1,721,031 research outputs found
Daptomycin underexposure in a young intravenous drug user who was affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection associated with bacteraemia
No full textWe describe the case of an intravenous drug user affected by life-threatening Staphylococcus aureus-complicated skin and soft tissue infection with associated bacteraemia who, while on replacement therapy with methadone, required 11 mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels similar to those observed with the standard dosage of 6 mg/kg in healthy volunteers (mean ± standard deviation: Cmin 12.35 ± 0.80 mg/L, C max 63.90 ± 8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug monitoring may be helpful for optimizing daptomycin exposure in these patients. Physicians should take into account that dosages much higher than the standard ones may be needed, probably as a consequence of augmented drug clearanc
Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation.
No full textObjectives: To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability. Methods: We performed a retrospective study of patients whose plasma Cmin and Cmax levels were measured during linezolid treatment. Adequate exposure was defined as a Cmin of 2-7 mg/L and/or an estimated AUC24 of 160-300 mg·h/L. Patients were divided into two subgroups (Group 1, 2-11 years; Group 2, 12-18 years). Monte Carlo simulation was performed to investigate whether or not the currently recommended dosages might enable a high probability of target attainment (PTA) of two thresholds for linezolid efficacy (AUC24/MIC ≥ 80 or ≥ 100). Data on demographic characteristics, disease, microbiology and haematochemical parameters and outcomes were collected. Results: A total of 23 patients were included. Standard dosages were suboptimal in 50.0% and 44.4% of patients in Group 1 and Group 2, respectively. Among those who underwent multiple instances of TDM, the dosages were increased in 33.3% of cases in both groups, and decreased in 6.6% and 9.5% of cases in Group 1 and Group 2, respectively. Co-treatment with phenobarbital, proton pump inhibitors and amiodarone accounted for most of the variability in Cmin (adjusted R2 of 0.692). Simulations showed a PTA of ≥90% with the current dosing regimens in both groups only for pathogens with an MIC ≤1 mg/L. Conclusions: Higher dosages of linezolid may be needed, especially in Group 1 when in the presence of pathogens with an MIC >1 mg/L. The role of TDM should be encouraged for optimization of linezolid exposure in the paediatric setting in the presence of infections caused by pathogens with borderline susceptibility and/or for patients co-treated with drugs that may alter linezolid exposure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections
No full textIntroduction: In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach. Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included. Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram-positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gram-negative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections
Stability of generic meropenem solutions for administration by continuous infusion at normal and elevated temperatures
No full textAdministration by continuous infusion may represent an effective tool for the treatment of multidrug-resistant gram-negative related infections with meropenem. Currently, no data on chemical stability of generic bioequivalent versions of meropenem over time are available. Triplicate samples of 5 mg/mL solutions of a generic meropenem formulation, Hospira, were evaluated for chemical stability at increasing temperatures (25°C, 30°C, 35°C, and 40°C) by means of a high-performance liquid chromatography technique over 4 separate days. Degradation of generic meropenem was both time and temperature dependent, and the aqueous solutions were stable for up to 8 hours in the temperature range between 25°C and 35°C, and for up to 5 hours at 40°C. Continuous infusion of generic meropenem Hospira may be applied in clinical settings with ambient temperature below 35°C, provided that the 5 mg/mL aqueous solution is reconstituted at most after 6-8 hours
Everolimus overexposure in a heart transplant patient receiving clarithromycin for the treatment of pneumonia
No full textMonitoring polypharmacy in healthcare systems through a multi-setting survey: Should we put more attention on long term care facilities?
No full textBackground. Polypharmacy is a main issue of patient safety in all healthcare settings (i.e. increase adverse drug reactions and incidence of drug-drug interactions, etc.). The main object of the study was to evaluate the prevalence of polypharmacy and the appropriateness of drugs prescriptions in the regional health system (RHS) of Friuli Venezia-Giulia Region, Italy. Design and methods. We carried out a point prevalence study in May 2014; 1582 patients ≥65 years were included from: 14 acute hospitals, 46 Long Term Care Facilities (LTCFs) and 42 general practitioners’ (GPs) clinics. Data analysis included the evaluation of potentially inappropriate prescriptions (PIPs) taking Beers criteria as a reference. Results. Patients in therapy with 10 drugs or more were 13.5%: 15.2% in hospitals, 9.7% in GPs’ clinics and 15.6% in LTCFs. According to Beers criteria we identified 1152 PIPs that involved globally almost half of patients (46.0%): 41.9% in hospitals, 59.6% in LTCFs and 37.0% in GP’s clinics. The 53.9% of patients received at least one mainly kidney excreted drug; for these patients the evaluation of serum creatinine was overall present in the 87.7% (747/852): 96.4% in hospital ones, 87.5% in GPs’ clinics and 77.8% in LTCFs. LTCFs residents were significantly (P<0.05) more exposed to PIPs and less monitored for the renal function. Conclusions. A reliable estimation of the phenomenon in all the main healthcare settings is a necessary prerequisite to set tailored policies for facing polypharmacy within a RHS; the results showed the necessity to put a special attention on LTCFs
A 1 year retrospective audit of quality indicators of clinical pharmacological advice for personalized linezolid dosing: One stone for two birds?
