Mark Wilcox

• University of Leeds

Clostridioides difficile is the most common cause of antibiotic-associated gastrointestinal infections. Capillary-electrophoresis (CE)-PCR ribotyping is currently the gold standard for C. difficile typing but lacks discriminatory power to study transmission and outbreaks in detail. New molecular methods have the capacity to differentiate better and...

Scope: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as fecal microbiota transplantation...

We review the evidence base for two newly introduced Infection prevention and control strategies within UK hospitals. The new standard infection control precaution of 2 metres physical distancing and the use of partition screens as a means of source control of infection for SARS-CoV-2. Following review of Ovid-MEDLINE and governmental SAGE outputs...

The wiping of high-touch healthcare surfaces made of metals, ceramics and plastics to remove bacteria is an accepted tool in combatting the transmission of healthcare-associated infections (HCAIs). In practice, surfaces may be repeatedly wiped using a single wipe, and the potential for recontamination may be affected by various factors. Accordingly...

Background Lower Clostridium difficile spore counts in feces from C difficile infection (CDI) patients treated with fidaxomicin versus vancomycin have been observed. We aimed to determine whether environmental contamination is lower in patients treated with fidaxomicin compared with those treated with vancomycin/metronidazole. Methods The CDI cases...

Background: Clostridioides difficile infection (CDI) remains a high burden worldwide. DAV131A, a novel adsorbent, reduces residual gut antimicrobial levels, reducing CDI risk in animal models. Objectives: We used a validated human gut model to investigate the efficacy of DAV131A in preventing moxifloxacin-induced CDI. Methods: C. difficile (CD...

Background . Pathogen whole-genome sequencing has huge potential as a tool to better understand infection transmission. However, rapidly identifying closely-related genomes among a background of thousands of other genomes is challenging. Methods . We describe a refinement to core-genome multi-locus sequence typing (cgMLST) where alleles at each gen...

Purpose.Clostridium difficile spores are extremely resilient to high temperatures. Sublethal temperatures are associated with the 'reactivation' of dormant spores, and are utilized to maximize C. difficile spore recovery. Spore eradication is of vital importance to the food industry. The current study seeks to elucidate the transient and persisting...

Background Gonorrhoea is a sexually transmitted infection of global public health concern. We investigated whole genome sequencing (WGS) as a partner notification (PN) tool in gonorrhoea management. Methods Between May-November 2018, all N. gonorrhoeae isolated from patients attending Leeds Sexual Health, UK, underwent WGS. Sequences were compared...

Background: Carbapenemase-producing Enterobacteriaceae (CPE) pose a major global health risk. Mobile genetic elements account for much of the increasing CPE burden. Objectives: To investigate CPE colonization and the impact of antibiotic exposure on subsequent resistance gene dissemination within the gut microbiota using a model to simulate the...

When this paper was first published one conflict of interest statement was omitted from the section. The correct statement is printed below in full: Conflict of interest statement M.H.W. has received honoraria from the European Tissue Symposium (ETS) for microbiological advice and lectures, and travel expenses to attend meetings. F.B. has received...

The molecular epidemiology of 38 non-duplicate toxigenic Clostridioides (previously Clostridium) difficile isolates from inpatients from a hospital in Brazil during a 6-year period (2012–2017) were investigated by multilocus sequence typing (MLST) and ribotyping. These isolates were classified into 20 sequence types (ST), six (30%) of which were no...

Objectives Fluoroquinolone resistance is common among epidemic Clostridioides difficile PCR ribotype (RT) 027 and may have contributed to outbreaks of C. difficile infection (CDI). We investigated the impact of fluoroquinolone mutations on the bacterial fitness (BF) of C. difficile RT027 isolates. Methods The BF of seven RT027 mutants with reduced...

Multi-drug resistant Gram negative bacteria are of major clinical concern. The increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE), resistant to all beta-lactams including carbapenems, and able to colonise the large intestine represent a key threat. Rapid, accurate detection of intestinal CPE colonisation is critical to minimi...

Multi-drug resistant Gram negative bacteria are of major clinical concern. The increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE), resistant to all beta-lactams including carbapenems, and able to colonise the large intestine represent a key threat. Rapid, accurate detection of intestinal CPE colonisation is critical to minimi...

Background: Guidelines recommend the use of an algorithm for the laboratory diagnosis of Clostridium difficile infection (CDI). Enzyme immunoassays (EIAs) detecting C. difficile (CD) toxins cannot be used as standalone tests due to sub-optimal sensitivity and molecular tests suffer from non-specificity by detecting colonization. Sensitive immunoass...

