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).