Antimicrobial-Resistant Strains of Clostridium difficile from North America

ABSTRACTA total of 316 toxigenicClostridium difficileclinical isolates of known PCR ribotypes from patients in North America were screened for resistance to clindamycin, metronidazole, moxifloxacin, and rifampin. Clindamycin resistance was observed among 16 different ribotypes, with ribotypes 017, 053, and 078 showing the highest proportions of resistance. All isolates were susceptible to metronidazole. Moxifloxacin resistance was present in >90% of PCR-ribotype 027 and 053 isolates but was less common among other ribotypes. Only 7.9% of theC. difficileisolates were resistant to rifampin. Multidrug resistance (clindamycin, moxifloxacin, and rifampin) was present in 27.5% of PCR-ribotype 027 strains but was rare in other ribotypes. These results suggest that antimicrobial resistance in North American isolates ofC. difficilevaries by strain type and parallels rates of resistance reported from Europe and the Far East.

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First confirmed cases of Clostridium difficile PCR ribotype 027 in Norway

Eurosurveillance ◽

10.2807/ese.13.02.08011-en ◽

2008 ◽

Vol 13 (2) ◽

pp. 9-10

Author(s):

A Ingebretsen ◽

G Hansen ◽

C Harmanus ◽

E J Kuijper

Keyword(s):

North America ◽

Clostridium Difficile ◽

European Countries ◽

Ribotype 027 ◽

Pcr Ribotype 027

Since 2003, the emergence and distribution of a hypervirulent strain of Clostridium difficile PCR ribotype 027 has been described in North America, Japan and several European countries [1-6]. In December 2007, C. difficile PCR ribotype 027 was found in two cases of C. difficile-associated disease treated in a hospital in Oslo, Norway.

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Precise Manipulation of the Clostridium difficile Chromosome Reveals a Lack of Association between thetcdCGenotype and Toxin Production

Applied and Environmental Microbiology ◽

10.1128/aem.00249-12 ◽

2012 ◽

Vol 78 (13) ◽

pp. 4683-4690 ◽

Cited By ~ 162

Author(s):

Stephen T. Cartman ◽

Michelle L. Kelly ◽

Daniela Heeg ◽

John T. Heap ◽

Nigel P. Minton

Keyword(s):

Clostridium Difficile ◽

Diarrheal Disease ◽

Genetic Manipulation ◽

Toxin Production ◽

Negative Regulator ◽

Toxin B ◽

Content Type ◽

Ribotype 027 ◽

High Level ◽

Pcr Ribotype 027

ABSTRACTClostridium difficilecauses a potentially fatal diarrheal disease through the production of its principal virulence factors, toxin A and toxin B. ThetcdCgene is thought to encode a negative regulator of toxin production. Therefore, increased toxin production, and hence increased virulence, is often inferred in strains with an aberranttcdCgenotype. This report describes the first allele exchange system for precise genetic manipulation ofC. difficile, using thecodAgene ofEscherichia colias a heterologous counterselection marker. It was used to systematically restore the Δ117 frameshift mutation and the 18-nucleotide deletion that occur naturally in thetcdCgene ofC. difficileR20291 (PCR ribotype 027). In addition, the naturally intacttcdCgene ofC. difficile630 (PCR ribotype 012) was deleted and then subsequently restored with a silent nucleotide substitution, or “watermark,” so the resulting strain was distinguishable from the wild type. Intriguingly, there was no association between thetcdCgenotype and toxin production in eitherC. difficileR20291 orC. difficile630. Therefore, an aberranttcdCgenotype does not provide a broadly applicable rationale for the perceived notion that PCR ribotype 027 strains are “high-level” toxin producers. This may well explain why several studies have reported that an aberranttcdCgene does not predict increased toxin production or, indeed, increased virulence.

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Epidemiology of Clostridium difficile toxinotype III, PCR-ribotype 027 associated disease in Belgium, 2006

Weekly releases (1997–2007) ◽

10.2807/esw.11.37.03045-en ◽

2006 ◽

Vol 11 (37) ◽

Cited By ~ 1

Author(s):

M Delmée ◽

I Ramboer ◽

J Van Broeck ◽

C Suetens

Keyword(s):

United Kingdom ◽

North America ◽

Clostridium Difficile ◽

The Netherlands ◽

Pulse Field ◽

Surveillance Systems ◽

Ribotype 027 ◽

Set Up ◽

Pcr Ribotype 027

As a result of the reports of outbreaks of diarrhoea due to Clostridium difficile North American Pulse field type 1, PCR ribotype 027, toxinotype III in North America, United Kingdom, the Netherlands and Belgium, two different surveillance systems for C. difficile-associated diarrhoea were set up in Belgium

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First isolation of Clostridium difficile PCR ribotype 027 in Finland

Weekly releases (1997–2007) ◽

10.2807/esw.12.45.03303-en ◽

2007 ◽

Vol 12 (45) ◽

Cited By ~ 4

Author(s):

O Lyytikäinen ◽

S Mentula ◽

E Kononen ◽

S Kotila ◽

E Tarkka ◽

...

