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https://www.readbyqxmd.com/read/28807922/are-standard-doses-of-piperacillin-in-piperacillin-tazobactam-regimens-adequate-for-the-management-of-febrile-neutropenia-answers-from-population-pharmacokinetic-modelling-and-monte-carlo-simulations
#1
Fekade Bruck Sime, Uwe Hahn, Morgyn S Warner, Ing Soo Tiong, Michael S Roberts, Jeffrey Lipman, Sandra L Peake, Jason A Roberts
Changes in the pharmacokinetics of piperacillin in febrile neutropenic patients have been reported to result in sub-optimal exposures. This study aimed to develop a population pharmacokinetic model for piperacillin and perform dosing simulation to describe optimal dosing regimens for haematological malignancy patients with febrile neutropenia. Concentration-time data were obtained from previous prospective observational pharmacokinetic and interventional therapeutic drug monitoring studies. Non-parametric population pharmacokinetic analysis and Monte Carlo dosing simulations were performed with Pmetrics® package for R...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28774898/fda-approval-summary-trabectedin-for-unresectable-or-metastatic-liposarcoma-or-leiomyosarcoma-following-an-anthracycline-containing-regimen
#2
Amy Barone, Dow-Chung Chi, Marc R Theoret, Huanyu Chen, Kun He, Dubravka Kufrin, Whitney S Helms, Sriram Subramaniam, Hong Zhao, Anuja Patel, Kirsten B Goldberg, Patricia Keegan, Richard Pazdur
On October 23, 2015, the U.S. Food and Drug Administration approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m(2) as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks to dacarbazine 1000 mg/m(2) i...
August 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28742113/addition-of-17-allylamino-17-demethoxygeldanamycin-to-a-suboptimal-caspofungin-treatment-regimen-in-neutropenic-rats-with-invasive-pulmonary-aspergillosis-delays-the-time-to-death-but-does-not-enhance-the-overall-therapeutic-efficacy
#3
Jeannine M Refos, Alieke G Vonk, Marian T Ten Kate, Kimberly Eadie, Henri A Verbrugh, Irma A J M Bakker-Woudenberg, Wendy W J van de Sande
Caspofungin (CAS) which is used as salvage therapy in patients with invasive pulmonary aspergillosis (IPA) inhibits the 1,3-β-D-glucan synthesis in Aspergillus fumigatus. Inhibiting 1,3-β-D-glucan synthesis induces a stress response and in an invertebrate model it was demonstrated that inhibiting this response with geldamycin enhanced the therapeutic efficacy of CAS. Since geldamycin itself is toxic to mammalians, the therapeutic efficacy of combining geldamycin with CAS was not studied in rodent models. Therefore in this study we investigated if the geldamycin derivate 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) was able to enhance the therapeutic efficacy of CAS in vitro and in our IPA model in transiently neutropenic rats...
2017: PloS One
https://www.readbyqxmd.com/read/28705670/empiric-antibiotic-protocols-for-cancer-patients-with-neutropenia-a-single-center-study-of-treatment-efficacy-and-mortality-in-patients-with-bacteremia
#4
Eyal Kleinhendler, Matan J Cohen, Allon E Moses, Ora Paltiel, Jacob Strahilevitz, Amos Cahan
BACKGROUND: A number of empiric antibiotic treatment options for febrile neutropenia exist, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients to that of various commonly used antibiotic treatment protocols. METHODS: Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments, in whom blood cultures were taken on admission were included...
July 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28692817/complications-of-hematopoietic-stem-transplantation-bacterial-infections
#5
REVIEW
Ali S Omrani, Reem S Almaghrabi
Bacterial infections remain a common complication of hematopoietic stem cell transplantation (HSCT), especially in the pre-engraftment phase. The risk of bacterial infections is mainly related to neutropenia, mucositis, and the presence of vascular lines. Most parts of the world have witnessed a shift in epidemiology toward Gram-negative bacteria; a large proportion of which are resistant to fluoroquinolones, extended-spectrum beta-lactams, carbapenems, and in some units even colistin. Meticulous infection control practices are essential for prevention of bacterial infections in HSCT...
July 3, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28660351/moxifloxacin-versus-levofloxacin-or-ciprofloxacin-prophylaxis-in-acute-myeloid-leukemia-patients-receiving-chemotherapy
#6
Daniel J Przybylski, David J Reeves
PURPOSE: Patients receiving intensive chemotherapy regimens are at high risk for infectious complications due to prolonged neutropenia and hospital stay. Fluoroquinolone antibiotics, mainly levofloxacin and ciprofloxacin, are the mainstay of prophylactic therapy for these patients. There is limited data regarding the utilization of other quinolone antibiotics including moxifloxacin in this setting. METHODS: A retrospective chart review was completed comparing the use of prophylactic moxifloxacin to that of levofloxacin or ciprofloxacin during periods of prolonged neutropenia...
