Community-associated C. Difficile Infection Research Articles

Clostridioides difficile from Fecally Contaminated Environmental Sources: Resistance and Genetic Relatedness from a Molecular Epidemiological Perspective.

Clostridioides difficile is the most important pathogen causing antimicrobial-associated diarrhea and has recently been recognized as a cause of community-associated C. difficile infection (CA-CDI). This study aimed to characterize virulence factors, antimicrobial resistance (AMR), ribotype (RT) distribution and genetic relationship of C. difficile isolates from diverse fecally contaminated environmental sources. C. difficile isolates were recovered from different environmental samples in Northern Germany. Antimicrobial susceptibility testing was determined by E-test or disk diffusion method. Toxin genes (tcdA and tcdB), genes coding for binary toxins (cdtAB) and ribotyping were determined by PCR. Furthermore, 166 isolates were subjected to whole genome sequencing (WGS) for core genome multi-locus sequence typing (cgMLST) and extraction of AMR and virulence-encoding genes. Eighty-nine percent (148/166) of isolates were toxigenic, and 51% (76/148) were positive for cdtAB. Eighteen isolates (11%) were non-toxigenic. Thirty distinct RTs were identified. The most common RTs were RT127, RT126, RT001, RT078, and RT014. MLST identified 32 different sequence types (ST). The dominant STs were ST11, followed by ST2, ST3, and ST109. All isolates were susceptible to vancomycin and metronidazole and displayed a variable rate of resistance to moxifloxacin (14%), clarithromycin (26%) and rifampicin (2%). AMR genes, such as gyrA/B, blaCDD-1/2, aph(3')-llla-sat-4-ant(6)-la cassette, ermB, tet(M), tet(40), and tetA/B(P), conferring resistance toward fluoroquinolone, beta-lactam, aminoglycoside, macrolide and tetracycline antimicrobials, were found in 166, 137, 29, 32, 21, 72, 17, and 9 isolates, respectively. Eleven "hypervirulent" RT078 strains were detected, and several isolates belonged to RTs (i.e., RT127, RT126, RT023, RT017, RT001, RT014, RT020, and RT106) associated with CA-CDI, indicating possible transmission between humans and environmental sources pointing out to a zoonotic potential.

Genomic Analysis of Clostridioides difficile Recovered from Horses in Western Australia.

Clostridioides difficile poses an ongoing threat as a cause of gastrointestinal disease in humans and animals. Traditionally considered a human healthcare-related disease, increases in community-associated C. difficile infection (CDI) and growing evidence of inter-species transmission suggest a wider perspective is required for CDI control. In horses, C. difficile is a major cause of diarrhoea and life-threatening colitis. This study aimed to better understand the epidemiology of CDI in Australian horses and provide insights into the relationships between horse, human and environmental strains. A total of 752 faecal samples from 387 Western Australian horses were collected. C. difficile was isolated from 104 (30.9%) horses without gastrointestinal signs and 19 (37.8%) with gastrointestinal signs. Of these, 68 (55.3%) harboured one or more toxigenic strains, including C. difficile PCR ribotypes (RTs) 012 (n = 14), 014/020 (n = 10) and 087 (n = 7), all prominent in human infection. Whole-genome analysis of 45 strains identified a phylogenetic cluster of 10 closely related C. difficile RT 012 strains of equine, human and environmental origin (0-62 SNP differences; average 23), indicating recent shared ancestry. Evidence of possible clonal inter-species transmission or common-source exposure was identified for a subgroup of three horse and one human isolates, highlighting the need for a One Health approach to C. difficile surveillance.

The Environment, Farm Animals and Foods as Sources of Clostridioides difficile Infection in Humans.