Restriction endonuclease analysis (REA) and PCR ribotyping are two typing systems that have been frequently utilized for molecular epidemiologic characterization of Clostridioides (Clostridium) difficile. To correlate typing data obtained from each method, we performed both REA and PCR ribotyping on a large and diverse set of historical and contemp...

Background: Hand hygiene is a fundamental component of infection prevention, but few studies have examined whether hand-drying method affects the risk of dissemination of potential pathogens. Materials/methods: We performed a multicentre, internal-crossover study comparing bacterial contamination levels in washrooms with hand-drying by either paper...

Background: Hand hygiene is a fundamental component of infection prevention, but few studies have examined whether hand-drying method affects the risk of dissemination of potential pathogens. Materials/methods: We performed a multicentre, internal-crossover study comparing bacterial contamination levels in washrooms with hand-drying by either pa...

Background and Objectives Point prevalence studies have reported higher carriage rates of C. difficile in IBD patients compared with the general population, but longitudinal prospective data are lacking. The objectives of this observational study were to investigate and molecularly characterise isolates of C. difficile, collected prospectively on a...

Background: Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods: Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006 - 2007 at six Canadian hospi...

We aimed to achieve a higher typing resolution within the three dominant Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A total of 50 C. difficile isolates we had previously typed by PCR-ribotyping, representing the major three ribotypes circulating in Colombia, were analyzed. Twenty-seven isolates of ribotype 591, 12 of...

Background: No previous study has used whole-genome sequencing (WGS) to investigate risk factors for C. difficile(CD) transmission between symptomatic cases, or assessed the impact of recent acquisition on patient outcome. Methods: This retrospective cohort study included consecutive diarrhoeal samples positive by cytotoxin assay in Leeds, UK(Au...

Abstract We aimed to achieve a higher typing resolution within the three dominant Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A total of 50 C. difficile isolates we had previously typed by PCR ribotyping, representing the major three ribotypes circulating in Colombia, were analyzed. Twenty-seven isolates of ribotype 5...

Background:The increasing incidence of Clostridium difficile infections (CDI) in healthcare settings in Europe since 2003 has affected both patients and healthcare systems. The implementation of effective CDI surveillance is key to enable monitoring of the occurrence and spread of C. difficile in healthcare and the timely detection of outbreaks. Ai...

An update of the diagnostic guidance document for Clostridium difficile infection (CDI) issued by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [1] was recently reviewed by Gateau et al. [2]. The aim of these publications was to optimize and improve CDI laboratory diagnostic on a global level by defining sample sele...

Introduction In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed. Methods A multidisciplinary group of clinicians in...

Wiping of surfaces contaminated with pathogenic bacteria is a key strategy for combating the transmission of healthcare associated infections. It is essential to understand the extent to which removal of bacteria is modulated by fiber properties, biocidal liquid impregnation and applied hand pressure. The influence of intrinsic and extrinsic factor...

Purpose: Some strains of C. difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of Clostridium difficile infection (CDI). Methods: Samples, isolates and clinical data were collected as pa...

Background Patients with symptomatic Clostridium difficile infection (CDI) are thought to be responsible for most transmission events, but whole genome sequencing (WGS) studies have raised interest in asymptomatic carriers’ role in transmission. Methods Patients with CDI and colonization were identified using weekly screening in a study conducted...

Background Bezlotoxumab (BEZ) and actoxumab (ACT) are monoclonal antibodies against C. difficile toxins B and A, respectively. Patients receiving a single infusion of BEZ alone or with ACT in the MODIFY I/II trials showed an absolute 10% (relative ~40%) reduction in rCDI over 12-weeks compared with placebo (PBO). The addition of ACT did not improve...

Background Bezlotoxumab (BEZ) and actoxumab (ACT) are monoclonal antibodies against C. difficile toxins B and A, respectively. Patients receiving a single infusion of BEZ alone or with ACT in the MODIFY I/II trials showed a consistent reduction in the rate of rCDI over a 12-week period compared with a placebo (PBO) infusion. Exploratory genome wide...

Background Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea associated with antimicrobial-mediated dysbiosis. Dysbiosis may be perpetuated by antibiotic (AB) CDI therapy, leading to recurrent CDI. Ridinilazole (RIDI) has very narrow activity against certain clostridia. We measured faecal microbiomes of Phase 2 subjects...

Background The objective of this study was to demonstrate the safety and efficacy of iclaprim, a new generation diaminopyrimidine, compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Methods REVIVE-1 was a Phase 3, 600 patient double-blind, randomized (1:1), active-controlled, mu...

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A...

Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC -Kpn ), are an increasing threat to patient safety. Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Materials and methods: Enterobacteriaceae with reduced...

