Piperacillin/Tazobactam in critically ill morbidly obese patients: A case series: The first One-Centre experience with TDM.

The aim of this article is to demonstrate extreme interindividual variability of piperacilin/tazobactam (PIP/TAZO) pharmacokinetics in critically ill morbidly obese patients and to emphasize the need for the practice of routine PIP/TAZO plasma concentrations measurement in order to ensure optimal efficacy and safety of antibiotic therapy.

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin.

BACKGROUND AND OBJECTIVE: Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance]. METHODS: We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. RESULTS: Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. CONCLUSION: We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.

[Evaluation of three dosage regimens of amikacin using pharmacokinetic models in patients with cystic fibrosis]. / Vyhodnocení trí dávkových rezimu amikacinu farmakokinetickým modelováním u pacientu s cystickou fibrózou.

BACKGROUND: Once-daily administration of aminoglykosides is routinely used, but comparative efficacy data for patients with cystic fibrosis are not available. METHODS AND RESULTS: The aim of the this study was to compare the predicted pharmacodynamic (PD) activity of amikacin at 28 mg/kg/den administered every 24 hod.(q24h), q12h, and q8h. Pharmacokinetic (PK) data were derived from analysis of the amikacin serum concentration from 42 CF children patients. Individual pharmacokinetics values were used to construct serum concentration--versus time curves and to determine various indices (c peak/MIC ratio and time during the concentration was less than the MIC--T < MIC) for all three dose regimens described above. MIC (minimal inhibitory concentration) for Pseudomonas aeruginosa was 4 mg/l. Significantly lower c peak/MIC but shorter T < MIC were noted when regimens of q8h versus q12h (p < 0.001), q8h vs. q24h (p < 0.001) and q12h vs. q24h (p < 0.001) were compared. This analysis suggests that the potential advantage of achieving a greater c peak/MIC with once-daily aminoglycoside administration may be neutralized by the significantly greater T < MIC in CF patients compared with that achieved with multiple-daily-dosing regimens. CONCLUSIONS: Routine use of once daily amikacin administration could not be recommended until the clinical data confirming efficiency of this dose modality are available.

[A new strategy for monitoring levels of cyclosporin A in the blood of patients after kidney transplantation]. / Nová strategie terapeutického monitorování hladin cyklosporinu A v krvi u pacientu po transplantaci ledvin.

Cyclosporine A (CyA), tacrolimus (FK 506), and mycophenolic acid are routinely utilised immunosuppressive drugs used in the prevention of allograft rejection and the treatment of several autoimmune diseases. The monitoring of CyA blood levels plays the most important role to individualize the dosage regiment and to minimize acute rejection risk and drug toxicity. Inadequate low CyA doses and levels may result in the rejection of transplanted organs. Toxic levels of CyA are associated with many serious side effects, including nephrotoxicity, hepatotoxicity, and a range of other complications. In the period of 1999-2002, 12,859 analyses of whole blood CyA levels were performed at our Department of Clinical Biochemistry. The aim of the present paper is to establish a new monitoring strategy of CyA that consists in the use of a single sampling point at 2 hours postdose and the estimation of blood concentration (C2). For the transplant patient, C2 monitoring is a significantly much better predictor of drug exposition and pharmacokinetic estimation than the trough concentration monitoring before the next dose (C0) used until now. The C2 monitoring strategy reduces the incidence and severity of both acute organ rejection and cyclosporine A toxicity.