Clostridium Difficile Infection Surveillance Research Articles

Antibiotic-Associated Clostridium difficile Diarrhoea in Tertiary Care Hospital – A Study from Western India

Antibiotic-associated Clostridium difficile (CD) diarrhoea is one of the common causes of healthcare-acquired infection. Cephalosporins, piperacillin-tazobactam and aminoglycosides are the common antibiotics which have the maximum chances of producing Clostridium difficile infection (CDI). Most Asian countries have easy accessibility to many of these antibiotics without prescription. Broad spectrum antibiotics have been indiscriminately used as empirical therapy over the last two decades which has resulted in an increased risk of C. difficile infection. In India, the prevalence of CDI is highly underestimated. This study aims to understand the prevalence, risk factors and comorbidities associated with CD diarrhoea in a tertiary care hospital from western India. 196 patients were included in the study who were diagnosed with antibiotic-associated diarrhoea (AAD) clinically. Stool samples collected were processed for anaerobic culture of C. difficile and immunochromatography test was done to detect C. difficile toxins A and B. The comorbidities associated as well as the use of antibiotics like cephalosporin or proton pump inhibitors were also noted for the patients with CDI. 32 samples yielded CD (16%), out of which toxin production was detected only in 16 isolates. The prevalence rate of CDI in our hospital was 5%. Most of the patients had history of chronic illnesses like diabetes mellitus, chronic kidney disease, ischemic heart disease, systemic hypertension, autoimmune diseases, or malignancy. Avoiding empirical therapy with antibiotics prone to cause AAD, Antimicrobial stewardship programme with proper infection control practices and epidemiological surveillance of CDI will help to reduce the burden of CDI in our country.

Linkage study of surveillance and hospital admission data to investigate Clostridium difficile infection in hospital patients in Perth, Western Australia

ObjectivesIncreasing incidence rates of Clostridium difficile infection (CDI) and outbreaks of emerging strains have highlighted the need for continuous monitoring and surveillance of CDI in Australia. Active surveillance captures all hospital-identified CDI cases in Western Australia (WA), where all C. difficile isolates recovered are routinely PCR ribotyped. The aim of this study was to determine incidence rates and descriptive and molecular epidemiology of CDI among patients in Perth, WA using linkage of surveillance and hospital administrative records. MethodsAll CDI cases (confirmed by tcdB PCR) from July 2012 to June 2014 captured in the Hospital Infection Surveillance WA dataset for three hospitals were linked with hospital admission records from the Patient Administration System and ribotyping data to calculate incidence rates of CDI and the distribution of various ribotypes (RTs). ResultsThere were 381 individual cases of CDI identified among 354 hospital patients (including outpatients and ED) who experienced ≥1 CDI episode during the study period. CDI was hospital-associated in 62.7% of cases and community-associated (CA)-CDI in 31.2%. The overall incidence rate was 4.40/10,000 patient days (PD, 95% CI 3.98–4.86), females across all age groups experienced higher incidence (risk ratio 1.29, p < 0.05). The risk ratio for CA-CDI was highest (7.76, p < 0.01) for females vs males aged 15–29 years. Overall, 10.8% of cases were admitted to ICU, 15.2% had a recurrent infection and the mortality rate was 7.2%. C. difficile RT 014/020 predominated (34.9%) among 339 isolates of 71 different RTs. ConclusionsThe incidence of CDI in WA is high and RT 014/020 continues to be the dominant molecular type in an otherwise diverse array of strains. High strain diversity suggests CDI cases arise from exposure to many different reservoirs.

Management of nosocomial infection of Clostridium difficile : surveillance, prevention and control

In recent years, the incidence of Clostridium difficile infection (CDI) has been in increase worldwide. Effective surveillance is the key to control the incidence and spread of CDI. The content of CDI surveillance mainly includes case definition, standardized diagnosis, CDI case source definition, CDI incidence and suggestions for CDI prevention and control. This review summarizes the pivotal components of effective CDI surveillance, and provides some practical prevention and control suggestions for the standardized surveillance and prevention and control of CDI in hospitals in China.

Laboratory-Based Surveillance of Clostridium difficile Infection in Australian Health Care and Community Settings, 2013 to 2018.

In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.