Background: Optimal hand hygiene may be compromised by contact with contaminated environmental surfaces. Aim: To investigate the in-vitro efficacy of a novel, alcohol-release doorplate to reduce surface contamination during hand contact. Methods: Prototype, horizontally-held, Surfaceskins, alcohol gel-impregnated and control (aluminium) doorpl...

Introduction Despite multiple risk factors and a high rate of colonisation for Clostridium difficile (CD), the occurrence of C. difficile infection (CDI) in patients with cystic fibrosis (CF) is rare. The aim of this study was to compare the prevalence of CD toxin-specific IgA, IgG and anti-toxin neutralising antibodies (NAb) in the sera of adults...

Introduction Extra-genital tests for gonorrhoea (NG) and chlamydia (CT) are important in MSM and increasingly in women as vulvovaginal swabs (VVS) alone can miss infections but rectum, pharynx and urogenital swabs treble the diagnostic cost.Self-sampling is frequently used despite no robust RCT assessing its efficacy. We compared clinician-taken ex...

Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are worldwide prevalent healthcare-associated pathogens. We have evaluated three Qiagen artus QS-RGQ assays for the detection of these pathogens. We examined 200 stool samples previously tested for C. difficile infection (CDI), 94 re...

Is AGREE II a counsel of perfection? A letter commenting on Lytvyn et al 1 - Sheldon P. Stone, Mark Wilcox, Peter Hawkey

Purpose: Lack of standardised Clostridium difficile testing is a potential confounder when comparing infection rates. We used an observational, systematic, prospective large scale sampling approach to investigate variability in C. difficile sampling to understand C. difficile infection (CDI) incidence rates. Methods: In-patient and institutional da...

Background The role of symptomatic patients who are toxigenic strain-positive (TS+) but fecal toxin negative (FT-) in transmission of Clostridium difficile is currently unknown. Methods We investigated the contribution of symptomatic TS+/FT- and TS+/FT+ patients in C. difficile transmission in two UK regions. From two-step testing, all glutamate de...

Purpose of review: Clostridium difficile infection has attained high prominence given its prevalence and impacts on patients and healthcare institutions. Multiple new approaches to the prevention and treatment of C. difficile infection (CDI) are undergoing clinical trials. Recent findings: Bezlotoxumab is a monoclonal antibody against toxin B th...

Mark Wilcox speaks to Georgia Patey, Commissioning Editor: Professor Mark Wilcox is a Consultant Microbiologist and Head of Microbiology at the Leeds Teaching Hospitals (Leeds, UK), the Professor of Medical Microbiology at the University of Leeds (Leeds, UK), and is the Lead on Clostridium difficile and the Head of the UK C. difficile Reference Lab...

Clostridium difficile is a leading nosocomial pathogen and molecular typing is a crucial part of monitoring its occurrence and spread. Over a three-year period (2013-2015), clinical Clostridium difficile isolates from 32 Czech hospitals were collected for molecular characterisation. Of 2,201 C. difficile isolates, 177 (8%) were non-toxigenic, 2,024...

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the EUCLID study, the largest C. difficile epidemiological study of its type, PCR-ribotype distribution of C. difficile isolates in Europe was investigated. PCR-ribotyping was performed on 1196 C. difficile isolates from diarrhoeal...

Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillan...

In 2009 the first European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline for diagnosing Clostridium difficile infection (CDI) was launched. Since then newer tests for diagnosing CDI have become available, especially nucleic acid amplification tests. The main objectives of this update of the guidance document are to sum...

Background Extra-genital tests for gonorrhoea and chlamydia are important in MSM and are increasingly important in women as vulvovaginal swabs (VVS) alone can miss infections. Self-sampling is frequently used but there has been no robust RCT against clinician-taken samples in MSM or women to assess its efficacy. Aim To compare self-taken extra-gen...

Background Extra-genital infections are common in MSM and women and are frequently the sole sites of infection. However, analysing samples from the rectum and pharynx, in addition to the urogenital tract, trebles the diagnostic cost. Aim Can samples from three sites be pooled into one NAAT container and still achieve the same sensitivity and speci...

Background/introduction BASHH standards recommend rectal chlamydia sampling in women with increased risk. However, studies show high rates of rectal chlamydia in women, with concerns over treatment failures and risk of genital re-infection Aim(s)/objectives To determine if rectal chlamydia screening in females should be universal. Methods As part...

Poster reporting results of in vitro experiments that describe the persistence of fidaxomicin on Clostridium difficile spores of different ribotypes whereas vancomycin does not. Persisting levels of FDX were greater following incubation/washing in faecal filtrate than PBS, indicating that persistence occurs in in vivo reflective conditions. The per...

Poster reporting results of antibiotic susceptibility testing of nearly 3000 clinical Clostridium difficile isolates, collected over 3 years from 41 hospital sites in 28 European countries as part of the ClosER study.

