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Carbapenem-resistance in Enterobacter spp due to acquisition of mobile carbapenemases is of concern. An Enterobacter spp grew on ChromID CARBA medium and was positive for the mCIM carbapenemase detection assay. Susceptibility testing showed resistance to aztreonam and reduced susceptibility to imipenem. Conventional PCR using FRI primers detected a blaFRI gene. Whole genome sequencing reveled a new variant; blaFRI-12 was closest in sequence to blaFRI-5 differing by 13 amino acids and was found on a unique 110Kb IncR plasmid. Given the intrinsic nature of Enterobacter spp. to be carbapenem non-susceptible, blaFRI-types may be under reported globally.
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Carbapenems are last-resort antibiotics for treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance is a rising global threat due to the acquisition of carbapenemase genes. Oxacillinase-48 (bla OXA-48)-type carbapenemases are increasing in abundance in Canada and elsewhere; these genes are frequently found on mobile genetic elements and are associated with specific transposons. This means that alongside clonal dissemination, bla OXA-48-type genes can spread through plasmid-mediated horizontal gene transfer. We applied whole genome sequencing to characterize 249 bla OXA-48-type-producing Enterobacterales isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short- and long-read sequencing, we obtained 70 complete and circular bla OXA-48-type-encoding plasmids. Using MOB-suite, four major plasmids clustered were identified, and we further estimated a plasmid cluster for 91.9â% (147/160) of incomplete bla OXA-48-type-encoding contigs. We identified different patterns of carbapenemase mobilization across Canada, including horizontal transmission of bla OXA-181/IncX3 plasmids (75/249, 30.1â%) and bla OXA-48/IncL/M plasmids (47/249, 18.9â%), and both horizontal transmission and clonal transmission of bla OXA-232 for Klebsiella pneumoniae ST231 on ColE2-type/ColKP3 plasmids (25/249, 10.0â%). Our findings highlight the diversity of OXA-48-type plasmids and indicate that multiple plasmid clusters and clonal transmission have contributed to bla OXA-48-type spread and persistence in Canada.
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Proteínas de Bactérias , Carbapenêmicos , Infecções por Enterobacteriaceae , Plasmídeos , Sequenciamento Completo do Genoma , beta-Lactamases , beta-Lactamases/genética , Plasmídeos/genética , Canadá/epidemiologia , Humanos , Carbapenêmicos/farmacologia , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/classificação , Transferência Genética Horizontal , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologiaRESUMO
Gram-negative metallo-ß-lactamase-producing bacteria can be extremely problematic, especially when found to be extensively drug-resistant (XDR). Cefiderocol is a novel antimicrobial that has been shown to overcome most carbapenemases, with very rare resistance reported to date. Within our institution, two multidrug-resistant and one XDR strains were isolated from a patient who recently emigrated from India. Each isolate underwent whole-genome sequencing to resolve plasmids and determine phylogenetics, strain typing, and mechanisms of resistance. The XDR E. coli was ST167, harbored NDM-5, cirA and PBP3 mutations, consistent with cefiderocol resistance. Our study suggests that the NDM region is required in conjunction with cirA and PBP3 mutations. It is not clear why; however, our study did determine a potential novel iron-transport region unique to the cefiderocol-resistant isolate. This is the first characterized cefiderocol-resistant E.coli reported from Canada. Health centers should be on alert for this clone.IMPORTANCEThe development of cefiderocol, a novel siderophore cephalosporin, has provided additional options to the treatment of extensively drug-resistant (XDR) Gram-negative bacteria. Resistance to cefiderocol is poorly understood and only recently described. Here, we describe a case of a patient with recent travel to India harboring three Escherichia coli isolates, one resistant and two susceptible to cefiderocol. Two isolates are highly similar genetically, allowing the mechanism of resistance to be described more closely. The importance of this manuscript contributes both globally to the understanding of cefiderocol resistance in E. coli as well as nationally as this is the first resistant case reported in Canada. This is especially concerning as cefiderocol is not currently approved in Canada. The implications of reporting emerging resistance to new antimicrobials for XDR Gram negatives are impactful to infectious disease specialists, clinical microbiologists, physicians, and public health.