The tcdA-negative and tcdB-positive Clostridium difficile ST81 clone exhibits a high level of resistance to fluoroquinolones: a multi-centre study in Beijing, China

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhoea worldwide. In order to gain a better understanding about the molecular epidemiology of C. difficile in Beijing, China, molecular typing, antimicrobial susceptibility testing and drug resistance gene sequencing were performed on 174 strains of C. difficile collected from four large tertiary hospitals in Beijing. In total, 31 sequence types (STs) were identified among the 174 strains. ST81 was found to be the most prevalent (26.4%, 46/174), followed by ST2 (16.7%, 29/174) and ST54 (9.8%, 17/174). All isolates were susceptible to metronidazole and vancomycin. The test strains displayed resistance rates of 97.1%, 44.3% and 44.3% for ciprofloxacin, levofloxacin and moxifloxacin, respectively. ST81 isolates displayed a drug resistance rate of 97.8% for levofloxacin and moxifloxacin, which was significantly higher than ST2 (0%), ST54 (17.6%) and ST42 (0%) isolates (P<0.05). An amino acid mutation (T82I) was identified in GyrA, and the total mutation rate of the C. difficile strains was 40.8% (71/174). The mutation rate of ST81 isolates was 95.7% (44/46). Three amino acid mutations (D426N, S366A and D426V) were identified in GyrB, and the total mutation rate of GyrB was 39.1%. A double-site mutation in GyrB (S366A+D426V) was identified in all ST81 (n=46) isolates. In conclusion, the C. difficile ST81 clone showed a high level of resistance to fluoroquinolones in Beijing, highlighting the need for nationwide surveillance of CDI.

2184. Surveillance System of Healthcare-Associated Infection in High and Upper-Middle Income Countries: A Scoping Review

BackgroundHealthcare-associated infection (HCAI) is a major public health concern. HCAI surveillance is one of the five areas of focus of the Japanese action plan for antimicrobial resistance. In order to establish a Japanese HCAI surveillance system, we performed a scoping review about HCAI surveillance systems in the world.MethodsThe search strategy consists of three Methods. academic literature review, Google search, and questionnaire to the Embassies of Japan in target countries. The target countries were 59 high and 79 upper-middle income countries defined by country income classification for the World Bank. The following information was reviewed: name of the system, official website, languages used in official website, foundation year, operating body, frequency, mode of participation, target population, types of target infections, types of target pathogens, definition of HCAI, and surveillance parameters. Online accessibility of the official websites was assessed through Google search.ResultsForty-one (29.7%) countries (34 [57.6%] high and 7 [8.8%] upper-middle income countries) are found to have national HCAI surveillance systems; 23 from Europe, 9 from Asia, 7 from Americas, and 2 from Oceania. Thirty-four (82.9%) countries have at least one official website, of which seven (20.6%) was identified in the top 30 hits through Google search in English. Surgical site infection (SSI) is the most surveyed infection (28 [68.3%] countries); catheter-related blood stream infection (CRBSI) in 25 (61.0%) countries, and catheter-associated urinary tract infection, ventilator-associated pneumonia, and Clostridium difficile infection (CDI) in 22 (53.7%) countries. MRSA is the most commonly surveyed pathogen (30 [73.2%] countries) followed by VRE in 22 (53.7%) countries. Most countries’ systems follow or modify CDC/NHSN definition. European countries tend to have CDI surveillance and to have more selected surveillance targets than others.ConclusionHCAI surveillance system is more in place in high income countries than in upper-middle income countries. Although surveillance targets vary between countries, SSI, CRBSI, and MRSA are surveyed in two thirds of the countries. Online accessibility of the official website is an area to be improved.Disclosures All authors: No reported disclosures.

486. Endemic Corridors: A Useful Tool for the Approach of Clostridium difficile: A 5-Year Epidemiologic Surveillance Program in a Teaching Hospital of a Middle-Income Country

