Duncan MacCannell

Epidemiology of Community-Associated Clostridium difficile Infection, 2009 Through 2011

IMPORTANCE Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. OBJECTIVES To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. DESIGN AND SETTING Active population-based and laboratory-based CDI surveillance in 8 US states. PARTICIPANTS Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). MAIN OUTCOMES AND MEASURES Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. RESULTS Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). CONCLUSIONS AND RELEVANCE Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

Molecular Analysis of Clostridium difficile PCR Ribotype 027 Isolates from Eastern and Western Canada

ABSTRACT The prevalence and characteristics of PCR ribotype 027 strains of Clostridium difficile have come into question following recent outbreaks in Eastern Canada and elsewhere. In order to determine the distribution of this strain in other regions in Canada, we screened a bank of 1,419 isolates recovered from three different Canadian health regions between 2000 and 2004. Among isolates from a Montreal area hospital, PCR ribotype 027 strains represented 115/153 strains (75.2%) from 2003 to 2004, but ribotype 027 strains were absent in 2000 and 2001. In Calgary, by contrast, ribotype 027 rates have remained relatively stable over 4 years of surveillance, representing 51/685 (7.4%) hospital isolates and 62/373 (16.6%) strains from the community (P < 0.001). PCR ribotype 027 accounted for 8/135 (5.9%) hospital isolates in the Fraser Health Region in 2004. repetitive extragenic palindromic PCR was used to subtype a random selection of 027 isolates from each region. All 10 of the isolates from Quebec were of a single subtype, which was also dominant among isolates from Alberta (8/10 isolates) and British Columbia (6/8 isolates). Comparative sequencing of the tcdC repressor gene confirmed the documented 18-bp deletion and identified a second, single-base-pair deletion at position 117. Both deletions were conserved across all three provinces and were identified in a United Kingdom reference strain. The presence of a frameshift in the early portion of the tcdC gene implies serious functional disruption and may contribute to the hypervirulence of the 027 phenotype. PCR ribotype 027 strains appear to be widely distributed, to predate the Montreal outbreak, and to have measurable community presence in Western Canada.

New Delhi Metallo-β-Lactamase–Producing Carbapenem-Resistant Escherichia coli Associated With Exposure to Duodenoscopes

IMPORTANCE Carbapenem-resistant Enterobacteriaceae (CRE) producing the New Delhi metallo-β-lactamase (NDM) are rare in the United States, but have the potential to add to the increasing CRE burden. Previous NDM-producing CRE clusters have been attributed to person-to-person transmission in health care facilities. OBJECTIVE To identify a source for, and interrupt transmission of, NDM-producing CRE in a northeastern Illinois hospital. DESIGN, SETTING, AND PARTICIPANTS Outbreak investigation among 39 case patients at a tertiary care hospital in northeastern Illinois, including a case-control study, infection control assessment, and collection of environmental and device cultures; patient and environmental isolate relatedness was evaluated with pulsed-field gel electrophoresis (PFGE). Following identification of a likely source, targeted patient notification and CRE screening cultures were performed. MAIN OUTCOMES AND MEASURES Association between exposure and acquisition of NDM-producing CRE; results of environmental cultures and organism typing. RESULTS In total, 39 case patients were identified from January 2013 through December 2013, 35 with duodenoscope exposure in 1 hospital. No lapses in duodenoscope reprocessing were identified; however, NDM-producing Escherichia coli was recovered from a reprocessed duodenoscope and shared more than 92% similarity to all case patient isolates by PFGE. Based on the case-control study, case patients had significantly higher odds of being exposed to a duodenoscope (odds ratio [OR], 78 [95% CI, 6.0-1008], P < .001). After the hospital changed its reprocessing procedure from automated high-level disinfection with ortho-phthalaldehyde to gas sterilization with ethylene oxide, no additional case patients were identified. CONCLUSIONS AND RELEVANCE In this investigation, exposure to duodenoscopes with bacterial contamination was associated with apparent transmission of NDM-producing E coli among patients at 1 hospital. Bacterial contamination of duodenoscopes appeared to persist despite the absence of recognized reprocessing lapses. Facilities should be aware of the potential for transmission of bacteria including antimicrobial-resistant organisms via this route and should conduct regular reviews of their duodenoscope reprocessing procedures to ensure optimal manual cleaning and disinfection.

Clostridium difficile Infections in a Canadian Tertiary Care Hospital before and during a Regional Epidemic Associated with the BI/NAP1/027 Strain

