Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line

Aguado, José María; Anttila, Veli‐Jukka; Galpérine, Tatiana; Goldenberg, Simon; Gwynn, Simon; Jenkins, David R.; Norén, Torbjörn; Petrosillo, Nicola; Seifert, Harald; Stallmach, Andreas; Warren, T.; Wenisch, Christoph

doi:10.1016/j.jhin.2015.03.001

Cited by 29 publications

(23 citation statements)

References 29 publications

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“…[2][3][4] Prevention of recurrence of C difficile infection has been identified as a key unmet need. 5 Recurrence is estimated to occur in up to 25% of patients treated with metronidazole or vancomycin, 5,6 is associated with a substantial health-care burden, 6 and is a particular problem in high-risk individuals. 7 Previous administration of antimicrobials typically results in disruption of the colonic microbiota, preceding C difficile colonisation.…”

Section: Introductionmentioning

confidence: 99%

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Guery

Menichetti

Anttila

et al. 2018

The Lancet Infectious Diseases

163

143

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Section: Introductionmentioning

confidence: 99%

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Guery

Menichetti

Anttila

et al. 2018

The Lancet Infectious Diseases

163

143

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“…Clostridium difficile, a spore forming Gram‐positive strict anaerobe, is a major cause of human morbidity and mortality in hospitals and the main cause of hospital‐acquired diarrhoea. C. difficile infections (CDI) place considerable economic pressure on healthcare systems, costing an estimated €3B per annum in the EU (Aguado et al ., ) and $4.8B in the USA (Lessa et al ., ). CDI results from gut dysbiosis, typically caused by antibiotic therapy disrupting the normal microbiota.…”

Section: Introductionmentioning

confidence: 99%

Peptidoglycan degradation machinery in Clostridium difficile forespore engulfment

Dembek

Kelly

Barwinska-Sendra

et al. 2018

Molecular Microbiology

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Summary Clostridium difficile remains the leading cause of antibiotic‐associated diarrhoea in hospitals worldwide, linked to significant morbidity and mortality. As a strict anaerobe, it produces dormant cell forms – spores – which allow it to survive in the aerobic environment. Importantly, spores are the transmission agent of C. difficile infections. A key aspect of sporulation is the engulfment of the future spore by the mother cell and several proteins have been proposed to be involved. Here, we investigated the role of the SpoIID, SpoIIM and SpoIIP (DMP) machinery and its interplay with the SpoIIQ:SpoIIIAH (Q:AH) complex in C. difficile. We show that, surprisingly, SpoIIM, the proposed machinery anchor, is not required for efficient engulfment and sporulation. We demonstrate the requirement of DP for engulfment due to their sequential peptidoglycan degradation activity, both in vitro and in vivo. Finally, new interactions within DMP and between DMP and Q:AH suggest that both systems form a single engulfment machinery to keep the mother cell and forespore membranes together throughout engulfment. This work sheds new light upon the engulfment process and on how different sporeformers might use the same components in different ways to drive spore formation.

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“…Clostridium difficile infection (CDI) is a major public health concern [ 1 ] and is associated with prolonged hospital stay [ 2 , 3 ], hospital readmissions [ 4 , 5 ] and increased mortality [ 6 – 8 ]. Recurrence of disease is a significant problem, with 20–30 % of patients experiencing a recurrent episode following initial resolution [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations

Goldenberg

Brown

Edwards

et al. 2015

Eur J Clin Microbiol Infect Dis

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Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

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Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line

Abstract: Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings.

Cited by 29 publications

References 29 publications

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial

Peptidoglycan degradation machinery in Clostridium difficile forespore engulfment

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations

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