June 28, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28630197/pharmacodynamics-of-cefepime-combined-with-tazobactam-against-clinically-relevant-enterobactereaceae-in-a-neutropenic-mouse-thigh-model
#7
Maria J Melchers, Anita C van Mil, Claudia Lagarde, Jan den Hartigh, Johan W Mouton
The lack of new antibiotics prompted the investigation of the combination of two existing agents cefepime, a broad-spectrum cephalosporin and tazobactam to broaden its efficacy against extended-spectrum beta-lactamase producing Enterobacteriaceae. We determined the pharmacokinetic and pharmacodynamic properties of the combination in a murine neutropenic thigh model in order to establishing its exposure- response relationships (ERR). The PK of cefepime was determined for five doses; that of tazobactam was determined in earlier studies (Melchers et al Antimicrob...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630185/in-vivo-biomarker-analysis-of-intranasally-dosed-pc945-a-novel-antifungal-triazole-on-aspergillus-fumigatus-infection-in-immunocompromised-mice
#8
Genki Kimura, Takahiro Nakaoki, Thomas Colley, Garth Rapeport, Pete Strong, Kazuhiro Ito, Yasuo Kizawa
PC945 is a novel triazole optimised for lung delivery and the objective of this study is to determine the effects of intranasally dosed PC945 on Aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. PC945, posaconazole or voriconazole was treated intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) post-infection in temporarily neutropenic A/J mice infected intranasally with A. fumigatus, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28618307/meta-analysis-of-selected-toxicity-endpoints-of-cdk4-6-inhibitors-palbociclib-and-ribociclib
#9
REVIEW
R Costa, R B Costa, Sarah M Talamantes, Irene Helenowski, Jonna Peterson, Jason Kaplan, B A Carneiro, Francis J Giles, W J Gradishar
PURPOSE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib and ribociclib are associated with distinct adverse effects (AEs) compared to other targeted therapies. This meta-analysis of clinical trials summarizes these agents' toxicity profile. METHODS: A librarian-guided literature search was conducted in March of 2017. The trials needed to have at least one of the study arms consisting of palbociclib or ribociclib monotherapy at currently FDA approved dose regimens...
June 12, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28588617/outcomes-of-six-dose-high-dose-cytarabine-as-a-salvage-regimen-for-patients-with-relapsed-refractory-acute-myeloid-leukemia
#10
Brandi Anders, Lauren Veltri, Abraham S Kanate, Alexandra Shillingburg, Nilay Shah, Michael Craig, Aaron Cumpston
Relapsed/refractory acute myeloid leukemia (RR-AML) is associated with poor prognosis and long-term disease-free survival requires allogeneic hematopoietic cell transplantation (allo-HCT). Limited data exists, regarding the optimal regimen to obtain remission prior to allo-HCT. Single agent high-dose cytarabine (10-12 doses administered every 12 hours) has been previously used as induction therapy. Six-dose high-dose cytarabine (HiDAC-6), commonly used as a consolidation regimen, has never been evaluated as induction therapy...
2017: Advances in Hematology
https://www.readbyqxmd.com/read/28577308/empirical-antibiotics-targeting-gram-positive-bacteria-for-the-treatment-of-febrile-neutropenic-patients-with-cancer
#11
REVIEW
Ofrat Beyar-Katz, Yaakov Dickstein, Sara Borok, Liat Vidal, Leonard Leibovici, Mical Paul
BACKGROUND: The pattern of infections among neutropenic patients with cancer has shifted in the last decades to a predominance of gram-positive infections. Some of these gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. OBJECTIVES: To assess the effectiveness of empirical anti-gram-positive (antiGP) antibiotic treatment for febrile neutropenic patients with cancer in terms of mortality and treatment failure...
June 3, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28556623/ultrasonography-driven-combination-antibiotic-therapy-with-tigecycline-significantly-increases-survival-among-patients-with-neutropenic-enterocolitis-following-cytarabine-containing-chemotherapy-for-the-remission-induction-of-acute-myeloid-leukemia
#12
Novella Pugliese, Paola Salvatore, Dora Vita Iula, Maria Rosaria Catania, Federico Chiurazzi, Roberta Della Pepa, Claudio Cerchione, Marta Raimondo, Claudia Giordano, Luigia Simeone, Simona Caruso, Fabrizio Pane, Marco Picardi
Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10-year period, for receiving chemotherapy protocols with 100-6000 mg/m(2) daily of cytarabine...