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Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Humanos , Masculino , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Canadá , Cefiderocol , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Índia , Testes de Sensibilidade Microbiana , Mutação , Filogenia , Plasmídeos/genética , Sequenciamento Completo do Genoma , IdosoRESUMO
The best whole genome assemblies are currently built from a combination of highly accurate short-read sequencing data and long-read sequencing data that can bridge repetitive and problematic regions. Oxford Nanopore Technologies (ONT) produce long-read sequencing platforms and they are continually improving their technology to obtain higher quality read data that is approaching the quality obtained from short-read platforms such as Illumina. As these innovations continue, we evaluated how much ONT read coverage produced by the Rapid Barcoding Kit v14 (SQK-RBK114) is necessary to generate high-quality hybrid and long-read-only genome assemblies for a panel of carbapenemase-producing Enterobacterales bacterial isolates. We found that 30× long-read coverage is sufficient if Illumina data are available, and that more (at least 100× long-read coverage is recommended for long-read-only assemblies. Illumina polishing is still improving single nucleotide variants (SNVs) and INDELs in long-read-only assemblies. We also examined if antimicrobial resistance genes could be accurately identified in long-read-only data, and found that Flye assemblies regardless of ONT coverage detected >96% of resistance genes at 100% identity and length. Overall, the Rapid Barcoding Kit v14 and long-read-only assemblies can be an optimal sequencing strategy (i.e., plasmid characterization and AMR detection) but finer-scale analyses (i.e., SNV) still benefit from short-read data.
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Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Bactérias Gram-Negativas/genética , Sequenciamento Completo do Genoma/métodos , beta-Lactamases/genética , Sequenciamento por Nanoporos/métodos , Biblioteca Gênica , Análise de Sequência de DNA/métodosRESUMO
Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Enterobacterales, but carbapenem resistance due to acquisition of carbapenemase genes is a growing threat that has been reported worldwide. Klebsiella pneumoniae carbapenemase (blaKPC) is the most common type of carbapenemase in Canada and elsewhere; it can hydrolyze penicillins, cephalosporins, aztreonam, and carbapenems and is frequently found on mobile plasmids in the Tn4401 transposon. This means that alongside clonal expansion, blaKPC can disseminate through plasmid- and transposon-mediated horizontal gene transfer. We applied whole genome sequencing to characterize the molecular epidemiology of 829 blaKPC carbapenemase-producing isolates collected by the Canadian Nosocomial Infection Surveillance Program from 2010 to 2021. Using a combination of short-read and long-read sequencing, we obtained 202 complete and circular blaKPC-encoding plasmids. Using MOB-suite, 10 major plasmid clusters were identified from this data set which represented 87% (175/202) of the Canadian blaKPC-encoding plasmids. We further estimated the genomic location of incomplete blaKPC-encoding contigs and predicted a plasmid cluster for 95% (603/635) of these. We identified different patterns of carbapenemase mobilization across Canada related to different plasmid clusters, including clonal transmission of IncF-type plasmids (108/829, 13%) in K. pneumoniae clonal complex 258 and novel repE(pEh60-7) plasmids (44/829, 5%) in Enterobacter hormaechei ST316, and horizontal transmission of IncL/M (142/829, 17%) and IncN-type plasmids (149/829, 18%) across multiple genera. Our findings highlight the diversity of blaKPC genomic loci and indicate that multiple, distinct plasmid clusters have contributed to blaKPC spread and persistence in Canada.
