Characterization of carbapenem-resistant and XDR Pseudomonas aeruginosa in Canada: results of the CANWARD 2007-16 study.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa are emerging worldwide with increasing reports of carbapenemase-producing isolates. Carbapenem-resistant isolates may also be XDR. This study characterized carbapenem-resistant and XDR P. aeruginosa isolated from patients receiving care at Canadian hospitals from 2007 to 2016. METHODS: Antimicrobial susceptibility testing was performed using CLSI broth microdilution methods. PCR was used to detect carbapenemases (GES, KPC, NDM, IMP, VIM, OXA-48) and other resistance markers; specific carbapenemase gene variants were identified by DNA sequencing. Genetic relatedness was assessed by MLST and PFGE. RESULTS: From 2007 to 2016, 3864 isolates of P. aeruginosa were collected; 466 (12.1%) isolates were carbapenem resistant. The prevalence of carbapenem-resistant P. aeruginosa reached a peak of 17.3% in 2014. Colistin (94% susceptible) and ceftolozane/tazobactam (92.5%) were the most active agents against carbapenem-resistant P. aeruginosa. XDR P. aeruginosa comprised 4.5% of isolates; they were found to be genetically diverse and remained susceptible to colistin and ceftolozane/tazobactam. Only 4.3% (n = 20) of carbapenem-resistant P. aeruginosa harboured a carbapenemase; most were blaGES-5 (35%, n = 7). Wide genetic diversity was observed among carbapenem-resistant P. aeruginosa with >200 different sequence types identified. CONCLUSIONS: Although the prevalence of carbapenem-resistant P. aeruginosa in Canada spiked in 2014 and 2015, carbapenemase-producing P. aeruginosa remain rare with only 20 (4.3%) isolates identified over a 10 year period. Broad genetic diversity was observed among both carbapenem-resistant and XDR phenotypes of P. aeruginosa. Pan-drug-resistant P. aeruginosa have not yet been identified in Canada.

Comparison of antimicrobial resistance patterns in Streptococcus pneumoniae from respiratory and blood cultures in Canadian hospitals from 2007-16.

OBJECTIVES: To compare the epidemiology and antimicrobial susceptibility patterns of Streptococcus pneumoniae collected from respiratory and blood culture samples in Canada between 2007 and 2016. METHODS: S. pneumoniae strains were obtained from Canadian hospitals as part of the ongoing national surveillance study, CANWARD. Isolates were serotyped using the Quellung method. Antimicrobial susceptibility testing was performed using the CLSI broth microdilution method. MDR and XDR were defined as resistance to three or more and five or more classes of antimicrobials, respectively. RESULTS: Of the 2581 S. pneumoniae isolates collected, 1685 (65.3%) and 896 (34.7%) were obtained from respiratory and blood samples, respectively. Respiratory isolates demonstrated lower rates of antimicrobial susceptibility than blood isolates to penicillin, ceftriaxone, clarithromycin, clindamycin, doxycycline and trimethoprim/sulfamethoxazole (P ≤ 0.03). From 2007 to 2016, invasive isolates demonstrated trends towards increasing penicillin susceptibility and decreasing clarithromycin susceptibility. MDR was significantly higher in respiratory S. pneumoniae compared with blood (9.1% versus 4.5%, P < 0.0001). Serotypes 11A, 16F, 19F, 23A/B/F, 34, 35B and non-typeable strains were more commonly isolated from respiratory specimens, while 4, 5, 7F, 8, 12F, 14 and 19A were more commonly invasive serotypes. Numerous serotypes, including 3 and 22F, were isolated frequently from both specimen sources. CONCLUSIONS: S. pneumoniae from respiratory samples demonstrated lower antimicrobial susceptibilities and higher MDR in a greater diversity of serotypes than isolates obtained from blood. Many serotypes were associated with one specific specimen source, while others were associated with both; genetic characterization is necessary to elucidate the specific factors influencing the ability of these serotypes to commonly cause both invasive and non-invasive disease.

Characterization of MRSA in Canada from 2007 to 2016.

