2.3 | Interventions (Figure 1)
2.3.1 | The method of infusing vancomycin
The patients were randomly assigned in a 1:1 ratio to receive either the
standard care, consisting of IIV (dose was given every 6 h at 40
mg.kg-1per day) 6,7. Alternately,
CIV was given as a maintenance infusion (20 mg/kg) over the remaining 23
h after a loading dose of 20 mg.kg-1 infused over 1 h
and which was started immediately after the loading infusion was
complete (the same dose was given at 40 mg.kg-1 per
day).
2.3.2 |Experimental materials,
instrumentation, and chromatographic conditions13
The ultra-high-performance liquid chromatography (UPLC) was used to
detect the plasma concentration of vancomycin in the children included
in the study.
2.3.3 | The index of PK/PD
In the IIV
group:
trough and peak concentrations were measured immediately before the
fifth dose or 30 min after the fifth dose6,7,12. In
the CIV group, 500 μl of venous blood was taken to determine the plasma
concentration at 24, 36, 48 h after the first administration, and the
mean value of the three consecutive data (and there was no statistical
difference before and after the difference) was used as the steady-state
concentration of vancomycin which was called
the
plateau concentration.
AUC0–24 h/MIC: Besides the MIC values based on the
measured values, the AUC0–24 h/MIC was calculated as
follows:
Lin trap = (Cmax + Cmin)/2 ×
Tinfusion
Log trap= [(Cmax - Cmin) ×
(Tau-Tinfusion)]/ln(Cmax/Cmin)
AUC0–Tau = (Lin trap) + ( Log trap)
AUC0–24h= (AUC0-Tau) × (24/Tau)
Tinfusion: drip time of vancomycin; Tau: administration
period; Cmax: Peak concentration; Cmin:
trough concentration.
2.3.4 | Index of clinical prognosis
The outcome of treatment was classified as cured14 if
the patients with cleared blood cultures demonstrated clinical
improvement, the disappearance of symptoms, and signs, and normal
laboratory tests at the time of initiation of vancomycin therapy. When
gram-positive infection resulted in worsened clinical symptoms, signs,
or laboratory results often leading to death, the outcome was a
treatment failure14.
The following blood tests were
performed for all the patients at or before randomization: full blood
examination;
urea,
creatinine, cystatin C (CysC), β2-microglobulin
(β2-MG), neutrophil gelatinase-associated lipocalin
(NGAL), kidney injury molecule-1 (KIM-1); C-reactive protein (CRP),
procalcitonin (PCT), cytokines such as tumor necrosis factor-α (TNF-α),
interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10).
Some tests like the full blood examination; C-reactive protein and
procalcitonin were repeated every 24, and 72 h for the first week then
weekly thereafter during the vancomycin therapy, and others were
repeated every 72 h for the first week before administration. The blood
culture of all the patients was examined before admission or
administration. If new infections were suspected upon re-examining the
blood cultures on the 3rd and 7thday, the culture would be notified as positive (Figure 1).
The brainstem auditory evoked potentials were monitored at a drug
concentration higher than 15 mg.L-1 to evaluate the
hearing impairment15. Other possible drug-related
adverse effects were observed throughout the trial including liver
injury, rash, and Red man syndrome (RMS).