The recent discovery of the same Clostridioides difficile ribotypes associated with human infection in a broad range of environments, animals and foods, coupled with an ever-increasing rate of community-acquired infections, suggests this pathogen may be foodborne. The objective of this review was to examine the evidence supporting this hypothesis. A review of the literature found that forty-three different ribotypes, including six hypervirulent strains, have been detected in meat and vegetable food products, all of which carry the genes encoding pathogenesis. Of these, nine ribotypes (002, 003, 012, 014, 027, 029, 070, 078 and 126) have been isolated from patients with confirmed community-associated C. difficile infection (CDI). A meta-analysis of this data suggested there is a higher risk of exposure to all ribotypes when consuming shellfish or pork, with the latter being the main foodborne route for ribotypes 027 and 078, the hypervirulent strains that cause most human illnesses. Managing the risk of foodborne CDI is difficult as there are multiple routes of transmission from the farming and processing environment to humans. Moreover, the endospores are resistant to most physical and chemical treatments. The most effective current strategy is, therefore, to limit the use of broad-spectrum antibiotics while advising potentially vulnerable patients to avoid high-risk foods such as shellfish and pork.

Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Degree of concordance of Clostridioides difficile strains in adults with community-associated C. difficile infection and infants with C. difficile colonization.

Infants asymptomatically excrete Clostridioides difficile during their first year of life, suggesting that they may represent a source of infection for adults who acquire community-associated C. difficile infection (CA-CDI). The genetic relationship of C. difficile strains from asymptomatic infants and adults with CA-CDI is not well defined. In this study, 50 infants were recruited at birth, and stool samples were collected at routine well-child visits. Adult stool samples collected during the same period and geographical area from patients who were diagnosed with CA-CDI were selected for comparison. C. difficile was cultivated and probed by PCR for toxin genes and were typed by PCR fluorescent ribotyping. Isolates from adults and infants with shared ribotypes were subjected to whole-genome sequencing (WGS). Of these 50 infants, 36 were positive for C. difficile at least once in their first year of life, with a peak incidence at 6 months. Among 180 infant stool samples, 48 were positive. Of 48 isolates from positive stools, 29 were toxigenic by polymerase chain reaction (PCR) and 8 of 48 stool samples were positive for toxin by enzyme immunoassays (EIAs). Ribotypes F106 and F014-020 were present in both colonized infants and adults with CA-CDI. WGS identified 1 adult-infant pair that differed by 5 single-nucleotide polymorphisms (SNPs). Also, 4 additional adult-infant clusters differed by ≤16 SNPs. Infants that are colonized with C. difficile share ribotypes with adults from the same geographical region with CA-CDI. Selected isolates in the 2 populations show a genetic relationship by WGS.

Prevalence, Colonization, Epidemiology, and Public Health Significance of Clostridioides difficile in Companion Animals.

Clostridioides difficile, previously Clostrdium difficile, is a major cause of antibiotic-associated enteric disease in humans in hospital settings. Increased incidence of C. difficile infection (CDI) in community settings raises concerns over an alternative source of CDI for humans. The detection of genetically similar and toxigenic C. difficile isolates in companion animals, including asymptomatic pets, suggests the potential role of household pets as a source of community-associated CDI. The close association between companion animals and humans, in addition to the use of similar antibiotics in both species, could provide a selective advantage for the emergence of new C. difficile strains and thus increase the incidental transmission of CDI to humans. Therefore, screening household pets for C. difficile is becoming increasingly important from a public health standpoint and may become a part of routine testing in the future, for the benefit of susceptible or infected individuals within a household. In this review, we analyze available information on prevalence, pathophysiology, epidemiology, and molecular genetics of C. difficile infection, focusing on companion animals and evaluate the risk of pet-borne transmission of CDI as an emerging public health concern. Molecular epidemiological characterization of companion animal C. difficile strains could provide further insights into the interspecies transmission of CDI. The mosaic nature of C. difficile genomes and their susceptibility to horizontal gene transfer may facilitate the inter-mixing of genetic material, which could increase the possibility of the emergence of new community-associated CDI strains. However, detailed genome-wide characterization and comparative genome analysis are warranted to confirm this hypothesis.