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Infecções por Klebsiella , beta-Lactamases , Humanos , Canadá/epidemiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Plasmídeos/genética , Proteínas de Bactérias/genética , Klebsiella pneumoniae , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Genômica , Infecções por Klebsiella/epidemiologia , Testes de Sensibilidade MicrobianaRESUMO
This study investigated the mechanism of carbapenem resistance in an Enterobacter cloacae complex positive by the modified carbapenem inactivation method (mCIM) but negative by the Rosco Neo-Rapid Carb Kit, ß CARBA, and conventional PCR for common carbapenemase genes (KPC, NDM, OXA-48, IMP, VIM, GES, and IMI/NMC). Using whole genome sequencing (WGS) data we confirmed the identification of Enterobacter asburiae (ST1639) and the presence of blaFRI-8 located on a 148kb IncFII(Yp) plasmid. This is the first occurrence of a clinical isolate harboring the FRI-8 carbapenemase and the second occurrence of FRI in Canada. This study highlights the need to use both WGS and phenotypic screening methods for detection of carbapenemase-producing strains if we consider the growing diversity of carbapenemases.
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Antibacterianos , Carbapenêmicos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Canadá , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/análise , beta-Lactamases , Sensibilidade e EspecificidadeRESUMO
Extended-spectrum cephalosporins (ESCs) resistance genes, such as blaCTX-M, blaCMY, and blaSHV, have been found regularly in bacteria from livestock. However, information on their distribution in dairy cattle in Canada and on the associated genome sequences of ESC-resistant Enterobacterales is sparse. In this study, the diversity and distribution of ESC-resistant Escherichia coli throughout manure treatments in six farms in Southern Ontario were assessed over a one-year period, and their ESC-resistance plasmids were characterized. The manure samples were enriched using selective media. The resulting isolates were screened via polymerase chain reaction for blaCTX-M, blaCMY, and blaSHV. No E. coli carrying blaSHV were detected. Escherichia coli (n = 248) carrying blaCTX-M or blaCMY underwent whole-genome sequencing using an Illumina MiSeq/NextSeq. These isolates were typed using multilocus sequence typing (MLST) and their resistance gene profiles. A subset of E. coli (n = 28) were sequenced using Oxford Nanopore Technologies. Plasmids were assembled using Unicycler and characterized via the resistance genes pattern, replicon type, plasmid MLST, phylogenetic analysis, and Mauve alignments. The recovery of ESC-resistant Enterobacterales (18 species, 8 genera) was drastically reduced in manure outputs. However, multiple treatment stages were needed to attain a significant reduction. 62 sequence types were identified, with ST10, ST46, ST58, ST155, ST190, ST398, ST685, and ST8761 being detected throughout the treatment pipeline. These STs overlapped with those found on multiple farms. The ESC-resistance determinants included CTX-M-1, -14, -15, -17, -24, -32, -55, and CMY-2. The plasmids carrying blaCTX-M were more diverse than were the plasmids carrying blaCMY. Known "epidemic plasmids" were detected for both blaCTX-M and blaCMY. IMPORTANCE The increase in antimicrobial resistance is of concern for human and animal health, especially when resistance is conferred to extended-spectrum cephalosporins, which are used to treat serious infections in both human and veterinary medicine. Bacteria carrying extended-spectrum cephalosporin resistance genes, including blaCTX-M and blaCMY, are frequently found in dairy manure. Manure treatment influences the loads and diversity of bacteria, including those carrying antimicrobial resistance genes, such as Enterobacterales and Escherichia coli. Any bacteria that survive the treatment process are subsequently applied to the environment. Enterobacterales carrying blaCTX-M or blaCMY can contaminate soil and crops consumed by humans and animals, thereby increasing the potential for antimicrobial resistance genes to integrate into the human gut microflora through horizontal gene transfer. This furthers the dissemination of resistance. Therefore, it is imperative to understand the effects manure treatments have on ESC-resistance in environmentally applied manure.
