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INTRODUCTION: Audits for monitoring the quality of antimicrobial prescribing are a main tool in antimicrobial stewardship programs; however, interobserver reliability has not been conclusively assessed. Our objective was to measure the level of agreement between pharmacists and physicians on the appropriateness of antimicrobials prescribing in hospitals. METHODS: A national multicenter, cross-sectional study was conducted of patients who were receiving antimicrobials one day of April 2021. Hospital participation was voluntary, and the study population was randomly selected. Pharmacists and physicians performed a simultaneous, independent assessment of the quality of antimicrobial prescriptions. The observers used an assessment method by which all indicators of the quality of antimicrobial use were considered. Finally, an algorithm was used to rate overall antimicrobial prescribing as appropriate, suboptimal, inappropriate, or not assessable. Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: In total, 101 hospitals participated, and 411 hospital antimicrobial prescriptions were reviewed. The strength of agreement was moderate regarding the overall quality of prescribing (AC1=0.51; 95%CI=[0.44-0.58]). A very good level of agreement (AC1>0.80) was observed between pharmacists and physicians in all indicators of the quality, except for duration of treatment, rated as good (AC1=0.79; 95%CI=[0.75-0.83]), and registration on the medical record, rated as fair (AC1=0.34; 95%CI=[0.26-0.43]). The agreement was greater in critical care, onco-hematology, and pediatric units than in medical and surgery units. CONCLUSIONS: In this point prevalence study, a moderate level of agreement was observed between pharmacists and physicians in the evaluation of the appropriateness of antimicrobials prescribing in hospitals.
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Docetaxel is a semi-synthetic taxane with cytotoxic anti-neoplastic activity and, currently used as anticancer agent in several types of cancer. Docetaxel is highly bound to plasma proteins, and this significantly determines its clearance and activity. Therefore, measurement of free docetaxel in plasma is pharmacologically important when pharmacokinetics is investigated. We developed and validated chromatographic methods by ultra-performance liquid chromatography-tandem mass spectrometry to measure total and free docetaxel concentration in human plasma. The final validated methods involved liquid-liquid extraction followed by dryness under nitrogen evaporation. To measure free docetaxel concentration, sample preparation was preceded by ultrafiltration. Chromatographic separation was achieved using an Acquity(®) UPLC(®) BEH™ (2.1×100 mm id, 1.7 µm) reverse-phase C18 column at a flow rate of 0.4 mL/min, using isocratic elution mode containing ammonium acetate/formic acid in water/methanol (30:70 v/v) as mobile phase. Docetaxel and its internal standard (paclitaxel) were detected by electrospray ionization mass spectrometry in positive ion multiple reaction monitoring mode using mass-to-charge (m/z) transitions of 808.3â527.0 (quantifier) and 808.3â509.0 (qualifier); and 854.3â569.0 (quantifier) and 854,3â509,0 (qualifier), respectively. The run time per sample was 3.5 min. The limits of quantification were 1,95 and 0.42 µg/L and linearity was observed between 1.95 and 1000 and 0.42-100 µg/L for total and free docetaxel, respectively. Coefficients of variation and absolute relative biases were less than 13.8% and 10.0%. Recovery values were greater than 79.4%. Evaluation of the matrix effect showed ion suppression and no carry-over was observed. The validated methods could be useful for both therapeutic drug monitoring and pharmacokinetic studies. They could be applied to daily clinical laboratory practice to measure the concentration of total and free docetaxel in plasma.