OBJECTIVES: This study assessed the demographic and molecular characteristics of community-associated (CA) and healthcare-associated (HA) MRSA genotypes in Canadian hospitals between 2007 and 2016. METHODS: A total of 1963 MRSA were identified among 9103 Staphylococcus aureus isolates collected from inpatients and outpatients presenting to tertiary-care medical centres across Canada. Antimicrobial susceptibility testing was performed by broth microdilution in accordance with CLSI standards (M7 11th edition, 2018). PCR was performed to detect the Panton-Valentine leucocidin (PVL) genes and molecular analysis was performed by spa typing. RESULTS: Between 2007 and 2016, the annual proportion of S. aureus that were MRSA decreased from 26.1% to 16.9% (P < 0.0001). The proportion of CA-MRSA genotypes increased significantly from 20.8% in 2007 to 56.3% in 2016 (P < 0.0001) while HA-MRSA genotypes decreased from 79.2% to 43.8% throughout the study period (P < 0.0001). Predominant genotypes included HA genotype CMRSA2 (USA100/800) (53.6%) and CA genotype CMRSA10 (USA300) (24.9%). PVL was present in 30.1% of all MRSA isolates, including 78.4% of CA-MRSA and 1.7% of HA-MRSA genotypes. Resistance to clarithromycin, clindamycin, trimethoprim/sulfamethoxazole and fluoroquinolones decreased significantly over time (P < 0.0001). CONCLUSIONS: The proportion of MRSA in Canada declined between 2007 and 2016. In contrast, the proportion of CA-MRSA strain types, particularly CMRSA10 (USA300), continues to increase. In 2016, CA-MRSA genotypes surpassed HA-MRSA as the most common cause of MRSA infections in Canadian hospitals.

Dramatic rise in the proportion of ESBL-producing Escherichia coli and Klebsiella pneumoniae among clinical isolates identified in Canadian hospital laboratories from 2007 to 2016.

OBJECTIVES: To assess the prevalence, antimicrobial susceptibilities and molecular characteristics of ESBL-producing Escherichia coli and Klebsiella pneumoniae infecting patients receiving care in Canadian hospitals from January 2007 to December 2016. METHODS: Clinical isolates of E. coli (n = 8387) and K. pneumoniae (n = 2623) submitted to CANWARD, an ongoing Canadian national surveillance study, were tested using the CLSI reference broth microdilution method to determine their susceptibility to 15 antimicrobial agents. ESBL-producing E. coli and K. pneumoniae confirmed by the CLSI phenotypic method and putative AmpC-producing E. coli underwent PCR testing and DNA sequencing to identify resistance genes. Annual proportions of isolates harbouring ESBL and AmpC genes were assessed by the Cochran-Armitage test of trend. RESULTS: The annual proportion of isolates of E. coli that were ESBL producing increased from 3.4% in 2007 to 11.1% in 2016 (P < 0.0001); >95% of ESBL-producing E. coli were susceptible to amikacin, colistin, ertapenem, meropenem and tigecycline. The proportion of isolates of K. pneumoniae that were ESBL producing increased from 1.3% in 2007 to 9.7% in 2016 (P < 0.0001); >95% of ESBL-producing K. pneumoniae were susceptible to amikacin and meropenem. CTX-M-15 was the predominant genotype in both ESBL-producing E. coli (64.2% of isolates) and ESBL-producing K. pneumoniae (51.0%). The annual proportion of isolates of E. coli that were AmpC producing [annual proportion mean 1.9% (range 0.3%-3.1%)] was unchanged from 2007 to 2016 (P > 0.5). CONCLUSIONS: The prevalence of both ESBL-producing E. coli and K. pneumoniae increased significantly in Canada during the study period while the prevalence of AmpC-producing E. coli remained low and stable.

42936 pathogens from Canadian hospitals: 10 years of results (2007-16) from the CANWARD surveillance study.

