Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis

Angela S. Loo; Michael Neely; Evan J. Anderson; Cybele Ghossein; Milena M. McLaughlin; Marc H. Scheetz

doi:10.1128/AAC.00474-13

DOI: 10.1128/AAC.00474-13

Article Figures & Data

Figures

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Fig 1
Concentration-time profiles for 6 patients after receiving a 2-g ceftazidime dose (27).
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Fig 2
Two-compartment models of observed versus predicted serum concentrations of ceftazidime (R² = 0.803 and 0.988). Predictions are based on the median population parameter values (left) and median individual Bayesian posterior parameter values (right).
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Fig 3
Probability of target attainment for 48-h dialysis.
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Fig 4
Probability of target attainment for 72-h dialysis.
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Fig 5
Simulated concentration-time curves for free ceftazidime for hemodialysis every 72 h (5th, 50th, and 95th percentiles are shown).

Tables

Figures

Table 1

Bayesian posterior density results^{^a}

Support point	k_el (1/h)	V (liters)	k_CP (1/h)	k_PC (1/h)	Weighting fraction
1	0.060	9.23	0.718	0.679	0.167
2	0.097	5.82	2.183	1.855	0.167
3	0.057	11.43	0.830	1.605	0.167
4	0.051	10.29	1.099	1.152	0.167
5	0.049	9.92	0.644	1.072	0.167
6	0.028	12.54	0.296	0.601	0.167

↵a k_el, elimination rate constant; V, volume of distribution; k_CP, rate transfer constant from central to peripheral compartment; k_PC, rate transfer constant from peripheral to central compartment.

Table 2
Covariance matrix in the lower triangular form^{^a}
Parameter Covariance
k_el V k_CP k_PC
k_el 0.00043
V −0.04094 4.420889
k_CP 0.011582 −1.12161 0.355167
k_PC 0.007308 −0.55211 0.217721 0.205454
↵a The full covariances were used in all simulations. See Table 1 and the text for parameter definitions.

Table 3

PTA values for different dosing regimens^{^a}

Dose and frequency	MIC (mg/liter)	Probability of target attainment (%)
		45%T_MIC, 72-h dialysis period			70%T_MIC, 72-h dialysis period			45%T_MIC, 48-h dialysis period			70%T_MIC, 48-h dialysis period
		Model 1	Model 2	Model 3	Model 1	Model 2	Model 3	Model 1	Model 2	Model 3	Model 1	Model 2	Model 3
500 mg q dialysis	0.25	100	100	100	100	100	100	100	100	100	100	100	100
	0.5	100	100	100	100	100	100	100	100	100	100	100	100
	1	100	100	100	100	100	100	100	100	100	100	100	100
	2	100	100	100	100	100	100	100	100	100	100	100	100
	4	100	100	100	73	73	69	100	100	100	100	100	100
	8	72	70	54	13	13	7	100	100	100	76	76	43
	16	2	3	0	0	1	0	19	20	3	5	5	0
	32	0	0	0	0	0	0	0	0	0	0	0	0
1,000 mg q dialysis	0.25	100	100	100	100	100	100	100	100	100	100	100	100
	0.5	100	100	100	100	100	100	100	100	100	100	100	100
	1	100	100	100	100	100	100	100	100	100	100	100	100
	2	100	100	100	100	100	100	100	100	100	100	100	100
	4	100	100	100	100	100	100	100	100	100	100	100	100
	8	100	100	100	73	73	69	100	100	100	100	100	100
	16	72	70	54	13	13	7	100	100	100	76	76	43
	32	2	3	0	0	1	0	19	20	3	5	5	0
2000 mg q dialysis	0.25	100	100	100	100	100	100	100	100	100	100	100	100
	0.5	100	100	100	100	100	100	100	100	100	100	100	100
	1	100	100	100	100	100	100	100	100	100	100	100	100
	2	100	100	100	100	100	100	100	100	100	100	100	100
	4	100	100	100	100	100	100	100	100	100	100	100	100
	8	100	100	100	100	100	100	100	100	100	100	100	100
	16	100	100	100	73	73	69	100	100	100	100	100	100
	32	72	70	54	13	13	7	100	100	100	76	76	43
500 mg q24h	0.25	100	100	100	100	100	100	100	100	100	100	100	100
	0.5	100	100	100	100	100	100	100	100	100	100	100	100
	1	100	100	100	100	100	100	100	100	100	100	100	100
	2	100	100	100	100	100	100	100	100	100	100	100	100
	4	100	100	100	100	100	100	100	100	100	100	100	100
	8	100	100	100	100	100	100	100	100	100	100	100	100
	16	100	100	100	100	99	88	100	100	100	99	98	44
	32	24	25	4	11	9	0	15	16	1	6	5	0
1,000 mg q24h	0.25	100	100	100	100	100	100	100	100	100	100	100	100
	0.5	100	100	100	100	100	100	100	100	100	100	100	100
	1	100	100	100	100	100	100	100	100	100	100	100	100
	2	100	100	100	100	100	100	100	100	100	100	100	100
	4	100	100	100	100	100	100	100	100	100	100	100	100
	8	100	100	100	100	100	100	100	100	100	100	100	100
	16	100	100	100	100	100	100	100	100	100	100	100	100
	32	100	100	100	100	99	88	100	100	100	100	98	43

↵a Model 1, primary model; model 2, primary model with covariance matrix × 3; model 3, full HFHD clearance. q dialysis, every dialysis session; q24h, every 24 h.