Background Clostridium difficile infection (CDI) is a healthcare-associated infection causing morbidity, mortality, and increase in the economic burden of health. Accurate and accesible methods to predict the epidemiologic trends of CDI are scarce. The systematic collection of data contributes to the development of an endemic corridor which estimates the expected cases in a period of time, facilitating the identification of outbreaks. In Guatemala, no obligatory report is required and no national surveillance programs for CDI exist. Therefore, understanding local epidemiologic trends of CDI is important in order to make future predictions.MethodsAll consecutive primary CDI eopisodes (January 2012–December 2017) obtained from active surveillance in the surgery department were included. CDI was defined as diarrhoea and a positive stool PCR test for C. difficile toxin A and/or B. An endemic corridor was developed to describe trends. The geometric mean and a 95% confidence interval were used to calculate upper and lower limits of weekly incidence. Demographics, clinical characteristics, antimicrobial treatment, and outcome of CDI were analyzed.ResultsA total of 208 CDI episodes were included in the study (9 healthcare workers). The incidence of CDI cases increased from 12.85/1,000 discharges (2016) to 18.53/1,000 discharges (2017). CDI was higher among male (54.8%) adults (18–64 years; 72.23%). NAP1 strain was identified in 38% of all cases, with a constant increase from 2012 to 2017. All cases were treated according to guidelines. No recurrences or deaths occurred during the studied time period. The highest incidence of CDI was observed between epidemiologic weeks 7, 8, and 42. Eleven outbreaks were identified in the studied time period, the first and major outbreak occurred in 2013; 2015 had the most outbreaks with 4. Both 2016 and 2017 had threeoutbreaks each.ConclusionOwing to the active and systematic surveillance of CDI, an endemic corridor was created. This will be a useful tool to develop interventions according to the epidemiologic trends of local CDI. Prompt identification of cases and strict adherence to patient isolation and treatment guidelines resulted in null mortality rates despite the alarming increase in NAP1 strains.Disclosures All authors: No reported disclosures.

490. Comparison of Clostridium difficile Infection Outcomes by Diagnostic Testing Method

BackgroundUS laboratories are increasingly using nucleic acid amplification tests (NAAT) to diagnose Clostridium difficile infection (CDI) due to their increased sensitivity over toxin enzyme immunoassays (EIA), but NAATs may be more likely than toxin EIAs to detect colonization rather than true disease. Limited data indicate patients positive by toxin EIA (toxin+) have worse outcomes than those positive by NAAT (NAAT+) only, suggesting toxin EIA detects true infection more often than NAAT. We used multisite CDI surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program to compare clinical course and outcomes between toxin+ and NAAT+ only patients.MethodsA case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases detected during 2014–2015 by a testing algorithm using toxin EIA and NAAT were classified as toxin+ or NAAT+ only. Medical charts were reviewed. Death data were obtained from state death registries. Multivariable logistic regression models were used to compare CDI recurrence and 90-day mortality between the two groups, adjusting for age, sex, race, Charlson comorbidity index, and receipt of oral vancomycin. For the outcome of recurrence, we also adjusted for history of CDI in the prior 6 months.ResultsOf 4,878 cases, 2160 (44%) were toxin+ and 2,718 (56%) were NAAT+ only. Toxin+ cases were more likely than NAAT+ only cases to be ≥65 years old (48% vs. 38%; P < 0.0001), have white blood cells ≥15,000/µL (483/1,539 [31%] vs. 423/1,978 [21%]; P < 0.0001), and have received oral vancomycin ≤3 days of diagnosis (32% vs. 29%; P = 0.03). Comparing toxin+ to NAAT+ only cases, 21% vs. 11% had a recurrence (P < 0.0001), of which 71% vs. 33% had a toxin+ recurrence (P < 0.0001), and 10% vs. 9% died ≤90 days of diagnosis (P = 0.12). In multivariable analysis, a toxin+ result was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61–2.22) but not with 90-day mortality (aOR: 0.99; 95% CI: 0.81–1.22).ConclusionToxin+ CDI is more severe by some markers and more likely to recur as toxin+. However, there was no difference in adjusted mortality, which may reflect an effect on mortality in NAAT+ only cases from mild CDI, receipt of unnecessary CDI treatment, or other factors.Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