Keyword(s):

Clostridium Difficile ◽

Ribotype 027 ◽

First Case ◽

Pcr Ribotype 027

On 18 October 2007, the first case of Clostridium difficile PCR ribotype 027-associated disease was detected in Finland.

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Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008

Eurosurveillance ◽

10.2807/ese.13.31.18942-en ◽

2008 ◽

Vol 13 (31) ◽

Cited By ~ 2

Author(s):

E J Kuijper ◽

F Barbut ◽

J S Brazier ◽

N Kleinkauf ◽

T Eckmanns ◽

...

Keyword(s):

Clostridium Difficile ◽

European Countries ◽

Epidemiological Surveillance ◽

Resistance Pattern ◽

Positive Type ◽

Ribotype 027 ◽

High Relapse Rate ◽

The United Kingdom ◽

Pcr Ribotype 027 ◽

Highly Virulent

Outbreaks of Clostridium difficile infections (CDI) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America and Europe. This emerging strain is referred to as PCR ribotype 027 (Type 027). Since 2005, individual countries have developed surveillance studies about the spread of type 027. C. difficile Type 027 has been reported in 16 European countries. It has been responsible for outbreaks in Belgium, Germany, Finland, France, Ireland, Luxembourg, The Netherlands, Switzerland and the United Kingdom (England, Wales, Northern Ireland and Scotland). It has also been detected in Austria, Denmark, Sweden, Norway, Hungary, Poland and Spain. Three countries experienced imported patients with CDI due to Type 027 who acquired the infection abroad. The antimicrobial resistance pattern is changing, and outbreaks due to clindamycin-resistant ermB positive Type 027 strains have occurred in three European countries. Ongoing epidemiological surveillance of cases of CDI, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of new, highly virulent clones.

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Clostridium difficile erm(B)-containing elements and the burden on the in vitro fitness

Journal of Medical Microbiology ◽

10.1099/jmm.0.057117-0 ◽

2013 ◽

Vol 62 (9) ◽

pp. 1461-1467 ◽

Cited By ~ 19

Author(s):

François Wasels ◽

Patrizia Spigaglia ◽

Fabrizio Barbanti ◽

Paola Mastrantonio

Keyword(s):

Clostridium Difficile ◽

Clinical Isolates ◽

Surveillance Study ◽

Conjugative Transposon ◽

Genetic Organization ◽

Ribotype 027 ◽

Pcr Ribotype 027

In Clostridium difficile, resistance to the macrolide-lincosamide-streptogramin B group of antibiotics generally relies on erm(B) genes. In this study, we investigated elements with a genetic organization different from Tn5398, the mobilizable non-conjugative element identified in C. difficile strain 630. Our results suggested that the elements most frequently found in strains isolated during the European surveillance study in 2005 were related to Tn6194, the conjugative transposon recently detected in different C. difficile types, including PCR-ribotype 027. We characterized a Tn6194-like and a novel element rarely found in clinical isolates. A burden on the in vitro fitness of C. difficile was observed after the acquisition of these elements as well as of Tn5398.

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Helminthology in its Applications to Marine Fisheries

Journal of Helminthology ◽

10.1017/s0022149x00001693 ◽

1933 ◽

Vol 11 (2) ◽

pp. 63-66

Author(s):

T. Southwell

Keyword(s):

North America ◽

South America ◽

Far East ◽

Marine Fishes ◽

The Arctic ◽

Marine Fisheries ◽

The Far East ◽

Indian Waters

Historical.—Our knowledge of the cestode parasites of marine fishes is due almost entirely to the work of Linton in North America, Shipley, Herdman and Hornell in Indian waters, Zschokke and Beauchamp in Europe. We know nothing regarding the tapeworms found in fishes in South America, round the coast of Africa, or in the Arctic; and our knowledge of those found in the Far East is limited to descriptions of about ten species by Yoshida. It will, therefore, be apparent that there still remain large areas to be investigated.

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Designed Ankyrin Repeat Protein (DARPin) Neutralizers of TcdB from Clostridium difficile Ribotype 027

mSphere ◽

10.1128/msphere.00596-19 ◽

2019 ◽

Vol 4 (5) ◽

Cited By ~ 2

Author(s):

Zeyu Peng ◽

Rudo Simeon ◽

Samuel B. Mitchell ◽

Junjie Zhang ◽

Hanping Feng ◽

...