OBJECTIVES: The CANWARD surveillance study was established in 2007 to annually assess the in vitro susceptibilities of a variety of antimicrobial agents against bacterial pathogens isolated from patients receiving care in Canadian hospitals. METHODS: 42 936 pathogens were received and CLSI broth microdilution testing was performed on 37 355 bacterial isolates. Limited patient demographic data submitted with each isolate were collated and analysed. RESULTS: Of the isolates tested, 43.5%, 33.1%, 13.2% and 10.2% were from blood, respiratory, urine and wound specimens, respectively; 29.9%, 24.8%, 19.0%, 18.1% and 8.2% of isolates were from patients in medical wards, emergency rooms, ICUs, hospital clinics and surgical wards. Patient demographics associated with the isolates were: 54.6% male/45.4% female; 13.1% patients aged ≤17 years, 44.3% 18-64 years and 42.7% ≥65 years. The three most common pathogens were Staphylococcus aureus (21.2%, both methicillin-susceptible and MRSA), Escherichia coli (19.6%) and Pseudomonas aeruginosa (9.0%). E. coli were most susceptible to meropenem and tigecycline (99.9%), ertapenem and colistin (99.8%), amikacin (99.7%) and ceftolozane/tazobactam and plazomicin (99.6%). Twenty-three percent of S. aureus were MRSA. MRSA were most susceptible to ceftobiprole, linezolid and telavancin (100%), daptomycin (99.9%), vancomycin (99.8%) and tigecycline (99.2%). P. aeruginosa were most susceptible to ceftolozane/tazobactam (98.3%) and colistin (95.0%). CONCLUSIONS: The CANWARD surveillance study has provided 10 years of reference antimicrobial susceptibility testing data on pathogens commonly causing infections in patients attending Canadian hospitals.

Trends in antimicrobial resistance over 10 years among key bacterial pathogens from Canadian hospitals: results of the CANWARD study 2007-16.

OBJECTIVES: We sought to analyse 10 years of longitudinal surveillance data (2007-16) from the CANWARD study and describe emerging trends in antimicrobial resistance for key bacterial pathogens across Canada. METHODS: Longitudinal data from CANWARD study sites that contributed isolates every year from 2007 to 2016 were analysed to identify trends in antimicrobial resistance over time using univariate tests of trend and multivariate regression models to account for the effects of patient demographics. RESULTS: Statistically significant increases occurred in the proportion of Escherichia coli isolates resistant to extended-spectrum cephalosporins, amoxicillin/clavulanate, trimethoprim/sulfamethoxazole and ciprofloxacin. Similarly, the proportion of Klebsiella pneumoniae isolates resistant to extended-spectrum cephalosporins, amoxicillin/clavulanate, trimethoprim/sulfamethoxazole, ciprofloxacin and carbapenems increased during the study. The proportion of Enterobacter cloacae isolates resistant to ceftazidime and trimethoprim/sulfamethoxazole increased. The proportion of both ESBL-positive E. coli and K. pneumoniae (including bloodstream isolates) increased significantly between 2007 and 2016. A reduction in the proportion of Pseudomonas aeruginosa that were ciprofloxacin, cefepime, colistin, amikacin and gentamicin resistant and an increase in the proportion of P. aeruginosa isolates non-susceptible to meropenem were observed. The proportion of isolates of Staphylococcus aureus non-susceptible to clarithromycin, clindamycin and trimethoprim/sulfamethoxazole decreased over time while an increase in the proportion of isolates of Streptococcus pneumoniae non-susceptible to clarithromycin, clindamycin and doxycycline was observed. CONCLUSIONS: Increases in Enterobacteriaceae resistance to multiple classes of antimicrobials, increases in ESBL-positive E. coli and K. pneumoniae, and the small but significant increase in carbapenem-resistant K. pneumoniae were the most remarkable changes in antimicrobial resistance observed from 2007 to 2016 in Canada.

Antimicrobial-resistant pathogens in Canadian ICUs: results of the CANWARD 2007 to 2016 study.