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Cefalosporinas , Infecções por Escherichia coli , Animais , Bovinos , Humanos , Cefalosporinas/farmacologia , Escherichia coli/genética , Esterco , Antibacterianos/farmacologia , Ontário , Tipagem de Sequências Multilocus , Filogenia , beta-Lactamases/genética , Infecções por Escherichia coli/microbiologia , Plasmídeos/genéticaRESUMO
Data regarding the epidemiology of extensively drug-resistant (XDR) carbapenemase-producing Enterobacterales (CPE) in Canada are scarce. Among CPE patients identified by the Canadian Nosocomial Infection Surveillance Program, the following were each significantly associated with XDR status: international travel history; CPE acquisition from a health care exposure abroad; presence of the New Delhi metallo-ß-lactamase (NDM) carbapenemase gene; E. coli sequence type (ST) 167, ST405, and ST648; E. cloaceae ST177; C. freundii ST22; and resistance to all antimicrobials except colistin, tigecycline, and ceftazidime-avibactam. IMPORTANCE Extensively drug-resistant (XDR) carbapenemase-producing Enterobacterales (CPE) are a global public health concern. XDR CPE are among the most drug-resistant and difficult-to-treat bacteria, and infected patients are likely to experience adverse outcomes. Because XDR status further reduces effective therapeutic options, it is critical for clinicians to consider resistance and therapeutic options not only in the context of a patient with CPE but also in the context of potential XDR status. Our study reports on patient characteristics associated with the acquisition of an XDR CPE. Our study also reports on the species and carbapenemases associated with XDR status among Enterobacterales identified in Canada. Among a panel of 22 antibiotics, including novel combination drugs, we showed which retained the highest activity against XDR CPE, which may help guide the selection of antibiotic treatments.
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Infecções por Enterobacteriaceae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Canadá/epidemiologia , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/tratamento farmacológico , Escherichia coli , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/genéticaRESUMO
Extended-spectrum ß-lactamases (ESBLs) confer resistance to extended-spectrum cephalosporins, a major class of clinical antimicrobial drugs. We used genomic analysis to investigate whether domestic food animals, retail meat, and pets were reservoirs of ESBL-producing Salmonella for human infection in Canada. Of 30,303 Salmonella isolates tested during 2012-2016, we detected 95 ESBL producers. ESBL serotypes and alleles were mostly different between humans (n = 54) and animals/meat (n = 41). Two exceptions were blaSHV-2 and blaCTX-M-1 IncI1 plasmids, which were found in both sources. A subclade of S. enterica serovar Heidelberg isolates carrying the same IncI1-blaSHV-2 plasmid differed by only 1-7 single nucleotide variants. The most common ESBL producer in humans was Salmonella Infantis carrying blaCTX-M-65, which has since emerged in poultry in other countries. There were few instances of similar isolates and plasmids, suggesting that domestic animals and retail meat might have been minor reservoirs of ESBL-producing Salmonella for human infection.
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Saúde Única , Salmonella enterica , Animais , Antibacterianos/farmacologia , Galinhas , Genômica , Plasmídeos/genética , Salmonella , beta-Lactamases/genéticaRESUMO
Infection prevention and control measures are used to contain outbreaks of carbapenemase-producing Enterobacteriaceae. We report the absence of transmission of Klebsiella pneumoniae carrying New Delhi metallo-ß-lactamase and oxacillinase-48 genes among 19 screened contacts of an index case after 14 months of routine practices in a long-term care facility.
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OBJECTIVES: This study assessed in vitro activities of cefepime/taniborbactam and comparator antimicrobial agents against ertapenem-non-susceptible Enterobacterales (ENSE) clinical isolates collected from the CANWARD study 2007-19, and associations between MIC and various mechanisms of ß-lactam resistance identified using WGS. METHODS: A total of 179 ENSE (MIC ≥â1â mg/L) isolates underwent susceptibility testing using reference CLSI broth microdilution. WGS was performed using the Illumina NextSeq platform. Carbapenemases, ESBLs and other ß-lactamases were identified using ResFinder 4.0. Alterations in ompC/F and ftsI (PBP3) were identified by comparing extracted sequences to the appropriate NCBI reference gene. Porin alterations were analysed with Provean v1.1.3. Specific alterations of interest in PBP3 included a YRIN or YRIK insertion after P333. RESULTS: Cefepime/taniborbactam was highly active (MIC50/MIC90, 0.5/2â mg/L; 177/179 isolates inhibited at ≤â8â mg/L) against ENSE with various antimicrobial resistance phenotypes. Thirteen (7.3%) of the 179 ENSE isolates demonstrated cefepime/taniborbactam MIC values ≥â4â mg/L and possessed combinations of ß-lactam resistance mechanisms, including a carbapenemase and/or ESBL and/or other ß-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3. Of the two Escherichia coli isolates that demonstrated a cefepime/taniborbactam MIC of 32â mg/L, one possessed NDM-5, OXA-181 and TEM-1B, an OmpC alteration and P333_Y334insYRIN in PBP3, while the second contained CTX-M-71, a truncated OmpF and a large alteration in OmpC (F182_R195delinsMTTNGRDDVFE). CONCLUSIONS: Cefepime/taniborbactam was highly active against ENSE with various antimicrobial resistance phenotypes/genotypes. ENSE isolates with cefepime/taniborbactam MIC values ≥â4â mg/L possessed combinations of ß-lactam resistance mechanisms, including ß-lactamase genes, as well as alterations in OmpC and/or OmpF and/or PBP3.