Clostridioides difficile infection in the Asia-Pacific region

ABSTRACT Clostridioides difficile causes healthcare-related diarrhoea in high-income countries. Highly resistant spores persist in healthcare facilities, primarily infecting patients who have recently received antimicrobials. C. difficile infection (CDI) has been studied in detail in North America and Europe; however, the epidemiology of CDI elsewhere, including the Asia-Pacific region, is largely unknown. A survey of CDI was performed in 13 Asia-Pacific countries. Epidemiological data on 600 cases were collected and molecular typing undertaken on 414 C. difficile isolates. Healthcare facility-associated CDI comprised 53.6% of cases, while community-associated CDI was 16.5%. The median age of cases was 63.0 years and 45.3% were female, 77.5% had used antibiotics in the previous 8 weeks, most frequently third-generation cephalosporins (31.7%), and 47.3% had used proton pump inhibitors. Recurrence (9.1%) and mortality (5.2%) rates were low, while complications including colitis or pseudomembranous colitis (13.8%), colectomy (0.4%), and toxic megacolon (0.2%) were uncommon. Common C. difficile strains were ribotypes 017 (16.7%), 014/020 (11.1%) and 018 (9.9%), with wide variation between countries. Binary toxin-positive strains of C. difficile were detected rarely. Overall, disease severity appeared mild, and mortality and recurrence were low. Continued education about, and surveillance of, CDI in Asia are required to reduce the burden of disease.

Clostridium difficile in Asia: Opportunities for One Health Management.

Clostridium difficile is a ubiquitous spore-forming bacterium which causes toxin-mediated diarrhoea and colitis in people whose gut microflora has been depleted by antimicrobial use, so it is a predominantly healthcare-associated disease. However, there are many One Health implications to C. difficile, given high colonisation rates in food production animals, contamination of outdoor environments by use of contaminated animal manure, increasing incidence of community-associated C. difficile infection (CDI), and demonstration of clonal groups of C. difficile shared between human clinical cases and food animals. In Asia, the epidemiology of CDI is not well understood given poor testing practices in many countries. The growing middle-class populations of Asia are presenting increasing demands for meat, thus production farming, particularly of pigs, chicken and cattle, is rapidly expanding in Asian countries. Few reports on C. difficile colonisation among production animals in Asia exist, but those that do show high prevalence rates, and possible importation of European strains of C. difficile like ribotype 078. This review summarises our current understanding of the One Health aspects of the epidemiology of CDI in Asia.

Increasing prevalence of the epidemic ribotype 106 in healthcare facility–associated and community-associated Clostridioides difficile infection

Clostridioides difficile is the leading cause of nosocomial diarrhea and antibiotics associated diarrhea, but it is also an increasingly common cause of community diarrhea. In recent years we have observed a progressive increase in the incidence of C. difficile infection (CDI) both at the hospital and community setting that could be explained by the dynamic epidemiology of C. difficile. The present study analyzes changes in the epidemiology of CDI for two years comparing healthcare facility–associated (HCFA) and community-associated (CA) CDI epidemiology, observed in a single laboratory setting. All new episodes of CDI diagnosed during the years 2015–2016 were included in the study and classified as HFCA-, CA- or indeterminate CDI. Isolates were characterized by ribotyping and antimicrobial susceptibility was also determined. A total of 272 primary episodes of different patients were included in the study and classified 55.5% as CA-, 32% as HO-HCFA, 6.25% as CO-HCFA and 6.25% as indeterminate CDI. Overall, ribotype 106 was the most prevalent and also, many patients who suffered recurrent episodes were associated with this ribotype (29%). In fact, ribotype 106 showed a significantly higher recurrence rate than other ribotypes (26% vs 11%, p = 0.03). Moreover, 46% of the moxifloxacin resistant isolates were ribotype 106. No significant differences of antimicrobial resistance were observed between HCFA- and CA-CDI isolates, although fluoroquinolone resistance rates were slightly higher in HCFA-CDI isolates (25% vs 18.5%), and fluoroquinolone resistant ribotypes 106 and 126 were more frequently associated to CA-CDI and ribotype 078 to HCFA-CDI. The increasing incidence of CDI in our health care area is partially explained by the growing prevalence of the epidemic ribotype 106, both in HFCA- and CA-CDI, probably favored by the higher resistance and recurrence rate associated to ribotype 106 isolates.