OBJECTIVES: To describe the microbiology and antimicrobial resistance patterns of cultured samples acquired from Canadian ICUs. METHODS: From 2007 to 2016, tertiary care centres from across Canada submitted 42938 bacterial/fungal isolates as part of the CANWARD surveillance study. Of these, 8130 (18.9%) were from patients on ICUs. Susceptibility testing guidelines and MIC interpretive criteria were defined by CLSI. RESULTS: Of the 8130 pathogens collected in this study, 58.2%, 36.3%, 3.1% and 2.4% were from respiratory, blood, wound and urine specimens, respectively. The top five organisms collected from Canadian ICUs accounted for 55.4% of all isolates and included Staphylococcus aureus (21.5%), Pseudomonas aeruginosa (10.6%), Escherichia coli (10.4%), Streptococcus pneumoniae (6.5%) and Klebsiella pneumoniae (6.4%). MRSA accounted for 20.7% of S. aureus collected, with community-associated (CA) MRSA genotypes increasing in prevalence over time (P < 0.001). The highest susceptibility rates among MRSA were 100% for vancomycin, 100% for ceftobiprole, 100% for linezolid, 99.7% for ceftaroline, 99.7% for daptomycin and 99.7% for tigecycline. The highest susceptibility rates among E. coli were 100% for tigecycline, 99.9% for meropenem, 99.7% for colistin and 94.2% for piperacillin/tazobactam. MDR was identified in 26.3% of E. coli isolates, with 10.1% producing an ESBL. The highest susceptibility rates among P. aeruginosa were 97.5% for ceftolozane/tazobactam, 96.1% for amikacin, 94.7% for colistin and 93.3% for tobramycin. CONCLUSIONS: The most active agents against Gram-negative bacilli were the carbapenems, tigecycline and piperacillin/tazobactam. Against Gram-positive cocci, the most active agents were vancomycin, daptomycin and linezolid. The prevalence of CA-MRSA genotypes and ESBL-producing E. coli collected from ICUs increased significantly over time.

In vitro activity of ceftolozane/tazobactam versus antimicrobial non-susceptible Pseudomonas aeruginosa clinical isolates including MDR and XDR isolates obtained from across Canada as part of the CANWARD study, 2008-16.

Objectives: Ceftolozane/tazobactam is a novel ß-lactam ß-lactamase inhibitor combination with a broad spectrum of activity that includes Pseudomonas aeruginosa. The purpose of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and relevant comparators versus a large collection of antimicrobial non-susceptible P. aeruginosa clinical isolates recovered from patients across Canada (CANWARD, 2008-16). Methods: Susceptibility testing was performed on P. aeruginosa clinical isolates obtained from sentinel hospitals across Canada between January 2008 and December 2016 using broth microdilution, as described by the CLSI. MDR P. aeruginosa were defined as isolates that tested non-susceptible to at least one antimicrobial from ≥3 classes. XDR P. aeruginosa were defined as isolates that tested non-susceptible to at least one antimicrobial from ≥5 classes. Results: In total, 3229 P. aeruginosa isolates were obtained as a part of CANWARD. Ceftolozane/tazobactam was the most active antimicrobial evaluated, with 98.3% of isolates testing susceptible. The percentage of antimicrobial non-susceptible isolates that remained susceptible to ceftolozane/tazobactam ranged from 85.3% (amikacin non-susceptible subset) to 95.0% (ciprofloxacin non-susceptible subset). Four-hundred and sixty-two P. aeruginosa isolates were MDR (14.3% of all isolates tested) and 84 were XDR (2.6% of all isolates tested). Ceftolozane/tazobactam demonstrated excellent in vitro activity versus the MDR and XDR isolates, with 90.5% and 78.6% remaining susceptible, respectively. Conclusions: Ceftolozane/tazobactam demonstrated excellent in vitro activity against antimicrobial non-susceptible P. aeruginosa clinical isolates, including MDR and XDR subsets. It may prove useful in the treatment of infections caused by these organisms.

Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011-15.

