Publications by authors named "Steeve Giguère"

123 Publications

Epidemiology and Molecular Basis of Multidrug Resistance in Rhodococcus equi.

Microbiol Mol Biol Rev 2021 May 14;85(2). Epub 2021 Apr 14.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA

SUMMARYThe development and spread of antimicrobial resistance are major concerns for human and animal health. The effects of the overuse of antimicrobials in domestic animals on the dissemination of resistant microbes to humans and the environment are of concern worldwide. is an ideal model to illustrate the spread of antimicrobial resistance at the animal-human-environment interface because it is a natural soil saprophyte that is an intracellular zoonotic pathogen that produces severe bronchopneumonia in many animal species and humans. Globally, is most often recognized as causing severe pneumonia in foals that results in animal suffering and increased production costs for the many horse-breeding farms where the disease occurs. Because highly effective preventive measures for are lacking, thoracic ultrasonographic screening and antimicrobial chemotherapy of subclinically affected foals have been used for controlling this disease during the last 20 years. The resultant increase in antimicrobial use attributable to this "screen-and-treat" approach at farms where the disease is endemic has likely driven the emergence of multidrug-resistant (MDR) in foals and their environment. This review summarizes the factors that contributed to the development and spread of MDR , the molecular epidemiology of the emergence of MDR , the repercussions of MDR for veterinary and human medicine, and measures that might mitigate antimicrobial resistance at horse-breeding farms, such as alternative treatments to traditional antibiotics. Knowledge of the emergence and spread of MDR is of broad importance for understanding how antimicrobial use in domestic animals can impact the health of animals, their environment, and human beings.
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http://dx.doi.org/10.1128/MMBR.00011-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139527PMC
May 2021

Physiologic and blood gas effects of xylazine-ketamine versus xylazine-tiletamine-zolazepam immobilization of white-tailed deer before and after oxygen supplementation: a preliminary study.

Vet Anaesth Analg 2021 May 4;48(3):356-363. Epub 2021 Mar 4.

Warnell School of Forestry and Natural Resources, University of Georgia, Athens, GA, USA.

Objective: To compare oxygenation and ventilation in white-tailed deer (Odocoileus virginianus) anesthetized with two treatments with and without oxygen supplementation.

Study Design: Randomized, blinded, crossover study.

Animals: A total of eight healthy adult white-tailed deer weighing 49-62 kg.

Methods: Each deer was anesthetized twice intramuscularly: 1) treatment XK, xylazine (2 mg kg) and ketamine (6 mg kg) and 2) treatment XTZ, xylazine (2 mg kg) and tiletamine-zolazepam (4 mg kg). With the deer in sternal position, arterial and venous blood was collected before and at 30 minutes during administration of oxygen at 1 L minute through a face mask. PaO and heart rate (HR) were compared using two-way repeated measures anova. pH, PaCO and lactate concentration were analyzed using mixed-effects linear models, p < 0.05.

Results: When breathing air, PaO was < 80 mmHg (10.7 kPa) in six and seven deer with XK and XTZ, respectively, and of these, PaO was < 60 mmHg (8.0 kPa) in three and five deer, respectively. With oxygen supplementation, PaO increased to 128 ± 4 and 140 ± 5 mmHg (17.1 ± 0.5 and 18.7 ± 0.7 kPa), mean ± standard error, with XK and XTZ, respectively (p < 0.001). PaO was not significantly different between treatments at either time point. HR decreased during oxygen supplementation in both treatments (p < 0.001). Lactate was significantly lower (p = 0.047) with XTZ than with XK (2.2 ± 0.6 versus 3.5 ± 0.6 mmol L) and decreased (p < 0.001) with oxygen supplementation (4.1 ± 0.6 versus 1.6 ± 0.6 mmol L). PaCO increased in XTZ during oxygen breathing.

Conclusions And Clinical Relevance: Treatments XK and XTZ resulted in hypoxemia, which responded to oxygen supplementation. Both treatments are suitable for immobilization of white-tailed deer under the study circumstances.
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http://dx.doi.org/10.1016/j.vaa.2020.10.013DOI Listing
May 2021

Association between antimicrobial treatment of subclinical pneumonia in foals and selection of macrolide- and rifampicin-resistant strains at horse-breeding farms in central Kentucky.