Background: PCR-ribotyping is based on variability of the intergenic spacer region between 16S and 23S ribosomal DNA, and is the most widely used typing method for C. difficile isolates. We aimed to: 1. Compare data obtained by two (recommended) protocols differing in PCR conditions, DNA polymerase and primer set design (Stubbs primers and Bidet pr...

Objectives: Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe(3+) saturated) bovine holo...

Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Mode...

Introduction Dalbavancin is a new lipoglycopeptide that is active against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It has a half-life of 14.4 days, permitting intravenous treatment of acute bacterial skin and skin structure infections without the need for daily dosing. Objective The objective of these analyses...

Clostridium difficile infection (CDI) is a leading cause of diarrhoea in health care settings with symptoms ranging from mild and self-limiting to life threatening. SMT19969 is a novel, non-absorbable antibiotic currently under development for the treatment of CDI. Here we report the results from a Phase I study. A double-blind, randomized, placebo...

Background. Actoxumab ((ACT) MK-3415) and bezlotoxumab ((BEZ) MK- 6072) are human monoclonal antibodies against Clostridium difficile toxins A and B, respectively. Methods. Combined data from 2 double-blind, randomized, phase 3 studies in adult patients receiving oral standard of care (SoC) (metronidazole, vancomycin, or fidaxomi- cin) for primary...

In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile . The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.

Objectives: We have previously shown that fidaxomicin (FDX) activity persists on C. difficile spores, and may prevent subsequent spore recovery. However the effects of this persistence on spore germination, vegetative cell proliferation and downstream toxin production have not been described. Here we investigate the effect of exposure to faecal mat...

Cadazolid, a novel fluoroquinolone-oxazolidinone antibiotic, exhibits potent in vitro activity against Clostridium difficile, including the epidemic BI/NAP1/027 strain. This multicenter, randomized, double-blind, active reference group, phase 2 study (NCT01222702; EUDRA-CT 2010-020941-29) evaluated the efficacy and safety of oral cadazolid in treat...

Next-generation sequencing technologies (e.g. 16S profiling) are increasingly used to investigate complex bacterial communities. They have advantages over classical methods, as a significant proportion of bacteria are ‘non-culturable’. However, they do not distinguish ‘viable’ and ‘non-viable’ populations, which may skew results, particularly follo...

Background: Fidaxomicin treatment reduces the risk of recurrent Clostridium difficile infection (CDI) compared with vancomycin. Extending duration of fidaxomicin therapy may further reduce recurrence. We compared the efficacy of four extended fidaxomicin regimens in an in vitro model of CDI. Methods: Four gut models were primed with human faeces,...

Prevention and management of Clostridium difficile Infection (CDI) can be improved by rapid and reliable diagnostics. The VIDAS® C. difficile GDH assay had comparable performance to the QUIK CHEK 60 assay (overall agreement 95%) and sensitivity of >93%; thus suitable as the first test in two-stage algorithms for CDI diagnosis. Copyright © 2015, Ame...

As a follow-up to our 2009 survey, in order to explore opinion and practice on the epidemiology and management of meticillin-resistant Staphylococcus aureus (MRSA) in Europe, we conducted a second survey to elicit current opinions on this topic, particularly around antibiotic choice, dose, duration and route of administration. We also aimed to furt...

This chapter describes the increasing development of services for administration of intravenous antibiotics to patients in the community. Various terms have been used to describe this, including community-based parenteral anti-infective therapy, hospital in the home therapy, and non-inpatient parenteral antimicrobial therapy. However, OPAT (outpati...

Chapter 13 discusses how antimicrobial agents are among the most commonly prescribed drugs, and how their use has had a majorimpact on the control of most bacterial infections in man. More recently, effective antiviral drugs against herpes virus infections and HIV have revolutionized the treatment of these infections. Likewise, antifungal agents ef...

This chapter outlines the replication cycle of the human immunodeficiency viruses (HIV) in order to provide a basis for understanding the various targets within that cycle which have been exploited in the development of antiretroviral drugs. All currently licensed antiretroviral drugs are then listed, together with the available combination formula...

Tuberculosis is caused by Mycobacterium tuberculosis and is transmitted between humans by aerosol. The World Health Organization estimates that a third of the world’s population is latently infected with M. tuberculosis; around 1 in 10 of these will develop clinical tuberculosis, falling to 1 in 3 if the individual is co-infected with HIV. Clinical...

This chapter deals with the crucial issue of resistance to antimicrobial agents. The types of resistance (acquired versus intrinsic) are reviewed, including historical and present-day key exemplars of pathogens with acquired resistance. The mechanisms underlying acquired resistance are examined. The clinical consequences of drug resistance are disc...