scholarly journals Treatment issues in recurrent Clostridioides difficile infections and the possible role of germinants

FEMS Microbes ◽  
2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Noah Budi ◽  
Nasia Safdar ◽  
Warren E Rose
Keyword(s):  
Antibiotic Therapy ◽  
Treatment Options ◽  
The United States ◽  
Current Treatment ◽  
Gi Tract ◽  
Spore Form ◽  
Environmental Cleaning ◽  
Clostridioides Difficile ◽  
Cleaning Procedures ◽  
Hospital Acquired

ABSTRACT Clostridioides difficile is the number one cause of hospital-acquired infections in the United States and one of the CDC's urgent-level pathogen threats. The inflammation caused by pathogenic C. difficile results in diarrhea and pseudomembranous colitis. Patients who undergo clinically successful treatment for this disease commonly experience recurrent infections. Current treatment options can eradicate the vegetative cell form of the bacteria but do not impact the spore form, which is impervious to antibiotics and resists conventional environmental cleaning procedures. Antibiotics used in treating C. difficile infections (CDI) often do not eradicate the pathogen and can prevent regeneration of the microbiome, leaving them vulnerable to recurrent CDI and future infections upon subsequent non-CDI-directed antibiotic therapy. Addressing the management of C. difficile spores in the gastrointestinal (GI) tract is important to make further progress in CDI treatment. Currently, no treatment options focus on reducing GI spores throughout CDI antibiotic therapy. This review focuses on colonization of the GI tract, current treatment options and potential treatment directions emphasizing germinant with antibiotic combinations to prevent recurrent disease.

Chemotherapy use in the treatment of glioblastoma multiforme: Comparing patient characteristics using the National Cancer Data Base (NCDB).

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 305-305
Author(s):  
Christopher J. Inserra ◽  
Nabin Khanal ◽  
Peter T. Silberstein
Keyword(s):  
Glioblastoma Multiforme ◽  
Treatment Options ◽  
Survival Rates ◽  
Patient Characteristics ◽  
The United States ◽  
Current Treatment ◽  
National Cancer Data Base ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Cancer Data

305 Background: Glioblastoma Multiforme (GBM) is the most common and most deadly type of human glioma. Nearly half of all gliomas are diagnosed as GBM at which point the median survival of patients is approximately one year and the two-year survival rates are approximately 10%. Current treatment options for GBM include surgical resection, external beam radiation, and oral temozolomide chemotherapy. However, the patterns of chemotherapy use in GBM as well as the patient characteristics that determine its use have yet to be investigated. Methods: This is a retrospective study of glioblastoma patients (n = 96,966, making this the largest trial ever on glioblastoma) diagnosed between 2000 and 2011 in the NCDB. The NCDB contains nearly 70% of new cancer cases diagnosed in the United States and consists of data from over 1,500 cancer programs across the country. A chi-squared test was used to determine any differences in the characteristics of patients who did or did not receive chemotherapy. Results: Patients who were younger than 70 years of age, male, white, had private/managed insurance, no comorbidities, household income greater than $49,000, were receiving radiation therapy, and diagnosed between 2004 and 2011 were significantly more likely to have received chemotherapy to treat glioblastoma (see Table). Conclusions: Understanding any potential barriers in the use of chemotherapy to treat glioblastoma can help improve its utilization among people of diverse socioeconomic backgrounds. [Table: see text]

scholarly journals Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257143
Author(s):  
Alexis Fong ◽  
Megan Ross ◽  
Justin Boudreau ◽  
Reza Nokhbeh ◽  
Kim Tilbe ◽  
...  
Keyword(s):  
United States ◽  
Therapeutic Agent ◽  
The United States ◽  
Primary Objective ◽  
Clinical Isolates ◽  
High Rate ◽  
Clostridioides Difficile ◽  
Lactam Antibiotic ◽  
Enteric Infections ◽  
Hospital Acquired

