Employing MIC Data for Mink Pathogens to Propose Tentative Epidemiological Cut-Off Values: A Step Toward Rationalizing Antimicrobial Use in Mink

Abstract

Optimizing antimicrobial dosage regimens and development of breakpoints for antimicrobial susceptibility testing are important prerequisites for rational antimicrobial use. The objectives of the study were (1) to produce MIC data for four mink pathogens and (2) to employ these MIC data to support the development of tentative epidemiological cutoff values (TECOFFs), which may be used for future development of mink-specific antimicrobial dosages and breakpoints. Broth microdilution was used to establish MIC distributions for 322 mink bacterial isolates of clinical origin from six European minkproducing countries. The included species were E. coli (n = 162), S. delphini (n = 63), S. canis (n = 42), and P. aeruginosa (n = 55). Sixty-four E. coli isolates and 34 S. delphini isolates were whole-genome sequenced and analyzed for antimicrobial resistance genes. No EUCAST MIC data are available on S. delphini and S. canis, hence tentative ECOFFs were suggested for the majority of the tested antimicrobials. For E. coli and P. aeruginosa, the wildtype distributions were in accordance with EUCAST data. Overall, the genotypes of the sequenced isolates were in concordance with the phenotypes. These data constitute an important piece in the puzzle of developing antimicrobial dosages and clinical breakpoints for mink. Until pharmacokinetic and clinical data become available, the (tentative) ECOFFs can be used for monitoring resistance development and as surrogates for clinical breakpoints.

Association between Antibiotic Consumption and Resistance in Mink Production

“…However, it is worth noticing that tetracycline NWT was the most frequently found NWT in the S. delphini ( Table 8 ). Furthermore, it has been reported that tetracycline-resistant S. delphini isolated from mink carries the tet (M) gene [ 27 ]. In one of the farms using zinc, MRSA and cefoxitin-resistant S. delphini were isolated.…”

“…The isolates were distinguished as WT or NWT according to the available epidemiological cut-off values (ECOFF) and tentative ECOFFs ( Supplementary Materials Table S1 ) [ 27 , 63 ]. The WT population consists of isolates that do not have phenotypically detectable resistance mechanisms, and the ECOFF is defined as the highest MIC in the WT population [ 63 ].…”

“…Antibiotic resistance against tetracyclines can be mediated by several mechanisms [ 26 ]. Resistance genes have been identified in clinical E. coli isolates from mink: tet (A) and tet (B), these genes mediate an inducible efflux mechanism, and tet (M) in S. delphini isolates, which all mediate ribosomal protection [ 27 , 28 ]. Antibiotic resistance mechanisms against aminopenicillins are commonly the enzyme induction and secretion of beta-lactamases [ 29 ].…”

“…Antibiotic resistance mechanisms against aminopenicillins are commonly the enzyme induction and secretion of beta-lactamases [ 29 ]. Beta-lactam resistance genes have been identified and are common in clinical isolates ( E. coli , S. delphini ) from mink [ 27 ]. One of three different mechanisms, rRNA methylation, efflux pumps, or enzymatic inactivation, may induce antibiotic resistance against macrolides [ 30 ].…”

“…One of three different mechanisms, rRNA methylation, efflux pumps, or enzymatic inactivation, may induce antibiotic resistance against macrolides [ 30 ]. Resistance genes belonging to the erm gene family (rRNA methylation) have been identified in clinical S. delphini isolates from mink [ 27 ].…”