J Am Vet Med Assoc 2021 Mar;258(6):648-653

Objective: To compare soil concentrations of macrolide- and rifampicin-resistant strains (MRRE) on horse-breeding farms that used thoracic ultrasonographic screening (TUS) to identify foals with subclinical pneumonia combined with subsequent administration of macrolides and rifampin to affected foals (TUS farms) versus soil concentrations on farms that did not (non-TUS farms), determine whether the combined use of TUS and antimicrobial treatment of subclinically affected foals was associated with soil concentration of MRRE, and assess whether there were temporal effects on soil concentrations of MRRE during the foaling season.

Samples: 720 soil samples and 20 completed questionnaires from 20 horse-breeding farms (10 TUS farms and 10 non-TUS farms) in central Kentucky.

Procedures: A questionnaire was used to gather information from participating farms about their 2019 foaling season. Soil samples were collected during January, March, May, and July 2019 for bacterial culture and antimicrobial susceptibility testing to identify any isolates of MRRE. Results were compared for TUS farms versus non-TUS farms. Linear mixed-effects modeling was used to evaluate for potential associations between the soil concentration of MRRE and the use of TUS.

Results: Overall, the sum of the mean soil concentrations of MRRE was significantly higher for TUS farms (8.85 log-transformed CFUs/g) versus non-TUS farms (7.37 log-transformed CFUs/g).

Conclusions And Clinical Relevance: Our findings indicated that farms that use TUS to identify foals with subclinical pneumonia for antimicrobial treatment select for antimicrobial-resistant strains. Because prognosis is worse for foals infected with resistant versus nonresistant strains of , prudent use of antimicrobials to treat foals with subclinical pulmonary lesions attributed to is recommended.
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http://dx.doi.org/10.2460/javma.258.6.648DOI Listing
March 2021

Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis.

Am J Reprod Immunol 2021 Feb 10:e13396. Epub 2021 Feb 10.

Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.

Problem: Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti-inflammatory effects of firocoxib when administered to mares with placentitis.

Methods: Mares (gestation D270-300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL-1β, IL-6, TNF-α, IL-10, PGF , and PGE in fluids were measured by ELISA. mRNA expression of IL-1β, IL-6, TNF-α, IL-8, IL-10, matrix metalloproteinases (MMPs) -1, 3, and 9 in fetal membranes/fetuses was quantified using real-time PCR.

Results: Allantoic TNF-α concentrations were lowest in FIRO at 8 hours and 24 hours post-infection; IL-6 concentrations were lower in FIRO than NORM at 8 hours, lower in FIRO than INFECT at 24 hours post-inoculation, and lower in NORM than FIRO or INFECT at birth. Marginal mean allantoic IL-β and IL-10 concentrations were lower in FIRO and NORM than INFECT. Amniotic fluid cytokines were lowest in NORM with all measurements in that group being below the limit of detection. Allantoic PGF concentrations were lower in FIRO and INFECT than NORM at 8 hours post-inoculation, and lower in FIRO than INFECT or NORM at 24 hours post-inoculation. Allantoic PGE concentrations were lower in FIRO than INFECT. Amniotic PGF and PGE concentrations were lower in NORM than INFECT. In fetal membranes, group differences with respect to IL-1β, IL-6, IL-8, and MMP1 were dependent on tissue type.

Conclusions: Data suggest a suppressive effect of firocoxib administration on cytokine and prostaglandin production in mares with placentitis.
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http://dx.doi.org/10.1111/aji.13396DOI Listing
February 2021

Spread of Multidrug-Resistant Rhodococcus equi, United States.

Emerg Infect Dis 2021 02;27(2):529-537

Multidrug resistance has been detected in the animal and zoonotic human pathogen Rhodococcus equi after mass macrolide/rifampin antibioprophylaxis in endemically affected equine farms in the United States. Multidrug-resistant (MDR) R. equi emerged upon acquisition of pRERm46, a conjugative plasmid conferring resistance to macrolides, lincosamides, streptogramins, and, as we describe, tetracycline. Phylogenomic analyses indicate that the increasing prevalence of MDR R. equi since it was first documented in 2002 is caused by a clone, R. equi 2287, attributable to coselection of pRErm46 with a chromosomal rpoB mutation driven by macrolide/rifampin therapy. pRErm46 spillover to other R. equi genotypes has given rise to a novel MDR clone, G2016, associated with a distinct rpoB mutation. Our findings illustrate that overuse of antimicrobial prophylaxis in animals can generate MDR pathogens with zoonotic potential. MDR R. equi and pRErm46-mediated resistance are currently disseminating in the United States and are likely to spread internationally through horse movements.
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http://dx.doi.org/10.3201/eid2702.203030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853588PMC
February 2021

The effect of foal or adult horse plasma on equine monocyte-derived dendritic cell phenotype and function.