Clostridioides difficile infection (CDI) is the primary cause of hospital-acquired diarrhea, and responsible for over 500,000 enteric infections a year in the United States alone. Although most patients with CDI are successfully treated with metronidazole or vancomycin, the high rate of recurrence is still a serious problem, in which case these antibiotics are usually not very effective. The primary objective of this research is to develop a potentially effective therapeutic agent against C. difficile that are resistant to metronidazole or vancomycin. The susceptibility to metronidazole and vancomycin was examined with 194 C. difficile clinical isolates. Sixty of these isolates chosen based on a variety of criteria were examined for their susceptibility against the 4-chloro-1-piperidin-1ylmethyl-1H-indole-2,3-dione compound (Raja 42), a novel isatin–benzothiazole analogue containing a gamma-lactam structure, as we previously found that this novel compound is effective against a variety of different bacteria. Most of the 60 isolates were resistant to ceftriaxone and ciprofloxacin, raising the possibility that they might have been exposed previously to these or structurally similar antibiotics (e.g., β-lactam and quinolone compounds). Among the isolates, 48 (80%) and 54 (90%) were susceptible to metronidazole and vancomycin, respectively. Raja 42 was found to be effective against most of the isolates, especially so against metronidazole-resistant C. difficile. Most importantly, five isolates that show resistance to metronidazole and vancomycin were sensitive to Raja 42. Thus, Raja 42, a gamma lactam antibiotic, has the potential to effectively control C. difficile strains that are resistant to metronidazole and vancomycin.

An evaluation of RAS testing and survival among mCRC patients in the United States.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
Enko Kiprilov ◽  
Laura Sangaré ◽  
Kimberly Lowe ◽  
Alexandra Christodoulopoulou
Keyword(s):  
Median Survival ◽  
Treatment Guidelines ◽  
Treatment Options ◽  
The United States ◽  
Current Treatment ◽  
First Line ◽  
Treatment Groups ◽  
The Status ◽  
Ras Family ◽  
Third Line

e15144 Background: The status of mutations in the rat sarcoma viral oncogene homolog ( RAS) family of genes, which includes Kirsten RAS ( KRAS) and Neuroblastoma RAS ( NRAS) predicts response to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. Current treatment guidelines recommend all mCRC patients to receive RAS testing prior to initiating treatment with an anti-EGFR agent. This study sought to establish estimates of RAS testing among mCRC patients in the US prior to initiation of first and third lines of treatment, and to describe median survival by treatment groups. Methods: Data from the Oncology Services Comprehensive Electronic Records (OSCER) 2.0 dataset were utilized. Patients diagnosed with mCRC between January 1, 2011 and July 31, 2017 were eligible. Patients were followed for up to 1 year, or until death, following their mCRC diagnosis. Results: A total of 17,387 mCRC patients were included in the analysis, among which 69% were RAS tested and 31% were never tested. Among the RAS tested patients, 23% were tested prior to their mCRC diagnosis 60% received RAS testing following mCRC diagnosis but prior to first line of treatment, 3% were tested following first line treatment but prior to third line, and the remaining 14% were tested following third line. Demographic variables did not differ between tested and untested groups, overall and by line of treatment. The overall median survival of RAS WT patients was 31.1 months (95% CI: 30.0, 32.4). MCRC patients who were not RAS tested had a lower median survival of 20.7 months (95% CI: 19.1, 22.5). Conclusions: The timing of when patients are being tested varies greatly. While nearly 70% of patients had a RAS test, approximately 30% failed to be tested, identifying a large gap in testing practices. Universal RAS testing provides patients and their physicians with knowledge of their anti-EGFR treatment options and may result in improved survival.

scholarly journals Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 327
Author(s):  
Darina Kohoutova ◽  
Dominic Worku ◽  
Hala Aziz ◽  
Julian Teare ◽  
Justin Weir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Symptom Control ◽  
Current Treatment ◽  
Gi Tract ◽  
Systemic Treatments ◽  
Precise Diagnosis ◽  
The Uk

Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

scholarly journals Structural elucidation of theClostridioides difficiletransferase toxin reveals a single-site binding mode for the enzyme

