Albumin concentration significantly impacts on free teicoplanin plasma concentrations in non-critically ill patients with chronic bone sepsis.

The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15-24) g/L. After 48 h, the median (IQR) free trough (fC(min)) and total trough (tC(min)) concentrations were 2.90 (2.67-3.47) mg/L and 15.54 (10.28-19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9-47.8) L/h and 7.0 (IQR 6.8-9.8) L/h, respectively (P<0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations (P=0.174), albumin concentration did (P<0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients.

Pharmacokinetics of once-daily dosing of ertapenem in critically ill patients with severe sepsis.

Adequate data on the pharmacokinetics of once-daily administration of ertapenem in critically ill patients are largely lacking. This single-centre, prospective, open-label study was performed on a cohort of eight critically ill patients with severe sepsis with normal renal function treated with 1g of ertapenem once daily. Samples of venous blood and urine were collected before infusion and at specific time points in the 24-h post-infusion period. Plasma and urine ertapenem levels were determined by reverse-phase high-performance liquid chromatography (HPLC) with ultraviolet detection. The non-protein-bound fraction was determined in the filtrate by HPLC using a Centrifree device. The current study showed a lower maximum plasma concentration (C(max)) (52.3.0mg/L vs. 253 mg/L) and area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) (188 mg h/L vs. 817 mg h/L) but higher volume of distribution at steady state (V(ss)) (26.8L vs. 5.7 L) compared with those observed in young healthy volunteers. For unbound ertapenem, geometric means of C(max) and AUC(0-infinity) were 29.5mg/L and 103.5 mg h/L, respectively, and correlated negatively with hypoalbuminaemia. Unbound levels failed to exceed a minimum inhibitory concentration of 1mg/L for more than 7.1h (30%) of the dosing interval in two patients. The highly variable and unpredictable intersubject pharmacokinetic parameters documented in this study resulted in suboptimal unbound concentrations in some patients. This raises the question as to whether ertapenem is an appropriate agent for initial use in critically ill patients with severe sepsis.

Determination of trinitrotoluene and metabolites in urine by means of gas-chromatography with mass detection.

Biological monitoring of chemicals and/or their metabolites has been a recent development in South Africa with the publication of the Hazardous Chemical Substance Regulations in 1995. Although trinitrotoluene (TNT) exposure has been included in recent legislative developments, only occupational exposure limits have been set. TNT does not have a biological exposure index in South Africa or internationally. This study was conducted to determine levels of TNT and its metabolite excretion in a sample of munition workers by using gas-chromatography with mass detection methodology. The metabolites 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT) in urine of exposed subjects, as well as total TNT (the sum of 4ADNT and 2ADNT), were used to determine absorption and excretion due to TNT exposure. Results indicated an increased absorption of TNT during the working week as compared to other published international studies. Post-shift values exceeded pre-shift levels in all samples. More reliable and specific research is necessary to set a biological threshold limit for TNT and its metabolites since monitoring indicated no definite symptoms, signs or biological effects due to increased excretion.