Genetic Environments of Plasmid-Mediated <i>bla</i>_CTXM-15 Beta-Lactamase Gene in Enterobacteriaceae from Africa

The most widely distributed blaCTX-M gene on a global scale is blaCTX-M-15. The dissemination has been associated with clonal spread and different types of mobile genetic elements. The objective of this review was to describe the genetic environments of the blaCTX-M-15 gene detected from Enterobacteriaceae in published literature from Africa. A literature search for relevant articles was performed through PubMed, AJOL, and Google Scholar electronic databases; 43 articles from 17 African countries were included in the review based on the eligibility criteria. Insertion sequences were reported as part of the genetic environment of blaCTX-M-15 gene in 32 studies, integrons in 13 studies, and plasmids in 23 studies. In this review, five insertion sequences including ISEcp1, IS26, orf447, IS903, and IS3 have been detected which are associated with the genetic environment of blaCTX-M-15 in Africa. Seven different genetic patterns were seen in the blaCTX-M-15 genetic environment. Insertion sequence ISEcp1 was commonly located upstream of the end of the blaCTX-M-15 gene, while the insertion sequence orf477 was located downstream. In some studies, ISEcp1 was truncated upstream of blaCTX-M-15 by insertion sequences IS26 and IS3. The class 1 integron (Intl1) was most commonly reported to be associated with blaCTX-M-15 (13 studies), with Intl1/dfrA17–aadA5 being the most common gene cassette array. IncFIA-FIB-FII multi-replicons and IncHI2 replicon types were the most common plasmid replicon types that horizontally transferred the blaCTX-M-15 gene. Aminoglycoside-modifying enzymes, and plasmid-mediated quinolone resistance genes were commonly collocated with the blaCTX-M-15 gene on plasmids. This review revealed the predominant role of ISEcp1, Intl1 and IncF plasmids in the mobilization and continental dissemination of the blaCTX-M-15 gene in Africa

Resistance to extended-spectrum cephalosporins in Escherichia coli and Salmonella enterica isolated from food-producing animals: Ecological study from selected national surveillance programs

© 2022 cc-by-nc-ndExtended-spectrum cephalosporins (ESC) are categorized by World Health Organization as critically important antimicrobials with limited therapeutic alternatives for the treatment of severe bacterial infections in humans. Preserving the effectiveness of ESC requires continuous monitoring of resistance and comparison of associated data across national surveillance programs in the face of globalization. In this ecological study, we compared ESC resistance in Escherichia coli and Salmonella enterica isolated from food-producing animals from 2003 to 2019 between nine countries (Canada, Denmark, Finland, Japan, Netherlands, Norway, Sweden, United Kingdom, and the United States). Using the beta-regression model, compared to Canada, non-selective ESC-R Salmonella enterica was less likely isolated from food producing animals in other eight countries (Odds ratio range: 0.07–0.76). We observed an interaction between the country and the year with a significantly decreased proportion (P < 0.05) of non-selective ESC-R Escherichia coli from the Netherlands, the United Kingdom, and the United States compared to Canada over the years. There was a linear correlation between non-selective ESC-R Escherichia coli and ESC use from Netherlands (Spearman's ρ = 0.91, P < 0.0001). For the six European countries, the interaction between the country and year showed a significant decrease in the proportion of selective ESC-R Escherichia coli over the years for the Netherlands compared to Denmark (P = 0.002). While there were variations in the proportion of beta-lactamase genes reported over the years, blaCTX-M and blaCMY-2 genes were commonly detected among the selective ESC-R Escherichia coli. This study reveals variability in the recovery of ESC-resistant bacteria among the countries that seems likely influenced by the individual country policy on the use of critically important antimicrobials and resistance surveillance programs. However, there is a need for harmonization and consistency in food animal sources of bacterial isolates used in surveillance programs within and between the countries for easy comparability

Predictive Modeling of Phenotypic Antimicrobial Susceptibility of Selected Beta-Lactam Antimicrobials from Beta-Lactamase Resistance Genes

The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34–3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81–0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06–5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39–67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae