Denise Gravel

Health care-associated Clostridium difficile infection in Canada: patient age and infecting strain type are highly predictive of severe outcome and mortality.

BACKGROUND C. difficile infection (CDI) has become an important and frequent nosocomial infection, often resulting in severe morbidity or death. Severe CDI is more frequently seen among individuals infected with the emerging NAP1/027/BI (NAP1) strain and in the elderly population, but the relative importance of these 2 factors remains unclear. We used a large Canadian database of patients with CDI to explore the interaction between these 2 variables. METHODS The Canada-wide CDI study, performed in 2005 by the Canadian Nosocomial Infection Surveillance Program (CNISP), was used to analyze the role of infecting strain type and patient age on the severity of CDI. A severe outcome was defined as CDI requiring intensive care unit care, colectomy, or causing death (directly or indirectly) within 30 days after diagnosis. RESULTS A total of 1008 patients in the CNISP database had both complete clinical data and infecting strain analysis documented. A total of 311 patients (31%) were infected with the NAP1 strain, 83 (28%) were infected with the NAP2/J strain, and the rest were infected with various other types. The proportion of NAP1 infections correlated with the incidence and the severity of CDI when analyzed by province. Thirty-nine (12.5%) of the infections due to the NAP1 strain resulted in a severe outcome, compared with only 41 (5.9%) of infections due to the other types (P < .001). The patients age was strongly associated with a severe outcome, and patients 60-90 years of age were approximately twice as likely to experience a severe outcome if the infection was due to NAP1, compared with infections due to other types. CONCLUSIONS Our study confirms the strong age association with infection due to the NAP1 strain and severe CDI. In addition, patients 60-90 years of age infected with NAP1 are approximately twice as likely to die or to experience a severe CDI-related outcome, compared with those with non-NAP1 infections. Patients >90 years of age experience high rates of severe CDI, regardless of strain type.

Health Care-Associated Clostridium difficile Infection in Adults Admitted to Acute Care Hospitals in Canada: A Canadian Nosocomial Infection Surveillance Program Study

BACKGROUND Clostridium difficile infection (CDI) is the most frequent cause of health care-associated infectious diarrhea in industrialized countries. The only previous report describing the incidence of health care-associated CDI (HA CDI) in Canada was conducted in 1997 by the Canadian Nosocomial Infection Surveillance Program. We re-examined the incidence of HA CDI with an emphasis on patient outcomes. METHODS A prospective surveillance was conducted from 1 November 2004 through 30 April 2005. Basic demographic data were collected, including age, sex, type of patient ward where the patient was hospitalized on the day HA CDI was identified, and patient comorbidities. Data regarding severe outcome were collected 30 days after the diagnosis of HA CDI; severe outcome was defined as an admission to the intensive care unit because of complications of CDI, colectomy due to CDI, and/or death attributable to CDI. RESULTS A total of 1430 adults with HA CDI were identified in 29 hospitals during the 6-month surveillance period. The overall incidence rate of HA CDI for adult patients admitted to these hospitals was 4.6 cases per 1000 patient admissions and 65 per 100,000 patient-days. At 30 days after onset of HA CDI, 233 patients (16.3%) had died from all causes; 31 deaths (2.2%) were a direct result of CDI, and 51 deaths (3.6%) were indirectly related to CDI, for a total attributable mortality rate of 5.7%. CONCLUSIONS The rates are remarkably similar to those found in our previous study; although we found wide variations in HA CDI among the participating hospitals. However, the attributable mortality increased almost 4-fold (5.7% vs. 1.5%; P<.001).

