Altered methotrexate clearance in the treatment of CNS lymphoma with concurrent use of nitrofurantoin for a urinary tract infection

2018 ◽  
Vol 25 (7) ◽  
pp. 1794-1797 ◽  
Author(s):  
Jasmine L Gowarty ◽  
Ina J Patel ◽  
Jon D Herrington
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cancer Resistance ◽  
First Case ◽  
Anion Transporter

Methotrexate is a widely used chemotherapy agent with a propensity for drug interactions placing the patient at risk for toxicities. There are several modes for altering methotrexate clearance including concomitant drugs leading to toxic effects on the kidneys, medications producing an acidic urine pH, and agents interfering with methotrexate transporters including the organic anion transporter and breast cancer resistance protein efflux pump. We report a case of a patient with central nervous system non-Hodgkin's lymphoma receiving high-dose methotrexate and being concomitantly treated for a urinary tract infection with nitrofurantoin. Subsequently, her initial methotrexate clearance was altered by the introduction of nitrofurantoin and returned to baseline when her nitrofurantoin was discontinued. This is the first case report describing the altered methotrexate clearance from concurrent administration of methotrexate and nitrofurantoin.

scholarly journals Raoultella ornithinolytica in MALT-type non-Hodgkin Lymphoma

2021 ◽  
Author(s):  
Rui Seixas ◽  
Adelaide Alves ◽  
Aurelia Selaru ◽  
Manuela Vanzeller ◽  
Teresa Shiang ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Hodgkin Lymphoma ◽  
Immunocompromised Patient ◽  
Bloodstream Infections ◽  
Immunocompromised Patients ◽  
Non Hodgkin Lymphoma ◽  
First Case ◽  
Tract Infections

Raoultella ornithinolytica is a bacterium that belongs to the Enterobacteriaceae family. The most frequently reported infections are gastrointestinal and hepatobiliary. Urinary tract infections are very rarely reported and bloodstream infections are usually reported without an identified source. This bacterium is responsible for an increasing number of infections, especially in immunocompromised patients. The authors describe the first case ever reported of an immunocompromised patient due to non-Hodgkin lymphoma MALT type and corticotherapy, who developed urinary tract infection and subsequently bacteriemia due to this pathogen.

scholarly journals In Vitro Evaluation of the Drug Interaction Potential of Doravirine

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Kelly Bleasby ◽  
Kerry L. Fillgrove ◽  
Robert Houle ◽  
Bing Lu ◽  
Jairam Palamanda ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Reversible Inhibitor ◽  
Drug Metabolizing Enzymes ◽  
Cancer Resistance ◽  
Metabolizing Enzymes ◽  
Anion Transporter ◽  
Major Drug

ABSTRACT Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 infection. In vitro studies were conducted to assess the potential for drug interactions with doravirine via major drug-metabolizing enzymes and transporters. Kinetic studies confirmed that cytochrome P450 3A (CYP3A) plays a major role in the metabolism of doravirine, with ∼20-fold-higher catalytic efficiency for CYP3A4 versus CYP3A5. Doravirine was not a substrate of breast cancer resistance protein (BCRP) and likely not a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) or OATP1B3. Doravirine was not a reversible inhibitor of major CYP enzymes (CYP1A2, -2B6, -2C8, -2C9, -2C19, -2D6, and -3A4) or of UGT1A1, nor was it a time-dependent inhibitor of CYP3A4. No induction of CYP1A2 or -2B6 was observed in cultured human hepatocytes; small increases in CYP3A4 mRNA (≤20%) were reported at doravirine concentrations of ≥10 μM but with no corresponding increase in enzyme activity. In vitro transport studies indicated a low potential for interactions with substrates of BCRP, P-glycoprotein, OATP1B1 and OATP1B3, the bile salt extrusion pump (BSEP), organic anion transporter 1 (OAT1) and OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin extrusion 1 (MATE1) and MATE2K proteins. In summary, these in vitro findings indicate that CYP3A4 and CYP3A5 mediate the metabolism of doravirine, although with different catalytic efficiencies. Clinical trials reported elsewhere confirm that doravirine is subject to drug-drug interactions (DDIs) via CYP3A inhibitors and inducers, but they support the notion that DDIs (either direction) are unlikely via other major drug-metabolizing enzymes and transporters.

scholarly journals Intravesical gossypiboma: our experience and the need for stringent checklist and training!

2019 ◽  
Vol 12 (2) ◽  
pp. e227278
Author(s):  
Ronal Kori ◽  
Lovenish Bains ◽  
Sudhir Kumar Jain
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Male Patient ◽  
Open Surgery ◽  
Recurrent Uti ◽  
First Case ◽  
Double J Stent ◽  
History Of ◽  
And Training

We present our experience of two cases: one of a 28-year-old male patient who presented with recurrent episodes of urinary tract infection (UTI) with passage of pus flakes in urine and a history of open cystolithotomy about 10 months ago. The second patient was a 26-year-old woman who underwent bladder exploration for a retained Double-J stent about 10 months ago and presented with recurrent UTI. The first case was treated with open surgery and in the second case, the gauze piece was retrieved endoscopically.

