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Healthcare Resource Utilization for Recurrent Clostridium difficile Infection in a Large University Hospital in Houston, Texas  [PDF]
Samuel L. Aitken, Tiby B. Joseph, Dhara N. Shah, Todd M. Lasco, Hannah R. Palmer, Herbert L. DuPont, Yang Xie, Kevin W. Garey
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102848
Abstract: Background There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI). Methods Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed. Results 372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6±6 days. Conclusion Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied.
Surveillance for Clostridium difficile Infection: ICD-9 Coding Has Poor Sensitivity Compared to Laboratory Diagnosis in Hospital Patients, Singapore  [PDF]
Monica Chan,Poh Lian Lim,Angela Chow,Mar Kyaw Win,Timothy M. Barkham
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015603
Abstract: Clostridium difficile infection (CDI) is an increasingly recognized nosocomial infection in Singapore. Surveillance methods include laboratory reporting of Clostridium difficile toxin assays (CDTA) or use of International Classification of Diseases, 9th Revision (ICD-9) discharge code 008.45. Previous US studies showed good correlation between CDTA and ICD-9 codes. However, the use of ICD-9 codes for CDI surveillance has not been validated in other healthcare settings.
Evaluation of an automated ultraviolet radiation device for decontamination of Clostridium difficile and other healthcare-associated pathogens in hospital rooms
Michelle M Nerandzic, Jennifer L Cadnum, Michael J Pultz, Curtis J Donskey
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-197
Abstract: The Tru-D? Rapid Room Disinfection device is a mobile, fully-automated room decontamination technology that utilizes ultraviolet-C irradiation to kill pathogens. We examined the efficacy of environmental disinfection using the Tru-D device in the laboratory and in rooms of hospitalized patients. Cultures for C. difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) were collected from commonly touched surfaces before and after use of Tru-D.On inoculated surfaces, application of Tru-D at a reflected dose of 22,000 μWs/cm2 for ~45 minutes consistently reduced recovery of C. difficile spores and MRSA by >2-3 log10 colony forming units (CFU)/cm2 and of VRE by >3-4 log10 CFU/cm2. Similar killing of MRSA and VRE was achieved in ~20 minutes at a reflected dose of 12,000 μWs/cm2, but killing of C. difficile spores was reduced. Disinfection of hospital rooms with Tru-D reduced the frequency of positive MRSA and VRE cultures by 93% and of C. difficile cultures by 80%. After routine hospital cleaning of the rooms of MRSA carriers, 18% of sites under the edges of bedside tables (i.e., a frequently touched site not easily amenable to manual application of disinfectant) were contaminated with MRSA, versus 0% after Tru-D (P < 0.001). The system required <5 minutes to set up and did not require continuous monitoring.The Tru-D Rapid Room Disinfection device is a novel, automated, and efficient environmental disinfection technology that significantly reduces C. difficile, VRE and MRSA contamination on commonly touched hospital surfaces.Environmental surfaces may play an important role in transmission of healthcare-associated pathogens such as Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) [1-6]. Patients may acquire these pathogens through direct contact with contaminated surfaces or healthcare workers' hands may transmit pathogens from contaminated surfaces to
Bench-to-bedside review: Clostridium difficile colitis
Carolyn V Gould, L Clifford McDonald
Critical Care , 2008, DOI: 10.1186/cc6207
Abstract: Since the discovery of Clostridium difficile-associated disease (CDAD) approximately 30 years ago [1,2], much progress has been made in our understanding of the pathogenesis and management of this infection. In recent years, however, the epidemiology of C. difficile has changed dramatically. Beginning in 2000, widespread regional outbreaks of C. difficile strains involving more severe and refractory disease have occurred, with greater numbers of complications, colectomies, and deaths than previously described [3-6]. Since most C. difficile acquisitions occur within healthcare settings, emphasis should be placed on implementing evidence-based strategies for infection control and prevention, early detection, and effective treatment for severe and relapsing CDAD.Toxin-producing strains of C. difficile, an anaerobic spore-forming bacillus, cause illnesses ranging from mild diarrhea to fulminant colitis and toxic megacolon leading to sepsis and even death. There are two essential requirements for CDAD to develop: exposure to antimicrobials and new acquisition of C. difficile, although the precise timing and order of these events is not well understood. An important third factor, possibly relating to host susceptibility or virulence factors of the bacterial strain, may then determine whether the clinical outcome will be asymptomatic colonization or CDAD [7].Acquisition of C. difficile occurs by oral ingestion of spores, which resist the acidity of the stomach and germinate into the vegetative form in the small intestine. Disruption of the commensal flora of the colon, typically through exposure to antimicrobials, allows C. difficile to flourish and produce toxins that lead to colitis. The primary toxins produced are toxins A and B, two large exotoxins that cause inflammation and mucosal damage. Both toxins appear to have cytotoxic effects through disruption of the actin cytoskeleton within cells [8]. Although previous evidence suggested that toxin A is the major enterotox