Vet Immunol Immunopathol 2020 Oct 23;228:110099. Epub 2020 Jul 23.

Department of Large Animal Medicine, 501 D.W. Brooks Drive, University of Georgia College of Veterinary Medicine, Athens, GA, 30602, USA.

Immunological and endocrine immaturity in foals increases foal morbidity and mortality from bacterial sepsis. Dendritic cells (DC) are critical in activating the adaptive immune response, but foal DC are phenotypically and functionally different than those of adult horses. Age-related variations in availability of some soluble plasma factors, such as hormones, might govern some age-related differences in DC function. Effects of exposure to plasma factors on equine DC phenotype and function have not been described. We hypothesized that exposure to plasma from foals or adult horses would differentially impact monocyte-derived DC (MoDC) phenotype and function. Eight healthy adult horses and 8 healthy foals were divided into pairs of one adult horse and one foal. Blood was collected from each pair for MoDC generation when foals were 1 and 30 days of age. MoDC from horses and foals were then exposed to killed whole-cell bacteria in the presence of their own age-matched plasma, plasma from the opposite-aged animal in the pair, and serum-free medium alone (control). Expression of DC-relevant surface markers (MHC class-II, CD86, and CD14) and endocytosis capability were measured by flow cytometry. Supernatant cytokine concentrations (IL-4, IL-17, IFN-γ, and IL-10) were quantified with a validated bead-based immunoassay. Data were analyzed using linear mixed-effects and Tobit regression models (P < 0.05). The percentage of MoDC expressing surface markers MHC class-II and CD86 was reduced in MoDC derived from 1-day-old foals in comparison to adult horse MoDC when cultured in medium alone or with either source of plasma (P = 0.0001). Foal and adult horse MoDC cultured in either source of plasma expressed more CD86 and less CD14 than cells cultured in serum-free medium alone (P ≤ 0.02). Adult horse and foal MoDC exposed to bacterial antigen in the presence of 1-day-old foal plasma secreted less IL-10 (P ≤ 0.0008) compared to those cultured in adult horse plasma. Endogenous production of IL-17 by MoDC from foals at day 1 of age cultured in adult plasma was increased compared to foal MoDC cultured in serum-free medium (P = 0.004). Phagocytosis of killed, labeled Staphylococcus aureus was reduced when MoDC generated from foals or adult horses were exposed to plasma from foals at day 1 or 30 of age (P ≤ 0.03). Age-related variation in soluble plasma factors appear to regulate equine MoDC function, but specific plasma factors capable of regulating MoDC phenotype or function were not defined in this study.
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http://dx.doi.org/10.1016/j.vetimm.2020.110099DOI Listing
October 2020

The effect of prior thecal puncture on cerebrospinal fluid analytes in normal adult horses.

J Vet Intern Med 2020 Sep 2;34(5):2117-2121. Epub 2020 Jul 2.

Department of Large Animal Medicine and Surgery, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.

Background: Serial cerebrospinal fluid (CSF) analysis might be required in clinical neurologic disease. The effect of lumbosacral (LS) or cervical (C1-C2) centesis on subsequent CSF cytologic analyses has not been investigated in horses.

Objective: To evaluate the effect of thecal puncture on subsequent CSF analyses ANIMALS: Ten healthy adult horses.

Methods: Prospective study. Horses were randomly assigned to undergo CSF collection twice, 14 days apart, from either the C1-C2 or LS space. After a 4-month washout period, CSF collection was repeated from the alternate site. Continuous data were analyzed using linear mixed-effects models and count data using mixed-effects negative binomial regression. Statistical significance was set at P < .05.