Objectives: To assess antimicrobial susceptibility for 14 agents tested against 6001 invasive isolates of Streptococcus pneumoniae cultured from invasive patient samples from 2011 to 2015 as a part of the annual SAVE study. Methods: Isolates of S. pneumoniae were tested using the standard CLSI broth microdilution method (M07-A10, 2015) with MICs interpreted by CLSI M100 27th Edition (2017) MIC breakpoints. Results: From 2011 to 2015, small but significant increases (P ≤ 0.05) in the percentage susceptibility for penicillin (interpreted by all three CLSI MIC breakpoint criteria) (increase of 1.7%-3.2%), clindamycin (3.1%) and ceftriaxone (interpreted by non-meningitis and meningitis CLSI MIC breakpoint criteria) (1.1%-1.5%) were observed. Susceptibility rates for clarithromycin and other commonly tested antimicrobial agents remained unchanged (P > 0.05) over the 5 year period. Isolates with an MDR phenotype (resistance to three or more antimicrobial agent classes) decreased significantly (P < 0.001) from 8.5% in 2011 to 5.6% in 2015. Antimicrobial susceptibility rates were not generally associated (P > 0.05) with patient gender (exception: clarithromycin) but were associated (P ≤ 0.05) with patient age (chloramphenicol and clindamycin) or specimen source (penicillin, doxycycline, trimethoprim/sulfamethoxazole and clindamycin), as well as geographic location in Canada and concurrent resistance to penicillin or clarithromycin. Conclusions: The in vitro susceptibility of invasive isolates of S. pneumoniae in Canada to penicillin, clindamycin and ceftriaxone increased from 2011 to 2015, coincident with a significant decrease in MDR phenotypes.

Analysis of multidrug resistance in the predominant Streptococcus pneumoniae serotypes in Canada: the SAVE study, 2011-15.

Objectives: This study assessed MDR invasive isolates of Streptococcus pneumoniae, in relation to serotype evolution in Canada between 2011 and 2015 as part of the annual SAVE study. Methods: As part of a collaboration between the Canadian Antimicrobial Resistance Alliance and Public Health Agency of Canada-National Microbiology Laboratory, 6207 invasive isolates of S. pneumoniae were evaluated. All isolates were serotyped and had antimicrobial susceptibility testing performed, in accordance with CLSI guidelines (M07-A10, 2015). Complete susceptibility profiles were available for 6001 isolates. MDR was defined as resistance to three or more classes of antimicrobial agents (with penicillin MIC ≥2 mg/L defined as resistant). Results: The overall rate of MDR S. pneumoniae was 6.2% (372/6001) in SAVE, decreasing significantly from 8.5% in 2011 to 5.6% in 2015 (P = 0.0041). MDR was observed in 32 serotypes, with serotypes 15A and 19A predominating (26.6% and 41.7% of the MDR isolates, respectively). The overall proportion of serotypes 19A, 7F and 33A decreased significantly (P < 0.0001) throughout the study. The annual proportion of serotypes 7C, 8, 9N, 10A, 20, 24F, 29, 31, 33F, 35B and 38 increased throughout the study; however, among these increasing serotypes, MDR was only notable (>5%) for 24F and 33F. Conclusions: In 2015, 56.3% of invasive MDR S. pneumoniae were serotypes included in the PCV-13 vaccine. PCV-13 includes the most commonly identified serotype, 19A; however, other increasingly important MDR serotypes, such as 15A, 24F and 33F, are notably not in the currently used vaccines.

Molecular characterization of predominant Streptococcus pneumoniae serotypes causing invasive infections in Canada: the SAVE study, 2011-15.

