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 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

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: trends in pyrethroid resistance during a WHO-coordinated multi-country prospective study.

BACKGROUND: Increasing pyrethroid resistance has been an undesirable correlate of the rapid increase in coverage of insecticide-treated nets (ITNs) since 2000. Whilst monitoring of resistance levels has increased markedly over this period, longitudinal monitoring is still lacking, meaning the temporal and spatial dynamics of phenotypic resistance in the context of increasing ITN coverage are unclear. METHODS: As part of a large WHO-co-ordinated epidemiological study investigating the impact of resistance on malaria infection, longitudinal monitoring of phenotypic resistance to pyrethroids was undertaken in 290 clusters across Benin, Cameroon, India, Kenya and Sudan. Mortality in response to pyrethroids in the major anopheline vectors in each location was recorded during consecutive years using standard WHO test procedures. Trends in mosquito mortality were examined using generalised linear mixed-effect models. RESULTS: Insecticide resistance (using the WHO definition of mortality < 90%) was detected in clusters in all countries across the study period. The highest mosquito mortality (lowest resistance frequency) was consistently reported from India, in an area where ITNs had only recently been introduced. Substantial temporal and spatial variation was evident in mortality measures in all countries. Overall, a trend of decreasing mosquito mortality (increasing resistance frequency) was recorded (Odds Ratio per year: 0.79 per year (95% CI: 0.79-0.81, P < 0.001). There was also evidence that higher net usage was associated with lower mosquito mortality in some countries. DISCUSSION: Pyrethroid resistance increased over the study duration in four out of five countries. Insecticide-based vector control may be compromised as a result of ever higher resistance frequencies

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  0.05) 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

Model Systems of Human Intestinal Flora, to Set Acceptable Daily Intakes of Antimicrobial Residues

The veterinary use of antimicrobial drugs in food producing animals may result in residues in food, that might modify the consumer gut flora. This review compares three model systems that maintain a complex flora of human origin: (i) human flora associated (HFA) continuous flow cultures in chemostats, (ii) HFA mice, and (iii) human volunteers. The "No Microbial Effect Level" of an antibiotic on human flora, measured in one of these models, is used to set the accept¬able daily intake (ADI) for human consumers. Human volunteers trials are most relevant to set microbio¬log¬ical ADI, and may be considered as the "gold standard". However, human trials are very expensive and unethical. HFA chemostats are controlled systems, but tetracycline ADI calculated from a chemostat study is far above result of a human study. HFA mice studies are less expensive and better controlled than human trials. The tetracycline ADI derived from HFA mice studies is close to the ADI directly obtained in human volunteers