Indications and Relative Utility of Lower Endoscopy in the Management of Clostridium difficile Infection  [PDF]
Nora E. Burkart,Mary R. Kwaan,Christopher Shepela,Robert D. Madoff,Yan Wang,David A. Rothenberger,Genevieve B. Melton
Gastroenterology Research and Practice , 2011, DOI: 10.1155/2011/626582
Abstract: Background. Diagnosis and management of Clostridium difficile infection (CDI) rely upon clinical assessments and diagnostic studies. Among diagnostic tests, lower gastrointestinal (GI) endoscopy in the setting of CDI remains controversial. Objective. To describe the role of lower endoscopy in CDI management. Methods. Retrospective study of lower endoscopies in CDI at four metropolitan hospitals, July 2005 through December 2007. Results. Of 1760 CDI inpatients, 45 lower endoscopies were performed on 43 patients. Most common indications were ruling out other etiologies (42%), inconclusive stool studies (36%), and worsening course (11%). Most endoscopies (73%) had positive findings, including pseudomembranous colitis (49%) and nonspecific colitis (24%). Biopsies were performed in 31 cases, more with nonspecific colitis (10/11, 92%) compared to pseudomembranous colitis (14/22, 64%). Conclusion. While not recommended as a primary screening tool, lower GI endoscopy can add valuable information in CDI when other colonic pathologies may exist, studies are inconclusive, or clinical status worsens. 1. Introduction Clostridium difficile infection (CDI) is a significant public health problem due to its association with antibiotic use and healthcare settings, increasing overall incidence, evolving epidemiology, and high associated health care costs. For any individual patient with symptomatic CDI, the spectrum of disease can vary widely. While initial treatment is effective in most cases, some cases are highly complex including patients with recalcitrant or recurrent disease [1], infections caused by increasingly virulent strains of Clostridium difficile (C. difficile) that are unresponsive to traditional medical therapy [2–4], and patients with fulminant colitis requiring surgery [5–10]. Stool studies like enzyme immunoassays for C. difficile toxins [3, 11] have improved our diagnostic abilities with CDI. The diagnosis, management, and treatment of CDI, particularly in the acute inpatient setting, rely upon a combination of ongoing clinical assessments and diagnostic studies. Lower gastrointestinal (GI) endoscopy, either flexible sigmoidoscopy or colonoscopy, can be used to (1) visualize the colon looking for inflammation or for the presence of pseudomembranes and (2) to obtain tissue and stool for diagnostic purposes. The optimal role of the lower GI endoscopy in the setting of CDI remains poorly defined and controversial. In the late 1970s and 1980s, some authors stressed the importance of endoscopy as a diagnostic tool [12, 13]. In the 1990s, with the
Hypervirulent Clostridium difficile PCR-Ribotypes Exhibit Resistance to Widely Used Disinfectants  [PDF]
Lisa F. Dawson, Esmeralda Valiente, Elizabeth H. Donahue, George Birchenough, Brendan W. Wren
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025754
Abstract: The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon?, Newgenn?, Proceine 40? and Hibiscrub?. Whereas, for Steri7? and Biocleanse? the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe? was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR-ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings.
Clinical Clostridium difficile: Clonality and Pathogenicity Locus Diversity  [PDF]
Kate E. Dingle,David Griffiths,Xavier Didelot,Jessica Evans,Alison Vaughan,Melina Kachrimanidou,Nicole Stoesser,Keith A. Jolley,Tanya Golubchik,Rosalind M. Harding,Tim E. Peto,Warren Fawley,A. Sarah Walker,Mark Wilcox,Derrick W. Crook
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019993
Abstract: Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings. The major virulence determinants are large clostridial toxins, toxin A (tcdA) and toxin B (tcdB), encoded within the pathogenicity locus (PaLoc). Isolates vary in pathogenicity from hypervirulent PCR-ribotypes 027 and 078 with high mortality, to benign non-toxigenic strains carried asymptomatically. The relative pathogenicity of most toxigenic genotypes is still unclear, but may be influenced by PaLoc genetic variant. This is the largest study of C. difficile molecular epidemiology performed to date, in which a representative collection of recent isolates (n = 1290) from patients with CDI in Oxfordshire, UK, was genotyped by multilocus sequence typing. The population structure was described using NeighborNet and ClonalFrame. Sequence variation within toxin B (tcdB) and its negative regulator (tcdC), was mapped onto the population structure. The 69 Sequence Types (ST) showed evidence for homologous recombination with an effect on genetic diversification four times lower than mutation. Five previously recognised genetic groups or clades persisted, designated 1 to 5, each having a strikingly congruent association with tcdB and tcdC variants. Hypervirulent ST-11 (078) was the only member of clade 5, which was divergent from the other four clades within the MLST loci. However, it was closely related to the other clades within the tcdB and tcdC loci. ST-11 (078) may represent a divergent formerly non-toxigenic strain that acquired the PaLoc (at least) by genetic recombination. This study focused on human clinical isolates collected from a single geographic location, to achieve a uniquely high density of sampling. It sets a baseline of MLST data for future comparative studies investigating genotype virulence potential (using clinical severity data for these isolates), possible reservoirs of human CDI, and the evolutionary origins of hypervirulent strains.
