scholarly journals U.S.-Based National Sentinel Surveillance Study for the Epidemiology of Clostridium difficile-Associated Diarrheal Isolates and Their Susceptibility to Fidaxomicin

2015 ◽  
Vol 59 (10) ◽  
pp. 6437-6443 ◽  
Author(s):  
D. R. Snydman ◽  
L. A. McDermott ◽  
N. V. Jacobus ◽  
C. Thorpe ◽  
S. Stone ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antimicrobial Susceptibility ◽  
The United States ◽  
Surveillance Study ◽  
Binary Toxin ◽  
Toxin Gene ◽  
Gene Profile ◽  
Geographic Variations ◽  
Convenience Sample ◽  
Content Type

ABSTRACTIn 2011 a surveillance study for the susceptibility to fidaxomicin and epidemiology ofClostridium difficileisolates in the United States was undertaken in seven geographically dispersed medical centers. This report encompasses baseline surveillance in 2011 and 2012 on 925 isolates. A convenience sample ofC. difficileisolates or toxin positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution (CLSI M11-A8). Clinical and Laboratory Standards Institute (CLSI), Food and Drug Administration, or European Union of Clinical Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of 322 strains, stratified by institution, underwent restriction endonuclease analysis (REA). The fidaxomicin MIC90was 0.5 μg/ml for all isolates regardless of REA type or toxin gene profile, and all isolates were inhibited at ≤1.0 μg/ml. By REA typing, BI strains represented 25.5% of the isolates. The toxin gene profile oftcdA,tcdB, andcdtA/Bpositive with atcdC18-bp deletion correlated with BI REA group. Moxifloxacin and clindamycin resistance was increased among either BI or binary toxin-positive isolates. Metronidazole and vancomycin showed reduced susceptibility (EUCAST criteria) in these isolates. Geographic variations in susceptibility, REA group and binary toxin gene presence were observed. Fidaxomicin activity againstC. difficileisolated in a national surveillance study did not change more than 1 year after licensure. This analysis provides baseline results for future comparisons.

scholarly journals U.S.-Based National Surveillance for Fidaxomicin Susceptibility ofClostridioides difficile-Associated Diarrheal Isolates from 2013 to 2016

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
C. M. Thorpe ◽  
L. A. McDermott ◽  
M. K. Tran ◽  
J. Chang ◽  
S. G. Jenkins ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Restriction Endonuclease Analysis ◽  
The United States ◽  
Toxin Gene ◽  
Geographic Variations ◽  
Surveillance Network ◽  
Content Type ◽  
Geographically Dispersed ◽  
Vancomycin Mics ◽  
Imipenem Resistance

ABSTRACTIn 2011, we initiated a sentinel surveillance network to assess changes inClostridioides(formerlyClostridium)difficileantimicrobial susceptibility to fidaxomicin from 6 geographically dispersed medical centers in the United States. This report summarizes data from 2013 to 2016.C. difficileisolates or toxin-positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution. CLSI, EUCAST, or FDA breakpoints were used, where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of approximately 40% of isolates, stratified by institution and year, was typed by restriction endonuclease analysis (REA). Among 1,889 isolates from 2013 to 2016, the fidaxomicin MIC90was 0.5 μg/ml; all isolates were inhibited at ≤1 μg/ml. There were decreases in metronidazole and vancomycin MICs over time. Clindamycin resistance remained unchanged (27.3%). An increase in imipenem resistance was observed. By 2015 to 2016, moxifloxacin resistance decreased in all centers. The proportion of BI isolates decreased from 25.5% in 2011 to 2012 to 12.8% in 2015 to 2016 (P< 0.001). The BI REA group correlated with moxifloxacin resistance (BI 84% resistant versus non-BI 12.5% resistant). Fidaxomicin MICs have not changed amongC. difficileisolates of U.S. origin over 5 years post licensure. There has been an overall decrease in MICs for vancomycin, metronidazole, moxifloxacin, and rifampin and an increase in isolates resistant to imipenem. Moxifloxacin resistance remained high among the BI REA group, but the proportion of BI isolates has decreased. Continued geographic variations in REA groups and antimicrobial resistance persist.

scholarly journals Laboratory-Based Surveillance of Clostridium difficile Infection in Australian Health Care and Community Settings, 2013 to 2018

2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Stacey Hong ◽  
Papanin Putsathit ◽  
Narelle George ◽  
Christine Hemphill ◽  
Peter G. Huntington ◽  
...  
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Diarrheal Disease ◽  
Gene Profiling ◽  
Binary Toxin ◽  
Toxin Gene ◽  
Community Settings ◽  
Content Type ◽  
Australian Health ◽  
Diagnostic Microbiology

ABSTRACT In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.

scholarly journals Strain Types and Antimicrobial Resistance Patterns of Clostridium difficile Isolates from the United States, 2011 to 2013

