Abstract | AIMS: METHODS: Patients with suspected septicaemic melioidosis were randomised to receive ceftazidime 40 mg kg(-1) 8 hourly by bolus injection or 4 mg kg(-1) h(-1) by constant infusion following a 12 mg kg(-1) priming dose and pharmacokinetic and pharmacodynamic parameters were compared. RESULTS: Of the 34 patients studied 16 (59%) died. Twenty patients had cultures positive for B. pseudomallei of whom 12 (60%) died. The median MIC90 of B. pseudomallei was 2 mg l(-1), giving a minimum target concentration (4*MIC) of 8 mg l(-1). The median (range) estimated total apparent volume of distribution, systemic clearance and terminal elimination half-lives of ceftazidime were 0.468 (0.241-0. 573) l kg(-1), 0.058 (0.005-0.159) l kg(-1) h(-1) and 7.74 (1.95-44.71) h, respectively. Clearance of ceftazidime and creatinine clearance were correlated closely (r = 0.71; P < 0.001) and there was no evidence of significant nonrenal clearance. CONCLUSIONS: Simulations based on these data and the ceftazidime sensitivity of the B. pseudomallei isolates indicated that administration by constant infusion would allow significant dose reduction and cost saving. With conventional 8 h intermittent dosing to patients with normal renal function, plasma ceftazidime concentrations could fall below the target concentration but this would be unlikely with a constant infusion. Correction for renal failure, which is common in patients with meliodosis is Clearance = k(*) creatinine clearance where k = 0.72. Calculation of a loading dose gives median (range) values of loading dose, DL of 18.7 mg kg(-1) (9.5-23) and infusion rate I = 3.5 mg k(-1) h(-1) (0.4-13) (which equals 84 mg kg(-1) day(-1)). A nomogram for adjustment in renal failure is given.
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Authors | B J Angus, M D Smith, Y Suputtamongkol, H Mattie, A L Walsh, V Wuthiekanun, W Chaowagul, N J White |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 50
Issue 2
Pg. 184-91
(Aug 2000)
ISSN: 0306-5251 [Print] England |
PMID | 10930972
(Publication Type: Clinical Trial, Corrected and Republished Article, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cephalosporins
- Ceftazidime
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Topics |
- Adult
- Aged
- Bacteremia
(drug therapy, economics, metabolism)
- Burkholderia pseudomallei
(drug effects, metabolism)
- Ceftazidime
(administration & dosage, economics, pharmacokinetics)
- Cephalosporins
(administration & dosage, economics, pharmacokinetics)
- Female
- Humans
- Infusions, Intravenous
- Linear Models
- Male
- Melioidosis
(drug therapy, economics, metabolism)
- Middle Aged
- Models, Biological
- Statistics, Nonparametric
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