Objectives: This study characterized the 11 most predominant serotypes of invasive Streptococcus pneumoniae infections collected by the annual SAVE study in Canada, between 2011 and 2015. Methods: A subset of the 11 most predominant serotypes (7F, 19A, 22F, 3, 12F, 11A, 9N, 8, 33F, 15A and 6C) collected by the SAVE study was analysed using PFGE and MLST, as well as PCR to identify pilus-encoding genes. WGS analyses were performed on a subset of the above isolates plus a random selection of background strains. Results: Of the predominant serotypes analysed, 7F, 33F and 19A were obtained more commonly from children <6 years of age, whereas 15A, 6C, 22F and 11A were more common in adults >65 years of age. Pneumococcal pilus PI-1 was identified in antimicrobial-susceptible serotype 15A (61/212) and <10% of 6C isolates (16/188). PI-2 was found in serotype 7F (683/701) and two-thirds of 11A isolates (162/241). Only serotype 19A-ST320 possessed both pili. Molecular and phylogenetic analyses identified serotypes 19A, 15A, 6C, 9N and 33F as highly diverse, whereas 7F, 22F and 11A demonstrated clonality. Antimicrobial resistance determinants were common within diverse serotypes, and usually similar within a clonal complex. Conclusions: Despite successful use of conjugate vaccines, S. pneumoniae remains a highly diverse organism in Canada. Several predominant serotypes, both antimicrobial susceptible and MDR, have demonstrated rapid clonal expansion or an increase in diversity. As S. pneumoniae continues to evolve in Canada, WGS will be a necessary component in the ongoing surveillance of antimicrobial-resistant and expanding clones.

Activity of Ertapenem against Enterobacteriaceae in seven global regions-SMART 2012-2016.

Antimicrobial resistance among Enterobacteriaceae has been increasing globally especially due to extended-spectrum-ß-lactamases (ESBLs), which typically necessitate the use of carbapenems for treatment of serious infections. Emerging carbapenem-resistant Enterobacteriaceae further complicate therapy. As part of the Study for Monitoring Antimicrobial Resistance Trends (SMART), this analysis examined the recent activity of a key carbapenem (ertapenem) and other important therapeutic options against Enterobacteriaceae. From 2012 to 2016, 224 hospitals in 57 countries collected up to 100 consecutive gram-negative bacilli from intra-abdominal (IAI) and 50 from urinary tract infections (UTI) per year, totaling 106,300 Enterobacteriaceae isolates. Susceptibility was determined using CLSI broth microdilution and breakpoints. Although statistically significant decreasing trends in ertapenem activity against Enterobacteriaceae were found in all regions except Middle East, the actual size of the decreases was < 3 percentage points, and susceptibility in 2015-2016 remained ca. 90% or higher, ranging from 89.5% in Asia to 97.3% in US/Canada. Of the comparators, only amikacin exceeded these results. Ertapenem was active against > 90% of isolates with ESBL phenotype from Latin America, Middle East, South Pacific, and US/Canada, and against > 80% of MDR isolates in all regions except Africa (72.9%), Asia (75.1%), and Europe (78.0%). Only imipenem, amikacin, and colistin exceeded these rates. Ertapenem, which is popular among clinicians due to its convenient once-daily dosing schedule and favorable safety and tolerability profile, remains highly active against Enterobacteriaceae from IAI and UTI, even as ESBLs and other resistance mechanisms limit therapeutic options, but continued susceptibility testing for surveillance and individual patients is important.

In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program.

Ceftaroline, the active metabolite of the prodrug ceftaroline-fosamil, is an advanced-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). This investigation provides in vitro susceptibility data for ceftaroline against 1,971 S. aureus isolates collected in 2012 from seven countries (26 centers) in the Asia-Pacific region as part of the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) program. Broth microdilution as recommended by the CLSI was used to determine susceptibility. In all, 62% of the isolates studied were MRSA, and the ceftaroline MIC90 for all S. aureus isolates was 2 µg/ml (interpretive criteria: susceptible, ≤1 µg/ml). The overall ceftaroline susceptibility rate for S. aureus was 86.9%, with 100% of methicillin-sensitive S. aureus isolates and 78.8% of MRSA isolates susceptible to this agent. The highest percentages of ceftaroline-nonsusceptible MRSA isolates came from China (47.6%), all of which showed intermediate susceptibility, and Thailand (37.1%), where over half (52.8%) of isolates were resistant to ceftaroline (MIC, 4 µg/ml). Thirty-eight ceftaroline-nonsusceptible isolates (MIC values of 2 to 4 µg/ml) were selected for molecular characterization. Among the isolates analyzed, sequence type 5 (ST-5) was the most common sequence type encountered; however, all isolates analyzed from Thailand were ST-228. Penicillin-binding protein 2a (PBP2a) substitution patterns varied by country, but all isolates from Thailand had the Glu239Lys substitution, and 12 of these also carried an additional Glu447Lys substitution. Ceftaroline-fosamil is a useful addition to the antimicrobial agents that can be used to treat S. aureus infections. However, with the capability of this species to develop resistance to new agents, it is important to recognize and monitor regional differences in trends as they emerge.