473. Molecular Typing of Clostridium difficile: Concordance Between PCR-Ribotyping and Multilocus Sequence Typing (MLST)

Background Clostridium difficile infection (CDI) incidence has increased dramatically in the past decade, making CDI one of the most common causes of infectious diarrhea and an urgent public health threat. Understanding the biological features and spread of C. difficile strains can help target control efforts. PCR-ribotyping, the current method of choice for C. difficile typing, remains subjective and challenging for interlaboratory comparisons. Multilocus sequence typing (MLST), based on the alleles of seven housekeeping genes, represents a more robust tool that would enhance interlaboratory reproducibility. However, a comprehensive translation system to ribotyping is a prerequisite. Here, we describe the concordance between MLST and PCR-ribotyping.MethodsThe Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program (EIP) conducts CDI surveillance in 10 US sites. C. difficile isolates cultured from a subset of cases underwent capillary-based PCR-ribotyping at CDC. A representative sample, selected from the top 30 ribotypes (RTs), underwent whole genome sequencing (WGS) at Minnesota Department of Health. An additional subset of isolates, representing the top 10 RTs, underwent WGS at CDC. At both laboratories, the Illumina MiSeq platform was used to obtain 250 bp paired-end sequencing reads. MLST analyses were done using the pubMLST C. difficile scheme.ResultsA total of 479 C. difficile isolates, including at least 10 isolates for each RT, were analyzed by WGS. Among the 30 RTs represented, 35 different MLST sequence types (STs) were identified. Twenty-two of the RTs (including 027) were each associated with a single unique ST, while 8 RTs (020, 014, 015, 076, 046, 153–251, A27, and 075) presented more genetic diversity with single-locus or double-locus variants, resulting in multiple STs within one ribotype. There were two instances of two different RTs sharing the same ST.ConclusionMultilocus sequence typing and PCR-Ribotyping showed comparable discriminatory abilities. However, the ST is not always predictive of the RT and vice versa. This represents the first step toward a transition to using WGS for standard C. difficile typing.Disclosures All authors: No reported disclosures.

492. Long-Term Outcomes of Clostridium difficile Infection Among Medicare Beneficiaries

Background Clostridium difficile infection (CDI) is a common healthcare-associated infection, particularly among older adults. We used laboratory-confirmed CDI surveillance data from 8 states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program linked to claims data for Centers for Medicare and Medicaid Services (CMS) beneficiaries to measure variation in 1-year outcomes associated with CDI.MethodsA CDI case was defined as a positive C. difficile stool test in 2014 in a person without a positive test in the prior 8 weeks. Cases aged ≥65 years were linked to their CMS beneficiary ID using unique combinations of date of birth, sex, and zip code. Each case was matched to five control beneficiaries who did not link to any case and were residents of the same catchment area. Inclusion criteria were continuous fee-for-service Medicare for the entire study period (1 year before and after event date), and no hospitalization or skilled nursing facility stay with an ICD-9-CM code for CDI in the year prior to their match date. Multivariable logistic regression models were used to compare mortality and hospitalization for 1 year following the event date between beneficiaries with and without CDI, adjusting for age, sex, race, catchment area, chronic conditions, number of hospitalizations in the prior year, and hospitalization status at the time of and 7 days preceding the event date.ResultsOf 5,097 cases aged ≥65, 3,082 (60%) were linked to a CMS ID, and 1,832 (59%) met inclusion criteria. In crude analysis, 34% of beneficiaries with CDI died within 1 year, compared with 5% of beneficiaries without CDI. Beneficiaries with CDI were also more likely to be hospitalized in the subsequent year (54% vs. 17%). Beneficiaries with CDI had a higher adjusted odds of death (adjusted OR 3.01, 95% CI: 2.46, 3.69) and hospitalization within 1 year (adjusted OR 1.93, 95% CI: 1.65, 2.25) than those without CDI.ConclusionOlder adults with CDI were three times more likely to die in the year following infection and nearly two times more likely to be hospitalized compared with those without CDI, revealing independent long-term risk of poor outcomes. This excess morbidity and mortality supports the need to develop novel CDI prevention strategies for this population.Disclosures All authors: No reported disclosures.

Trends in mortality following Clostridium difficile infection in Scotland, 2010–2016: a retrospective cohort and case–control study