2020 ◽  
Vol 117 (11) ◽  
pp. 6139-6144 ◽  
Author(s):  
Michael J. Sheedlo ◽  
David M. Anderson ◽  
Audrey K. Thomas ◽  
D. Borden Lacy
Keyword(s):  
Single Molecule ◽  
Mammalian Cells ◽  
Binding Mode ◽  
The United States ◽  
Binding Interaction ◽  
Toxin B ◽  
Clostridioides Difficile ◽  
Cryo Electron Microscopy ◽  
Hospital Acquired ◽  
Site Binding

Clostridioides difficileis a Gram-positive, pathogenic bacterium and a prominent cause of hospital-acquired diarrhea in the United States. The symptoms ofC. difficileinfection are caused by the activity of three large toxins known as toxin A (TcdA), toxin B (TcdB), and theC. difficiletransferase toxin (CDT). Reported here is a 3.8-Å cryo–electron microscopy (cryo-EM) structure of CDT, a bipartite toxin comprised of the proteins CDTa and CDTb. We observe a single molecule of CDTa bound to a CDTb heptamer. The formation of the CDT complex relies on the interaction of an N-terminal adaptor and pseudoenzyme domain of CDTa with six subunits of the CDTb heptamer. CDTb is observed in a preinsertion state, a conformation observed in the transition of prepore to β-barrel pore, although we also observe a single bound CDTa in the prepore and β-barrel conformations of CDTb. The binding interaction appears to prime CDTa for translocation as the adaptor subdomain enters the lumen of the preinsertion state channel. These structural observations advance the understanding of how a single protein, CDTb, can mediate the delivery of a large enzyme, CDTa, into the cytosol of mammalian cells.

scholarly journals 728. Prophylactic Vancomycin Therapy in Long Term Care Patients Colonized with Clostridioides difficile to Reduce Hospital-Acquired C. diff Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S414-S415
Author(s):  
Sumayya Muneer ◽  
Monika Sadlak ◽  
Gitanjali Lobo ◽  
Dominique Brandt ◽  
Stephen P Blatt
Keyword(s):  
Antibiotic Therapy ◽  
Hospital Stay ◽  
Low Dose ◽  
Long Term Care ◽  
Oral Vancomycin ◽  
Vancomycin Therapy ◽  
Term Care ◽  
Clostridioides Difficile ◽  
Hospital Acquired

Abstract Background Clostridioides difficile (C. diff) is a common hospital-acquired infection with increasing rates of morbidity and mortality in elderly patients. Per the CDC, there are about 500,000 cases yearly in which 1 out of 11 patients die over the age of 65 due to complications from healthcare-associated C. diff infection (CDI). Oral Vancomycin has been shown to prevent recurrent CDI. Approximately 40% of patients admitted to Good Samaritan Hospital (GSH), who were colonized with C. diff developed active CDI while on antibiotic therapy during their hospitalization. In January 2017, GSH initiated a quality improvement intervention in which all patients admitted from long term care (LTC) facilities who were positive for C. diff colonization were given prophylactic oral Vancomycin with prescribed antibiotics. Methods This study is a retrospective cohort study within TriHealth facilities. The population included hospitalized patients from extended care, intermediate care, subacute rehabilitation, and nursing homes, who tested positive for C. Diff colonization from April 1, 2017, through June 30, 2018. Patients were screened for risk factors for C. diff. The primary outcomes were to determine whether patients developed CDI within 90-days of discharge and to evaluate for any events of CDI during their hospital stay. Results Among the 1,241 LTC patients who were admitted and screened for C. diff colonization, 213 (17%) were positive, 135 (63%) met inclusion criteria, and 5 (4%) patients who were admitted with CDI were excluded. 0% of patients treated with low dose Vancomycin developed CDI during their hospital stay, and a total of 5% of patients were found to have recurrent CDI within 90-day of hospital discharge. Patients who were already on antibiotics at the time of admission were at a higher risk of developing CDI (60% vs. 15%, p=0.034). Adherence to the study protocol was 78.5% and 19% of patients did not receive low-dose Vancomycin while on antibiotic therapy. Image 1: Screening diagram to select patients for study Table 1: Population characteristics Conclusion Review of CDI via TriHealth statistics revealed an overall reduction of hospital-acquired CDI since the implementation of prophylactic oral Vancomycin therapy. The next step will be to determine the duration of low dose vancomycin therapy for the prevention of future CDI as some patients did develop CDI within 90 days of discharge. Image 2: C. diff infection rate throughout TriHealth facilities (Post Vancomycin prophylaxis) Disclosures All Authors: No reported disclosures

scholarly journals Phylogenomic analysis reveals persistence of gonococcal strains with reduced-susceptibility to extended-spectrum cephalosporins and mosaic penA-34

