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  • 1
    Online Resource
    Online Resource
    Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children
    American Society for Microbiology ; 2016
    In:  Antimicrobial Agents and Chemotherapy Vol. 60, No. 1 ( 2016-01), p. 522-531
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 1 ( 2016-01), p. 522-531
    Abstract: The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions ( T MIC ) of ≥50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean ± standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 ± 3 years, 17 ± 6.2 kg, and 118 ± 41 ml/min/1.73 m 2 , respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam were as follows: clearance, 0.22 ± 0.07 and 0.19 ± 0.07 liter/h/kg, respectively; volume of distribution, 0.43 ± 0.16 and 0.37 ± 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of 〉 90% at MICs of ≤16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of 〉 90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of ≥80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02089-15
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
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    Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy
    Wiley ; 2016
    In:  The Journal of Clinical Pharmacology Vol. 56, No. 10 ( 2016-10), p. 1277-1287
    Details
    In: The Journal of Clinical Pharmacology, Wiley, Vol. 56, No. 10 ( 2016-10), p. 1277-1287
    Abstract: Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14–16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa , optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre‐ and post‐PIRRT. Ertapenem 500 mg followed by 500 mg post‐PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae . Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation.
    Type of Medium: Online Resource
    ISSN: 0091-2700 , 1552-4604
    URL: Issue
    URL: Article
    DOI: 10.1002/jcph.v56.10
    DOI: 10.1002/jcph.727
    RVK:
    XA 52835
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2010253-7
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  • 3
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    Population Pharmacokinetics and Pharmacodynamics of Meropenem in Nonobese, Obese, and Morbidly Obese Patients
    Wiley ; 2017
    In:  The Journal of Clinical Pharmacology Vol. 57, No. 3 ( 2017-03), p. 356-368
    Details
    In: The Journal of Clinical Pharmacology, Wiley, Vol. 57, No. 3 ( 2017-03), p. 356-368
    Abstract: The study objective was to evaluate meropenem population pharmacokinetics and pharmacodynamics in nonobese, obese, and morbidly obese patients. Forty adult patients—11 nonobese (body mass index [BMI] 〈 30 kg/m 2 ), 9 obese (30 kg/m 2 ≤ BMI 〈 40 kg/m 2 ), and 20 morbidly obese (BMI ≥ 40 kg/m 2 )—received meropenem 500 mg every 6 hours (q6h), q8h, or q12h or 1 g q6h or q8h, infused over 0.5 hour. Population pharmacokinetic modeling was performed using NONMEM, and 5000‐patient Monte‐Carlo simulations were performed to calculate probability of target attainment (PTA) for 5 dosing regimens, infused over 0.5 and 3 hours, using f T 〉 MIC of 40%, 54%, and 100% of the dosing interval. A 2‐compartment linear‐elimination model best described the serum concentration‐time data, and creatinine clearance was significantly associated with systemic clearance. Pharmacokinetic parameters were not significantly different among patient groups. In patients with creatinine clearances ≥50 mL/min, all simulated dosing regimens achieved 〉 90% PTA at 40% f T 〉 MIC in all patient groups at MICs ≤2 mg/L. Only 500 mg q8h, infused over 0.5 hour, did not achieve 〉 90% PTA at 54% f T 〉 MIC in nonobese and morbidly obese patients. At 100% f T 〉 MIC, 1 g q6h and 2 g q8h, infused over 3 hours, reliably achieved 〉 90% PTA in all patient groups. Meropenem pharmacokinetics are comparable among nonobese, obese, and morbidly obese patients. Standard dosing regimens provide adequate pharmacodynamic exposures for susceptible pathogens at 40% and 54% f T 〉 MIC, but prolonged infusions of larger doses are needed for adequate exposures at 100% f T 〉 MIC. Dosage adjustments based solely on body weight are unnecessary.
