Quantifying Transmission of Clostridium difficile within and outside Healthcare Settings.
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ABSTRACT:
SUBMITTER: Durham DP
PROVIDER: S-EPMC4806959 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe conducted a systematic review of mathematical models of transmission dynamic of Clostridium difficile infection (CDI) in healthcare settings, to provide an overview of existing models and their assessment of different CDI control strategies.MethodsWe searched MEDLINE, EMBASE and Web of Science up to February 3, 2016 for transmission-dynamic models of Clostridium difficile in healthcare settings. The models were compared based on their natural history representation of Clostridium difficile, which could include health states (S-E-A-I-R-D: Susceptible-Exposed-Asymptomatic-Infectious-Resistant-Deceased) and the possibility to include healthcare workers and visitors (vectors of transmission). Effectiveness of interventions was compared using the relative reduction (compared to no intervention or current practice) in outcomes such as incidence of colonization, CDI, CDI recurrence, CDI mortality, and length of stay.ResultsNine studies describing six different models met the inclusion criteria. Over time, the models have generally increased in complexity in terms of natural history and transmission dynamics and number/complexity of interventions/bundles of interventions examined. The models were categorized into four groups with respect to their natural history representation: S-A-I-R, S-E-A-I, S-A-I, and S-E-A-I-R-D. Seven studies examined the impact of CDI control strategies. Interventions aimed at controlling the transmission, lowering CDI vulnerability and reducing the risk of recurrence/mortality were predicted to reduce CDI incidence by 3-49%, 5-43% and 5-29%, respectively. Bundles of interventions were predicted to reduce CDI incidence by 14-84%.ConclusionsAlthough CDI is a major public health problem, there are very few published transmission-dynamic models of Clostridium difficile. Published models vary substantially in the interventions examined, the outcome measures used and the representation of the natural history of Clostridium difficile, which make it difficult to synthesize results and provide a clear picture of optimal intervention strategies. Future modeling efforts should pay specific attention to calibration, structural uncertainties, and transparent reporting practices.
| S-EPMC5045168 | biostudies-literature
Project description:BackgroundClostridium difficile is the leading cause of infectious diarrhea in hospitalized patients. Its epidemiology has shifted in recent years from almost exclusively infecting elderly patients in whom the gut microbiota has been disturbed by antimicrobials, to now also infecting individuals of all age groups with no recent antimicrobial use.MethodsA stochastic mathematical model was constructed to simulate the modern epidemiology of C. difficile in a healthcare setting, and, to compare the efficacies of interventions.ResultsBoth the rate of colonization and the incidence of symptomatic disease in hospital inpatients were insensitive to antimicrobial stewardship and to the prescription of probiotics to expedite healthy gut microbiota recovery, suggesting these to be ineffective interventions to limit transmission. Comparatively, improving hygiene and sanitation and reducing average length of stay more effectively reduced infection rates. Although the majority of new colonization events are a result of within-hospital ward exposure, simulations demonstrate the importance of imported cases with new admissions.ConclusionsBy analyzing a wide range of screening sensitivities, we identify a previously ignored source of pathogen importation: although capturing all asymptomatic as well as symptomatic introductions, individuals who are exposed but not yet colonized will be missed by even a perfectly sensitive screen on admission. Empirical studies to measure the duration of this latent period of infection will be critical to assessing C. difficile control strategies. Moreover, identifying the extent to which the exposed category of individual contributes to pathogen importation should be explicitly considered for all infections relevant to healthcare settings.
| S-EPMC3751620 | biostudies-literature
Project description:The correlation of Clostridium difficile infection (CDI) with in-hospital morbidity is important in hospital settings where broad-spectrum antimicrobial agents are routinely used, such as in Greece. The C. DEFINE study aimed to assess point-prevalence of CDI in Greece during two study periods in 2013.There were two study periods consisting of a single day in March and another in October 2013. Stool samples from all patients hospitalized outside the ICU aged ≥18 years old with diarrhea on each day in 21 and 25 hospitals, respectively, were tested for CDI. Samples were tested for the presence of glutamate dehydrogenase antigen (GDH) and toxins A/B of C. difficile; samples positive for GDH and negative for toxins were further tested by culture and PCR for the presence of toxin genes. An analysis was performed to identify potential risk factors for CDI among patients with diarrhea.5,536 and 6,523 patients were screened during the first and second study periods, respectively. The respective point-prevalence of CDI in all patients was 5.6 and 3.9 per 10,000 patient bed-days whereas the proportion of CDI among patients with diarrhea was 17% and 14.3%. Logistic regression analysis revealed that solid tumor malignancy [odds ratio (OR) 2.69, 95% confidence interval (CI): 1.18-6.15, p = 0.019] and antimicrobial administration (OR 3.61, 95% CI: 1.03-12.76, p = 0.045) were independent risk factors for CDI development. Charlson's Comorbidity Index (CCI) >6 was also found as a risk factor of marginal statistical significance (OR 2.24, 95% CI: 0.98-5.10). Median time to CDI from hospital admission was shorter with the presence of solid tumor malignancy (3 vs 5 days; p = 0.002) and of CCI >6 (4 vs 6 days, p = 0.009).The point-prevalence of CDI in Greek hospitals was consistent among cases of diarrhea over a 6-month period. Major risk factors were antimicrobial use, solid tumor malignancy and a CCI score >6.