ABSTRACT Since 2002, an epidemic of Clostridium difficile infections has occurred in southern Quebec, Canada. At Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada, the incidence of C. difficile infections increased from 11/1,000 admissions (1999 to 2002) to 27/1,000 admissions (2003 to 2005). We compared the exposures and outcomes for patients infected with strains with different ribopatterns isolated before (n = 55) and during (n = 175) the epidemic, as well as the in vitro activities of antibiotics against those isolates. During the preepidemic period, 46 isolates (84%) were of ribotype 001, 1 was of ribotype 027, and 8 were of other ribopattern types. During the epidemic period, ribotype 027 strains accounted for 140 (80%) isolates; 26 (15%) were of ribotype 001, and 7 were of other ribopattern types. Ribotype 027 strains were highly resistant to fluoroquinolones (FQs) but were susceptible to clindamycin. A pattern of prior specific antibiotic exposure that selected for antibiotic-resistant ribotype C. difficile infections was observed for FQs (ribotype 027) and clindamycin (ribotype 001). The rate of mortality was higher among older patients, those with a high Charlson comorbidity index, and those with longer previous hospitalizations. By multivariate analysis, patients infected with ribotype 027 were twice as likely to die within 30 days of diagnosis than patients infected with other ribotypes (adjusted odds ratio, 2.06; 95% confidence interval, 1.00 to 4.22). The observations from this study support the notion that continued selective antibiotic pressure resulted in the superimposition of the hypertoxigenic ribotype 027 clone on top of the prior dominant ribotype 001 clone in a setting of preexisting high endemicity, thus leading to the high rates of morbidity and mortality seen in the Quebec outbreak. Stringent antibiotic stewardship measures, combined with aggressive infection control, are required to curtail the epidemic of C. difficile infections.

Development and Validation of an Internationally-Standardized, High-Resolution Capillary Gel-Based Electrophoresis PCR-Ribotyping Protocol for Clostridium difficile

PCR-ribotyping has been adopted in many laboratories as the method of choice for C. difficile typing and surveillance. However, issues with the conventional agarose gel-based technique, including inter-laboratory variation and interpretation of banding patterns have impeded progress. The method has recently been adapted to incorporate high-resolution capillary gel-based electrophoresis (CE-ribotyping), so improving discrimination, accuracy and reproducibility. However, reports to date have all represented single-centre studies and inter-laboratory variability has not been formally measured or assessed. Here, we achieved in a multi-centre setting a high level of reproducibility, accuracy and portability associated with a consensus CE-ribotyping protocol. Local databases were built at four participating laboratories using a distributed set of 70 known PCR-ribotypes. A panel of 50 isolates and 60 electronic profiles (blinded and randomized) were distributed to each testing centre for PCR-ribotype identification based on local databases generated using the standard set of 70 PCR-ribotypes, and the performance of the consensus protocol assessed. A maximum standard deviation of only ±3.8bp was recorded in individual fragment sizes, and PCR-ribotypes from 98.2% of anonymised strains were successfully discriminated across four ribotyping centres spanning Europe and North America (98.8% after analysing discrepancies). Consensus CE-ribotyping increases comparability of typing data between centres and thereby facilitates the rapid and accurate transfer of standardized typing data to support future national and international C. difficile surveillance programs.

Good laboratory practice for clinical next-generation sequencing informatics pipelines

Amy S Gargis, Centers for Disease Control & Prevention Lisa Kalman, Centers for Disease Control & Prevention David P Bick, Medical College of Wisconsin Cristina da Silva, Emory University David P Dimmock, Medical College of Wisconsin Birgit H Funke, Partners Healthcare Personalized Medicine Sivakumar Gowrisankar, Partners Healthcare Personalized Medicine Madhuri Hegde, Emory University Shashikant Kulkarni, Washington University Christopher E Mason, Cornell University

Community-associated Clostridium difficile Infections, Monroe County, New York, USA

Judicious use of antimicrobial drugs will reduce infections.

Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement

Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.

Genomic Analysis of the Emergence and Rapid Global Dissemination of the Clonal Group 258 Klebsiella pneumoniae Pandemic

Multidrug-resistant Klebsiella pneumoniae producing the KPC carbapenemase have rapidly spread throughout the world, causing severe healthcare-associated infections with limited antimicrobial treatment options. Dissemination of KPC-producing K. pneumoniae is largely attributed to expansion of a single dominant strain, ST258. In this study, we explore phylogenetic relationships and evolution within ST258 and its clonal group, CG258, using whole genome sequence analysis of 167 isolates from 20 countries collected over 17 years. Our results show a common ST258 ancestor emerged from its diverse parental clonal group around 1995 and likely acquired bla KPC prior to dissemination. Over the past two decades, ST258 has remained highly clonal despite diversity in accessory elements and divergence in the capsule polysaccharide synthesis locus. Apart from the large recombination event that gave rise to ST258, few mutations set it apart from its clonal group. However, one mutation occurs in a global transcription regulator. Characterization of outer membrane protein sequences revealed a profile in ST258 that includes a truncated OmpK35 and modified OmpK37. Our work illuminates potential genomic contributors to the pathogenic success of ST258, helps us better understand the global dissemination of this strain, and identifies genetic markers unique to ST258.

Development of a consensus method for culture of Clostridium difficile from meat and its use in a survey of U.S. retail meats

Three previously described methods for culture of Clostridium difficile from meats were evaluated by microbiologists with experience in C. difficile culture and identification. A consensus protocol using BHI broth enrichment followed by ethanol shock and plating to selective and non-selective media was selected for use, and all participating laboratories received hands-on training in the use of this method prior to study initiation. Retail meat products (N = 1755) were cultured for C. difficile over 12 months during 2010-2011 at 9 U.S. FoodNet sites. No C. difficile was recovered, although other clostridia were isolated.