Dataset Information

Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes.

ABSTRACT: Background:No study has used whole-genome sequencing (WGS) to investigate risk factors for Clostridium difficile (CD) transmission between cases, or assessed the impact of recent acquisition on patient outcome. Methods:This 20 month retrospective cohort study included consecutive cytotoxin-positive diarrheal samples, which underwent culture, ribotyping, and WGS (Illumina). Sequenced isolates were compared using single nucleotide variants (SNVs). Independent predictors of acquisition from another case, onward transmission, 120-day recurrence, and 30-day mortality were identified using logistic regression with backwards elimination. Results:Of 660 CD cases, 640 (97%) were sequenced, of which 567 (89%) shared a ribotype with a prior case, but only 227 (35%) were ?2 SNVs from a prior case, supporting recent acquisition. Plausible (<2 SNVs) recent ward-based acquisition from a symptomatic case was more frequent in certain ribotypes; 64% (67/105) for ribotype-027 cases, compared with 11% (6/57) for ribotype-078. Independent risk factors (adjusted P < .05) for CD acquisition included older age, longer inpatient duration, and ribotype; these factors, and male sex, increased onward transmission. Patients with a plausible donor had a greater risk of recurrence (adjusted P = .001) and trended towards greater 30-day mortality (adjusted P = .06). Ribotype had no additional mortality or recurrence impact after adjusting for acquisition (P > .1). Conclusions:Greater transmission of certain lineages suggests CD may have different reservoirs and modes of transmission. Acquiring CD from a recent case is associated with poorer clinical outcomes. Clinical characteristics associated with increased healthcare-associated CD transmission could be used to target preventative interventions.

SUBMITTER: Martin JSH

PROVIDER: S-EPMC6186849 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes.

Martin Jessica S H JSH Eyre David W DW Fawley Warren N WN Griffiths David D Davies Kerrie K Mawer Damian P C DPC Peto Timothy E A TEA Crook Derrick W DW Walker A Sarah AS Wilcox Mark H MH

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20181001 9

<h4>Background</h4>No study has used whole-genome sequencing (WGS) to investigate risk factors for Clostridium difficile (CD) transmission between cases, or assessed the impact of recent acquisition on patient outcome.<h4>Methods</h4>This 20 month retrospective cohort study included consecutive cytotoxin-positive diarrheal samples, which underwent culture, ribotyping, and WGS (Illumina). Sequenced isolates were compared using single nucleotide variants (SNVs). Independent predictors of acquisiti ...[more]

PMID: 29659753

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Project description:BackgroundClostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent and epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to have contributed to their emergence and virulence.Methods5232 previously whole-genome sequenced C. difficile isolates were analysed. Clinical isolates were used to investigate the impact of trehalose metabolism variants on mortality. Import data were used to estimate changes in dietary trehalose. Ribotype-027 virulence was investigated in a clinically reflective gut model.FindingsTrehalose metabolism variants found in ribotype-027 and ribotype-017 were widely distributed throughout C. difficile clade-2 and clade-4 in 24/29 (83%) and 10/11 (91%) of sequence types (STs), respectively. The four-gene trehalose metabolism cluster described in ribotype-078 was common in genomes from all five clinically-important C. difficile clades (40/167 [24%] STs). The four-gene cluster was variably present in 208 ribotype-015 infections (98 [47%]); 27/208 (13%) of these patients died within 30-days of diagnosis. Adjusting for age, sex, and infecting ST, there was no association between 30-day all-cause mortality and the four-gene cluster (OR 0.36 [95%CI 0.09-1.34, p = 0.13]). Synthetic trehalose imports in the USA, UK, Germany and the EU were  < 1 g/capita/year during 2000-2006, and  < 9 g/capita/year 2007-2012, compared with dietary trehalose from natural sources of ~100 g/capita/year. Trehalose supplementation did not increase ribotype-027 virulence in a clinically-validated gut model.InterpretationTrehalose metabolism variants are common in C. difficile. Increases in total dietary trehalose during the early-mid 2000s C. difficile epidemic were likely relatively minimal. Alternative explanations are required to explain why ribotype-027, ribotype-078 and ribotype-017 have been successful.FundingNational Institute for Health Research. Gut model experiments only: Hayashibara Co. Ltd.

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.

Dataset Information

Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes.

Publications

Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes.

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