Assessment of the In Vitro Activity of Ceftazidime-Avibactam against Multidrug-Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study, 2012 to 2014.

Increasing resistance in Gram-negative bacilli, including Klebsiella spp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-ß-lactam ß-lactamase inhibitor, protects ß-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum ß-lactamases (ESBLs) and serine carbapenemases, including Ambler class A and/or class C and some class D enzymes. In this analysis, we report the in vitro activity of ceftazidime-avibactam and comparators against multidrug-resistant (MDR) Klebsiella spp. from the 2012-2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%) Klebsiella species isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an ESBL screen-positive phenotype, and 27.4% were not susceptible to meropenem as an example of a carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90 values of 0.5/2 µg/ml and 96.6% of all MDR isolates and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value of ≤8 µg/ml). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-ß-lactamases) either alone or in combination with other enzymes. These in vitro results support the continued investigation of ceftazidime-avibactam for the treatment of MDR Klebsiella species infections.

In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolates Collected in 2012 from Latin American Countries as Part of the AWARE Surveillance Program.

The in vitro activities of ceftaroline and comparators, using broth microdilution, were determined against 1,066 Staphylococcus aureus isolates from hospitalized patients. Seventeen medical centers from Latin American countries contributed isolates. Methicillin-resistant S. aureus (MRSA) percentages ranged from 46% (Brazil) to 62% (Argentina). All methicillin-susceptible S. aureus (MSSA) isolates were susceptible to ceftaroline. Ceftaroline activity against MRSA varied with MIC90s of 0.5 (Venezuela) to 2 (Brazil, Chile, and Colombia) µg/ml, which was the highest MIC value. ST-5 was the most common sequence type.

Characterization of MDR and XDR Streptococcus pneumoniae in Canada, 2007-13.

OBJECTIVES: The goal of this study was to characterize Streptococcus pneumoniae demonstrating MDR (resistant to three or more antimicrobial classes) or XDR (resistant to five or more classes) phenotypes, collected from Canada during the CANWARD 2007-13 study. METHODS: From 2007 to 2013 inclusive, S. pneumoniae isolates were collected as a part of the CANWARD surveillance study. MDR and XDR isolates were subjected to PFGE, MLST, molecular detection of pneumococcal pili and macrolide resistance determinants mef(A/E) and erm(B), sequencing of PBPs 1A, 2B and 2X and comparison with Pneumococcal Molecular Epidemiology Network (PMEN) clones. RESULTS: Of 2129 S. pneumoniae isolates collected during the CANWARD 2007-13 study, 61 (2.9%) were found to be MDR. Of these MDR isolates, 43 (70.5%) were XDR. The most common serotypes for both MDR and XDR S. pneumoniae were 19A and 19F. Twenty-nine of 61 isolates (48%) demonstrated resistance to clarithromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulfamethoxazole. All isolates possessed at least one macrolide resistance determinant and mutations in PBPs 1A, 2B and 2X. The most common clone was piliated, XDR ST320, an internationally circulating double-locus variant of Taiwan(19F)-14 (ST236). CONCLUSIONS: Though the rate of MDR S. pneumoniae has remained relatively stable since 2007, XDR strains have emerged in Canada. These strains are virulent, possess resistance determinants and are related to international clones.

Assessment of multidrug resistance, clonality and virulence in non-PCV-13 Streptococcus pneumoniae serotypes in Canada, 2011-13.