Keyword(s):

Clostridium Difficile ◽

Laboratory Strain ◽

Ankyrin Repeat ◽

Content Type ◽

Ribotype 027 ◽

Binding Interface ◽

Proteoglycan 4 ◽

Ankyrin Repeat Proteins ◽

Hospital Acquired

ABSTRACT Clostridium difficile infection (CDI) is a leading cause of hospital-acquired diarrhea. In recent decades, the emergence of the “hypervirulent” BI/NAP1/027 strains of C. difficile significantly increased the morbidity and mortality of CDI. The pathogenesis of CDI is primarily mediated by the action of two toxins, TcdA and TcdB, with TcdB being the major virulent factor in humans. In this report, we describe the engineering of a panel of designed ankyrin repeat proteins (DARPins) that potently neutralize TcdB from the BI/NAP1/027 strains (e.g., TcdBUK1). The most effective DARPin, D16, inhibits TcdBUK1 with a 50% effective concentration (EC50) of 0.5 nM, which is >66-fold lower than that of the FDA-approved anti-TcdB antibody bezlotoxumab (EC50, ∼33 nM). Competitive enzyme-linked immunosorbent assays (ELISAs) showed that D16 blocks interactions between TcdB and its receptor, chondroitin sulfate proteoglycan 4 (CSPG4). The dimeric DARPin U3D16, which pairs D16 with DARPin U3, a disrupter of the interaction of TcdB with Frizzled 1/2/7 receptor, exhibits 10-fold-to-20-fold-enhanced neutralization potency against TcdB from C. difficile strains VPI 10463 (laboratory strain) and M68 (CF/NAP9/017) but identical activity against TcdBUK1 relative to D16. Subsequent ELISAs revealed that TcdBUK1 did not significantly interact with Frizzled 1/2/7. Computation modeling revealed 4 key differences at the Frizzled 1/2/7 binding interface which are likely responsible for the significantly reduced binding affinity. IMPORTANCE We report the engineering and characterization of designed ankyrin proteins as potent neutralizers of TcdB toxin secreted by a hypervirulent ribotype 027 strain of Clostridium difficile. We further show that although TcdB toxins from both ribotype 027 and VPI 10461 interact efficiently with TcdB receptors CSPG4 and Pvrl3, TcdB027 lacks significant ability to bind the only known physiologically relevant TcdB receptor, Frizzled 1/2/7.

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ANDRÉ RAYMOND (1925–2011)

International Journal of Middle East Studies ◽

10.1017/s0020743811001152 ◽

2011 ◽

Vol 43 (4) ◽

pp. 779-781

Author(s):

Jane Hathaway ◽

Randi Deguilhem

Keyword(s):

United States ◽

North America ◽

Middle East ◽

Small Town ◽

Far East ◽

The United States ◽

The Far East ◽

The University ◽

Middle East Studies

André Raymond, who passed away at his home in Aix-en-Provence on 18 February 2011, leaves an international legacy in Middle East studies. Born in 1925 in Montargis, a small town situated about seventy-five miles south of Paris, Monsieur Raymond, as he was known to his numerous students and to younger scholars in Europe, Russia, the Middle East, the Far East, and North America, taught for many years at the University of Provence and, after his retirement, in the United States.

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Platinum price outlook clouded by uncertain demand

Emerald Expert Briefings ◽

10.1108/oxan-db216912 ◽

2016 ◽

Keyword(s):

South African ◽

Far East ◽

Global Market ◽

Uncertain Demand ◽

Automotive Sector ◽

Far East Of Russia ◽

Content Type ◽

The Far East ◽

Car Sales ◽

Market Outlook

Subject The platinum market outlook. Significance After declining in 2015, the platinum price has remained modest this year, underperforming other mined commodities. The closely watched ratio to the gold price is near a historic low. Demand from the automotive sector has yet to recover from emission test scandals, despite car sales in China growing by 15.6% year-on-year in the first eleven months of 2016. South African miners are capital-constrained and the global market is currently estimated to be in a supply deficit of around 500 thousand ounces (koz). However, registered above-ground stocks are still significant at 1.9 million ounces (moz). Impacts Higher steel prices may increase scrap-steel demand, which may boost vehicle scrapping and increase recycling of platinum auto-catalysts. World leader Amplats will lose 75 koz of refined platinum production following a leak at the Waterval smelter. Production of alluvial platinum in the far east of Russia is entering terminal decline after two decades of operation.

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