475. Burden of Clostridium difficile Infection in South Carolina: A Population-Based Study

Background Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in the United States. The aims of this cross-sectional population-based study are to determine overall Incidence rate of CDI in the State of South Carolina and estimate the healthcare and financial burden of community-associated C. difficile infection (CA-CDI).MethodsSouth Carolina CDI initiative identified CDI cases from National Healthcare Safety Network (NHSN), and the South Carolina Infectious Disease and Outbreak Network (SCION) from January 1, 2015 to June 30, 2016 through complete enumeration of the state’s population, excluding infants <1 year old. A positive stool C.difficile test was regarded as a “CDI case” for purposes of this study. Only first and recurrent episodes after 8 weeks of initial one were included in this analysis.ResultsDuring the 18-month study period, 10,254 unique CDI events were identified in South Carolina residents ≥1 year old. Over one-half of CDI cases were CA-CDI (5192; 51%), 2,678 (26%) were community-onset healthcare facility associated (CO-HCFA), and 2,384 (23%) were hospital-onset (HO) cases. Overall incidence rate of CDI in South Carolina per 100,000 person-years was 141 (71, 37, and 33 for CA-CDI, CO-HCFA CDI, and HO-CDI, respectively). Among 5,192 episodes of CA-CDI, 2127 (41%) required hospitalization with a median length of stay of 5 days and median cost of $31,270. Additionally, 574 (11%) of CA-CDI cases were treated in emergency rooms without admission to the hospital. The annual burden of CA-CDI on the South Carolina’s healthcare system was estimated at 387 ambulatory emergency room visits and 9,282 hospital days. The estimated annual hospital charges for patients with CA-CDI in South Carolina were $68,491,046.ConclusionThe incidence rate of CA-CDI in South Carolina has surpassed both CO-HCFA CDI and HO-CDI combined. The heavy burden of CA-CDI justifies dedication of public health resources to combat CDI in ambulatory settings. Antimicrobial stewardship initiatives targeting unnecessary and inappropriate antimicrobial use in the community may reduce the burden of CDI in South Carolina.Disclosures All authors: No reported disclosures.

Socioeconomic Status Factors Associated with Increased Incidence of Community-Associated Clostridium difficile Infection

BackgroundTraditionally a hospital-acquired pathogen, Clostridium difficile is increasingly recognized as an important cause of diarrhea in community settings. Health disparities in C. difficileinfection (CDI) have been reported, but little is known about the social determinants of health that influence community-associated (CA) CDI incidence. We sought to identify socioeconomic status (SES) factors associated with increased CA-CDI incidence.MethodsPopulation-based CDI surveillance is conducted in 35 U.S. counties through the Centers for Disease Control and Prevention’s Emerging Infections Program. A CA-CDI case is defined as a positive C. difficile stool specimen collected as an outpatient or within three days of hospitalization in a person aged ≥ 1 year who did not have a positive test in the prior 8 weeks or an overnight stay in a healthcare facility in the prior 12 weeks. ArcGIS software was used to geocode 2014–2015 CA-CDI case addresses to a 2010 census tract (CT). Incidence rate was calculated using 2010 Census population denominators. CT-level SES factors were obtained from the 2011–2015 American Community Survey 5-year estimates and divided into deciles. To account for CT-level clustering effects, separate generalized linear mixed models with negative binomial distribution were used to evaluate the association between each SES factor and CA-CDI incidence, adjusted by age, sex and race.ResultsOf 9686 CA-CDI cases, 9417 (97%) had addresses geocoded to a CT; of these, 62% were female, 82% were white, and 35% were aged ≥65 years. Annual CA-CDI incidence was 42.9 per 100,000 persons. After adjusting for age, sex and race, CT-level SES factors significantly associated with increased CA-CDI incidence included living under the poverty level (rate ratio [RR] 1.12; 95% confidence interval [CI] 1.09–1.53), crowding in homes (RR 1.11; 95% CI 1.01–1.21), low education (RR 1.11; 95% CI 1.07–1.15), low income (RR 1.15; 95% CI 1.12–1.17), having public health insurance (RR 1.21; 95% CI 1.18–1.24), receiving public assistance income (RR 1.69; 95% CI 1.55–1.84), and unemployment (RR 1.14; 95% CI 1.07–1.22).ConclusionAreas with lower SES have modestly increased CA-CDI incidence. Understanding the mechanisms by which SES factors impact CA-CDI incidence could help guide prevention efforts in these higher-risk areas.Disclosures All authors: No reported disclosures.