July 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28555084/mitoxantrone-etoposide-and-cytarabine-following-epigenetic-priming-with-decitabine-in-adults-with-relapsed-refractory-acute-myeloid-leukemia-or-other-high-grade-myeloid-neoplasms-a-phase-1-2-study
#13
A B Halpern, M Othus, E M Huebner, S A Buckley, E L Pogosova-Agadjanyan, K F Orlowski, B L Scott, P S Becker, P C Hendrie, T L Chen, M-E M Percival, E H Estey, D L Stirewalt, R B Walter
DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D)...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28526536/trastuzumab-emtansine-versus-capecitabine-plus-lapatinib-in-patients-with-previously-treated-her2-positive-advanced-breast-cancer-emilia-a-descriptive-analysis-of-final-overall-survival-results-from-a-randomised-open-label-phase-3-trial
#14
Véronique Diéras, David Miles, Sunil Verma, Mark Pegram, Manfred Welslau, José Baselga, Ian E Krop, Kim Blackwell, Silke Hoersch, Jin Xu, Marjorie Green, Luca Gianni
BACKGROUND: The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. METHODS: EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28416552/in-vivo-pharmacodynamic-target-assessment-of-eravacycline-against-escherichia-coli-in-a-murine-thigh-infection-model
#15
Miao Zhao, Alexander J Lepak, Karen Marchillo, Jamie VanHecker, David R Andes
Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug resistance phenotypes. The goal of the studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six Escherichia coli isolates were utilized for the studies. MICs were determined using CLSI methods and ranged from 0.125 to 0.25 mg/liter. A neutropenic murine thigh infection model was utilized for all treatment studies...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416551/comparative-pharmacodynamics-of-telavancin-and-vancomycin-in-the-neutropenic-murine-thigh-and-lung-infection-models-against-staphylococcus-aureus
#16
Alexander J Lepak, Miao Zhao, David R Andes
The pharmacodynamics of telavancin and vancomycin were compared using neutropenic murine thigh and lung infection models. Four Staphylococcus aureus strains were included. The telavancin MIC ranged from 0.06 to 0.25 mg/liter, and the vancomycin MIC ranged from 1 to 4 mg/liter. The plasma pharmacokinetics of escalating doses (1.25, 5, 20, and 80 mg/kg of body weight) of telavancin and vancomycin were linear over the dose range. Epithelial lining fluid (ELF) pharmacokinetics for each drug revealed that penetration into the ELF mirrored the percentage of the free fraction (the fraction not protein bound) in plasma for each drug...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28396549/in-vivo-pharmacokinetics-and-pharmacodynamics-of-zti-01-fosfomycin-for-injection-in-the-neutropenic-murine-thigh-infection-model-against-escherichia-coli-klebsiella-pneumoniae-and-pseudomonas-aeruginosa
#17
Alexander J Lepak, Miao Zhao, Brian VanScoy, Daniel S Taylor, Evelyn Ellis-Grosse, Paul G Ambrose, David R Andes
Fosfomycin is a broad-spectrum agent with activity against Gram-positive and Gram-negative bacteria, including drug-resistant strains, such as extended-spectrum-beta-lactamase (ESBL)-producing and carbapenem-resistant (CR) Gram-negative rods. In the present study, the pharmacokinetic/pharmacodynamic (PK/PD) activity of ZTI-01 (fosfomycin for injection) was evaluated in the neutropenic murine thigh infection model against 5 Escherichia coli, 3 Klebsiella pneumoniae, and 2 Pseudomonas aeruginosa strains, including a subset with ESBL and CR phenotypes...
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28395668/delayed-rhabdomyolysis-with-paclitaxel-ifosfamide-carboplatin-and-etoposide-regimen-a-case-report
#18
Alexandra Sokolova, Onyee Chan, Waqas Ullah, Auon Abbas Hamdani, Faiz Anwer
BACKGROUND: High-dose chemotherapy with autologous stem cell rescue is commonly used for the treatment of relapsed germ cell tumors. We report the first case of delayed rhabdomyolysis with paclitaxel, ifosfamide, carboplatin, and etoposide regimen. CASE PRESENTATION: We report a case of a 21-year-old African-American man diagnosed with relapsed non-seminomatous germ cell tumor who received high-dose chemotherapy with carboplatin and etoposide following TIGER trial arm B off-protocol...
April 11, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28358279/incidence-of-late-onset-neutropenia-associated-with-rituximab-use-in-b-cell-lymphoma-patients-undergoing-autologous-stem-cell-transplantation
#19
Vincent H Ha, Sunita Ghosh, Catherine Leyshon, Nikki Ryan, Carole R Chambers, Douglas A Stewart
Reversible late onset neutropenia associated with rituximab has been reported with incidence rates varying from 15 to 70% in B cell lymphoma patients receiving autologous stem cell transplantation. We conducted a retrospective descriptive study at one tertiary care center in adult B cell lymphoma patients treated with rituximab and autologous stem cell transplantation between 1 January 2004 and 30 June 2014. Late onset neutropenia was defined as an absolute neutrophil count <1.0 × 10(9) cells/L after neutrophil engraftment and less than six months post autologous stem cell transplantation...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28355465/clinical-considerations-in-the-early-treatment-of-invasive-mould-infections-and-disease
#20
Toine Mercier, Johan Maertens
Different therapeutic strategies for invasive fungal diseases have been explored, each with particular strengths and weaknesses. Broad-spectrum antifungal prophylaxis seems logical, but selective use is important due to its substantial disadvantages, including interference with diagnostic assays, selection for resistance, drug toxicity and drug-drug interactions. Antimould prophylaxis should be restricted to high-risk groups, such as patients undergoing intensive chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome, allogeneic HSCT patients with prior invasive fungal infection, graft-versus-host-disease or extended neutropenia, recipients of a solid organ transplant, or patients with a high-risk inherited immunodeficiency...
March 1, 2017: Journal of Antimicrobial Chemotherapy
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