2014 ◽  
Vol 58 (7) ◽  
pp. 4214-4218 ◽  
Author(s):  
Isabella A. Tickler ◽  
Richard V. Goering ◽  
Joseph D. Whitmore ◽  
Ashley N. W. Lynn ◽  
David H. Persing ◽  
...  
Keyword(s):  
United States ◽  
Clostridium Difficile ◽  
Antimicrobial Resistance ◽  
Antimicrobial Susceptibility ◽  
The United States ◽  
Geographic Region ◽  
Content Type ◽  
Resistance Patterns ◽  
Strain Type ◽  
Susceptibility Patterns

ABSTRACTWe determined the PCR ribotypes and antimicrobial susceptibility patterns of 508 toxigenicClostridium difficileisolates collected between 2011 and 2013 from 32 U.S. hospitals. Of the 29 PCR ribotypes identified, the 027 strain type was the most common (28.1%), although the rates varied by geographic region. Ribotype 014/020 isolates appear to be emerging. Clindamycin and moxifloxacin resistances (36.8% and 35.8%, respectively) were the most frequent resistance phenotypes observed. Reduced susceptibility to vancomycin was observed in 39.1% of 027 isolates.

scholarly journals Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

2012 ◽  
Vol 56 (7) ◽  
pp. 3943-3949 ◽  
Author(s):  
Chun-Hsing Liao ◽  
Wen-Chien Ko ◽  
Jang-Jih Lu ◽  
Po-Ren Hsueh
Keyword(s):  
Clostridium Difficile ◽  
Care Setting ◽  
Antimicrobial Agents ◽  
Teaching Hospitals ◽  
Binary Toxin ◽  
Content Type ◽  
Vancomycin Mics ◽  
Major Teaching ◽  
Southern Taiwan

ABSTRACTA total of 403 nonduplicate isolates ofClostridium difficilewere collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC90of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC90of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (n= 81, 20.1%) was accompanied by single or multiple mutations ingyrAandgyrBgenes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreportedgyrBmutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains ofC. difficilein the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potentin vitroactivity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns.

scholarly journals Inflammasome Activation Contributes to Interleukin-23 Production in Response to Clostridium difficile

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Carrie A. Cowardin ◽  
Sarah A. Kuehne ◽  
Erica L. Buonomo ◽  
Chelsea S. Marie ◽  
Nigel P. Minton ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Disease Severity ◽  
Tissue Damage ◽  
The United States ◽  
Host Cells ◽  
Inflammasome Activation ◽  
Content Type ◽  
Danger Signals ◽  
Interleukin 23 ◽  
Molecular Patterns

ABSTRACT  Clostridium difficileis the most common hospital-acquired pathogen, causing antibiotic-associated diarrhea in over 250,000 patients annually in the United States. Disease is primarily mediated by toxins A and B, which induce potent proinflammatory signaling in host cells and can activate an ASC-containing inflammasome. Recent findings suggest that the intensity of the host response to infection correlates with disease severity. Our lab has identified the proinflammatory cytokine interleukin-23 (IL-23) as a pathogenic mediator during C. difficile infection (CDI). The mechanisms by which C. difficile induces IL-23, however, are not well understood, and the role of toxins A and B in this process is unclear. Here, we show that toxins A and B alone are not sufficient for IL-23 production but synergistically increase the amount of IL-23 produced in response to MyD88-dependent danger signals, including pathogen-associated molecular patterns (PAMPs) and host-derived damage associated molecular patterns (DAMPs). Danger signals also enhanced the secretion of IL-1β in response to toxins A and B, and subsequent IL-1 receptor signaling accounted for the majority of the increase in IL-23 that occurred in the presence of the toxins. Inhibition of inflammasome activation in the presence of extracellular K+likewise decreased IL-23 production. Finally, we found that IL-1β was increased in the serum of patients with CDI, suggesting that this systemic response could influence downstream production of pathogenic IL-23. Identification of the synergy of danger signals with toxins A and B via inflammasome signaling represents a novel finding in the mechanistic understanding of C. difficile-induced inflammation.IMPORTANCEClostridium difficileis among the leading causes of death due to health care-associated infection, and factors determining disease severity are not well understood. C. difficile secretes toxins A and B, which cause inflammation and tissue damage, and recent findings suggest that some of this tissue damage may be due to an inappropriate host immune response. We have found that toxins A and B, in combination with both bacterium- and host-derived danger signals, can induce expression of the proinflammatory cytokines IL-1β and IL-23. Our results demonstrate that IL-1β signaling enhances IL-23 production and could lead to increased pathogenic inflammation during CDI.

scholarly journals Evaluation of the Cepheid Xpert C. difficile/Epiand Meridian Bioscienceillumigene C. difficile Assays for Detecting Clostridium difficile Ribotype 033 Strains