| S-EPMC5559069 | biostudies-other
Project description:IntroductionCombined genotyping/whole genome sequencing and epidemiological data suggest that in endemic settings only a minority of Clostridium difficile infection, CDI, is acquired from other cases. Asymptomatic patients are a potential source for many unexplained cases.MethodsWe prospectively screened a cohort of medical inpatients in a UK teaching hospital for asymptomatic C. difficile carriage using stool culture. Electronic and questionnaire data were used to determine risk factors for asymptomatic carriage by logistic regression. Carriage isolates were compared with all hospital/community CDI cases from the same geographic region, from 12 months before the study to 3 months after, using whole genome sequencing and hospital admission data, assessing particularly for evidence of onward transmission from asymptomatic cases.ResultsOf 227 participants recruited, 132 provided ?1 stool samples for testing. 18 participants were culture-positive for C. difficile, 14/132(11%) on their first sample. Independent risk factors for asymptomatic carriage were patient reported loose/frequent stool (but not meeting CDI criteria of ?3 unformed stools in 24 hours), previous overnight hospital stay within 6 months, and steroid/immunosuppressant medication in the last 6 months (all p?0.02). Surprisingly antibiotic exposure in the last 6 months was independently associated with decreased risk of carriage (p?=?0.005). The same risk factors were identified excluding participants reporting frequent/loose stool. 13/18(72%) asymptomatically colonised patients carried toxigenic strains from common disease-causing lineages found in cases. Several plausible transmission events to asymptomatic carriers were identified, but in this relatively small study no clear evidence of onward transmission from an asymptomatic case was seen.ConclusionsTransmission events from any one asymptomatic carrier are likely to be relatively rare, but as asymptomatic carriage is common, it may still be an important source of CDI, which could be quantified in larger studies. Risk factors established for asymptomatic carriage may help identify patients for inclusion in such studies.
| S-EPMC3827041 | biostudies-literature
Project description:BackgroundClostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting.MethodsWe developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI susceptibility, and tracks contamination levels of ward rooms by C. difficile. Interventions include two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination.ResultsIncreased HCW compliance with CDI patients was ranked as the most effective intervention in decreasing colonizations, with reductions up to 56%. Antibiotic stewardship practices were highly ranked after contact precaution compliance. Vaccination and reduction of high-risk antibiotics were the most effective intervention in decreasing CDI. Vaccination reduced CDI cases to up to 90%, and the reduction of high-risk antibiotics decreased CDI cases up to 23%.ConclusionsOverall, interventions that decrease patient susceptibility to colonization by C. difficile, such as antibiotic stewardship, were the most effective interventions in reducing both colonizations and CDI cases.
| S-EPMC7594474 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a primarily nosocomial pathogen that, in recent years, has increasingly spread to the general population. The rising prevalence of MRSA in the community implies more frequent introductions in healthcare settings that could jeopardize the effectiveness of infection-control procedures. To investigate the epidemiological dynamics of MRSA in a low-prevalence country, we developed an individual-based model (IBM) reproducing the population's sociodemography, explicitly representing households, hospitals, and nursing homes. The model was calibrated to surveillance data from the Norwegian national registry (2008-2015) and to published household prevalence data. We estimated an effective reproductive number of 0.68 (95% CI 0.47-0.90), suggesting that the observed rise in MRSA infections is not due to an ongoing epidemic but driven by more frequent acquisitions abroad. As a result of MRSA importations, an almost twofold increase in the prevalence of carriage was estimated over the study period, in 2015 reaching a value of 0.37% (0.25-0.54%) in the community and 1.11% (0.79-1.59%) in hospitalized patients. Household transmission accounted for half of new MRSA acquisitions, indicating this setting as a potential target for preventive strategies. However, nosocomial acquisition was still the primary source of symptomatic disease, which reinforces the importance of hospital-based transmission control. Although our results indicate little reason for concern about MRSA transmission in low-prevalence settings in the immediate future, the increases in importation and global circulation highlight the need for coordinated initiatives to reduce the spread of antibiotic resistance worldwide.
| S-EPMC6642346 | biostudies-literature
Project description:The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing.Here we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions.Our results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.
| S-EPMC4056369 | biostudies-literature
Project description:The burden of Clostridioides difficile infection (CDI) has greatly increased. We evaluated the risks for CDI transmission to community members after hospitalized patients are discharged. We conducted a systematic literature review in MEDLINE/PubMed, EMBASE, CINAHL plus EBSCO, Web of Science, Cochrane Library, and gray literature during January 2000‒February 2019 and identified 4,798 citations were identified. We eliminated 4,554 citations through title and abstract screening; 217 additional citations did not meet full criteria. We reviewed texts for the 27 remaining articles qualitatively for internal/external validity. A few identified studies describing risks to community members lacked accurate risk measurement or preventative strategies. Primary data are needed to assess efficacy of and inform current expertise-driven CDI prevention practices. Raising awareness among providers and researchers, conducting clinical and health services research, linking up integrated monitoring and evaluation processes at hospitals and outpatient settings, and developing and integrating CDI surveillance systems are warranted.
| S-EPMC8237889 | biostudies-literature
Project description:Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.
| S-EPMC3605770 | biostudies-literature
Project description:Clostridium difficile is a major cause of chronic antibiotic-associated diarrhea and a significant health care-associated pathogen that forms highly resistant and infectious spores. Spo0A is a highly conserved transcriptional regulator that plays a key role in initiating sporulation in Bacillus and Clostridium species. Here, we use a murine model to study the role of the C. difficile spo0A gene during infection and transmission. We demonstrate that C. difficile spo0A mutant derivatives can cause intestinal disease but are unable to persist within and effectively transmit between mice. Thus, the C. difficile Spo0A protein plays a key role in persistent infection, including recurrence and host-to-host transmission in mice.
| S-EPMC3434595 | biostudies-literature