A Prospective Study of Voriconazole Therapeutic Drug Monitoring (TDM) in Patients with Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1018-1018
Author(s):  
Jack Seki ◽  
Joseph Brandwein ◽  
Richard Ward ◽  
Narinder Paul ◽  
Heather Russell ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Clinical Outcomes ◽  
Invasive Fungal Disease ◽  
Response To Therapy ◽  
Therapeutic Drug ◽  
Consolidation Chemotherapy ◽  
Oral Medications ◽  
A Prospective Study ◽  
Kinetics Of ◽  
Slow Metabolizers

Abstract Abstract 1018 Poster Board I-40 Background: Voriconazole (VOR) is an expanded spectrum azole that is often used to treat suspected or proven invasive aspergillosis (IA). VOR plasma drug levels are not routinely monitored and their correlation with clinical response and toxicity is unclear. We sought to clarify the kinetics of levels in patients started on VOR and their relationship with CYP2C19 genotype and clinical outcomes. Methods: We prospectively enrolled inpatients undergoing induction or consolidation chemotherapy for AML who were able to take oral medications and started on VOR for suspected invasive aspergillosis (IA). All patients received an initial intravenous loading dose of 6mg/kg bid for two doses, then 200mg bid. VOR dose could be increased at the physician's discretion. Trough VOR levels (μg/mL) were monitored at days 0,2,4,6 and performed using HPLC. Patients also underwent genotyping for CYP2C19. Clinical and radiologic responses were graded independently by two physicians. Hepatotoxicity was correlated to peak VOR levels. Results: We enrolled 33 patients of which 60.6% were male and 39.4% female. Mean age was 60.2±15.4 yrs. The distribution of peak VOR levels was as follows: <2 μg/mL (n=6); 2-6 μg/mL (n=22); >6 μg/mL (n=5). Mild hepatotoxicity (liver enzymes greater than 2x baseline) was seen in 6/22 (27.2%) of patients with levels between 2-6 μg/mL and 1/5 (20%) of patients with levels >6 μg/mL. No hepatotoxicity was noted in those with peak VOR <2 μg/mL. No significant correlation was seen in mg/kg dose of VOR and levels. Of the 33 patients, 19 (57.6%) met the EORTC/MSG criteria for possible, probable, or proven invasive fungal disease. Of these 9 (47.4%) patients had a response to therapy. Mean peak VOR levels in responders vs. nonresponders was 3.78 vs. 3.12 (p=0.63). Response to therapy was 2/2 (100%) if levels were <2 μg/mL, 6/14 (42.9%) if levels were 2-6 μg/mL, and 1/3 (33%) if levels were >6 μg/mL. Breakthrough infections occurred in 5/33 (15.2%) patients given VOR, all of whom had peak levels between 2-6 μg/mL. Genotyping was performed on 11/33 (33.3%) patients and included slow metabolizers (n=5; median peak VOR 3.0), rapid metabolizers (n=5; median peak VOR 3.0) and undetermined (n=1). Genotype did not correlate with clinical outcomes. Conclusions: The majority of patients attained voriconazole levels > 2 μg/mL by day 6 of treatment. Voriconazole levels do not appear to predict response to therapy or breakthrough infection although mild hepatotoxicity can occur if levels are >2 μg/mL. Disclosures: Seki: Astellas: Honoraria; Pfizer: Honoraria; Merck: Consultancy, Honoraria, Research Funding. Kumar:Merck: Honoraria; Pfizer: Honoraria.

scholarly journals Effect of Obesity on Clinical Failure of Patients Treated with Beta-Lactams

2021 ◽  
Author(s):  
Nathan A Pinner ◽  
Natalie G Tapley ◽  
Katie E Barber ◽  
Kayla R Stover ◽  
Jamie L Wagner
Keyword(s):  
Treatment Failure ◽  
Clinical Outcomes ◽  
Hospital Length Of Stay ◽  
Source Control ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Obese Patients ◽  
Definitive Therapy ◽  
All Cause Mortality ◽  
The Impact

Abstract Background Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a beta-lactam (BL) have worse clinical outcomes compared to non-obese patients and to identify if therapeutic drug monitoring (TDM) may be beneficial. Methods This multi-center, retrospective cohort included hospitalized adults admitted from July 2015-July 2017 treated with a BL as definitive monotherapy against a Gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required &gt;1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): non-obese (BMI ≤29.9 kg/m 2) and obese (BMI ≥30.0 kg/m 2). The primary outcome was clinical treatment failure, and secondary were hospital length of stay (LOS), inpatient all-cause mortality, and 30-day all-cause readmission. Results There were 257 (43.6%) obese patients and 332 (56.4%) non-obese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by 3 rd generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) non-obese patients (p&lt;0.001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than non-obese patients (p=0.002), but no differences were found for all-cause mortality (p=0.117) or infection-related readmission (0=0.112). Conclusions Obese patients treated with BLs have higher rates of treatment failure and longer hospitalization periods than non-obese patients. Future studies are needed to assess the impact of TDM and specific dosing recommendations for targeted infection types.

scholarly journals Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 502
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Angelo Borsarelli Carvalho de Brito ◽  
Alexcia Camila Braun ◽  
Milena Shizue Tariki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Prospective Study ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Predictive Biomarkers ◽  
Multi Drug Resistance ◽  
Cell Counts ◽  
Potential Clinical Benefit ◽  
A Prospective Study