OBJECTIVES: Serotype replacement in Streptococcus pneumoniae following the implementation of a new vaccine has been associated with the emergence of non-vaccine serotypes as prominent causes of invasive pneumococcal disease (IPD). The aim of this study was to characterize specific non-PCV-13 serotypes 15A, 22F, 33F and 35B from IPD, isolated in Canada post-PCV-13 introduction in 2010. METHODS: Of 3802 IPD isolates collected from across Canada in 2011-13, 18.4% were found to be serotypes 15A, 22F, 33F and 35B. These 699 isolates were subjected to antimicrobial susceptibility testing, PFGE, MLST, molecular detection of pneumococcal pili and comparison with Pneumococcal Molecular Epidemiology Network (PMEN) clones. RESULTS: This study demonstrated clonal spread of specific STs, including MDR ST63 and its Sweden(15A)-25-related variants, the increasingly common ST433 and a variant of piliated, penicillin-non-susceptible ST558, related to PMEN clone Utah(35B)-24 (ST377). New STs of serotype 33F were identified. Several potential capsular switching events were identified within these serotypes. CONCLUSIONS: Non-PCV-13 serotype 22F is increasing in Canada through the rapid clonal expansion of ST433. Numerous new STs associated with serotype 33F indicate the potential divergence of the serotype. Serotypes 15A and 35B in Canada are related to international clones of S. pneumoniae.

Global in vitro activity of tigecycline and comparator agents: Tigecycline Evaluation and Surveillance Trial 2004-2013.

BACKGROUND: The Tigecycline Evaluation and Surveillance Trial (TEST) is a global antimicrobial susceptibility surveillance study which has been ongoing since 2004. This report examines the in vitro activity of tigecycline and comparators against clinically important pathogens collected globally between 2004 and 2013. METHODS: Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute. The Cochran Armitage Trend Test was used to identify statistically significant changes in susceptibility between 2004 and 2013. RESULTS: Among the Enterobacteriaceae susceptibility was highest to the carbapenems [imipenem 97.1% (24,655/25,381), meropenem 97.0% (90,714/93,518)], tigecycline (97.0%, 115,361/118,899) and amikacin (96.9%, 115,200/118,899). Against Acinetobacter baumannii the highest rates of susceptibility were for minocycline (84.5%, 14,178/16,778) and imipenem (80.0%, 3,037/3,795). The MIC90 for tigecycline was 2 mg/L. 40% (6,743/16,778) of A. baumannii isolates were multidrug-resistant. Enterococci were highly susceptible to tigecycline and linezolid (>99%); vancomycin resistance was observed among 2% of Enterococcus faecalis (325/14,615) and 35% of Enterococcus faecium (2,136/6,167) globally. 40% (14,647/36,448) of Staphylococcus aureus were methicillin-resistant while 15% (2,152/14,562) of Streptococcus pneumoniae were penicillin-resistant. Against S. aureus and S. pneumoniae susceptibility to linezolid, vancomycin, and tigecycline was ≥99.9%. Globally, 81% (331/410) of statistically significant susceptibility changes during the study period were decreases in susceptibility. CONCLUSIONS: Amikacin, the carbapenems, and tigecycline were active against most gram-negative pathogens while linezolid, tigecycline, and vancomycin retained activity against most gram-positive pathogens collected in TEST during 2004-2013.

Global incidence of carbapenemase-producing Escherichia coli ST131.

We characterized Escherichia coli ST131 isolates among 116 carbapenemase-producing strains. Of isolates from 16 countries collected during 2008-2013, 35% belonged to ST131 and were associated with blaKPC, H30 lineage, and virotype C. This study documents worldwide incidents of resistance to "last resort" antimicrobial drugs among a common pathogen in a successful sequence type.

In Vitro activity of fosfomycin against Escherichia coli isolated from patients with urinary tract infections in Canada as part of the CANWARD surveillance study.

We tested 868 urinary isolates of Escherichia coli collected from 2010 to 2013 as part of the Canadian national surveillance study CANWARD against fosfomycin by using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method with MIC interpretation in accordance with the CLSI M100-S23 (2013) criteria. The concentrations of fosfomycin inhibiting 50 and 90% of the isolates were ≤1 and 4 µg/ml; 99.4% of the isolates were susceptible to fosfomycin.