Clostridium difficile phages: still difficult?  [PDF]
Katherine R. Hargreaves,Martha R. J. Clokie
Frontiers in Microbiology , 2014, DOI: 10.3389/fmicb.2014.00184
Abstract: Phages that infect Clostridium difficile were first isolated for typing purposes in the 1980s, but their use was short lived. However, the rise of C. difficile epidemics over the last decade has triggered a resurgence of interest in using phages to combat this pathogen. Phage therapy is an attractive treatment option for C. difficile infection, however, developing suitable phages is challenging. In this review we summarize the difficulties faced by researchers in this field, and we discuss the solutions and strategies used for the development of C. difficile phages for use as novel therapeutics. Epidemiological data has highlighted the diversity and distribution of C. difficile, and shown that novel strains continue to emerge in clinical settings. In parallel with epidemiological studies, advances in molecular biology have bolstered our understanding of C. difficile biology, and our knowledge of phage–host interactions in other bacterial species. These three fields of biology have therefore paved the way for future work on C. difficile phages to progress and develop. Benefits of using C. difficile phages as therapeutic agents include the fact that they have highly specific interactions with their bacterial hosts. Studies also show that they can reduce bacterial numbers in both in vitro and in vivo systems. Genetic analysis has revealed the genomic diversity among these phages and provided an insight into their taxonomy and evolution. No strictly virulent C. difficile phages have been reported and this contributes to the difficulties with their therapeutic exploitation. Although treatment approaches using the phage-encoded endolysin protein have been explored, the benefits of using “whole-phages” are such that they remain a major research focus. Whilst we don’t envisage working with C. difficile phages will be problem-free, sufficient study should inform future strategies to facilitate their development to combat this problematic pathogen.
Evaluation of a hand-held far-ultraviolet radiation device for decontamination of Clostridium difficile and other healthcare-associated pathogens
Michelle M Nerandzic, Jennifer L Cadnum, Kevin E Eckart, Curtis J Donskey
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-120
Abstract: We examined the efficacy of disinfection using the Sterilray device in the laboratory, in rooms of hospitalized patients, and on surfaces outside of patient rooms (i.e. keyboards and portable medical equipment). Cultures for C. difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) were collected from commonly-touched surfaces before and after use of the Sterilray device.On inoculated surfaces in the laboratory, application of the Sterilray device at a radiant dose of 100?mJ/cm2 for?~?5 seconds consistently reduced recovery of C. difficile spores by 4.4?CFU log10, MRSA by 5.4 log10CFU and of VRE by 6.9 log10CFU. A >3 log10 reduction of MRSA and VRE was achieved in ~2 seconds at a lower radiant dose, but killing of C. difficile spores was significantly reduced. On keyboards and portable medical equipment that were inoculated with C. difficile spores, application of the Sterilray device at a radiant dose of 100?mJ/cm2 for?~?5 seconds reduced contamination by 3.2 log10CFU. However, the presence of organic material reduced the lethal effect of the far-UV radiation. In hospital rooms that were not pre-cleaned, disinfection with the Sterilray device significantly reduced the frequency of positive C. difficile and MRSA cultures (P =0.007).The Sterilray? Disinfection Wand is a novel environmental disinfection technology that rapidly kills C. difficile spores and other healthcare-associated pathogens on surfaces. However, the presence of organic matter reduces the efficacy of far-UV radiation, possibly explaining the more modest results observed on surfaces in hospital rooms that were not pre-cleaned.
Aerial Dissemination of Clostridium difficile spores
Katherine Roberts, Caroline F Smith, Anna M Snelling, Kevin G Kerr, Kathleen R Banfield, P Andrew Sleigh, Clive B Beggs
BMC Infectious Diseases , 2008, DOI: 10.1186/1471-2334-8-7
Abstract: In a survey undertaken during February (two days) 2006 and March (two days) 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study) during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control). Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates.On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air). One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007.This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C. difficile, a finding which may help to explain why CDAD is so persistent within hospitals and difficult to eradicate. Although preliminary, the findings reinforce concerns that current C. difficile control measures may be inadequate and suggest that improved ward ventilation may help to reduce the spread of CDAD in healthcare facilities.Clostridium difficile-associated diarrhoea (CDAD) is a frequently occurring nosocomial infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. In many countries the incidence of CDAD seems to be increasing and a toxin-hyperproducing strain (ribotype 027) is becoming more common [1,2], despite the fact that many hospitals have made stri
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