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Antibiotics (Basel, Switzerland) Oct 2023Antibiotics are widely used for prophylaxis and therapy, reducing morbidity and mortality produced by bacterial pathogensin pigs, including infections caused by . The...
Antibiotics are widely used for prophylaxis and therapy, reducing morbidity and mortality produced by bacterial pathogensin pigs, including infections caused by . The aim of this study was to characterise antibiotic resistance phenotypes and genotypes in isolates in pigs in West Romanian grower farms. Differential phenotypic susceptibility profiles and the contribution of resistance genes to phenotypic expression of susceptibility or resistance were evaluated. A total of 76 isolates were identified and confirmed by the MicroScan Walk Away System. The occurrence of four resistance genes, ampC, blaZ, blaTEM and tetK in strains resistant to 13 antibiotics was assessed. Of the isolates, 0% showed resistance to meropenem, 3.9% to tigecycline and 10.5% to piperacillin/tazobactam, whereas, in contrast, 100% were resistant to ampicillin and mezlocillin, 76.31% to piperacillin and 59.3% to tetracycline. The prevalence of resistance genes in resistant isolates detected by q-PCR analysis was 97.0% for ampC, 96% for blaZ, 32.9% for blaTEM and 58.8% for tetK. Penetrance (the proportion of individuals carrying a particular variant of a gene that also expresses an associated trait) was 50% for ampC (32% for amoxicillin/clavulanate, 62% for cefazolin, 32% for cefepime, 100% for cefotaxime, 56% for cefuroxime and 99% for ampicillin), 65% for blaZ (32% for amoxicillin/clavulanate and 99% for ampicillin), 51% for blaTEM (81% for piperacillin) and 44% for the tetK gene (83% for tetracycline). The result of phenotypic antibiotic resistance testing may indicate the presence of plasmid-borne resistance, with a diagnostic odds ratio of a positive phenotypic resistance for tetK being 4.52. As a management decision, the maximum penetrance admitted for using a specific antibiotic for infections in pigs is recommended to be less than 20%.
PubMed: 37887245
DOI: 10.3390/antibiotics12101544 -
ACS Infectious Diseases Apr 2024Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we...
Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R group. Crystal structures show that the ureido β-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of β-lactams with improved activity against ESC-resistant .
Topics: Humans; Ceftriaxone; Neisseria gonorrhoeae; Gonorrhea; Penicillin-Binding Proteins; Cefoperazone; Cephalosporins; Piperacillin; beta-Lactams
PubMed: 38446051
DOI: 10.1021/acsinfecdis.3c00713