2014 ◽  
Vol 53 (3) ◽  
pp. 973-975 ◽  
Author(s):  
Grace O. Androga ◽  
Alan M. McGovern ◽  
Briony Elliott ◽  
Barbara J. Chang ◽  
Timothy T. Perkins ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Binary Toxin ◽  
Content Type ◽  
Toxin Genes ◽  
Production Animals

Clostridium difficilePCR ribotype 033 (RT033) is found in the gastrointestinal tracts of production animals and, occasionally, humans. TheillumigeneC. difficileassay (Meridian Bioscience, Inc.) failed to detect any of 52C. difficileRT033 isolates, while all strains signaled positive for the binary toxin genes but were reported as negative forC. difficileby the XpertC. difficile/Epiassay (Cepheid).

scholarly journals Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

2015 ◽  
Vol 53 (11) ◽  
pp. 3702-3704 ◽  
Author(s):  
Grace O. Androga ◽  
Julie Hart ◽  
Niki F. Foster ◽  
Adrian Charles ◽  
David Forbes ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clostridium Difficile ◽  
Young Patient ◽  
Diagnostic Methods ◽  
Binary Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Content Type ◽  
Severe Diarrhea ◽  
Clinically Significant

Large clostridial toxin-negative, binary toxin-positive (A−B−CDT+) strains ofClostridium difficileare almost never associated with clinically significantC. difficileinfection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A−B−CDT+ribotype 033 (RT033) strain ofC. difficilefrom a young patient with ulcerative colitis and severe diarrhea.

scholarly journals Antimicrobial Susceptibility to Azithromycin among Salmonella enterica Isolates from the United States

2011 ◽  
Vol 55 (9) ◽  
pp. 3985-3989 ◽  
Author(s):  
Maria Sjölund-Karlsson ◽  
Kevin Joyce ◽  
Karen Blickenstaff ◽  
Takiyah Ball ◽  
Jovita Haro ◽  
...  
Keyword(s):  
United States ◽  
Antimicrobial Susceptibility ◽  
Salmonella Enterica ◽  
Antimicrobial Agents ◽  
The United States ◽  
Outcome Data ◽  
Content Type ◽  
Susceptibility Data ◽  
Retail Meat ◽  
Clinical Breakpoints

ABSTRACTDue to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasiveSalmonellainfections. In the present study, 696 isolates of non-TyphiSalmonellacollected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-twoSalmonella entericaserotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-TyphiSalmonellaisolates, azithromycin MICs among human isolates ranged from 1 to 32 μg/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 μg/ml and 4 to 16 μg/ml, respectively. AmongSalmonellaserotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 μg/ml. The highest MIC observed in the present study was 32 μg/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-typeSalmonellaof ≤16 μg/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin andSalmonella enterica.

scholarly journals Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages

2016 ◽  
Vol 55 (3) ◽  
pp. 865-876 ◽  
Author(s):  
M. D. Cairns ◽  
M. D. Preston ◽  
C. L. Hall ◽  
D. N. Gerding ◽  
P. M. Hawkey ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Resistance Genes ◽  
Binary Toxin ◽  
Human Origins ◽  
Comparative Genome Analysis ◽  
Toxin B ◽  
Content Type ◽  
Global Spread ◽  
Animal Isolates ◽  
Evolutionary Lineages

ABSTRACT The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.

Examining the influence of transculturation on work ethic in the United States

2015 ◽  
Vol 22 (1) ◽  
pp. 145-162 ◽  
Author(s):  
Dwight M. Hite ◽  
Joshua J. Daspit ◽  
Xueni Dong
Keyword(s):  
Ethnic Groups ◽  
Work Ethic ◽  
Ethnically Diverse ◽  
The United States ◽  
Convenience Sample ◽  
Content Type ◽  
Significant Difference ◽  
The Usa ◽  
Generational Groups ◽  
Survey Responses

Purpose – The purpose of this paper is to explore the influence of cultural assimilation – termed “transculturation” – on work ethic perceptions, thus this study examines trends in work ethic across ethnic and generational groups within the USA. Design/methodology/approach – Following a literature review on work ethic, ethnicity, and transculturation, an analysis of variance based on 873 survey responses is presented. The sample includes undergraduate and graduate students at several public universities within the USA. Findings – An empirical analysis supports the hypothesis that the variation of work ethic perceptions within the Millennial generation is significantly less than the variation among older generations. The authors find no significant difference in general work ethic perceptions among Millennial ethnic groups. Research limitations/implications – While the study is conducted using a convenience sample, the demographics are closely representative of the USA labor force. The results suggest that Millennials, while a more diverse ethnic population, exhibit less variation among work ethic perceptions than earlier generational groups. Practical implications – Understanding differences in work ethic perceptions across various ethnic groups is valuable for managers interested in designing jobs that appropriately exploit the full value of a multi-generational workforce. Originality/value – The findings of this study offer new insights into how more recent generations, while more ethnically diverse, exhibit a convergence in perceptions of work ethic.

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