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In the context of a recent rise in prevalence of NDM-encoding carbapenemase-producing Enterobacterales (CPE) in the province of QC, Canada, the genetic environment of blaNDM-1 was investigated. Three NDM-producing clinical isolates of Enterobacter hormaechei recovered from hospitalized patients involved in a putative outbreak were further characterized by whole-genome sequencing (WGS). Two isolates were confirmed by pulsed-field gel electrophoresis and WGS to be closely related. In addition to a â¼128 kb IncFII conjugative multidrug-resistance (MDR) plasmid, these isolates possessed a â¼45 kb mobilizable IncR MDR plasmid containing 2 MDR regions: a complex class 1 integron harboring blaNDM-1 and 7 other AMR genes, and the IS26-mph(A)-mrx-mphR(A)-IS6100 azithromycin resistance unit. The predicted antimicrobial resistance (AMR) genes correlated with the antimicrobial susceptibility testing results. The multidrug-resistant phenotype in addition to the presence of two important mobile genetic elements, suggest a potent role as a reservoir of antibiotic resistance for such a small IncR plasmid. IMPORTANCE Analyzing the genetic environment of clinically relevant MDR genes can provide information on the way in which such genes are maintained and disseminated. Understanding this phenomenon is of interest for clinicians as it can also provide insight on where these genes might have been sourced, possibly supporting outbreak investigations.
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Antibacterianos/farmacologia , Azitromicina/farmacologia , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Infecções por Enterobacteriaceae/microbiologia , Plasmídeos/genética , beta-Lactamases/metabolismo , Surtos de Doenças , Farmacorresistência Bacteriana , Enterobacter/enzimologia , Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/metabolismo , Quebeque/epidemiologia , beta-Lactamases/genéticaRESUMO
At a hospital system (H1) in Ontario, Canada, we investigated whether whole-genome sequencing (WGS) altered initial epidemiological interpretation of carbapenemase-producing Enterobacterales (CPE) transmission. We included patients with CPE colonization/infection identified by population-based surveillance from October 2007 to August 2018 who received health care at H1 in the year before/after CPE detection. H1 reported epidemiological transmission clusters. We combined single nucleotide variant (SNV) analysis, plasmid characterization, and epidemiological data. Eighty-five patients were included. H1 identified 7 epidemiological transmission clusters, namely, A to G, involving 24/85 (28%) patients. SNV analysis confirmed transmission clusters C, D, and G and identified two additional cases belonging to cluster A. One was a travel-related case that was the likely index case (0 to 6 SNVs from other isolates); this case stayed on the same unit as the initially presumed index case 4 months prior to detection of the initially presumed index case on another unit. The second additional case occupied a room previously occupied by 5 cluster A cases. Plasmid sequence analysis excluded a case from cluster A and identified clusters E and F as possibly two parts of a single cluster. SNV analysis also identified a case without direct epidemiologic links that was 18 to 21 SNVs away from cluster B, suggesting possible undetected interhospital transmission. SNV and plasmid sequence analysis identified cases belonging to transmission clusters that conventional epidemiology missed and excluded other cases. Implementation of routine WGS to complement epidemiological transmission investigations has the potential to improve prevention and control of CPE in hospitals.