National surveillance of Clostridium difficile infection (CDI) in Scotland enables the monitoring of trends in incidence rates but not mortality. To assess factors associated with mortality for all CDI cases aged ≥15 years in Scotland between 2010 and 2016. All CDI cases aged ≥15 years in Scotland between 2010 and 2016 were linked to hospital admission and mortality datasets. Logistic regression was used to assess factors associated with mortality (30-day all-cause). A case-control study of a hospitalized subset of cases and matched hospitalized controls assessed the impact of CDI on mortality and length of stay. Thirty-day all-cause mortality decreased over the seven-year period (from 20.5% to 15.6%; P<0.001), mainly among healthcare-associated CDI (HA-CDI). Increased age, higher Charlson score, HA-CDI, as well as liver, heart and malignancy comorbidities were associated with higher mortality. No association was observed between polymerase chain reaction ribotype and higher mortality, though 015 and 078 were associated with lower mortality. Adjusted odds ratio (OR) for 30-day mortality in hospitalized CDI cases compared to controls was 2.67 (95% confidence interval (CI): 2.42-2.94; P<0.001). Whereas mortality declined over time in cases and controls, the trend in ORs remained relatively stable. Having CDI increased additional mean length of stay beyond infection by 22.3% (95% CI: 18.0-26.8%; P<0.001). CDI is associated with an almost three-fold increase in 30-day mortality and places an increased burden on hospital resources by increasing mean LOS beyond the infection date by 22.3%. The decreasing CDI mortality trends may be due to overall improvements in mortality among the general and hospital population of Scotland. Therefore, despite large declines in incidence rates, CDI remains a serious healthcare problem.

Incidence, Epidemiology and Control of Clostridium difficile Infection in a Tertiary Care Private Hospital in India

Purpose:Clostridium difficile infection (CDI) is a serious healthcare-associated infection (HAI) now being increasingly reported from hospitals across India. However, there is a paucity of data on the incidence of and impact of control measures on CDI in India. Materials and Methods: This is a retrospective study conducted at a tertiary care hospital in Mumbai from January 2016 to December 2017. All patients with healthcare-onset diarrhoea were tested for C. difficile by glutamate dehydrogenase (GDH)/toxin assay or nucleic acid amplification test (NAAT). CDI was defined as either GDH and toxin positive or NAAT positive. The incidence of CDI was calculated per 1000 patient days. Demographic features of patients with CDI including age, sex, duration of hospitalisation before onset of CDI, antibiotic use and treatment administered were summarised. Results: A total of 67 patients had CDI in the study period with a mean incidence of 0.2/1000 patient days. A halving of the CDI incidence was seen after intensification of the CDI prevention bundle. The mean age of affected patients was 64 years and CDI occurred at a median duration of 2 weeks after hospitalisation. Eighty-seven per cent of the patients were on antibiotics at the time of diagnosis of CDI. The crude mortality rate was 22%. Conclusions: CDI is an emerging HAI in India. All hospitals need to set up policies for surveillance, testing, treatment and prevention of CDI based on recent international guidelines and local infrastructure/logistics.

Molecular Characterization of Clostridium difficile Isolates in China From 2010 to 2015.

Clostridium difficile infection (CDI) has become a worldwide public health problem causing high mortality and a large disease burden. Molecular typing and analysis is important for surveillance and infection control of CDI. However, molecular characterization of C. difficile across China is extremely rare. Here, we report on the toxin profiles, molecular subtyping with multilocus sequence typing (MLST) and PCR ribotyping, and epidemiological characteristics of 199 C. difficile isolates collected between 2010 through 2015 from 13 participating centers across China. We identified 35 STs and 27 ribotypes (RTs) among the 199 C. difficile isolates: ST35 (15.58%), ST3 (15.08%), ST37 (12.06%), and RT017 (14.07%), RT001 (12.06%), RT012 (11.56%) are the most prevalent. One isolate with ST1 and 8 isolates with ST 11 were identified. We identified a new ST in this study, denoted ST332. The toxin profile tcdA+tcdB+tcdC+tcdR+tcdE+CDT- (65.83%) was the predominant profile. Furthermore, 11 isolates with positive binary toxin genes were discovered. According to the PCR ribotyping, one isolate with RT 027, and 6 isolates with RT 078 were confirmed. The epidemiological characteristics of C. difficile in China shows geographical differences, and both the toxin profile and molecular types exhibit great diversity across the different areas.

Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients.

Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. We performed a prospective, multicenter study of CDI within 365days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12weeks post-transplant and while hospitalized and contacted monthly up to 18months post-transplantation. Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27days vs 90days; P=.037). CDI was associated with significantly higher mortality from 31 to 180days post-index date among the allogeneic HCT recipients (Hazard ratio [HR]=1.80; P=.007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180days post-index date (HR=4.7, P=.09). The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

The Need for European Surveillance of CDI.

