One Health Genomic Analysis of Extended-Spectrum ß-Lactamase‒Producing Salmonella enterica, Canada, 2012‒2016.

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.

Correlation between Phenotypic and In Silico Detection of Antimicrobial Resistance in Salmonella enterica in Canada Using Staramr.

Whole genome sequencing (WGS) of Salmonella supports both molecular typing and detection of antimicrobial resistance (AMR). Here, we evaluated the correlation between phenotypic antimicrobial susceptibility testing (AST) and in silico prediction of AMR from WGS in Salmonella enterica (n = 1321) isolated from human infections in Canada. Phenotypic AMR results from broth microdilution testing were used as the gold standard. To facilitate high-throughput prediction of AMR from genome assemblies, we created a tool called Staramr, which incorporates the ResFinder and PointFinder databases and a custom gene-drug key for antibiogram prediction. Overall, there was 99% concordance between phenotypic and genotypic detection of categorical resistance for 14 antimicrobials in 1321 isolates (18,305 of 18,494 results in agreement). We observed an average sensitivity of 91.2% (range 80.5-100%), a specificity of 99.7% (98.6-100%), a positive predictive value of 95.4% (68.2-100%), and a negative predictive value of 99.1% (95.6-100%). The positive predictive value of gentamicin was 68%, due to seven isolates that carried aac(3)-IVa, which conferred MICs just below the breakpoint of resistance. Genetic mechanisms of resistance in these 1321 isolates included 64 unique acquired alleles and mutations in three chromosomal genes. In general, in silico prediction of AMR in Salmonella was reliable compared to the gold standard of broth microdilution. WGS can provide higher-resolution data on the epidemiology of resistance mechanisms and the emergence of new resistance alleles.

A One-Health Genomic Investigation of Gentamicin Resistance in Salmonella from Human and Chicken Sources in Canada, 2014 to 2017.

We investigated whether the increased prevalence of gentamicin resistance in Salmonella from human infections was related to a similar increased prevalence in isolates from broiler chickens and whether this increase may have been due to coselection from use of lincomycin-spectinomycin in chickens on farms. Whole-genome sequencing was performed on gentamicin-resistant (Genr) Salmonella isolates from human and chicken sources collected from 2014 to 2017 by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). We determined the genomic relatedness of strains and characterized resistance genes and plasmids. From 2014 to 2017, 247 isolates of Genr Salmonella were identified by CIPARS: 188 were from humans, and 59 were from chicken sources (26 from live animals on farm and 33 from retail meat). The five most common Genr serovars were Salmonella enterica serovars Heidelberg (n = 93; 31.5%), 4,[5],12:i:- (n = 42; 14.2%), Kentucky (n = 37; 12.5%), Infantis (n = 33; 11.2%), and Typhimurium (n = 23; 7.8%). Phylogenomic analysis revealed that for S. Heidelberg and S. Infantis, there were closely related isolates from human and chicken sources. In both sources, resistance to gentamicin and spectinomycin was most frequently conferred by aac(3)-VIa and ant(3'')-Ia, respectively. Plasmid closure confirmed linkages of gentamicin and spectinomycin resistance genes and revealed instances of similar plasmids from both sources. Gentamicin and spectinomycin resistance genes were linked on the same plasmids, and some plasmids and isolates from humans and chickens were genetically similar, suggesting that the use of lincomycin-spectinomycin in chickens may be selecting for gentamicin-resistant Salmonella in broiler chickens and that these resistant strains may be acquired by humans.

Randomized controlled trial of chlorhexidine gluconate, intranasal mupirocin, rifampin, and doxycycline versus chlorhexidine gluconate and intranasal mupirocin alone for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization.