    Type of Medium: Online Resource
    ISSN: 0091-2700 , 1552-4604
    URL: Issue
    URL: Article
    DOI: 10.1002/jcph.v57.3
    DOI: 10.1002/jcph.812
    RVK:
    XA 52835
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2010253-7
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  • 4
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    2553. Addressing Knowledge and Practice Gaps in HIV Management with Engaging Continuing Education
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S887-S887
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S887-S887
    Abstract: Given the rapid evolution of HIV management guidelines and the emergence of new treatment paradigms, infectious disease specialists are challenged to stay current on the latest evidence-based care and how to tailor treatment to optimally meet an individual patient’s needs. To address identified knowledge and practice gaps regarding the care of patients with HIV, an engaging continuing education (CE) initiative was implemented, and the impact of the education on provider knowledge and practice was measured. Methods Vindico Medical Education partnered with Purdue University College of Pharmacy to deliver a highly engaging, 2.0-credit hour, CE initiative at ID week in October 2018. The symposium was comprised of multiple formats, including didactic presentations, case-based discussion, and the gamified segment, Wheel of HIV Knowledge. Coverage of the live program was posted to Healio.com, extending the reach of the education. Analysis of the impact of this education was achieved via pre- and post-test test assessment. Results 357 healthcare providers participated in the live session, and 236 have accessed the web activity as of April 2019. The gamified and case-based segments of the live activity engaged on average 70% of learners and revealed insights into current practice patterns and persisting gaps in knowledge regarding the latest, evidence-based HIV care. Across the curriculum, there was a 46% relative increase in knowledge and competence. A total of 223 providers who see on average 15 patients per month with HIV completed the education, resulting in approximately 2,500 patients with HIV per month who are more likely to receive the latest evidence-based care. Moreover, 3 months following the education, 55% of providers reported implementing practice improvements, including applying the latest clinical guidelines and recommendations. Of those providers who implemented changes, 47% observed patient improvements such as improved adherence, satisfaction, and reduced viral loads. Conclusion In recent years of rapid advances for HIV management, providers are challenged to administer the latest evidence-based care. This study highlights the power of engaging CE to address persisting knowledge and practice gaps toward the delivery of enhanced care for patients with HIV. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz360.2231
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 5
    Online Resource
    Online Resource
    Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients
    Wiley ; 2015
    In:  The Journal of Clinical Pharmacology Vol. 55, No. 8 ( 2015-08), p. 899-908
    Details
    In: The Journal of Clinical Pharmacology, Wiley, Vol. 55, No. 8 ( 2015-08), p. 899-908
    Type of Medium: Online Resource
    ISSN: 0091-2700
    URL: Issue
    URL: Article
    DOI: 10.1002/jcph.v55.8
    DOI: 10.1002/jcph.505
    RVK:
    XA 52835
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2010253-7
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  • 6
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    Implementing Extended-Infusion Cefepime as Standard of Care in a Children’s Hospital : A Prospective Descriptive Study
    SAGE Publications ; 2015
    In:  Annals of Pharmacotherapy Vol. 49, No. 4 ( 2015-04), p. 419-426
    Details
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 49, No. 4 ( 2015-04), p. 419-426
    Abstract: Background: Extended-infusion cefepime (EIC) has been associated with decreased mortality in adults, but to our knowledge, there are no studies in children. Objective: The objective of this study was to determine the feasibility of implementing EIC as the standard dosing strategy in a pediatric population. Methods: This was a descriptive study of children aged 1 month to 17 years, including patients in the intensive care unit, who received cefepime after admission to a freestanding, tertiary care children’s hospital. Patients were excluded if they were admitted to the neonatal intensive care unit or received cefepime in the outpatient, operating, or emergency department areas. Demographic and clinical data for patients who received cefepime from April through August 2013, the period following EIC implementation, were extracted from the medical records. Results: A total of 150 patients were included in the study, with a median age (interquartile range [IQR]) of 6 years (2-12.3 years) and median weight (IQR) of 20.7 kg (13.2-42.8 kg); 143 patients received cefepime via extended infusions, and 10 (7.0%) of those were changed to a 30-minute infusion during treatment. The most common reasons for infusion time change were intravenous (IV) incompatibility and IV access concerns, responsible for 50% of changes. Dosing errors and reported incidents during therapy were sparse (n = 12, 8.0%) and were most commonly related to renal dosing errors and/or initial dose error by prescriber. Conclusions: Because 93.0% of the patients who initially received EIC remained on EIC, implementation of EIC as the standard dosing strategy was feasible in this pediatric hospital.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028014566447
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2053518-1
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  • 7
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    Population Pharmacokinetics and Pharmacodynamics of Doripenem in Obese, Hospitalized Patients
    SAGE Publications ; 2017
    In:  Annals of Pharmacotherapy Vol. 51, No. 3 ( 2017-03), p. 209-218
    Details
    In: Annals of Pharmacotherapy, SAGE Publications, Vol. 51, No. 3 ( 2017-03), p. 209-218
    Abstract: Background: Doripenem population pharmacokinetics and dosing recommendations are limited in obesity. Objective: To evaluate the population pharmacokinetics and pharmacodynamics of doripenem in obese patients. Methods: Hospitalized adults with a body mass index (BMI) ≥ 40 kg/m 2 or total body weight (TBW) ≥45.5 kg over their ideal body weight received doripenem 500 mg every 8 hours, infused over 1 hour. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed for 5 intermittent and prolonged infusion dosing regimens to calculate probability of target attainment (PTA) at 40% and 100% fT 〉 MIC (free drug concentrations above the minimum inhibitory concentration). Results: A total of 20 patients were studied: 10 in an intensive care unit (ICU) and 10 in a non-ICU. A 2-compartment model with first-order elimination best described the serum concentration-time data. Doripenem clearance (CL) was significantly associated with creatinine CL (CRCL), volume of the central compartment with TBW and ICU residence, and volume of the peripheral compartment with TBW ( P 〈 0.05). Using 40% fT 〉 MIC, PTA was 〉 90% for all simulated dosing regimens at MICs ≤2 mg/L. Using 100% fT 〉 MIC, prolonged infusions of 1 g every 6 hours and 2 g every 8 hours achieved 〉 90% PTA at MICs ≤2 mg/L. Conclusions: CRCL, ICU residence, and TBW are significantly associated with doripenem pharmacokinetics. Currently approved dosing regimens provide adequate pharmacodynamic exposures at 40% fT 〉 MIC for susceptible bacteria in obese patients. However, prolonged infusions of larger doses are needed if a higher pharmacodynamic target is desired.