Since the turn of the millennium, the epidemiology of Clostridium difficile infection (CDI) has continued to challenge. Over the last decade there has been a growing awareness that improvements to surveillance are needed. The increasing rate of CDI and emergence of ribotype 027 precipitated the implementation of mandatory national surveillance of CDI in the UK. Changes in clinical presentation, severity of disease, descriptions of new risk factors and the occurrence of outbreaks all emphasised the importance of early diagnosis and surveillance.However a lack of consensus on case definitions, clinical guidelines and optimal laboratory diagnostics across Europe has lead to the underestimation of CDI and impeded comparison between countries. These inconsistencies have prevented the true burden of disease from being appreciated.Acceptance that a multi-country surveillance programme and optimised diagnostic strategies are required not only to detect and control CDI in Europe, but for a better understanding of the epidemiology, has built the foundations for a more robust, unified surveillance. The concerted efforts of the European Centre for Disease Prevention and Control (ECDC) CDI networks, has lead to the development of an over-arching long-term CDI surveillance strategy for 2014-2020. Fulfilment of the ECDC priorities and targets will no doubt be challenging and will require significant investment however the hope is that both a national and Europe-wide picture of CDI will finally be realised.

Differences in Clinical Characteristics and Outcomes of Patients with Community-Onset Clostridium difficile Infection who Tested Positive by EIA Compared with NAAT through a Two-Step Algorithm

BackgroundThe low sensitivity of toxin enzyme immunoassay (EIA) for the diagnosis of Clostridium difficile infection (CDI) motivated many laboratories to add nucleic acid amplification tests (NAAT) to their testing protocol. However, NAAT do not distinguish between colonization and infection, and indiscriminant testing could lead to over treatment of CDI.MethodsActive, population-based CDI surveillance has been conducted through the Emerging Infections Program in Bernalillo County, NM since 2011, with test type collected at the individual level since 2014. Community-onset (CO) CDI cases with a first positive test diagnosed by a two-step algorithm (concurrent EIA/GDH, with discordant results reflexed to NAAT) in 2014–2015 were included. We analyzed clinical characteristics and outcomes of patients EIA positive compared with NAAT positive. Demographics, risk factors, treatment, and outcomes were assessed through medical record review.ResultsAmong 1,063 cases, 559 (52.6%) were EIA positive only and 504 (47.4%) were NAAT positive only. Of those with stool collected as a hospital inpatient, 57% were NAAT positive (P < 0.001); this increased from 43.4% if tested the day of admission to 61.4% when tested on day three. Conversely, 38.6% of patients with stool collected in an emergency department were NAAT positive (P = 0.004). Fewer cases with complicated outcomes were NAAT positive (40.7%, P = 0.023). Among those with no documentation of recent antibiotic use, 64.3% were NAAT positive (P < 0.001), and 67.8% of cases with no CDI treatment were NAAT positive (P = 0.005). Only 28.3% percent of cases with recurrent CDI were initially NAAT positive (P < 0.001).ConclusionEIA negative and NAAT positive CO-CDI cases tended to have a milder clinical presentation than those that were EIA positive. This suggests that some patients positive only by NAAT may have mild CDI or be colonized, rather than infected, with C. difficile. These individuals were less likely to have complicated outcomes, have recent documented antibiotic use, be treated for CDI, or have a recurrent CDI episode than those positive by EIA. Longer hospital stay correlated with increased proportion of testing NAAT positive. Providers may benefit from considering testing protocol and clinical correlation when assessing patients with positive C. difficile test results.Disclosures All authors: No reported disclosures.

Hospital-acquired Clostridium difficile infection in Mainland China: A seven-year (2009\u20132016) retrospective study in a large university hospital

Clostridium difficile infection (CDI) is associated with risk for severe disease and high mortality. Little is known about the extent of hospital-acquired CDI in Mainland China. In this study, we aimed to investigate the annual CDI incidence, bacterial genotypes, risk factors for severe CDI and survival over a 7-year period. A total of 307 hospital-acquired CDI patients were enrolled, and 70.7% of these cases were male. CDI incidence was 3.4 per 10,000 admissions. Thirty-three different sequence types (STs) were identified, among which ST-54 (18.2%), ST-35 (16.6%) and ST-37 (12.1%) were the most prevalent. During the follow-up period, 66 (21.5%) patients developed severe CDI and 32 (10.4%) patients died in 30 days. Multivariate analysis revealed that bloodstream infection, pulmonary infection and C-reactive protein were significantly associated with severe CDI. After adjustment for potential confounders, old age, bloodstream infection, fever, mechanical ventilation, connective tissue disease, macrolide use and hypoalbuminaemia were independently associated with 30-day mortality in patients with CDI. The CDI prevalence has been low and stable in our center, and STs of Clostridium difficile were different from dominant STs in Western countries. Our data emphasize the need of continued education and surveillance of CDI to reduce the CDI burden in China.

