Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

DOI: 10.1128/AAC.02102-19

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FIG 1
Mean log₁₀ CFU/ml versus time profile for each isolate against fosfomycin-laden urine collected from subjects during the QOD dosing regimen on day 1 (A) and day 5 (B) and during the QD dosing regimen on day 1 (C) and day 5 (D). Curves represent average concentrations for triplicate experiments. The y axis is in the log scale.
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FIG 2
Mean log₁₀ CFU/ml versus time profile for each isolate against fosfomycin-laden urine collected from subjects during the QOD dosing regimen on day 5 without G6P (A) and with 25 mg/liter G6P (B) and during the QD dosing regimen on day 5 without G6P (C) and with 25 mg/liter G6P (D). Curves represent average concentrations for triplicate experiments. The y axis is in the log scale.

TABLE 1
Genotypic and phenotypic susceptibilities obtained against isolates included in the study
↵a According to CLSI M100-S29 (16). NA, CLSI breakpoints not available; S, susceptible; I, intermediate; R, resistant.
↵b Reference broth microdilution method includes 25 mg/liter G6P. MIC results obtained in the absence of G6P were interpreted for comparison purposes only.
↵c The following genes and respective alterations were observed in isolate UIC45 compared with wild-type ATCC 25922: uhpB (P84S, S374T, Q441H, G459D, Q463H, H482T), uhpC (T72P, A177S, S417A, A435T), and cyaA (S222G, A349E, S356K, G359E, E362D, D837E, T840A).
↵d The transport system regulator UhpABC was not detected.
↵e The following genes and respective alterations were observed in the ATCC 700603 compared with wild-type ATCC 43816: uhpA (T3I, A25T, T41A, E64A, I87V, S183N), uhpC (E55D, A185T, C192G, M236L, S237T, A240E, V415A, T438A), uhpT (V434I), glpT (G196A, K234E, E237Q, I260V, V337I, P344A, I429V), ptsI (S241N), and murA (S148N, T206S, S210T).
TABLE 2
Median reciprocal fosfomycin UBT and AUBT₂₄ for all 18 subjects against the first 5 isolates tested
TABLE 3
Median reciprocal fosfomycin UBT and AUBT₂₄ for 5 representative subjects against all 8 isolates tested on study day 5 with and without 25 mg/liter G6P