A Diagnostic Algorithm for the Detection of Clostridium difficile-Associated Diarrhea.

Clostridium difficile is a common cause of hospital-acquired diarrhea, which is usually associated with previous antibiotic use. The clinical manifestations of C. difficile infection (CDI) may range from mild diarrhea to fulminant colitis. Clostridium difficile should be considered in diarrhea cases with a history of antibiotic use within the last 8 weeks (community-associated CDI) or with a hospital stay of at least 3 days, regardless of the duration of antibiotic use (hospital-acquired CDI). This study investigated the frequency of CDI in diarrheic patients and evaluated the efficacy of the triple diagnostic algorithm that is proposed here for C. difficile detection. Cross-sectional study. In this study, we compared three methods currently employed for C. difficile detection using 95 patient stool samples: an enzyme immunoassay (EIA) for toxin A/B (C. diff Toxin A+B; Diagnostic Automation Inc.; Calabasas, CA, USA), an EIA for glutamate dehydrogenase (GDH) (C. DIFF CHEK-60TM, TechLab Inc.; Blacksburg, VA, USA), and a polymerase chain reaction (PCR)-based assay (GeneXpert(®) C. difficile; Cepheid, Sunnyvale, CA, USA) that detects C. difficile toxin genes and conventional methods as well. In this study, 50.5% of the patients were male, 50 patients were outpatients, 32 were from inpatient clinics and 13 patients were from the intensive care unit. Of the 95 stool samples tested for GDH, 28 were positive. Six samples were positive by PCR, while nine samples were positive for toxin A/B. The hypervirulent strain NAP-1 and binary toxin was not detected. The rate of occurrence of toxigenic C. difficile was 5.1% in the samples. Cefaclor, ampicillin-sulbactam, ertapenem, and piperacillin-tazobactam were the most commonly used antibiotics by patients preceding the onset of diarrhea. Among the patients who were hospitalized in an intensive care unit for more than 7 days, 83.3% were positive for CDI by PCR screening. If the PCR test is accepted as the reference: C. difficile Toxin A/B ELISA sensitivity and specificity were 67% and 94%, respectively, and GDH sensitivity and specificity were 100% and 75%, respectively. Tests targeting C. difficile toxins are frequently applied for the purpose of diagnosing CDI in a clinical setting. However, changes in the temperature and reductant composition of the feces may affect toxin stability, potentially yielding false-negative test results. Therefore, employment of a GDH EIA, which has high sensitivity, as a screening test for the detection of toxigenic strains, may prevent false-negative results, and its adoption as part of a multistep diagnostic algorithm may increase accuracy in the diagnosis of CDIs.

Complicated Clostridium difficile colitis in children with cystic fibrosis: Association with gastric acid suppression?

Patients with cystic fibrosis (CF) have several risk factors for Clostridium difficile colonization such as frequent hospitalization and exposure to a broad array of antibiotics utilized for the control, eradication, and prophylaxis of respiratory pathogens. However, despite this high rate of colonization, the occurrence of C. difficile infection (CDI) in CF is rare. We report three children with CF who presented with severe community-associated CDI. All three children had complicated courses and one died. These children were in good health without significant morbidities, and were not frequently hospitalized nor did they receive frequent antibiotic courses. The occurrence of 3 severe cases within a 15-month period prompted us to report these cases and review the literature in regard to CDI. We reviewed the CF GI tract as possible risk factors for a high rate of C. difficile colonization in individuals with CF. Since a high percentage of individuals with CF are on gastric acid blocking agents, we also focused on gastric acid suppression as a potential risk factor for CDI.