Background: Several decolonization regimens have been studied to prevent recurrent methicillin-resistant Staphylococcus aureus (MRSA) infections. Clinical equipoise remains with regard to the role of MRSA decolonization. We compared initial MRSA clearance and subsequent MRSA recolonization rates over a 12-month period after standard decolonization (using topical chlorhexidine gluconate, and intranasal mupirocin) or systemic decolonization (using topical chlorhexidine gluconate, intranasal mupirocin, oral rifampin, and oral doxycycline). Methods: MRSA-colonized patients were randomized to receive either standard or systemic decolonization. Follow-up with MRSA screening was obtained at approximately 3, 6, and 12 months after completion of therapy. Kaplan-Meier survival curves were calculated and assessed for significant differences using log-rank tests. Results: Of 98 enrolled patients (25 standard decolonization, 73 systemic decolonization), 24 patients (7 standard decolonization, 17 systemic decolonization) did not complete the study. Univariate analysis showed a marginally significant difference in the probability of remaining MRSA-negative post-treatment (p = 0.043); patients who received standard decolonization had a 31.9% chance of remaining MRSA-negative compared with a 49.9% chance among those who received systemic decolonization. With multivariate analysis, there was no difference in the probability of remaining MRSA-negative between systemic and standard decolonization (p = 0.165). Initial MRSA clearance was more readily achieved with systemic decolonization (79.1%; 95% CI 32.4% to 71.6%) than with standard decolonization (52.0%; 95% CI 69.4% to 88.8%; p = 0.0102). Conclusions: Initial MRSA clearance is more readily achieved with systemic decolonization than with standard decolonization. There is no significant difference in the probability of sustained MRSA clearance.

Historique: Plusieurs schémas de décolonisation ont été étudiés pour prévenir la récurrence d'infections à Staphylococcus aureus résistant à la méthicilline (SARM). La pondération clinique demeure à l'égard du rôle de la décolonisation du SARM. Les chercheurs ont comparé la clairance initiale du SARM et les taux de recolonisation subséquents par le SARM sur une période de 12 mois après une décolonisation standard (au moyen de gluconate de chlorhexidine topique et de mupirocine intranasale) ou de décolonisation systémique (au moyen de gluconate de chlorhexidine topique, de mupirocine intranasale, de rifampine par voie orale et de doxycycline par voie orale). Méthodologie: Des patients colonisés par le SARM ont été choisis au hasard pour recevoir une décolonisation standard ou systémique. Les chercheurs ont obtenu les données de suivi par un dépistage du SARM environ trois, six et 12 mois après la fin du traitement. Ils ont calculé la courbe de survie de Kaplan-Meier et l'ont évaluée pour déterminer les différences importantes au moyen des tests logarithmiques par rang. Résultats: Des 98 patients inscrits (25 par décolonisation standard, 73 par décolonisation systémique), 24 n'ont pas terminé l'étude (sept par décolonisation standard, 17 par décolonisation systémique). L'analyse univariée a révélé une différence légèrement significative quant à la probabilité de demeurer négatif au SARM après le traitement (p = 0,043). En effet, les patients qui avaient reçu une décolonisation standard avaient 31,9 % de chances de demeurer négatifs au SARM, par rapport à 49,9 % de chances chez ceux qui avaient reçu une décolonisation systémique. À l'analyse multivariée, il n'y avait pas de différence entre la probabilité de demeurer négatif au SARM après une décolonisation systémique ou standard (p = 0,65). La clairance initiale du SARM était obtenue plus rapidement par la décolonisation systémique (79,1 %; IC à 95 % 32,4 % à 71,6 %) que standard (52,0 %; IC à 95 % 69,4 % à 88,8 %; p = 0,0102). Conclusions: La clairance initiale du SARM est plus facile à obtenir par une décolonisation systémique que standard. La clairance initiale du SARM était obtenue plus rapidement par la décolonisation systémique que standard. Il n'y a pas de différence significative dans la probabilité de clairance soutenue du SARM.

An unusual case of meningitis.