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Infecções por Enterobacteriaceae , Viagem , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/epidemiologia , Genômica , Hospitais , Humanos , Ontário , Doença Relacionada a Viagens , beta-Lactamases/genéticaRESUMO
In 2018 to 2019, PCR for carbapenemases in routine Gram-negative isolates submitted to the National Microbiology Laboratory revealed an increase in IMP-type metalloenzyme-positive isolates, mostly among Morganellaceae Whole-genome sequencing revealed that 23 Morganellaceae harbored blaIMP-27 within a chromosomal Tn7 element. Phylogenomics indicated diversity of isolates but also the presence of a few clonal isolates dispersed geographically. These isolates may be difficult to detect due to carbapenem susceptibility and false-negative results in phenotypic testing.IMPORTANCE Over the last decade or so, the frequency of isolation of clinical carbapenemase-producing organisms (CPOs) has increased among health care-associated infections. This may seriously compromise antimicrobial therapy, as carbapenems are considered the last line of defense against these organisms. The ability of carbapenemases to hydrolyze most ß-lactams in addition to the co-occurrence of mechanisms of resistance to other classes of antimicrobials in CPOs can leave few options for treating infections. The class B metalloenzymes are globally distributed carbapenemases, and the most commonly found include the NDM, VIM, and IMP types. Our study describes a sudden emergence of IMP-27-harboring Morganellaceae during 2018 to 2019 in Canada. There is a paucity of literature on IMP-27 isolates, and our data bolster the information on the genetic context, antimicrobial profiles, and phylogenomics of this group of CPOs.
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Proteínas de Bactérias/genética , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Filogenia , beta-Lactamases/genética , Antibacterianos/farmacologia , Canadá/epidemiologia , Carbapenêmicos/farmacologia , Infecção Hospitalar/microbiologia , Enterobacteriaceae/classificação , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. METHODS: We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. RESULTS: Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40). CONCLUSIONS: Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.
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Infecções por Enterobacteriaceae , Proteínas de Bactérias/genética , Humanos , Ontário/epidemiologia , beta-Lactamases/genéticaRESUMO
OBJECTIVES: To investigate a persistent multispecies OXA-204 outbreak occurring simultaneously in multiple distant hospitals in the province of Quebec, Canada. METHODS: OXA-204 carbapenemase-producing Enterobacterales (CPE) isolated from multiple hospitals between January 2016 and October 2018 were included in the study. An epidemiological inquiry was conducted in order to elucidate possible transmission routes and a putative source. Isolates were characterized by standardized antibiotic susceptibility testing and by WGS, using Illumina short-read data and MinION long-read data. RESULTS: The outbreak comprised 65 patients and 82 isolates from four hospital sites. Most patients were ≥65 years old, had multiple comorbidities and had received antibiotics recently. The infection to colonization ratio was 1:20. No persistent environmental reservoir was identified. The most frequent organism was Citrobacter freundii (n = 78), followed by Klebsiella spp. (n = 3) and Escherichia coli (n = 1). WGS analysis showed 77/78 C. freundii isolates differing by 0-26 single nucleotide variants (SNVs). Results of WGS analysis showed blaOXA-204 was present on three plasmids types (IncX1, IncA/C2 and IncFII/FIB/A/C2) and on a prophage. All C. freundii isolates harboured multiple copies of blaOXA-204, both on the chromosome and a plasmid. Plasmid IncFII/FIB/A/C2 was observed in all three species. CONCLUSIONS: Transfer of OXA-204 plasmids likely occurred between species within the same patient, highlighting the plasticity of these plasmids and potential for widespread dissemination. OXA-204 carbapenemase has been introduced into Quebec and has rapidly disseminated. Although the infection to colonization ratio was low in this outbreak, this carbapenemase has been associated with severe infection elsewhere.
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Antibacterianos , Proteínas de Bactérias , Surtos de Doenças , beta-Lactamases , Idoso , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/farmacologia , Canadá , Humanos , Plasmídeos/genética , Quebeque/epidemiologia , beta-Lactamases/genética , beta-Lactamases/farmacologiaRESUMO
This report describes two hypervirulent Klebsiella pneumoniae isolates that produced K. pneumoniae carbapenemase (KPC), which were identified from a rectal swab and a urine culture upon hospital admission. The patient had recently traveled to Greece, where he was hospitalized. The isolates were sequence type 86 and contained an IncHI1B IncFIBK hypervirulent plasmid and an IncFIIK plasmid harboring KPC.
