Els Ampe

Implementation of a protocol for administration of vancomycin by continuous infusion: pharmacokinetic, pharmacodynamic and toxicological aspects.

Optimising antibiotic administration is critical when dealing with pathogens with reduced susceptibility. Vancomycin activity is dependent on the area under the concentration-time curve over 24 h at steady-state divided by the minimum inhibitory concentration (AUC/MIC), making continuous infusion (CI) or conventional twice daily administration pharmacodynamically equipotent. Because CI facilitates drug administration and serum level monitoring, we have implemented a protocol for CI of vancomycin by: (i) examining whether maintaining stable serum concentrations (set at 25-30 mg/L based on local susceptibility data of Gram-positive target organisms) can be achieved in patients suffering from difficult-to-treat infections; (ii) assessing toxicity (n = 94) and overall efficacy (n = 59); and (iii) examining the correlation between AUC/MIC and the clinical outcome in patients for whom vancomycin was the only active agent against a single causative pathogen (n = 20). Stable serum levels at the expected target were obtained at the population level (loading dose 20mg/kg; infusion of 2.57 g/24 h adjusted for creatinine clearance) for up to 44 days, but large intrapatient variations required frequent dose re-adjustments (increase in 57% and decrease in 16% of the total population). Recursive partitioning analysis of AUC/MIC ratios versus success or failure suggested threshold values of 667 (total serum level) and 451 (free serum level), corresponding to organisms with a MIC>1 mg/L. Nephrotoxicity potentially related to vancomycin was observed in 10% of patients, but treatment had to be discontinued in only two of them.

Stability and compatibility of vancomycin for administration by continuous infusion

BACKGROUND Vancomycin is increasingly used by continuous infusion, but few specific data are available about stability under practical conditions of preparation and use, and compatibility with other intravenous drugs commonly used in the routine hospital setting. METHODS Vancomycin stability [defined as recovery ≥ 93% of the original content (validated HPLC assay)] was examined throughout the whole process of centralized preparation, storage and use in the ward by infusion for up to 48 h, with allowances for deviations from recommended practice [exposure to high temperature; use of concentrated solutions (up to 83 g/L)]. Compatibility was assessed by mimicking co-administration in a single line via Y-shaped connectors with contact of 1 h at 25°C, followed by visual inspection (professional viewer), detection of particulate matter (particle analyser) and HPLC assay of vancomycin. RESULTS Vancomycin was stable during the whole process and also during 72 h exposure of concentrated solutions at temperatures up to 37°C. Major incompatibilities were seen with β-lactams (temocillin, piperacillin/tazobactam, ceftazidime, imipenem, cefepime and flucloxacillin) and moxifloxacin, but not with ciprofloxacin, aminoglycosides and macrolides. Propofol, valproic acid, phenytoin, theophylline, methylprednisolone and furosemide were also incompatible, whereas ketamine, sufentanil, midazolam, morphine, piritramide, nicardipine, urapidil, dopamine, dobutamine and adrenaline were compatible. No effect or incompatibility with N-acetyl-cysteine or amino acid solutions was detected. CONCLUSIONS Centralized preparation of vancomycin and its use by continuous infusion in wards is safe concerning stability, but careful attention must be paid to incompatibilities. Several drugs (including all β-lactams) require distinct intravenous lines or appropriate procedures to avoid undue contact.

Ability of deferasirox to bind iron during measurement of iron.

Iron overload leads to toxic damage to organs, such as the heart, liver and endocrine glands, with severe, life threatening consequences (1). Iron chelation therapy is an important treatment for patients that receive regular red blood cell transfusions as supportive therapy for chronic anemias, such as b-thalassemia and the myelodysplastic syndromes (2). Deferasirox mobilizes tissue iron deposits, and is becoming widely adopted as oral chelation therapy. Its long halflife (8–16 h) allows for once daily administration (3). Chelated iron from reticuloendothelial cells and tissues is thought to be transported into the blood stream and cleared by biliary excretion (4). Deferasirox is a tridentate iron chelator and the major complex form in serum (pHf7.4) is Fewdeferasiroxx2 (5). Ferrous ion (Fe) is weakly bound, and the Ferric (Fe) deferasirox complex is dissociated under acidic conditions and various iron containing species, such as Fe-deferasirox and unbound ferric ion occur (6). Routine methods for serum iron determination use acidic and reducing conditions (7). In our laboratory, we observed an increase in serum iron concentration in patients receiving deferasirox treatment. Thus, we investigated the effects of acidic and reducing conditions on the ability of deferasirox to bind iron during iron measurements. Fresh serum pool from donors (80 mL) was distributed as follows: 20 mL spiked with 2 mg of deferasirox (Novartis Pharma AG, Basel, Switzerland), 20 mL spiked with 2 mg