Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of Escherichia coli and Klebsiella pneumoniae Infection in the Lower Urinary Tract

In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of <i>E. coli</i> and <i>K. pneumoniae</i>. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with <i>E. coli</i> and <i>K. pneumoniae</i> strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in <i>E. coli</i> concentrations in the kidneys in immunocompetent and immunocompromised mice and in <i>K. pneumoniae</i> in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of <i>E. coli</i> in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating <i>E. coli</i> infection in the kidneys at a neutral urine pH and showed reduced efficacy against <i>K. pneumoniae</i> at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals' immunocompetence status.