower pH values has been reported for fluoroquinolones, acidification is a widely recommended practice for the prophylaxis and treatment of uncomplicated urinary tract infections (UTIs). Until now, there is little evidence for the influence of pH on the activity on other antimicrobial classes in urine.
  
  
  METHODS
  Bacterial growth curves of Staphylococcus aureus (ATCC 29213), Klebsiella oxytoca (ATCC 700324), Proteus mirabilis (ATCC 14153), Escherichia coli (ATCC 25922) and Enterococcus faecalis (ATCC 29212) were performed in Mueller-Hinton broth and in pooled human urine with a pH of between 5.0 and 8.0. Bacterial killing of trimethoprim, fosfomycin, amikacin, colistin and ertapenem against the five strains (where appropriate) was determined consecutively at concentrations equal to the MIC.
  
  
  RESULTS
  While no difference in the bacterial growth of E. coli, S. aureus, P. mirabilis and K. oxytoca was observed at different pH values, bacterial growth of E. faecalis was significantly reduced at low pH. Acidification to pH 5 impaired the antimicrobial activity of all investigated antibiotics, i.e. the net effect of bacterial growth and killing resulted in increased colony-forming units/ml at the end of the experiment.
  
  
  CONCLUSIONS
  The present in vitro findings indicate that acidification of urine during the treatment of UTIs should be carefully considered. While growth curves of one strain supports the concept of therapeutic or prophylactic acidification during UTIs, the most common pathogen, E. coli, was not affected by low pH. Independent of the investigated strain or antibiotic, pH values below 6 lead to a reduction of antimicrobial activity.
authors.affiliation: Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Burian
authors.forename: Z
authors.initials: Z
authors.lastname: Erdogan
authors.forename: C
authors.initials: C
authors.lastname: Jandrisits
authors.forename: M
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D003091:Colistin / Q000494:pharmacology; D000077727:Ertapenem; D005578:Fosfomycin / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D014295:Trimethoprim / Q000494:pharmacology; D014556:Urine / Q000737:chemistry*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D005578:Fosfomycin; D000583:Amikacin; D014295:Trimethoprim; D000077727:Ertapenem; D003091:Colistin