Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin

Abstract

Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69). Initial urine pH, antimicrobial therapy, and clinical and microbiological outcomes, and one- and six-month follow-up were assessed. Fosfomycin was prescribed in 88 (76.5%) E. coli and 46 (66.7%) K. pneumoniae UTI episodes in the total cohort. When the urine pH ≤ 6, fosfomycin was prescribed in 60 (52.2%) E. coli and 29 (42.0%) K. pneumoniae. Initial urine pH ≤ 6 in E. coli UTI was associated with symptomatic episodes (8/60 vs. 0/55, p = 0.04) at one-month follow-up, with a similar trend in those patients receiving fosfomycin (7/47 vs. 0/41, p = 0.09). Acidic urine pH was not associated with microbiological or clinical cure in K. pneumoniae UTI. At pH 5, the ciprofloxacin MIC₉₀ increased from 8 to >8 mg/L in E. coli and from 4 to >8 mg/L in K. pneumoniae. At pH 5, the fosfomycin MIC₉₀ decreased from 8 to 4 mg/L in E. coli and from 512 to 128 mg/L in K. pneumoniae. Acidic urine is not associated with the microbiological efficacy of fosfomycin and ciprofloxacin in KTRs with UTI, but it is associated with symptomatic UTI episodes at one-month follow-up in E. coli episodes.

Keywords: Escherichia coli; Klebsiella pneumoniae; ciprofloxacin; fosfomycin; kidney transplant recipients; urinary tract infections; urine pH.

Figure 1

Ciprofloxacin and fosfomycin MIC values distributions determined at pH 5 (pink bars), pH 7 (white bars), and pH 8 (blue bars) against Escherichia coli (N = 115) and Klebsiella pneumoniae (N = 69) urine clinical isolates. S: susceptible; LLQR: Low-level quinolone resistance; LLFR: Low-level fosfomycin resistance; R: resistant; EUCAST: European Committee on Antimicrobial Susceptibility Testing interpretative criteria 2023 (ciprofloxacin resistant: MIC > 0.5 g/L; fosfomycin resistant: MIC > 8 g/L).

Figure 2

Bactericidal activity of ciprofloxacin and fosfomycin at MIC concentrations in MHB and urine, determined at pH 5 (pink bars), pH 7 (white bars), and pH 8 (blue bars) (dark grey bars) against Escherichia coli strains. Panels (A,B) E. coli NU14 wild-type strain, susceptible to ciprofloxacin (MIC 0.03 mg/L) and fosfomycin (MIC 2 mg/L). Panels (C,D) E. coli HUVR94 clinical strain, susceptible to ciprofloxacin (MIC 0.03 mg/L) and fosfomycin (MIC 0.5 mg/L). Panels (E,F) E. coli Nu79 gyrA (D87G) strain with low-level quinolone resistance (MIC 0.12 mg/L) and susceptible to fosfomycin (MIC 0.5 mg/L). Panels (G,H) E. coli Nu14 glpT missense mutation strains with low-level fosfomycin resistance (MIC 32 mg/L) and susceptible to ciprofloxacin (MIC 0.01 mg/L). Results are represented as differences (log₁₀ CFU/mL) relative to the initial time-point (0 h).

Figure 3

Bactericidal activity of ciprofloxacin and fosfomycin at MIC concentrations in MHB and urine, determined at pH 5 (pink bars), pH 7 (white bars), and pH 8 (blue bars) against Klebsiella pneumoniae strains. Panels (A,B) K. pneumoniae HUVR42 susceptible to ciprofloxacin (MIC 0.007 mg/L) and fosfomycin (4 mg/L). Panels (C,D) K. pneumoniae HUVR5 resistant to ciprofloxacin (MIC 8 mg/L) and fosfomycin (128 mg/L. Panels (E,F) K. pneumoniae HUVR110 resistant to ciprofloxacin (MIC 8 mg/L) and susceptible to fosfomycin (MIC 4 mg/L). Panels (G,H) K. pneumoniae HUVR91 resistant fosfomycin (MIC 64 mg/L) and susceptible to ciprofloxacin (MIC 0.06 mg/L). Results are represented as differences (log₁₀ CFU/mL) relative to the initial time-point (0 h).