No full textAim This study explored the clinical and economic impact of clinical pharmacological advice (CPA) (based on therapeutic drug monitoring [TDM] results, and on patients' characteristics and co-medications) on personalized linezolid therapy in a tertiary care hospital. Methods A 1 year retrospective analysis of quality indicators of CPA (clinicians' adherence rate to CPA, pre-post rate of linezolid trough concentrations within the desired range and cost balance analysis) was conducted. Results Five hundred and forty-four CPAs were provided to clinicians during 2014 for personalizing linezolid therapy in 168 patients. Clinicians' adherence to CPAs was very high (94.7%). The pre-post rate of linezolid Cmin distribution showed a favourable impact of CPA on patient care (pre-post ratio of Cmin within the desired range + 23.4%, pre, 51.2% vs. post, 74.6%). Overall, linezolid dosage was mainly reduced (56.9% of cases), whereas dose augmentation was needed only in a minority of cases (7.7%). Cost balance analysis showed that overall 1258 standard doses of linezolid (unitary dose 600 mg) were spared for treating 168 patients with a personalized dosage for a median duration of 11 days (range 3-128 days) with a cost saving of 60038.05 €. Conclusion Active computerized advice elaborated by the clinical pharmacologist on the basis of TDM results and of patient's pathophysiological data and co-medications may be cost-effective for personalizing linezolid treatment
Polytherapy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in three different settings (hospital, community, long-term care facilities) of the Friuli Venezia Giulia region, Italy: are the very elderly at higher risk of PIPs?
No full textPurpose: The aim of this point-prevalence study was to assess the occurrence of polypharmacy and hyperpolypharmacy and the risk of potentially inappropriate prescriptions (PIPs) among elderly and very elderly patients in different health-care settings of the Friuli–Venezia Giulia region in the North-East of Italy. Methods: Prescription pattern of elderly (65–79 years) and very elderly (>79 years) patients in three different health-care settings [hospitals, general practitioners, and long-term care facilities (LTCFs)] was assessed in March 2014, and PIPs were assessed according to the Beers criteria. Other situations at potentially high risk were checked. Results: A total of 1582 patients (hospital, n = 528; outpatients, n = 527; nursing homes, n = 527) were included. Very elderly were more represented in hospitals (60.4%) and LTCFs (77.1%) than among general practitioners (37.6%). Polypharmacy and hyperpolypharmacy rates ranged 57.7–73.7% and 9.7–15.6%, respectively. The most frequently prescribed drugs were the proton pump inhibitors, whereas the most common PIPs resulted the benzodiazepines. Multinomial regression analysis showed that female sex, age > 79 years, hyperpolypharmacy, and chronic kidney disease were associated with the risk of having ≥2 PIPs. Two situations at high risk of PIPs not contemplated by the Beers criteria were recurrent in the study population and concerned the statins and metformin. Conclusions: Polypharmacy and hyperpolypharmacy among elderly and very elderly are strictly associated with the risk of multiple PIPs. The findings offer the opportunity to remark that improvement of the knowledge of safe drug use is generally needed in aging societies and may become of utmost relevance among health-care workers operating in LTCFs. Copyright © 2016 John Wiley & Sons, Ltd
Antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia: dose intensification coupled with avoidance of proton pump inhibitors is beneficial in shortening time to effective concentrations.
No full textThis study aimed to assess the influence of dose frequency and the presence or absence of cotreatment with proton pump inhibitors (PPIs) on the time to a target trough concentration (Cmin) of>700 ng/ml with posaconazole in the first 8 days of antifungal prophylaxis in hematological patients. This was a retrospective, observational study performed with 42 adult patients with acute myeloid leukemia who underwent posaconazole prophylaxis with 200 mg every 8 h (q8h) or 200 mg q6h after receiving induction chemotherapy and who had at least three subsequent therapeutic drug monitoring assessments during the first 8 days of treatment. The cohort was split into four groups (group 1, 200 mg q8h without PPI; group 2, 200 mg q8h with PPI; group 3, 200 mg q6h without PPI; group 4, 200 mg q6h with PPI). Rapid attainment of the target Cmin was obtained only in group 3 (P<0.01) (median Cmin on day 4 of 935.5 ng/ml [interquartile range, 760.0 to 1,270.0 ng/ml] in group 3, versus 567.0 ng/ml [346 to 906 ng/ml] in group 1, 420.0 ng/ml [326.2 to 527.2 ng/ml] in group 2, and 514.0 ng/ml [403.7 to 564.7 ng/ml] in group 4). A linear accumulation of posaconazole over time was observed among patients in groups 1 and 3, regardless of the total daily dosage, differently from what occurred among those receiving PPI cotreatment (groups 2 and 4). Dose intensification (200 mg q6h) coupled with avoidance of PPI coadministration may represent a very powerful strategy to rapidly achieve effective concentrations with posaconazole in neutropenic hematological patients. Copyright © 2013, American Society for Microbiology. All Rights Reserved
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