Laboratory-based surveillance of Clostridium difficile strains circulating in the Australian healthcare setting in 2012

Clostridium difficile infection (CDI) has risen in prominence in Australia recently. We conducted laboratory-based surveillance of CDI to examine C.difficile circulating in Australia in October/November 2012. We collected 542 isolates from all States and Territories of Australia except the Northern Territory. The most common ribotypes (RTs) were RTs 014/020 (25.5%), 002 (10.5%), 056 (5.9%) and 070 (4.2%). The survey results were compared with results from a similar Australian survey conducted in 2010. Proportions of RTs 014/020 and 002 remained similar, while RTs 056 (5.9%), 015 (4.1%), 017 (3.3%) and 244 (2.4%) increased in prevalence. Basic clinical and demographic data were available for 338 cases. The majority were healthcare facility-associated (HCFA-CDI, 51.5%) while 17.5% were community-associated (CA-CDI). While no RTs were associated with CA-CDI, RTs 056 and 126 were recently found in Australian production animals, indicating a possible community health threat in Australia.

Surveillance of Clostridium difficile Infections: Results from a Six-Year Retrospective Study in Nine Hospitals of a North Italian Local Health Authority.

Clostridium difficile is an emerging cause of healthcare associated infections. In nine hospitals of an Italian Local Health Authority the episodes of C. difficile infection (CDI) were identified using the data registered by the centralized Laboratory Information System, from 2010 to 2015. CDI incidence (positive patients for A and/or B toxins per patients-days) was analysed per year, hospital, and ward. A number of cases approximately equivalent to the mean of identified cases per year were studied retrospectively to highlight the risk factors associated to CDI and their severity. Nine hundred and forty-two patients affected by CDI were identified. The overall incidence was 3.7/10,000 patients-days, with a stable trend across the six years and the highest rates observed in smaller and outlying hospitals (up to 17.8/10,000), where the admitted patients were older and the wards with the highest incidences (long-term-care: 7.6/10,000, general medicine: 5.7/10,000) were more represented. The mean age of patients in each hospital was correlated with CDI rates. Of the 101 cases selected for the retrospective study, 86.1% were healthcare associated, 10.9% community acquired; 9.1% met the criteria for recurrent case and 23.8% for severe case of CDI. The overall mortality rate was 28.7%. Comorbidity conditions occurred in 91.1%, previous exposure to antibiotics in 76.2%, and proton pump inhibitors in 77.2%. Recurrent and severe cases were significantly associated with renal insufficiency and creatinine levels ≥2 mg/dL. The survey based on the centralized laboratory data was useful to study CDI epidemiology in the different centres in order to identify possible weaknesses and plan control strategies, in particular the reinforcement of staff training, mainly targeted at compliance with contact precautions and hand hygiene.

Survey of Clostridium difficile infection surveillance systems in Europe, 2011.

To develop a European surveillance protocol for Clostridium difficile infection (CDI), existing national CDI surveillance systems were assessed in 2011. A web-based electronic form was provided for all national coordinators of the European CDI Surveillance Network (ECDIS-Net). Of 35 national coordinators approached, 33 from 31 European countries replied. Surveillance of CDI was in place in 14 of the 31 countries, comprising 18 different nationwide systems. Three of 14 countries with CDI surveillance used public health notification of cases as the route of reporting, and in another three, reporting was limited to public health notification of cases of severe CDI. The CDI definitions published by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC) were widely used, but there were differing definitions to distinguish between community- and healthcare-associated cases. All CDI surveillance systems except one reported annual national CDI rates (calculated as number of cases per patient-days). Only four surveillance systems regularly integrated microbiological data (typing and susceptibility testing results). Surveillance methods varied considerably between countries, which emphasises the need for a harmonised European protocol to allow consistent monitoring of the CDI epidemiology at European level. The results of this survey were used to develop a harmonised EU-wide hospital-based CDI surveillance protocol.