    Type of Medium: Online Resource
    ISSN: 1060-0280 , 1542-6270
    URL: Article
    DOI: 10.1177/1060028016676831
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2053518-1
    SSG: 15,3
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  • 8
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    1547. Modeling Pharmacokinetics and Pharmacodynamics of Meropenem Utilizing a Novel Infusion Method of Bolus to Prolonged Infusion
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S564-S565
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S564-S565
    Abstract: Dose optimization of antibiotics has been shown to increase the likelihood of achieving pharmacodynamic efficacy targets and improve clinical outcomes. For carbapenems, achieving greater than 40% time above minimum inhibitory concentration (T 〉 MIC) has been shown to be correlated with clinical efficacy. Increasing bacterial resistance and rising MICs makes it more difficult for clinicians to rely on traditional dosing strategies to meet pharmacodynamic goals. Further optimization methods beyond extended infusion may be necessary to achieve certain pharmacodynamics goals. Methods We performed a Monte Carlo simulation investigating a novel method of meropenem administration, bolus to prolonged infusion (BPI). Multiple meropenem dosing regimens utilizing BPI were evaluated over 5000 patients utilizing pharmacokinetic profiles from 30 total patients. Patients were studied in 3 separate groups: 〈 120 kg, ≥120 kg/non-critically ill and ≥120 kg/critically-ill. Bolus doses varied from 250–1000 mg and were paired with infusion doses varying from 500–1500 mg. Bolus plus infusion time totaled 3 hours and each dose was modeled with an 8-hour interval for both first dose and at steady state; BPI dosing was utilized for each dose. The primary outcome was probability of target attainment (PTA) of 40% time above minimum inhibitory concentration (T 〉 MIC). Secondary outcomes included PTA 54% T 〉 MIC and PTA 100% T 〉 MIC. Results All doses studied achieved 〉 90% PTA of 40% T 〉 MIC for MICs of ≤8 μg/mL at both first dose and steady state in the 〈 120 kg and ≥120 kg/non-critically ill patient groups. In the ≥120 kg/critically ill patient group, all doses achieved 〉 90% PTA of 40% T 〉 MIC for MICs of ≤4 μg/mL. Conclusion BPI achieves high probability of target attainment at nonresistant MICs for Pseudomonas aeruginosa and enteric Gram-negative organisms across the 3 patient groups studied. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz360.1411
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 9
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    Outcomes of Lung Transplantation for Cystic Fibrosis in the Setting of Extensively Drug-Resistant Organisms
    SAGE Publications ; 2019
    In:  Progress in Transplantation Vol. 29, No. 3 ( 2019-09), p. 220-224
    Details
    In: Progress in Transplantation, SAGE Publications, Vol. 29, No. 3 ( 2019-09), p. 220-224
    Abstract: Since the largest study on extensively drug-resistant organisms and lung transplantation in patients with cystic fibrosis, there have been innovations and advancements in the treatment of Pseudomonas aeruginosa. Research Question: What differences exist for patients with cystic fibrosis with a history of extensively drug-resistant infections who undergo lung transplantation despite treatment advances with antimicrobial therapy? Study Design: Two-center, retrospective, cohort study conducted in 44 patients with cystic fibrosis chronically infected with extensively drug-resistant organisms who received a lung transplant from January 2008 through August 2016. Patients in the resistant cohort were chronically infected with pan-resistant P aeruginosa, polymyxin-sensitive only, or sensitive to 2 antibiotic classes (polymyxin plus one other); remaining patients with more susceptible P aeruginosa or no P aeruginosa remained in the control cohort. The primary outcome is a composite of patient survival, retransplantation, chronic lung allograft dysfunction, and acute rejection 12 months posttransplant. Categorical variables were analyzed using χ 2 testing. The independent samples t test was utilized for continuous variables. Results: There was no difference in the primary outcome (40% vs 37%, P = .831). Differences between patient survival (84% vs 95%, P = .487), the incidence of acute rejection (20% vs 33%, P = .323), and the incidence of chronic lung allograft rejection (12% vs 5%, P = .441) were not different between groups. Discussion: Recipients chronically infected with an extensively resistant P aeruginosa had similar outcomes compared to those infected with more sensitive organisms.
    Type of Medium: Online Resource
    ISSN: 1526-9248 , 2164-6708
    URL: Article
    DOI: 10.1177/1526924819853830
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2019
    detail.hit.zdb_id: 2864264-8
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