A Genome-Wide Analysis of Variants Influencing Methotrexate Clearance Replicates SLCO1B1.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2466-2466 ◽  
Author(s):  
Laura B. Ramsey ◽  
John C Panetta ◽  
Colton Smith ◽  
Wenjian Yang ◽  
Yiping Fan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
High Dose ◽  
Genome Wide Analysis ◽  
Anion Transporter ◽  
Genome Wide ◽  
A Genome

Abstract Abstract 2466 High-dose methotrexate (HDMTX) is an important element of chemotherapy for acute lymphoblastic leukemia (ALL) and other malignancies. Methotrexate clearance influences cure and toxicity in children with acute lymphoblastic leukemia (ALL). HDMTX schedules and doses vary widely among treatment protocols. The Children's Oncology Group (COG) tested the efficacy of 6 courses of 2 g/m2 over 4 hours versus 1 g/m2 over 24 hours (P9904 and P9905 protocols). Patients were assigned to one of four arms for consolidation: A, 24-hour methotrexate infusion (1 g/m2) and no delayed intensification (DI); B, 4-hour methotrexate infusion (2 g/m2) with no DI; C, 24-hour methotrexate infusion with DI; D, 4-hour methotrexate infusion with DI. We estimated methotrexate clearance for 1279 patients treated on these protocols, with two plasma MTX concentrations per course, using a Bayesian pharmacokinetic modeling approach. Germline genetic variation was assessed using the Affymetrix 6.0 array, and other single nucleotide polymorphisms (SNPs) were imputed based on 1000 Genomes reference data, yielding 5.2 million SNP genotypes evaluable per patient. Average MTX clearance was highly variable, with a median (range) of 164 (65–355) and 109 (49–290) ml/min/m2 for the 24-hour and 4-hour infusions, respectively. Methotrexate clearance was lower in older children (p = 7 × 10−7), girls (p = 2.7 × 10−4), and patients who received a delayed intensification phase during consolidation (p = 0.0022). Adjusting for age, gender, race, and treatment arm, a genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in SLCO1B1(p = 2.1 × 10−11), a gene that encodes for an organic anion transporter that is known to transport methotrexate. This replicates our previous findings (Trevino et al, J Clin Oncol. 2009;27(35):5972-8) that polymorphisms in SLCO1B1 influence methotrexate clearance in ALL patients treated on St. Jude protocols with three different HDMTX schedules. In a combined meta-analysis including the 1279 COG patients and 699 St. Jude patients, and adjusting for age, gender, race, and treatment arm, the association of methotrexate clearance with SLCO1B1 SNP rs4149056 yields a p-value of 3.1 × 10−19 (Figure). Even after adjustment for the rs4149056 SNP, other polymorphisms in SLCO1B1 remained significantly related to methotrexate clearance, indicating that there are multiple variants in SLCO1B1 that can influence methotrexate clearance. Validation of the association of this gene with five different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. Disclosures: No relevant conflicts of interest to declare.

scholarly journals First case of vanA-positive Enterococcus mundtii in human urinary tract infection in Iran

2016 ◽  
Vol 11 ◽  
pp. 68-70 ◽  
Author(s):  
M. Sharifi-Rad ◽  
S. Shadanpour ◽  
A. van Belkum ◽  
A. Soltani ◽  
J. Sharifi-Rad
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
First Case ◽  
Enterococcus Mundtii

scholarly journals Enterococcus hirae as a cause of bacteremic urinary tract infection: first case report from Turkey

2020 ◽  
Vol 14 (12) ◽  
pp. 1780-1482
Author(s):  
Heval Can Bilek ◽  
Aydın Deveci ◽  
Sema Ünal ◽  
Yeliz Tanrıverdi Çaycı ◽  
Esra Tanyel
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Day Treatment ◽  
Molecular Techniques ◽  
Diagnostic Methods ◽  
Enterococcus Hirae ◽  
Clinical Specimens ◽  
First Case ◽  
Sensitivity Pattern

Introduction: Enterococcus hirae (E. hirae) constitutes less than 1% of the enterococci strains in human clinical specimens. In this article, we report the first case of urinary tract infection-related bacteremia due to E. hirae from Turkey. Case Presentation: A 74-year-old male patient with a history of coronary artery disease, hypertension, and chronic renal failure was admitted to the emergency department with abdominal pain, dysuria, and fever. The urine sample collected from the urinary catheter resulted as ampicillin-sensitive E. hirae. On the 4th day of hospitalization, E. hirae growth with the same sensitivity pattern was also reported in blood culture. Intravenous ampicillin 4×2 g/day treatment was initiated. There was no growth in subsequent blood and urine cultures. Fever resolved and general condition improved. The patient was discharged on the thirteenth day with clinical improvement after moxifloxacin treatment for four days and ampicillin treatment for nine days. Discussion: The patient's medical history included risk factors for enterococcal bacteremia. There are a limited number of reports in the literature describing human infections caused by E. hirae. The reason for the rare isolation of E. hirae from clinical specimens may be the difficulty of identifying with standard diagnostic approaches. Conclusions: For diagnostic purposes, as in our case, rapid and high sensitive diagnostic methods such as Matrix-assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) and molecular techniques may be useful to guide the selection of the least toxic and optimal duration of antibiotic treatment.

