Therapeutic Drug Monitoring and Nephrotoxicity of Teicoplanin Therapy in Chinese Children: A Retrospective Study

Figures & data

Table 1 Patients’ Characteristics

Characteristics	Value
Number of patients, n	186
Gender, males/female, n (%)	105/81 (56.5%/43.5%)
Age (year), median (IQR)	3.82 (1.53, 6.27)
Weight (kg), median (IQR)	15.3 (11.0, 21.0)
Teicoplanin loading dose (mg/kg), median (IQR)	10.0 (9.7, 10.00)
Teicoplanin maintenance dose (mg/kg), median (IQR)	10.00 (9.7, 10.00)
Duration of teicoplanin therapy (days), median (IQR)	12 (9, 16)
Type of infection, n (%)
Skin and soft tissue infection	14 (7.5%)
Respiratory infection	108 (58.1%)
Bloodstream infection	45 (24.2%)
Bone and joint infections	17 (9.1%)
Other infections	2 (1.1%)
Isolated gram-positive organisms, n (%)
Staphylococcus	18 (9.7%)
Enterococcus	9 (4.8%)
Streptococcus	9 (4.8%)
Others	12 (6.5%)
Comorbid conditions, n (%)
Malignancy	86 (46.2%)
Congenital heart disease	21 (11.3%)
Hypoalbuminemia	32 (17.2%)
Baseline WBC (10^9/L), median (IQR)	5.24 (1.20, 11.23)
Baseline NEUT%, median (IQR)	52.1 (28.9, 69.7)
Baseline albumin (g/L), median (IQR)	35.0 (30.7, 39.6)
Baseline ALT (U/L), median (IQR)	20.0 (12.0, 42.0)
Baseline AST (U/L), median (IQR)	27.5 (20.0, 43.0)
Baseline SCr (µmol/L), median (IQR)	26 (20, 33)
Baseline Ccr (mL/min)^a, median (IQR)	95.2 (66.9, 127.2)

Note: ^aEstimated by Cockcroft-Gault.

Abbreviations: IQR, interquartile range; C_min, trough concentration; WBC, white blood cell; NEUT%, neutrophil percentage; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SCr, serum creatinine; Ccr, creatinine clearance.

Figure 1 Distribution of teicoplanin trough concentrations. Panel (A) shows the distribution of C_min on day 3 or day 4 after teicoplanin administration. Panel (B) shows the distribution of teicoplanin C_min at steady state.

Table 2 Univariate and Multivariate Analyses of the Variables Tested for Potential Association with C^3/4_min/D_CLD

Variables	Univariate Analysis		Multivariate Analysis
	R^2	P value	P value	β (95% CI)
Gender (Male)	0.082	0.032	–
Age (year)	0.209	0.001	0.008	0.69 (0.019–0.119)
Weight (kg)	0.064	0.061	0.039	−0.015 (−0.029–0.001)
Concomitant medication	–	–	–
Antibacterial drugs	–	–	–
Cephalosporins	0.023	0.270	–
Carbapenems	0.065	0.058	0.080	−0.194 (−0.413–0.024)
Antifungal drug	0.001	0.856	–
Antiviral drugs	0.001	0.918	–
Others	0.035	0.138	–
Comorbid conditions	–	–	–
Malignancy	0.044	0.121	–
Congenital heart disease	0.002	0.771	–
Hypoalbuminemia	0.010	0.453	–
WBC (10^9/L)	0.004	0.636	–
ALT (U/L)	0.004	0.648	–
AST (U/L)	0.000	0.915	–
Albumin (g/L)	0.023	0.268	–
SCr (µmol/L)	0.279	0.001	0.022	0.007 (0.001–0.013)
Ccr (mL/min)^a	0.048	0.106	–

Note: ^aEstimated by Cockcroft-Gault.

Abbreviations: C^3/4_min/D_CLD, the ratio between C_min on day 3 or day 4 after teicoplanin administration and the cumulative loading dose; CI: confidence interval; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SCr, serum creatinine; Ccr, creatinine clearance.

Table 3 Univariate and Multivariate Analyses of the Variables Tested for Potential Association with C^SS_min/D_MD

Variables	Univariate Analysis		Multivariate Analysis
	R^2	P value	P value	β (95% CI)
Gender (Male)	0.034	0.007	0.014	0.395 (0.080–0.709)
Age (year)	0.003	0.402	–
Weight (kg)	0.025	0.021	–
Concomitant medication	–	–	–
Antibacterial drugs	–	–	–
Penicillins	0.004	0.346	–
Cephalosporins	0.008	0.190	–
Carbapenems	0.001	0.966	–
Antifungal drug	0.002	0.512	–
Antiviral drugs	0.001	0.650	–
Others	0.012	0.118	–
Cumulative loading dose (mg/kg)	0.008	0.182	–
Comorbid conditions	–	–	–
Malignancy	0.010	0.153	–
Congenital heart disease	0.012	0.115	–
Hypoalbuminemia	0.003	0.432	–
WBC (10^9/L)	0.001	0.727	–
ALT (U/L)	0.001	0.965	–
AST (U/L)	0.001	0.977	–
Albumin (g/L)	0.001	0.891	–
SCr (µmol/L)	0.041	0.003	0.006	0.014 (0.004–0.025)
Ccr (mL/min)^a	0.004	0.352	–

Note: ^aEstimated by Cockcroft-Gault.

Abbreviations: C^SS_min/D_MD, the ratio between the teicoplanin C_min at steady state and the maintenance dose; CI: confidence interval; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; SCr, serum creatinine; Ccr, creatinine clearance.

Table 4 Univariable and Multivariable Analysis of Risk Factors for Nephrotoxicity in Patients Receiving Teicoplanin

Variables	Univariate Analysis		Multivariate Analysis
	Wald χ^2	P value	P value	OR (95% CI)
Gender (Male)	0.816	0.217	–
Age (year)	0.003	0.956	–
Weight (kg)	0.013	0.908	–
Concomitant nephrotoxic drugs	–	–	–
Aminoglycosides	0.001	0.999	–
Loop diuretics	1.731	0.188	–
Acyclovir	0.001	0.999	–
Amphotericin B	15.509	0.001	0.001	0.285 (0.183–0.388)
Cis-platinum	0.001	0.999	-
Comorbid conditions	-	-	-
Malignancy	0.373	0.541	-
Congenital heart disease	1.005	0.316	-
Hypoalbuminemia	0.179	0.672	-
Teicoplanin Cmin (mg/L)	5.511	0.019	0.012	0.005 (0.001–0.008)
Baseline SCr (µmol/L)	0.078	0.780	-
Baseline Ccr (mL/min)^a	0.034	0.853	-

Note: ^aEstimated by Cockcroft-Gault.

Abbreviations: OR, odds ratio; CI: confidence interval; C_min, trough concentration; SCr, serum creatinine; Ccr, creatinine clearance.

Figure 2 Classification and regression tree model for the nephrotoxicity of teicoplanin therapy. A value of 0 indicated that no nephrotoxicity was observed and a value of 1 indicated that nephrotoxicity was observed.