Third-Generation Cephalosporin- and Tetracycline-ResistantEscherichia coliand Antimicrobial Resistance Genes from Metagenomes of Mink Feces and Feed
FOODBORNE PATHOGENS AND DISEASE
Authors: Agga, Getahun E.; Silva, Philip J.; Martin, Randal S.
Abstract
American mink (Neovison vison) is a significant source of global fur production. Except for a few studies from Denmark and Canada reporting antimicrobial resistance in bacteria isolated from clinical cases, studies from the general mink population are scarce and absent in the United States. Mink feces (n = 42) and feed (n = 8) samples obtained from a mink farm were cultured for the enumeration and detection of tetracycline-resistant (TET (R))- and third-generation cephalosporin-resistant (TGC (R))-Escherichia coli. Isolates were characterized phenotypically for their resistance to other antibiotics and genotypically for resistance genes. TET (R) E. coliwere detected from 98% of feces samples (mean concentration = 6 log(10)) and from 100% of feed samples (mean concentration = 3.2 logs). Among TET (R) E. coliisolates, 44% (n = 41) of fecal- and 50% (n = 8) of feed isolates were multidrug resistant (MDR; resistance to >= 3 antimicrobial classes), and 96% (n = 49) of TET (R) isolates were positive fortet(A) and/ortet(B). TGC (R) E. coliwere detected from 95% of feces and 75% of feed samples with 78% (n = 40) of fecal isolates, and all six of the feed isolates were MDR. Nearly two-thirds (65%) of the TGC (R) E. coliisolates (n = 46) were positive forbla(CMY-2); the remaining 35% were positive forbla(CTX-M,)with thebla(CTX-M-14)being the predominant (75%,n = 16) variant detected. Metagenomic DNA was extracted directly from feces and feed samples, and it was tested for 84 antimicrobial resistance genes by using quantitative polymerase chain reaction (PCR) array; selected genes were also quantified by droplet digital PCR. The genes detected from the fecal samples belonged mainly to five antimicrobial classes: macrolide-lincosamide-streptogramin B (MLSB; 100% prevalence), TETs (88.1%), beta-lactams (71.4%), aminoglycosides (66.7%), and fluoroquinolones (47.6%). beta-Lactam, MLSB, and TET resistance genes were also detected from feed samples. Our study serves as a baseline for further studies and to streamline antimicrobial use in mink production in accordance with current regulations as in food animals.
Pharmacokinetics of doxycycline after oral administration of multiple doses in dogs
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Authors: De Lucas, Jose Julio; Rodriguez, Casilda; San Andres, Maria Dolores; Sainz, Angel; Villaescusa, Alejandra; Garcia-Sancho, Mercedes; Rodriguez-Franco, Fernando; San Andres, Manuel I.
Abstract
The aim of this study was to determine the pharmacokinetic parameters of doxycycline in dogs and assess the efficacy of an oral drug dosage regimen of 10 mg/kg daily for 28 days through Pharmacokinetic/Pharmacodynamic (PK/PD) target analysis based on Monte Carlo simulation, using previously published data for the zoonotic pathogen Staphylococcus pseudintermedius. After a multiple-dosage regimen, the accumulation index was 1.88 +/- 0.82. The Cmax(ss) and Cmin(ss) values were 5.18 +/- 1.81 mu g/ml and 1.91 +/- 1.35 mu g/ml, respectively. There were statistically significant differences for Cmax, Cmin at 24 hr, MRTt, AUCt and AUC infinity between days 1 and 28. The Cmin(ss) value was over the MIC of the principal pathogens, and Cmax(ss) was higher than the resistance values (>2 mu g/ml). For AUC/MIC indices of 12, 25 and 40, the cumulative fraction responses (CFR) were 94.01%, 69.55% and 60.86%, respectively; for an MIC value of 2 mu g/ml, the corresponding probability of target attainment (PTA) was 99.94%, 84.78% and 45.16%, respectively. Doxycycline was used against numerous localized infections in different organs and tissues. For the strains with MIC < 1 mu g/mL, PTA was close to 100%, even for the most demanding ones, specifically 94.98% for an index of 40% and 99.9% for an index of 25.