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

scholarly journals Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1942
Author(s):  
Evangelos Terpos ◽  
Ioannis P. Trougakos ◽  
Vangelis Karalis ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Sentiljana Gumeni ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Health Workers ◽  
Antibody Responses ◽  
Healthy Individuals ◽  
Younger Age ◽  
Constant Rate ◽  
Rate Of Decline ◽  
A Prospective Study ◽  
Kinetics Of ◽  
Over Time

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.

scholarly journals Kinetics of SARS-CoV-2 antibody responses pre-COVID-19 and post-COVID-19 convalescent plasma transfusion in patients with severe respiratory failure: an observational case–control study

2021 ◽  
pp. jclinpath-2020-207356
Author(s):  
Matthew N Klein ◽  
Elizabeth Wenqian Wang ◽  
Paul Zimand ◽  
Heather Beauchamp ◽  
Caitlin Donis ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Clinical Outcomes ◽  
Ecmo Support ◽  
Survival Duration ◽  
Severe Respiratory Failure ◽  
Loess Regression ◽  
Antibody Titres ◽  
Similar Survival ◽  
Kinetics Of ◽  
Control Study

AimsWhile the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes.MethodsPatients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively.ResultsPrior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls.ConclusionsCCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.

Clinical outcomes from a prospective study evaluating the role of ambulation during medical termination of pregnancy

Contraception ◽  
2012 ◽  
Vol 85 (4) ◽  
pp. 398-401 ◽  
Author(s):  
Kamal Ojha ◽  
David J. Gillott ◽  
Patricia Wood ◽  
Elizabeth Valcarcel ◽  
Arti Matah ◽  
...  
Keyword(s):  
Prospective Study ◽  
Clinical Outcomes ◽  
Termination Of Pregnancy ◽  
Medical Termination Of Pregnancy ◽  
Medical Termination ◽  
A Prospective Study

scholarly journals Clinical outcomes and kinetics of propanil following acute self-poisoning: a prospective case series

2009 ◽  
Vol 9 (1) ◽  
Author(s):  
Darren M Roberts ◽  
Renate Heilmair ◽  
Nick A Buckley ◽  
Andrew H Dawson ◽  
Mohamed Fahim ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Case Series ◽  
Prospective Case Series ◽  
Kinetics Of

Isavuconazole: Case Report and Pharmacokinetic Considerations

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 253-256 ◽  
Author(s):  
Francesco Marchesi ◽  
Corrado Girmenia ◽  
Bianca Maria Goffredo ◽  
Emanuela Salvatorelli ◽  
Atelda Romano ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Real Life ◽  
Concomitant Administration ◽  
Invasive Fungal Disease ◽  
High Plasma ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Hepatic Toxicity ◽  
Maintenance Chemotherapy

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a “probable” IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

scholarly journals Correlation of clinical outcomes with bremsstrahlung and Y-90 PET/CT imaging findings following Y-90 radiosynoviorthesis: a prospective study

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Thomas W. Barber ◽  
Martin H. Cherk ◽  
Anne Powell ◽  
Kenneth S. K. Yap ◽  
Baki Billah ◽  
...  
Keyword(s):  
Prospective Study ◽  
Clinical Outcomes ◽  
Ct Imaging ◽  
Imaging Findings ◽  
Pet Ct ◽  
A Prospective Study

scholarly journals NPM1 mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy

2019 ◽  
Vol 3 (6) ◽  
pp. 922-933 ◽  
Author(s):  
Guillermo Montalban-Bravo ◽  
Rashmi Kanagal-Shamanna ◽  
Koji Sasaki ◽  
Keyur Patel ◽  
Irene Ganan-Gomez ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Myeloproliferative Neoplasm ◽  
Normal Karyotype ◽  
Progression Free Survival ◽  
Disease Status ◽  
Response To Therapy ◽  
Intensive Chemotherapy ◽  
Clinicopathologic Characteristics ◽  
Mutation Burden ◽  
The Impact

Abstract Nucleophosmin (NPM1) mutations are common in acute myeloid leukemia and are associated with high remission rates and prolonged survival with intensive chemotherapy. NPM1 mutations are rare in myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and the clinical outcomes of these patients, when treated with intensive chemotherapy, are unknown. We retrospectively evaluated the clinicopathologic characteristics and the impact of therapy in 31 patients with MDS or MDS/MPN and NPM1 mutations. Next-generation sequencing was performed at diagnosis in 22 patients. Median age was 62 years (range, 19-86). Twenty-four patients (77%) had normal karyotype, and all had multilineage dysplasia. Most patients could be classified as MDS with excess blasts (19/31, 61%). NPM1 mutations were detected at a median allele frequency of 0.38 (range, 0.09-0.49). Mutation burden did not correlate with bone marrow blast frequency, and its clearance seemed to be associated with decreased morphologic dysplasia. Ten of the 31 patients (32%) received cytotoxic chemotherapy, 20 (65%) hypomethylating agents, and 1 (4%) lenalidomide. Sequential sequencing was available in 16 (52%) patients, and mutation burden correlated with disease status and response to therapy. Patients treated with chemotherapy had higher complete response rates (90% vs 28%, P = .004), longer median progression-free survival (not reached vs 7.5 months, P = .023), and overall survival (not reached vs 16 months, P = .047). Intensive chemotherapy and allogeneic stem cell transplantation (SCT) may be associated with improved clinical outcomes in patients with NPM1-mutated MDS or MDS/MPN who are candidates for this form of therapy.

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