3 | Results
3.1 | Baseline Characteristics (Table 1)
As showed in Table 1, the 90 patients (63.3% males; average age 2.4
years, range 1 month–14 years) included 63 children younger than 3
years. The median time of hospitalization was 16 days in the CIV group
and 17 days in the IIV group. The median therapy time was 9.5 days for
CIV and 13 days for IIV. According to the scoring system of pediatric
critical cases, 9 of the CIV group and 11 of the IIV group were
extremely critical patients defined by a score lower than 70. The CIV
group had no significant difference (P > 0.05) in
terms of the baseline parameters like age, gender, and hospitalization
time compared to the IIV group.
The most common diagnoses were that of pneumonia (35 of 90, 38.9%) and
sepsis (35 of 90, 38.9%), central nervous system infections (11 of 90,
12.2%), skin and soft tissue infection (9 of 90, 10%). 26.7% of
patients (24 of 90) had one more underlying diseases, such as
hemopoietic system malignant or tumor (12/90, 13.3%), intracranial
hemorrhage (4/90, 4.4%), congenital heart diseases (4/90, 4.4%),
genetic metabolic diseases (3/90, 3.3%), surgical diseases (2/90,
2.2%), endocrine and rheumatic diseases (2/90, 2.2%), epilepsy (1/90,
1.1%), bronchopulmonary dysplasia (1/90, 1.1%).
A positive blood culture result was found in the case of 42(42/90,
46.7%) patients (Table 2) , indicating infection byStaphylococcus aureus (19/42, 45.2%), Streptococcus
pneumonia (9/42, 21.4%), Streptococcus agalactiae (GBS) (4/42,
9.5%), and Enterococcus spp. (3/42, 7.1%).
The
blood cultures were repeated on the 7th day for two
infants in the IIV group and three infants in the CIV group with
gram-positive bacteremia which did not turn negative on the
3rd day. The baseline characteristics such as the days
of medication and the positive rate of bacterial culture were similar
between both the groups.
3.2 | Attainment
of the target level in PK/PD
The average drug concentration at 24, 36, 48 h in the CIV group were
8.96 mg.L-1 (IQR 5.32, 11.70), 16.1
mg.L-1 (IQR 9.59, 19.30) and 19.50
mg.L-1 (IQR 12.98, 25.0), respectively. The plateau
concentration in the CIV group was 15.22 mg.L-1 (IQR
10.07, 17.18). The median of the trough and peak concentration in the
IIV group were 6.25 mg.L-1 (median 6.25
mg.L-1; IQR 3.73, 11.07) and 17.91
mg.L-1 (IQR 7.09,88.31). The higher target levels were
achieved with the same dosing regimen of 40
mg.kg-1.d-1 in the CIV
group
(median 15.22 mg.L-1; IQR 10.07, 17.18) compared to
that in the IIV group (median 6.25 mg.L-1; IQR 3.73,
11.07) (P < 0.05) (Figure 2) .
The proportion of patients who achieved target concentrations
(therapeutic drug monitoring concentration of vancomycin is up to 10
mg.L-1) was 26% (13 of 50) in the IIV group compared
to 75% (30 of 40) in the CIV group (P < 0.01). In the
CIV group, a higher proportion of blood concentration up to 15
mg.L-1 was found compared to that in the IIV group
(72.5% VS 28.0%, P < 0.05).
Among all the patients, 46.7% (42 of 90) with the minimum inhibitory
concentration (MIC) of vancomycin showed a median of
AUC0–24h/MIC ratio of 429.60 (220.92, 769.20) and
391.45 (251.45, 898.16)
in
the CIV and IIV groups (P = 0.582) (Figure 2). Based on the
studies and guidelines of treatment of S. aureus bacteremia and
pneumonia3, the bacteria were found to be cleared
quickly and improved the clinical symptoms quickly when the
AUC0–24 h/MIC ratio ≥ 400. The proportion of patients
with AUC0–24 h/MIC ≥ 400 between the two groups was
52.9% (9/17) and 48.0% (12/25), respectively, and there was no
statistical significance (P = 0.753).
3.3 |Drug-related adverse
effects
The
serum creatinine and urea levels were determined between the time points
before the initial dosing and the 1st,
3rd, 7th, and 14thday after vancomycin treatment in all the patients in both two groups.
The data showed that (Figure 3) there was no increase in the
creatinine, urea, KIM-1, CysC, β2-MG in the blood and
NGAL levels at the end compared to that at the start of the treatment in
both the groups. In the CIV group, the β2-MG in the
urine had higher baseline parameters at the start of treatment. However,
there was no significant difference (P > 0.05) at
the end of the trial compared to the IIV group. No patients in each of
the groups had an increased creatinine level >1.5 times the
baseline creatinine. Vancomycin was well-tolerated, with no documented
vancomycin-related
adverse effects in either group.
Supratherapeutic concentrations were found in 12.5% (5 of 40) and
12.0% (6 of 50) patients in the CIV and IIV groups. However,
none of them had hearing impairment such as high-frequency sensorineural
hearing loss during hospitalization and later follow-up. About 23.3%
(21 of 90) patients had a liver injury, including 20.0% (8/40) and
26.0% (13/50) patients in the CIV and IIV group, respectively. However,
combining the clinical characteristics of the patients and comparing the
liver function before and after treatment, showed no parallel
relationship between the degree of liver damage and the duration of
treatment with vancomycin and the increase in the concentration of
vancomycin. In addition, one patient in the CIV group developed the Red
man syndrome.
3.4 |Clinicalprognoses
The body temperature of the two groups during the treatment showed a
downward trend. The CIV group could return to normal body temperature
after about 3.43 days, while the IIV group regained the normal body
temperature in 3.96 days. There was no significant difference in the
time required for regaining the normal body temperature between the CIV
and IIV groups (P = 0.405).
There
was no significant difference in the clinical indices such as
CRP,
PCT, and cytokines in either group (Figure 4), suggesting that
the therapeutic effect was achieved irrespective of the methods of
infusion of vancomycin.