The CANWARD surveillance study has provided important data on the antimicrobial susceptibility of pathogens commonly causing infections in Canadian hospitals.
Candidemia and invasive candidiasis (C/IC) are life-threatening opportunistic infections that add excess morbidity, mortality and cost to the management of patients with a range of potentially curable underlying conditions. The Association of Medical Microbiology and Infectious Disease Canada developed evidence-based guidelines for the approach to the diagnosis and management of these infections in the ever-increasing population of at-risk adult patients in the health care system. Over the past few years, a new and broader understanding of the epidemiology and pathogenesis of C/IC has emerged and has been coupled with the availability of new antifungal agents and defined strategies for targeting groups at risk including, but not limited to, acute leukemia patients, hematopoietic stem cell transplants and solid organ transplants, and critical care unit patients. Accordingly, these guidelines have focused on patients at risk for C/IC, and on approaches of prevention, early therapy for suspected but unproven infection, and targeted therapy for probable and proven infection.
We describe here the characteristics of Alberta, Canada, patients with infections or colonizations with carbapenemase-producing Gram-negative bacteria during 2010 to 2013 that were linked to recent travel outside Canada. Antimicrobial susceptibility was determined by broth microdilution, and isolates were characterized using PCR, sequencing, and multilocus sequencing typing. A broth mating study was used to assess the transferability of resistance plasmids, which were subsequently characterized. All the patients (n ؍ 12) included in our study had contact with a health care system while abroad. Most of the patients presented with urinary tract infections (UTIs) and were admitted to hospitals within weeks after their return to Alberta.
Carbapenem-resistant Enterobacter cloacae complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A bla NMC-A or bla IMI -type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and hsp60 gene analysis. The genes were found in various Enterobacter cloacae complex species; however, bla NMC-A was highly associated with Enterobacter ludwigii. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (n ϭ 10), IMI-1 (n ϭ 5), and IMI-9 (n ϭ 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes, bla and bla , were harbored on different IncFII-type plasmids. Enterobacter cloacae complex isolates harboring bla NMC-A/IMI -type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential.KEYWORDS carbapenemase E nterobacter species bacteria are facultative Gram-negative rods belonging to the Enterobacteriaceae family and are ubiquitous in the environment in soil, sewage, and water and as commensal enteric bacteria in animals and humans (1). Enterobacter cloacae can also cause clinically relevant human infections. The genetically related group "E. cloacae complex" consists of several species, subspecies, and genetic clusters that have been characterized by sequence analysis of the hsp60 gene, multilocus sequence analysis, or comparative genomic hybridization (2-4). Enterobacter spp. are intrinsically resistant to first-generation cephalosporins and variably express an AmpC
Clinical cervical cytology specimens (n ؍ 466) collected in PreservCyt (Hologic Inc.) were used to evaluate the agreement between Hybrid Capture 2 (hc2; Qiagen) and cobas 4800 (c4800; Roche Molecular Diagnostics) for the detection of high-risk human papillomavirus (HR HPV) genotype infections. The agreement between the two assays was 93.8% (kappa ؍ 0.87; 95% confidence interval, 0.828 to 0.918), with 186 and 251 concordant positive and negative results, respectively. All 186 concordant positives were confirmed using the Linear Array (LA; Roche Molecular Diagnostics) genotyping test. Of the 29 samples with discordant results (6.2%), 18 were hc2 positive and LA verified 17 as positive for HR HPV. Eleven discordant specimens were c4800 positive, and LA confirmed 5 as positive for HR HPV. As of October 2009, practice guidelines in Alberta, Canada, recommend reflex HPV testing for women over 30 years old with atypical squamous cells of undetermined significance (ASCUS) and for women over 50 years old with low-grade squamous intraepithelial lesions (LSIL) to help prioritize those who should undergo further evaluation. In this study, agreement between hc2 and c4800 results for samples from women over 30 years old with ASCUS cytology was 92.3% (n ؍ 13), while no samples from women over 50 years old with LSIL cytology were identified for analysis. Studies have shown that cervical cancer is a preventable disease, and its incidence and associated mortality rate have declined since the advent of Papanicolau (Pap) test screening programs (13,17). Opportunities for primary prevention and enhanced secondary prevention exist because of the understanding that human papillomaviruses (HPV) cause cervical cancer (33). To date, about 120 HPV genotypes have been classified (2); approximately 60 genotypes are known to infect the human genital tract, of which 12 genotypes (HPV 16,18,31,33, 35, 39, 45, 51, 52, 56, 58, and 59) are considered oncogenic or high risk (HR) and 5 genotypes (HPV 26, 53, 66, 68, and 72) are considered possibly oncogenic as their significance in cervical cancer incidence is unclear (21, 26). Persistent HR HPV infection is a requirement for progression from squamous intraepithelial lesions (SIL) to cervical intraepithelial neoplasia (CIN) and finally cervical cancer (7,10,16,27,30). Studies worldwide have shown that HPV 16 is detected most often (50 to 60%) in cervical cancer cases, followed by HPV 18 (10 to 12%) and HPV 31 and HPV 45 (4 to 5% each) (3). In the vast majority of women, HPV infections occur at a young age shortly after sexual debut and are transient. Detection of HR HPV in women over the age of 30 years is an indication that persistent infection may be occurring (7), which is necessary for the development of cervical cancer.Pap testing has limitations such as interoperator variability and low sensitivity. High-risk HPV testing (when used as either primary screening or for reflex testing following a nonnegative cytology result) improves patient management by providing a more accurate risk as...
Objectives Understanding the epidemiology of invasive Candida infections is essential to patient management decisions and antifungal stewardship practices. This study characterized the species distribution and antifungal susceptibilities of prospectively collected isolates of Candida species causing bloodstream infections (BSIs) in patients admitted to tertiary care hospitals located in 14 cities across 8 of the 10 Canadian provinces between 2011 and 2016. Methods Antifungal susceptibility testing was performed by broth microdilution using CLSI methods, breakpoints and epidemiological cut-off values. DNA sequencing of fks loci was performed on all echinocandin-non-susceptible isolates. Results Candida albicans (49.6%), Candida glabrata (20.8%) and Candida parapsilosis complex (12.0%) were the most common species out of 1882 isolates associated with BSIs. Candida tropicalis (5.2%), Candida krusei (4.3%), Candida dubliniensis (4.1%), Candida lusitaniae (1.4%) and Candida guilliermondii (1.1%) were less frequently isolated. Between 2011 and 2016, the proportion of C. albicans significantly decreased from 60.9% to 42.1% (P < 0.0001) while that of C. glabrata significantly increased from 16.4% to 22.4% (P = 0.023). C. albicans (n = 934), C. glabrata (n = 392) and C. parapsilosis complex (n = 225) exhibited 0.6%, 1.0% and 4.9% resistance to fluconazole and 0.1%, 2.5% and 0% resistance to micafungin, respectively. Mutations in fks hot-spot regions were confirmed in all nine micafungin non-susceptible C. glabrata. Conclusions Antifungal resistance in contemporary isolates of Candida causing BSIs in Canada is uncommon. However, the proportion of C. glabrata isolates has increased and echinocandin resistance in this species has emerged. Ongoing surveillance of local hospital epidemiology and appropriate antifungal stewardship practices are necessary to preserve the utility of available antifungal agents.
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