Biomedical subjects

Donatella Poz

Publications and source records attributed to Donatella Poz.

4 recordsLinked to original sources

PubMed2006

Which reliable pharmacodynamic breakpoint should be advised for ciprofloxacin monotherapy in the hospital setting? A TDM-based retrospective perspective.

OBJECTIVES: To define in critically ill patients receiving intravenous (iv) ciprofloxacin (200 mg or 400 mg twice daily) and undergoing routine therapeutic drug monitoring (TDM) the interindividual pharmacokinetic variability and the reliable pharmacodynamic breakpoint enabled by these fixed dosing regimens according to the PK/PD principles and to the pattern of susceptibility to this antibiotic. METHODS: Ciprofloxacin plasma concentrations [trough (Cmin) and 30 min post-dose peak (Cmax) levels] were analysed by means of an HPLC method. Optimal pharmacodynamic exposure was assessed by estimating the theoretical pharmacodynamic breakpoints (PD BP) for either Cmax or AUC. RESULTS: The final database included 177 sets of Cmin and Cmax performed in 89 patients (200 mg twice daily group, n=68; 400 mg twice daily group, n=21). A very wide interindividual scatter of results was observed for both the 200 mg group and the 400 mg group. Interestingly, for both groups only moderate log-linear relationships between estimated renal function (CLCR) on one hand and either Cmin (r2=0.08, 0.28) or estimated AUC24 (r2=0.10, 0.34) on the other hand were found. Median PD BP, respectively, in the 200 mg twice daily group and the 400 mg twice daily group, were 0.16 and 0.28 mg/L for Cmax, and 0.19 and 0.29 mg/L for AUC24. CONCLUSIONS: Lowering ciprofloxacin dosage in the presence of renal failure seems in most cases unnecessary, since drug accumulation occurred only in a few cases. Optimal pharmacodynamic exposure with fixed 200 or 400 mg twice daily regimens of ciprofloxacin may be ensured only against fully susceptible microorganisms with an MIC<0.3 mg/L. This supports the use of higher dosages in critically ill hospitalized patients, whereas the wide unpredictable interindividual pharmacokinetic variability suggests the usefulness of TDM with the intent of optimizing efficacy with ciprofloxacin therapy.

Analysis of Variance↗

PubMed2006

The effect of multifactorial, multidisciplinary educational interventions on appropriate use of teicoplanin.

The aim of this study was to determine the effect of multifactorial, multidisciplinary educational interventions over a 3-year period on the appropriate use of teicoplanin. Teicoplanin was considered a valid surrogate marker of good antibiotic use in clinical practice owing to its peculiar pharmacokinetics (i.e. necessity for an initial loading dose regardless of the patient's renal function for early achievement of optimal exposure, namely C(min) > or = 10 mg/L) and to the opportunity of comparing current routine therapeutic drug monitoring (TDM) results with those of a historical retrospective study. A significantly higher proportion of patients received appropriate loading doses of teicoplanin in the present prospective study than in the retrospective study, both when considered as a whole (66.6% versus 38.6%, respectively; P<0.001) or when stratified according to the degree of estimated renal function (78.4% versus 60.4% for creatinine clearance (CL(Cr)) > 50 mL/min; 59.8% versus 26.8% for CL(Cr) 20-50 mL/min; and 27.7% versus 5.5% for CL(Cr) <20 mL/min). The highest adherence was observed in haematological wards (97.7%). The percentages of patients with teicoplanin C(min) > or = 10 mg/L during the treatment period in the present and retrospective study, respectively, were: 61.4% versus 3.2% on Day 2; 88% versus 35% on Day 4; 94% versus 70% on Day 7; and 99% versus 90% on Day 11. Our findings suggest that continuous application of a multifactorial educational programme including active TDM may be efficacious in improving and maintaining over time the appropriate use in a hospital setting of a theoretically difficult-to-use drug such as teicoplanin.

Aged↗

PubMed2006

Acute oxcarbazepine, benazepril, and hydrochlorothiazide overdose with alcohol.

An epiletic patient, suffering from partial complex seizures and hypertension, ingested approximately 42 g of oxcarbazepine (OXC) and an undefined number of tablets containing an association of benazepril and hydrochlorothiazide along with some glasses of wine. Four hours later he was brought to the emergency room. He was stuporous and gradually became unconscious. Therefore he was intubated and, approximately 6 hours after the overdose, transferred to the intensive care unit, where he underwent a 4-hour hemodialysis. Even if this procedure did not accelerate the elimination of the prodrug nor its active metabolite (monohydrocarbazepine), 3 hours after the end of dialysis the patient was fully recovered.

Anticonvulsants↗

PubMed2002

TDM coupled with Bayesian forecasting should be considered an invaluable tool for optimizing vancomycin daily exposure in unstable critically ill patients.

A randomized two-arm prospective study was planned to assess the role of therapeutic drug monitoring (TDM) coupled with a Bayesian approach in tailoring vancomycin dosages in unstable critically ill patients. Group A (n=16) had their regimen adjusted day-by-day according to TDM and Bayesian forecasting (D(a)); group B (n=16) had their regimen adjusted day-by-day according to Moellering's nomogram (D(M)). Blood samples were collected every 1-2 days to assess the trough and peak plasma concentrations. In group A, the tailored D(a) required for optimizing vancomycin exposure were considerably higher than the D(M) in 7/16 cases, and lower than the D(M) in 1/16 cases. In group B, standard D(M) caused under-treatment in 3/16 cases and over-treatment in 4/16 cases. Most of these patients concomitantly had some conditions that might have altered vancomycin disposition. The TDM-guided Bayesian-based approach should be considered an invaluable tool for clinicians to handle appropriately on real-time vancomycin therapy in critically ill patients.

Adult↗