3.2 Urinary output and urinary biomarkers
Mean total urine output increased on Day 1 following the first dose in the vancomycin-treated groups. Vancomycin + flucloxacillin resulted in higher urinary volume when compared with baseline and saline-treated animals on days 3 and 4 days. Urinary output increased on every study day for vancomycin+flucloxacillin, whereas in the vancomycin group it was elevated after the first dose only. Mean urinary output is significantly increased with vancomycin+flucloxacillin compared to vancomycin and vancomycin+ imipenem-cilastatin following the 3rd dose (FIG 1a). There was a gradual increase in the mean total urine output in the flucloxacillin-treated animals compared with baseline and saline-treated animals on Days 2 and 3.
In the vancomycin group, absolute amount of urinary KIM-1 over 24 h was significantly increased from Day 1 compared to the saline and flucloxacillin control groups (Table 1, FIG 1b ). While in the vancomycin+flucloxacillin group, KIM-1 was significantly increased following the 3rd day compared to vancomycin. In the vancomycin+ imipenem-cilastatin group, KIM-1 was significantly decreased on Days 1 and 2 compared to vancomycin. Similar trends were observed in the vancomycin+flucloxacillin group for clusterin and osteopontin (FIG 1c,d). Locally weighted scatterplot smoothing (LOWESS) trendlines with 95% confidence intervals visually confirmed similar findings for all comparisons (FIG1 supplemental).