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jesse C. Thomas ◽  
Sandeep J. Joseph ◽  
John C. Cartee ◽  
Cau D. Pham ◽  
Matthew W. Schmerer ◽  
...  
Keyword(s):  
Treatment Options ◽  
The United States ◽  
Current Treatment ◽  
Mechanisms Of Action ◽  
Sequence Type ◽  
Phylogenomic Analysis ◽  
Genome Sequences ◽  
Extended Spectrum ◽  
Recent Emergence ◽  
Global Data

AbstractThe recent emergence of strains of Neisseria gonorrhoeae associated with treatment failures to ceftriaxone, the foundation of current treatment options, has raised concerns over a future of untreatable gonorrhea. Current global data on gonococcal strains suggest that several lineages, predominately characterized by mosaic penA alleles, are associated with elevated minimum inhibitory concentrations (MICs) to extended spectrum cephalosporins (ESCs). Here we report on whole genome sequences of 813 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project in the United States. Phylogenomic analysis revealed that one persisting lineage (Clade A, multi-locus sequence type [MLST] ST1901) with mosaic penA-34 alleles, contained the majority of isolates with elevated MICs to ESCs. We provide evidence that an ancestor to the globally circulating MLST ST1901 clones potentially emerged around the early to mid-20th century (1944, credibility intervals [CI]: 1935–1953), predating the introduction of cephalosporins, but coinciding with the use of penicillin. Such results indicate that drugs with novel mechanisms of action are needed as these strains continue to persist and disseminate globally.

scholarly journals Peripartum Cardiomyopathy: A Current Review

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Katie M. Twomley ◽  
Gretchen L. Wells
Keyword(s):  
African American Women ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Treatment Options ◽  
The United States ◽  
Current Treatment ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Objective Evidence ◽  
A Current

Peripartum cardiomyopathy (PPCM) is a rare but potentially lethal complication of pregnancy occurring in approximately 1 : 3,000 live births in the United States although some series report a much higher incidence. African-American women are particularly at risk. Diagnosis requires symptoms of heart failure in the last month of pregnancy or within five months of delivery in the absence of recognized cardiac disease prior to pregnancy as well as objective evidence of left ventricular systolic dysfunction. This paper provides an updated, comprehensive review of PPCM, including emerging insights into the etiology of this disorder as well as current treatment options.

scholarly journals Epidemiology of community-acquired and recurrent Clostridioides difficile infection

2021 ◽  
Vol 14 ◽  
pp. 175628482110162
Author(s):  
Yichun Fu ◽  
Yuying Luo ◽  
Ari M Grinspan
Keyword(s):  
Large Scale ◽  
Infection Prevention ◽  
The United States ◽  
Future Research ◽  
Clostridioides Difficile ◽  
Epidemiologic Surveillance ◽  
Scale Population ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated ◽  
Hospital Acquired

Clostridioides difficile infection is a leading cause of healthcare-associated infections with significant morbidity and mortality. For the past decade, the bulk of infection prevention and epidemiologic surveillance efforts have been directed toward mitigating hospital-acquired C. difficile. However, the incidence of community-associated infection is on the rise. Patients with community-associated C. difficile tend to be younger and have lower mortality rate. Rates of recurrent C. difficile infection overall have decreased in the United States, but future research and public health endeavors are needed to standardize and improve disease detection, stratify risk factors in large-scale population studies, and to identify regional and local variations in strain types, reservoirs and transmission routes to help characterize and combat the changing epidemiology of C. difficile.

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