Indigenous Transmission of Mycobacterium africanum in Canada: A Case Series and Cluster Analysis.

Mycobacterium africanum is an important cause of human tuberculosis and is found almost exclusively in West Africa. We identified a cluster of patients in Montreal, Canada, with M africanum disease that share identical genotypic signatures by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing and a putative epidemiological link, thus providing evidence of possible local transmission of M africanum in Montreal over a 10-year period.

Clostridium difficile: Investigating Transmission Patterns Between Infected and Colonized Patients Using Whole Genome Sequencing.

Background: Whole genome sequencing (WGS) studies can enhance our understanding of the role of patients with asymptomatic Clostridium difficile colonization in transmission. Methods: Isolates obtained from patients with Clostridium difficile infection (CDI) and colonization identified in a study conducted during 2006-2007 at 6 Canadian hospitals underwent typing by pulsed-field gel electrophoresis, multilocus sequence typing, and WGS. Isolates from incident CDI cases not in the initial study were also sequenced where possible. Ward movement and typing data were combined to identify plausible donors for each CDI case, as defined by shared time and space within predefined limits. Proportions of plausible donors for CDI cases that were colonized, infected, or both were examined. Results: Five hundred fifty-four isolates were sequenced successfully, 353 from colonized patients and 201 from CDI cases. The NAP1/027/ST1 strain was the most common strain, found in 124 (62%) of infected and 92 (26%) of colonized patients. A donor with a plausible ward link was found for 81 CDI cases (40%) using WGS with a threshold of ≤2 single nucleotide polymorphisms to determine relatedness. Sixty-five (32%) CDI cases could be linked to both infected and colonized donors. Exclusive linkages to infected and colonized donors were found for 28 (14%) and 12 (6%) CDI cases, respectively. Conclusions: Colonized patients contribute to transmission, but CDI cases are more likely linked to other infected patients than colonized patients in this cohort with high rates of the NAP1/027/ST1 strain, highlighting the importance of local prevalence of virulent strains in determining transmission dynamics.

Predictors of asymptomatic Clostridium difficile colonization on hospital admission.

BACKGROUND: Clostridium difficile (CD) is the leading cause of health care-associated diarrhea and can result in asymptomatic carriage. Rates of asymptomatic CD colonization on hospital admission range from 1.4%-21%. The objective of this study was to evaluate host and bacterial factors associated with colonization on admission. METHODS: The Consortium de recherche québécois sur le Clostridium difficile study provided data for analysis, including demographic information, known risk factors, and potential confounding factors, prospectively collected for 5,232 patients from 6 hospitals in Quebec and Ontario over 15 months from 2006-2007. Stool or rectal swabs were obtained for culture on admission. Pulsed-field gel electrophoresis was performed on the isolates. The presence of antibody against CD toxins A and B was measured. RESULTS: There were 212 (4.05%) patients colonized with CD on admission, and 5,020 patients were not colonized with CD. Multivariate logistic regression analysis showed that hospitalization within the last 12 months, use of corticosteroids, prior CD infection, and presence of antibody against toxin B were associated with colonization on admission. Of patients colonized on admission, 79.4% had non-NAP1, non-NAP2 strains. CONCLUSION: There are identifiable risk factors among asymptomatic CD carriers that could serve in their detection and provide a basis for targeted screening.

Host and pathogen factors for Clostridium difficile infection and colonization.

BACKGROUND: Clostridium difficile infection is the leading cause of health care-associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. METHODS: We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. RESULTS: A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. CONCLUSIONS: In this study, health care-associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.).

Clostridium difficile infections in a Canadian tertiary care hospital before and during a regional epidemic associated with the BI/NAP1/027 strain.

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.

A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Québec.

BACKGROUND: An increase in the incidence and severity of Clostridium difficile-associated disease in Québec and the United States has been associated with a hypervirulent strain referred to as North American pulsed-field type 1 (NAP1)/027. METHODS: In 2005, a prospective study was conducted in 88 Québec hospitals, and 478 consecutive nosocomial isolates of C. difficile were obtained. The isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing, antimicrobial susceptibility testing, and detection of binary toxin genes and tcdC gene deletion. Data on patient age and occurrence of complications were collected. RESULTS: PFGE typing of 478 isolates of C. difficile yielded 61 PFGE profiles. Pulsovars A (57%), B (10%), and B1 (8%) were predominant. The PFGE profile of pulsovar A was identical to that of strain NAP1. It showed 67% relatedness with 15 other PFGE patterns, among which 11 had both binary toxin genes and a partial tcdC deletion but different antibiotic susceptibility profiles. Pulsovars B and B1 were identical to strain NAP2/ribotype 001. In hospitals showing a predominant clonal A or B-B1 PFGE pattern, incidence of C. difficile-associated disease was 2 and 1.3 times higher, respectively, than in hospitals without any predominant clonal PFGE pattern. Severe disease was twice as frequent among patients with strains possessing binary toxin genes and tcdC deletion than among patients with strains lacking these virulence factors. CONCLUSIONS: This study helped to quantify the impact of strain NAP1 on the incidence and severity of C. difficile-associated disease in Québec in 2005. The identification of the geographic dissemination of this predominant strain may help to focus regional infection-control efforts.

In vitro susceptibility of Clostridium difficile clinical isolates from a multi-institutional outbreak in Southern Québec, Canada.

Clostridium difficile isolates from a 2004 outbreak in Québec, Canada, were all found to be susceptible to metronidazole, vancomycin, rifampin, and meropenem but resistant to bacitracin, cefotaxime, ciprofloxacin, and levofloxacin, and most (>80%) were resistant to ceftriaxone, clarithromycin, gatifloxacin, and moxifloxacin. The predominant NAP1 isolates were susceptible to clindamycin, while the NAP2 isolates were resistant.

A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.

BACKGROUND: In March 2003, several hospitals in Quebec, Canada, noted a marked increase in the incidence of Clostridium difficile-associated diarrhea. METHODS: In 2004 we conducted a prospective study at 12 Quebec hospitals to determine the incidence of nosocomial C. difficile-associated diarrhea and its complications and a case-control study to identify risk factors for the disease. Isolates of C. difficile were typed by pulsed-field gel electrophoresis and analyzed for binary toxin genes and partial deletions in the toxin A and B repressor gene tcdC. Antimicrobial susceptibility was evaluated in a subgroup of isolates. RESULTS: A total of 1703 patients with 1719 episodes of nosocomial C. difficile-associated diarrhea were identified. The incidence was 22.5 per 1000 admissions. The 30-day attributable mortality rate was 6.9 percent. Case patients were more likely than matched controls to have received fluoroquinolones (odds ratio, 3.9; 95 percent confidence interval, 2.3 to 6.6) or cephalosporins (odds ratio, 3.8; 95 percent confidence interval, 2.2 to 6.6). A predominant strain, resistant to fluoroquinolones, was found in 129 of 157 isolates (82.2 percent), and the binary toxin genes and partial deletions in the tcdC gene were present in 132 isolates (84.1 percent). CONCLUSIONS: A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak of C. difficile-associated diarrhea. Exposure to fluoroquinolones or cephalosporins was a risk factor.