Mupirocin-Resistant, Methicillin-Resistant Staphylococcus aureus Strains in Canadian Hospitals

ABSTRACT Mupirocin resistance in Staphylococcus aureus is increasingly being reported in many parts of the world. This study describes the epidemiology and laboratory characterization of mupirocin-resistant methicillin-resistant S. aureus (MRSA) strains in Canadian hospitals. Broth microdilution susceptibility testing of 4,980 MRSA isolates obtained between 1995 and 2004 from 32 Canadian hospitals was done in accordance with CLSI guidelines. The clinical and epidemiologic characteristics of strains with high-level mupirocin resistance (HLMupr) were compared with those of mupirocin-susceptible (Mups) strains. MRSA strains were characterized by pulsed-field gel electrophoresis (PFGE) and typing of the staphylococcal chromosomal cassette mec. PCR was done to detect the presence of the mupA gene. For strains with mupA, plasmid DNA was extracted and subjected to Southern blot hybridization. A total of 198 (4.0%) HLMupr MRSA isolates were identified. The proportion of MRSA strains with HLMupr increased from 1.6% in the first 5 years of surveillance (1995 to 1999) to 7.0% from 2000 to 2004 (P < 0.001). Patients with HLMupr MRSA strains were more likely to have been aboriginal (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 9.4; P = 0.006), to have had community-associated MRSA (OR, 2.2; 95% CI, 1.0 to 5.0; P = 0.05), and to have been colonized with MRSA (OR, 1.7; 95% CI, 1.0 to 3.0; P = 0.04). HLMupr MRSA strains were also more likely to be resistant to fusidic acid (21% versus 4% for mupirocin-susceptible strains; P < 0.001). All HLMupr MRSA strains had a plasmid-associated mupA gene, most often associated with a 9-kb HindIII fragment. PFGE typing and analysis of the plasmid profiles indicate that both plasmid transmission and the clonal spread of HLMupr MRSA have occurred in Canadian hospitals. These results indicate that the incidence of HLMupr is increasing among Canadian strains of MRSA and that HLMupr MRSA is recovered from patients with distinct clinical and epidemiologic characteristics compared to the characteristics of patents with Mups MRSA strains.

Livestock-associated Methicillin- Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada

Recent emergence of infections resulting from this strain is of public health concern.

Methicillin-Resistant Staphylococcus aureus Colonization or Infection in Canada: National Surveillance and Changing Epidemiology, 1995-2007

OBJECTIVE To determine the incidence and describe the changing epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in Canadian hospitals from 1995-2007. SETTING Forty-eight hospitals participating in the Canadian Nosocomial Infection Surveillance Program. DESIGN Prospective, laboratory-based surveillance for incident cases of MRSA colonization or infection among hospitalized patients. METHODS Clinical and epidemiologic data were obtained by review of hospital records. Standard criteria were used to determine whether MRSA colonization or infection was present and whether the MRSA strain was healthcare associated or community associated. A representative subset of isolates was characterized by use of pulsed-field gel electrophoresis and staphylococcal cassette chromosome (SCC) mec typing. RESULTS From 1995 to 2007, a total of 37,169 hospitalized patients were newly identified as either infected or colonized with MRSA, and the overall incidence of both MRSA colonization and MRSA infection increased from 0.65 to 11.04 cases per 10,000 patient-days (P < .001). Of these 37,169 patients, 11,828 (32%) had an MRSA infection, and infection rate increased from 0.36 to 3.43 cases per 10,000 patient-days. The proportion of community-associated MRSA strains increased from 6% to 23% (P < .001). The most common genotype (47% of isolates) was CMRSA-2 (USA100/800); in 2007, CMRSA-10 (USA300) was the second most common strain (27% of isolates), associated with SCCmec type IV. Patients with CMRSA-10 were predominantly from western Canada and were more likely to be children (odds ratio [OR], 10.0 [95% confidence interval {CI}, 7.4-13.4]) and to have infection (OR, 2.3 [95% CI, 1.9-2.7]), especially skin and/or soft tissue infection (OR, 5.9 [95% CI, 5.0-6.9]). CONCLUSIONS The overall incidence of both MRSA colonization and MRSA infection increased 17-fold in Canadian hospitals from 1995 to 2007. There has also been a dramatic increase in cases of community-associated MRSA infection due to the CMRSA-10 (USA300) clone. Continued surveillance is needed to monitor the ongoing evolution of MRSA colonization or infection in Canada and globally.

