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 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 Evolutionary History of the Global Emergence of the Escherichia coli Epidemic Clone ST131

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Nicole Stoesser ◽  
Anna E. Sheppard ◽  
Louise Pankhurst ◽  
Nicola De Maio ◽  
Catrin E. Moore ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Evolutionary History ◽  
Mobile Genetic Elements ◽  
The United States ◽  
Sequence Type ◽  
E Coli ◽  
Genetic Elements ◽  
Extended Spectrum ◽  
History Of

ABSTRACT Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection ( n = 215) of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/ H 30R and C2/ H 30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/ H 30Rx clade driven by the acquisition of a bla CTX-M-15 -containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration of bla CTX-M within subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, the bla CTX-M-14/14-like group. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli . These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages. IMPORTANCE Escherichia coli , perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specific E. coli lineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.

scholarly journals Draft Genome Sequences of 14 Livestock-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 Isolates from Swine Farms in the United States

2017 ◽  
Vol 5 (44) ◽  
Author(s):  
Samantha J. Hau ◽  
Darrell O. Bayles ◽  
David P. Alt ◽  
Timothy S. Frana ◽  
Tracy L. Nicholson
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Draft Genome ◽  
The United States ◽  
Sequence Type ◽  
Genome Sequences ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa St398

ABSTRACT Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is a bacterium carried by or obtained from swine and other livestock. The initial and predominant swine-associated LA-MRSA sequence type (ST) identified is ST398. Here, we present 14 draft genome sequences from LA-MRSA ST398 isolates found in the United States.

scholarly journals Rapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland Due to Spread of Common Plasmids and International Clones

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Edgar I. Campos-Madueno ◽  
Odette J. Bernasconi ◽  
Aline I. Moser ◽  
Peter M. Keller ◽  
Francesco Luzzaro ◽  
...  
Keyword(s):  
Core Genome ◽  
The United States ◽  
Sequence Type ◽  
Shigella Sonnei ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Content Type ◽  
Phylogenetic Comparison ◽  
The United Kingdom ◽  
Extended Spectrum

ABSTRACT The Swiss Centre for Antibiotic Resistance (ANRESIS) has recently noted an increase of extended-spectrum cephalosporin-resistant (ESC-R) Shigella sonnei isolates nationwide (3.8% in 2016 versus 37.5% in 2019). To understand this phenomenon, we analyzed 25 representative isolates (of which 14 were ESC-R) collected in Switzerland during 2016 to 2019. Whole-genome sequencing was achieved using both the Illumina and the Nanopore platforms. Both ESC-R and extended-spectrum cephalosporin-susceptible isolates belonged to sequence type 152 (ST152). The ESC-R isolates carried blaCTX-M-3 in IncI1-pST57 (n = 5), blaCTX-M-15 in IncFII (F2:A-:B-) (n = 5), blaCTX-M-15 in IncI1-pST16, and blaCTX-M-27, blaCTX-M-55, or blaCTX-M-134 in other IncFII plasmids (n = 1 each). Plasmids having the same bla and Inc group exhibited high degrees of genetic identity to each other but also to plasmids previously reported in other Enterobacterales. Core-genome analysis showed that there were 4 main clusters, each of which included strains that differed by <58 single nucleotide variants (SNVs) and that consisted of both blaCTX-M-positive and blaCTX-M-negative isolates. Moreover, most isolates belonging to the same cluster shared an identical core-genome sequence type (cgST). For instance, cluster 1 included 4 isolates of cgST113036, of which only 3 harbored the IncI1-pST57 blaCTX-M-3-positive plasmid. The 25 S. sonnei isolates were also subjected to phylogenetic comparison with deposited international strains. As a result, matching isolates (isolates that had the same cgST and that differed by <8 SNVs) have been reported in the United Kingdom, the United States, France, and the Netherlands. Overall, our results suggest that some common S. sonnei clusters can spread between continents and can be imported into other nations after international trips. Such clusters include, in part, isolates that do not possess blaESBL-harboring plasmids, indicating their tendency to acquire them from other Enterobacterales.

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.