scholarly journals Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wen Huang ◽  
Jin Zhou ◽  
Juanjuan Guo ◽  
Wen Hu ◽  
Guanghui Chen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Organic Anion ◽  
Maternal Serum ◽  
Farnesoid X Receptor ◽  
Organic Anion Transporter ◽  
Cancer Resistance ◽  
Rat Serum ◽  
Altered Expression ◽  
Anion Transporter ◽  
Fetal Serum

Abstract Background The use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism. Methods Clinical data and human placentas were collected and analyzed. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.2 mg/kg per day) from gestational day 9 to 20. The metabolomic spectra of BAs in maternal and fetal rat serum were determined by LC-MS. Human and rat placentas were collected for histological and gene expression analysis. BeWo human placental cell line was treated with dexamethasone (20–500 nM). Results Human male neonates born after prenatal dexamethasone treatment showed an increased serum BA level while no significant change was observed in females. Moreover, the expression of organic anion transporter polypeptide-related protein 2B1 (OATP2B1) and breast cancer resistance protein (BCRP) in the male neonates’ placenta was decreased, while multidrug resistance-associated protein 4 (MRP4) was upregulated. In experimental rats, dexamethasone increased male but decreased female fetal serum total bile acid (TBA) level. LC-MS revealed that primary BAs were the major component that increased in both male and female fetal serum, and all kinds of BAs were significantly increased in maternal serum. The expression of Oatp2b1 and Bcrp were reduced, while Mrp4 expression was increased in the dexamethasone-treated rat placentas. Moreover, dexamethasone increased glucocorticoid receptor (GR) expression and decreased farnesoid X receptor (FXR) expression in the rat placenta. In BeWo cells, dexamethasone induced GR translocation into the nucleus; decreased FXR, OATP2B1, and BCRP expression; and increased MRP4 expression. Furthermore, GR was verified to mediate the downregulation of OATP2B1, while FXR mediated dexamethasone-altered expression of BCRP and MRP4. Conclusions By affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.

First case of Serratia liquefaciens isolated from urinary tract infection in sows and associated clinicopathological and pathological findings

2020 ◽  
Vol 70 (4) ◽  
pp. 259-262
Author(s):  
V.G. Papatsiros ◽  
L.V. Athanasiou ◽  
V.M. Spanou ◽  
I. Stylianaki ◽  
G. Papakonstantinou ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Pathological Findings ◽  
Serratia Liquefaciens ◽  
First Case

scholarly journals The Emerging Role of the SLCO1B3 Protein in Cancer Resistance

2019 ◽  
Vol 27 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Ruipu Sun ◽  
Ying Ying ◽  
Zhimin Tang ◽  
Ting Liu ◽  
Fuli Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Anticancer Drugs ◽  
Organic Anion ◽  
Chemotherapy Resistance ◽  
Organic Anion Transporter ◽  
Cancer Drug ◽  
Cancer Resistance ◽  
Anticancer Chemotherapy ◽  
Anion Transporter ◽  
Transporter Family

Currently, chemotherapy is one of the mainstays of oncologic therapies. But the efficacy of chemotherapy is often limited by drug resistance and severe side effects. Consequently, it is becoming increasingly important to investigate the underlying mechanism and overcome the problem of anticancer chemotherapy resistance. The solute carrier organic anion transporter family member 1B3 (SLCO1B3), a functional transporter normally expressed in the liver, transports a variety of endogenous and exogenous compounds, including hormones and their conjugates as well as some anticancer drugs. The extrahepatic expression of SLCO1B3 has been detected in different cancer cell lines and cancer tissues. Recently, accumulating data indicates that the abnormal expression and function of SLCO1B3 are involved in resistance to anticancer drugs, such as taxanes, camptothecin and its analogs, SN-38, and Androgen Deprivation Therapy (ADT) in breast, prostate, lung, hepatic, and colorectal cancer, respectively. Thus, more investigations have been implemented to identify the potential SLCO1B3-related mechanisms of cancer drug resistance. In this review, we focus on the emerging roles of SLCO1B3 protein in the development of cancer chemotherapy resistance and briefly discuss the mechanisms of resistance. Elucidating the function of SLCO1B3 in chemoresistance may bring out novel therapeutic strategies for cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document