Pasteurella multocida is a rare cause of bacterial meningitis. A 56-year-old man with several pets developed a profoundly decreased level of consciousness following left tympanomastoidectomy. Lumbar puncture produced cerebrospinal fluid with the typical findings of meningitis (low glucose, high protein, high leukocytes). Cultures from the cerebrospinal fluid and a swab of the left ear revealed Gram-negative coccobacillus identified as P multocida. The organism was sensitive to ceftriaxone, ampicillin and penicillin, and a 14-day course of intravenous penicillin was used as definitive treatment, resulting in full recovery. Although rare, P multocida should be considered as a potential cause of meningitis in patients with animal exposure, particularly in the setting of recent cranial surgery.

Le Pasteurella multocida est une rare cause de méningite bactérienne. Un homme de 56 ans propriétaire de plusieurs animaux a présenté une importante diminution de son niveau de conscience après une tympanomastoïdectomie gauche. Le liquide céphalorachidien prélevé par ponction lombaire présentait les caractéristiques classiques de la méningite (glycémie basse, protéine élevée, leucocytes élevés). Les cultures du liquide céphalorachidien et un écouvillon de l'oreille gauche ont révélé un coccobacille à Gram négatif, le P multocida. L'organisme était sensible à la ceftriaxone, à l'ampicilline et à la pénicilline. Un traitement de pénicilline administré par voie intraveineuse pendant 14 jours a favorisé un rétablissement complet. Même si c'est rare, le P multocida doit être envisagé comme cause de méningite chez des patients exposés à des animaux, particulièrement après avoir subi une opération crânienne.

Ciprofloxacin-resistant Salmonella enterica serovar Kentucky in Canada.

We report emergence of ciprofloxacin-resistant Salmonella enterica serovar Kentucky in Canada during 2003-2009. All isolates had similar macrorestriction patterns and were multilocus sequence type ST198, which has been observed in Europe and Africa. Ciprofloxacin-resistant S. enterica serovar Kentucky represents 66% of all ciprofloxacin-resistant nontyphoidal Salmonella sp. isolates observed in Canada since 2003.

Emergence of multidrug-resistant Salmonella enterica serotype 4,[5],12:i:- involving human cases in Canada: results from the Canadian Integrated Program on Antimicrobial Resistance Surveillance (CIPARS), 2003-10.

OBJECTIVES: Over the last decade, a marked increase in Salmonella enterica serotype 4,[5],12:i:- with a core resistance to ampicillin, streptomycin, sulphonamides and tetracycline (ASSuT) has been observed in Europe. This study describes the emergence and characterization of isolates of multidrug-resistant Salmonella 4,[5],12:i:- in Canada. METHODS: Human clinical isolates of Salmonella 4,[5],12:i:- were identified by provincial laboratories from 2003 to 2010. Serotyping and phage typing were performed by standardized methodologies. MIC values were determined using broth microdilution. PCR was used to determine the presence of resistance genes. Multilocus sequence typing was performed on a selected number of isolates. RESULTS: A total of 26 251 Salmonella were submitted as part of the Canadian Integrated Program on Antibiotic Resistance Surveillance (CIPARS). Of these, Salmonella 4,[5],12:i:- accounted for a total of 766 isolates (2.9%), and the number increased significantly from 42 (1.4%) in 2003 to 164 (4.8%) in 2010. The ASSuT+ phenotype was observed in 11.9% (n = 91) of Salmonella 4,[5],12:i:- isolates and increased from two isolates in 2003 to 35 isolates in 2010. Two sequence types (STs) were observed. ST34 was mainly associated with the ASSuT isolates (n = 24; 38%), which contained blaTEM, strA-strB, tet(B) and sul2. ST19 was more likely to be associated with the ACSSuT phenotype and contained blaTEM, floR, strA-strB, sul2 and tet(A) or blaPSE-1, floR, aadA2, sul1 and tet(G). CONCLUSIONS: The prevalence of Salmonella 4,[5],12:i:- has significantly increased from 2003 to 2010 and it is now the fifth most common serotype reported in Canada causing human disease. Similar antimicrobial resistance patterns, phage types and STs have been observed in Europe.