Ketamina, un nuevo agente terapéutico para la depresión

2020 ◽  
Vol 63 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Rodrigo Pérez-Esparza ◽  
Luis Fabián Kobayashi-Romero ◽  
Ana María García Mendoza ◽  
Reyna Minerva Lamas-Aguilar ◽  
Melissa Vargas Sosa ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Treatment Options ◽  
Current Treatment ◽  
Mechanisms Of Action ◽  
Key Words Depression ◽  
Major Depressive ◽  
Factors Associated ◽  
Rapid Action ◽  
Treatment Of Depression

Major depressive disorder affects about one in every 10 people in Mexico and is one of the first 5 causes of disability worldwide. Current treatment options are limited and only act upon some factors associated in its physiopathology. Moreover, the effects on depression are not immediate, which is a great limitation in obtaining a benefit over disability caused by this disorder and impedes a rapid action in the scenario of suicidality. Recently, ketamine (an anesthetic) has shown to have antidepressant properties by acting in the glutamate neurotransmission system (while no other current treatment acts on this level). It offers benefits in depressive symptoms in a matter of hours and has proven to be useful in patients that do not benefit from current therapeutic options. Recently, it has been approved for the treatment of depression. However, there are still many questions about its antidepressant mechanisms of action, safety, side effects, among others. Key words: Depression; antidepressants; ketamine.

scholarly journals Epidemic Emergence in the United States of Escherichia coli Sequence Type 131-H30 (ST131-H30), 2000 to 2009

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
James R. Johnson ◽  
Stephen Porter ◽  
Paul Thuras ◽  
Mariana Castanheira
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Single Agent ◽  
Temporal Trends ◽  
Virulence Gene ◽  
The United States ◽  
Sequence Type ◽  
Content Type ◽  
E Coli ◽  
Recent Emergence

ABSTRACT The H30 subclone of Escherichia coli sequence type 131 (ST131-H30) has become the leading antimicrobial resistance E. coli lineage in the United States and often exhibits resistance to one or both of the two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from E. coli clinical isolates collected systematically across the United States by the SENTRY Antimicrobial Surveillance Program in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESC-reduced susceptibility, regardless of FQ phenotype (ESC-RS); (ii) FQ resistance, ESC susceptible (FQ-R); and (iii) FQ susceptible, ESC susceptible (FQ-S). Susceptibility profiles, phylogroup, ST, ST131 subclone, and virulence genotypes were determined, and temporal trends and between-variable associations were assessed statistically. From 2000 to 2006, concurrently with the emergence of ESC-RS and FQ-R strains, the prevalence of (virulence-associated) phylogroup B2 among such strains also rose dramatically, due entirely to rapid emergence of ST131, especially H30. By 2009, H30 was the dominant E. coli lineage overall (22%), accounting for a median of 43% of all single-agent and multidrug resistance (68% for ciprofloxacin). H30's emergence increased the net virulence gene content of resistant (especially FQ-R) isolates, giving stable overall virulence gene scores despite an approximately 4-fold expansion of the historically less virulent resistant population. These findings define more precisely the timing and tempo of H30's emergence in the United States, identify possible reasons for it, and suggest potential consequences, including more frequent and/or aggressive antimicrobial-resistant infections.

scholarly journals Draft Genome Sequences of 63 Swine-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 5 Isolates from the United States

2017 ◽  
Vol 5 (44) ◽  
Author(s):  
Samantha J. Hau ◽  
Darrell O. Bayles ◽  
David P. Alt ◽  
Timothy S. Frana ◽  
Tracy L. Nicholson
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Draft Genome ◽  
The United States ◽  
Sequence Type ◽  
Public Concern ◽  
Genome Sequences ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACT Methicillin-resistant Staphylococcus aureus colonizes humans and other animals such as swine. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) sequence type 5 (ST5) isolates are a public concern due to their pathogenicity and ability to acquire mobile genetic elements. This report presents draft genome sequences for 63 LA-MRSA ST5 isolates in the United States.

scholarly journals A Comprehensive View of Frozen Shoulder: A Mystery Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel de la Serna ◽  
Santiago Navarro-Ledesma ◽  
Fany Alayón ◽  
Elena López ◽  
Leo Pruimboom
Keyword(s):  
Risk Factors ◽  
Manual Therapy ◽  
Treatment Options ◽  
Frozen Shoulder ◽  
Current Treatment ◽  
Mechanisms Of Action ◽  
Pathophysiological Mechanisms ◽  
Comprehensive View ◽  
Limited Success ◽  
Corticosteroid Injections

Frozen shoulder is a common epidemiological affliction. Data acquired from people who suffer from this type of damage in other joints such as the hip, wrist and ankle also exist; although these syndromes are less common. Treatment for frozen shoulder is primarily physical (physiotherapy, manual therapy), secondary medical (corticosteroid injections) and finally surgical but with limited success. The difficulty in treating this type of condition successfully lies in the lack of knowledge about the risk factors involved and the pathophysiology underlying this mysterious syndrome. This review gives an overview of the current scientific position of frozen shoulder in terms of evolutionary factors, etiology, the different mechanisms of action involved, current treatment options and other possible interventions based on recent discoveries of pathophysiological mechanisms. The overall objective is to clarify several unknown aspects of a syndrome that affects up to 5% of the world's population.

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