Carbapenem-resistant Gram-negative bacilli in Canada 2009–10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP)

OBJECTIVES To investigate the occurrence and molecular mechanisms associated with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian cases. METHODS Twenty hospital sites across Canada submitted isolates for a 1 year period starting 1 September 2009. All Enterobacteriaceae with MICs ≥ 2 mg/L and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs ≥ 16 mg/L of carbapenems were submitted to the National Microbiology Laboratory (NML) where carbapenem MICs were confirmed by Etest and isolates were characterized by PCR for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid isolation. RESULTS A total of 444 isolates (298 P. aeruginosa, 134 Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274 (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the inclusion criteria as determined by Etest. Carbapenemase genes were identified in 30 isolates: bla(GES-5) (n = 3; P. aeruginosa), bla(KPC-3) (n = 7; Enterobacteriaceae), bla(NDM-1) (n = 2; Enterobacteriaceae), bla(VIM-2) and bla(VIM-4) (n = 8; P. aeruginosa) bla(SME-2) (n = 1; Enterobacteriaceae) and bla(OXA-23) (n = m9; A. baumannii). PFGE identified a cluster in each of Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were identified where indistinguishable plasmid patterns were identified in unrelated clinical isolates. CONCLUSIONS Carbapenemases were rare at the time of this study. Dissemination of carbapenemases was due to both dominant clones and common plasmid backbones.

Hypervirulent Clostridium difficile strains in hospitalized patients, Canada.

To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004-2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008.

Cluster of cases of severe acute respiratory syndrome among Toronto healthcare workers after implementation of infection control precautions: a case series.

OBJECTIVE To review the severe acute respiratory syndrome (SARS) infection control practices, the types of exposure to patients with SARS, and the activities associated with treatment of such patients among healthcare workers (HCWs) who developed SARS in Toronto, Canada, after SARS-specific infection control precautions had been implemented. METHODS A retrospective review of work logs and patient assignments, detailed review of medical records of patients with SARS, and comprehensive telephone-based interviews of HCWs who met the case definition for SARS after implementation of infection control precautions. RESULTS Seventeen HCWs from 6 hospitals developed disease that met the case definition for SARS after implementation of infection control precautions. These HCWs had a mean age (+/-SD) of 39+/-2.3 years. Two HCWs were not interviewed because of illness. Of the remaining 15, only 9 (60%) reported that they had received formal infection control training. Thirteen HCWs (87%) were unsure of proper order in which personal protective equipment should be donned and doffed. Six HCWs (40%) reused items (eg, stethoscopes, goggles, and cleaning equipment) elsewhere on the ward after initial use in a room in which a patient with SARS was staying. Use of masks, gowns, gloves, and eyewear was inconsistent among HCWs. Eight (54%) reported that they were aware of a breach in infection control precautions. HCWs reported fatigue due to an increased number and length of shifts; participants worked a median of 10 shifts during the 10 days before onset of symptoms. Seven HCWs were involved in the intubation of a patient with SARS. One HCW died, and the remaining 16 recovered. CONCLUSION Multiple factors were likely responsible for SARS in these HCWs, including the performance of high-risk patient care procedures, inconsistent use of personal protective equipment, fatigue, and lack of adequate infection control training.

Detection and Characterization of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Isolates in Canada: Results from the Canadian Nosocomial Infection Surveillance Program, 1995-2006

ABSTRACT We describe the epidemiology of heterogeneously resistant Staphylococcus aureus (hVISA) identified in Canadian hospitals between 1995 and 2006. hVISA isolates were confirmed by the population analysis profiling-area under the curve method. Only 25 hVISA isolates (1.3% of all isolates) were detected. hVISA isolates were more likely to have been health care associated (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.9 to 14.2) and to have been recovered from patients hospitalized in central Canada (OR, 3.0; 95% CI, 1.2 to 7.4). There has been no evidence of vancomycin “MIC creep” in Canadian strains of methicillin (meticillin)-resistant S. aureus, and hVISA strains are currently uncommon.

Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate.

Background Clostridium difficile are Gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15–35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. Methodology/Principal Findings Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. Conclusions/Significance This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.