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Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/patogenicidade , Idoso de 80 Anos ou mais , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/etiologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Masculino , Plasmídeos/genética , Quebeque , Reto/microbiologia , Urina/microbiologia , Virulência/genética , beta-LactamasesRESUMO
Objectives: Globally there is an increased prevalence of carbapenem-resistant Acinetobacter spp. (CRAs) and carbapenemase-producing Acinetobacter spp. (CPAs) in the hospital setting. This increase prompted the Canadian Nosocomial Infection Surveillance Program (CNISP) to conduct surveillance of CRA colonizations and infections identified from patients in CNISP-participating hospitals between 2010 and 2016. Methods: Participating acute care facilities across Canada submitted CRAs from 1 January 2010 to 31 December 2016. Patient data were collected from medical records using a standardized questionnaire. WGS was conducted on all CRAs and data underwent single nucleotide variant analysis, resistance gene detection and MLST. Results: The 7 year incidence rate of CRA was 0.02 per 10â000 patient days and 0.015 per 1000 admissions, with no significant increase observed over the surveillance period (P > 0.73). Ninety-four CRA isolates were collected from 58 hospitals, of which 93 (98.9%) were CPA. Carbapenemase OXA-235 group (48.4%) was the most common due to two separate clusters, followed by the OXA-23 group (41.9%). Patients with a travel history were associated with 38.8% of CRA cases. The all-cause 30 day mortality rate for infected cases was 24.4 per 100 CRA cases. Colistin was the most active antimicrobial agent (95.8% susceptibility). Conclusions: CRA remains uncommon in Canadian hospitals and the incidence did not increase from 2010 to 2016. Almost half of the cases were from two clusters harbouring OXA-235-group enzymes. Previous medical treatment during travel outside of Canada was common.
Assuntos
Infecções por Acinetobacter/epidemiologia , Acinetobacter baumannii/isolamento & purificação , Infecção Hospitalar/epidemiologia , Monitoramento Epidemiológico , Hospitais/estatística & dados numéricos , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/enzimologia , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Canadá/epidemiologia , Carbapenêmicos/farmacologia , Criança , Pré-Escolar , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Adulto Jovem , beta-Lactamases/genéticaRESUMO
Background: The standard epidemiologic investigation of outbreaks typically relies on spatiotemporal data and pulsed-field gel electrophoresis (PFGE), but whole genome sequencing (WGS) is becoming increasingly used. This investigation aimed to characterize a carbapenemase-producing Acinetobacter baumannii (CPAb) nosocomial outbreak using WGS compared to a standard outbreak investigation. Methods: The CPAb outbreak occurred in a single center between 2012 and 2014. The standard investigation used spatiotemporal data and PFGE to generate a chain of transmission. A separate WGS investigation generated a chain of transmission based solely on WGS and date of sampling and was blinded to all other spatiotemporal data and PFGE. Core single nucleotide variant (SNV) phylogenetic analysis was performed on WGS data generated using the Illumina MiSeq platform. The chains of transmission were compared quantitatively and qualitatively to assess the concordance between both methods. Results: 28 colonized and infected cases were included. Of the 27 transmission events identified using the standard investigation, 12 (44%) were identical to the transmission events using WGS. WGS identified several transmission events that had not been detected by traditional method, and numerous transmission events that had occurred on different hospital wards than suspected by standard methods. The average number (standard deviation [SD]) of SNVs per transmission events was 1.63 (SD, 1.31) by traditional method and 0.63 (SD, 0.79) by WGS (p = 0.001) All isolates harbored the rare carbapenemase blaOXA-237. Conclusions: The traditional and WGS investigations had moderate concordance. When used alongside epidemiologic data and clinical information, WGS could help improve the mapping of transmission events.