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.

Global antimicrobial resistance and use surveillance system (GLASS 2022): Investigating the relationship between antimicrobial resistance and antimicrobial consumption data across the participating countries.

For the first time since 2015, the World Health Organization's (WHO) global Antimicrobial Resistance and Use Surveillance (GLASS) featured both global reports for antimicrobial resistance (AMR) and antimicrobial consumption (AMC) data in its annual reports. In this study we investigated the relationship of AMR with AMC within participating countries reported in the GLASS 2022 report. Our analysis found a statistically significant correlation between beta-lactam/cephalosporin and fluoroquinolones consumption and AMR to these antimicrobials associated with bloodstream E. coli and Klebsiella pneumoniae among the participating countries (P<0.05). We observed that for every 1 unit increase in defined daily dose DDD of beta-lactam/cephalosporins and quinolone consumptions among the countries, increased the recoveries of bloodstream-associated beta-lactam/cephalosporins-resistant E. coli/Klebsiella spp. by 11-22% and quinolone-resistant E. coli/Klebsiella spp. by 31-40%. When we compared the antimicrobial consumptions between the antimicrobial ATC (Alphanumeric codes developed by WHO) groups and countries, we observed a statistically significant higher daily consumption of beta-lactam-penicillins (J01C, DDD difference range: 5.23-8.13) and cephalosporins (J01D, DDD difference range: 2.57-5.13) compared to other antimicrobial groups among the countries (adjusted for multiple comparisons using Tukey's method). Between the participating countries, we observed a statistically significant higher daily consumption of antimicrobial groups in Iran (DDD difference range: 3.63-4.84) and Uganda (DDD difference range: 3.79-5.01) compared to other participating countries (adjusted for multiple comparisons using Tukey's method). Understanding AMC and how it relates to AMR at the global scale is critical in the global AMR policy development and implementation of global antimicrobial stewardship.

Comparing individual antimicrobial resistant and multi-drug resistant Salmonella enterica across serotypes, sampling sources, sampling periods, and food animal types in the United States (2014-2018).

This study aimed to compare the antimicrobial-resistant Salmonella enterica profiles from three sampling sources cecal contents, HACCP (during processing), and retail meat using phenotypic antibiotic susceptibility and serotype data gathered from 2014 and 2018. Antimicrobial resistance data for 29 major Salmonella serotypes from three sampling sources and associated food animal types (cattle, swine, chicken, and turkey) were obtained from the database of the United States National Antimicrobial Resistance Monitoring System. Using multivariable logistic regression models, we compared individual and multi-drug resistance (MDR) in Salmonella enterica between the three sampling sources, food animal types, sampling period, and Salmonella serotypes. Across the three sources and throughout the sampling period, the recovery of antimicrobial-resistant Salmonella enterica - including MDR, MDR-AmpC, and ACSSuT - among food animal types were dependent on the sampling period and, in some cases, sampling sources and period for the selected antimicrobials. The predicted probability of antimicrobial resistance was greater in Salmonella serotypes from turkey compared to other food animal types, conditional on sampling sources. Ceftriaxone-resistant (OR=0.83, 95% CI: 0.69-0.99), and Sulfisoxazole-resistant (OR=0.84, 95% CI: 0.72-0.98) Salmonella serotypes were less likely to be recovered from the Hazard Analysis and Critical Control Point (HACCP) sources than with the cecal sources. Except for Salmonella serotypes Dublin and Newport, most of the Salmonella serotypes were less likely to be resistant to the selected antimicrobials, or found as MDR, compared to serotype Typhimurium. This study offers an integrated view on the predicted probability of MDR Salmonella serotypes, as well as insights into which serotypes are persistent, emerging or declining across sampling sources and food animal types in the United States.

Genomic Characterization of Fecal Escherichia coli Isolates with Reduced Susceptibility to Beta-Lactam Antimicrobials from Wild Hogs and Coyotes.

This study was carried out to determine the antimicrobial resistance (AMR) genes and mobile genetic elements of 16 Escherichia coli isolates-with reduced susceptibility to ceftazidime and imipenem-that were recovered from the fecal samples of coyotes and wild hogs from West Texas, USA. Whole-genome sequencing data analyses revealed distinct isolates with a unique sequence type and serotype designation. Among 16 isolates, 4 isolates were multidrug resistant, and 5 isolates harbored at least 1 beta-lactamase gene (blaCMY-2, blaCTX-M-55, or blaCTX-M-27) that confers resistance to beta-lactam antimicrobials. Several isolates carried genes conferring resistance to tetracyclines (tet(A), tet(B), and tet(C)), aminoglycosides (aac(3)-IId, ant(3″)-Ia, aph(3')-Ia, aph(3″)-lb, aadA5, and aph(6)-ld), sulfonamides (sul1, sul2, and sul3), amphenicol (floR), trimethoprim (dfrA1 and dfrA17), and macrolide, lincosamide, and streptogramin B (MLSB) agents (Inu(F), erm(B), and mph(A)). Nine isolates showed chromosomal mutations in the promoter region G of ampC beta-lactamase gene, while three isolates showed mutations in gyrA, parC, and parE quinolone resistance-determining regions, which confer resistance to quinolones. We also detected seven incompatibility plasmid groups, with incF being the most common. Different types of virulence genes were detected, including those that enhance bacterial fitness and pathogenicity. One blaCMY-2 positive isolate (O8:H28) from a wild hog was also a Shiga toxin-producing E. coli and was a carrier of the stx2A virulence toxin subtype. We report the detection of blaCMY-2, blaCTX-M-55, and blaCTX-M-27 beta-lactamase genes in E. coli from coyotes for the first time. This study demonstrates the importance of wildlife as reservoirs of important multi-drug-resistant bacteria and provides information for future comparative genomic analysis with the limited literature on antimicrobial resistance dynamics in wildlife such as coyotes.