Results: There was no significant effect of collection day (day 0 or day 14) for any CSF analytes, including protein concentration (C1-C2: 45 [95% CI: 33-57] mg/dL day 0 vs 49 [95% CI: 39-62] mg/dL day 14, P = .12; LS: 64 [95% CI: 41-100] mg/dL day 0 vs 83 [95% CI: 53-129] mg/dL day 14, P = .37), or nucleated cell count (C1-C2: 2 [95% CI: 1-4] cells/μL day 0 vs 3 [95% CI: 1-4] cells/μL day 14, P = .65; LS: 3 [95% CI: 2-5] cells/μL day 0 vs 5 [95% CI: 3-8] cells/μL day 14, P = .10). There was no significant difference in EPM titer or EPM serum : CSF ratio between days 0 and 14.

Conclusions And Clinical Importance: Repeat thecal puncture from the LS or C1-C2 space 2 weeks apart does not appear to impact CSF analytes.
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http://dx.doi.org/10.1111/jvim.15842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517835PMC
September 2020

The novel and transferable erm(51) gene confers macrolides, lincosamides and streptogramins B (MLS ) resistance to clonal Rhodococcus equi in the environment.

Environ Microbiol 2020 07 4;22(7):2858-2869. Epub 2020 May 4.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.

The use of mass antimicrobial treatment has been linked to the emergence of antimicrobial resistance in human and animal pathogens. Using whole-genome single-molecule real-time (SMRT) sequencing, we characterized genomic variability of multidrug-resistant Rhodococcus equi isolated from soil samples from 100 farms endemic for R. equi infections in Kentucky. We discovered the novel erm(51)-encoding resistance to MLS in R. equi isolates from soil of horse-breeding farms. Erm(51) is inserted in a transposon (TnErm51) that is associated with a putative conjugative plasmid (pRErm51), a mobilizable plasmid (pMobErm51), or both enabling horizontal gene transfer to susceptible organisms and conferring high levels of resistance against MLS in vitro. This new resistant genotype also carries a previously unidentified rpoB mutation conferring resistance to rifampicin. Isolates carrying both vapA and erm(51) were rarely found, indicating either a recent acquisition of erm(51) and/or impaired survival when isolates carry both genes. Isolates carrying erm(51) are closely related genetically and were likely selected by antimicrobial exposure in the environment.
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http://dx.doi.org/10.1111/1462-2920.15020DOI Listing
July 2020

Phenotypic characterization of equine monocyte-derived dendritic cells generated ex vivo utilizing commercially available serum-free medium.

Vet Immunol Immunopathol 2020 Apr 17;222:110036. Epub 2020 Mar 17.

Departments of Large Animal Medicine, 2200 College Station Road, University of Georgia College of Veterinary Medicine, Athens, GA, 30602, USA.

The impact of culture conditions on equine monocyte-derived dendritic cells (MoDC) generation has not been fully characterized. We hypothesized that 1) MoDC could be cultured in a commercially available serum-free medium (AIM-V); and 2) that differential culture conditions would influence MoDC viability, yield and phenotype. MoDC generated from adult horses were cultured under variable conditions in a series of experiments. Viability was assessed using trypan blue and propidium iodide staining. Yield was determined by manual hemocytometer counting. Phenotype was assessed by flow cytometric analysis of surface markers (MHC class-II, CD86 and CD14). Data were analyzed using paired t-tests and repeated measures ANOVA. Two MoDC populations that differed in size and phenotype were identified: larger MoDC (LgMoDC) and smaller MoDC (SmMoDC). Medium type, plate chemistry, or length of monocyte adhesion time did not impact MoDC viability or yield. LgMoDC generated in serum-free medium expressed more MHC class-II and CD86 (P ≤ 0.03). A prolonged duration in culture reduced MoDC yield (P ≤ 0.04). MoDC can be consistently and reliably generated using AIM-V serum-free medium in standard tissue culture plates with a recommended culture duration of 3-4 days.
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http://dx.doi.org/10.1016/j.vetimm.2020.110036DOI Listing
April 2020

Horizontal Spread of Rhodococcus equi Macrolide Resistance Plasmid pRErm46 across Environmental .

Appl Environ Microbiol 2020 04 17;86(9). Epub 2020 Apr 17.

Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom.

Conjugation is one of the main mechanisms involved in the spread and maintenance of antibiotic resistance in bacterial populations. We recently showed that the emerging macrolide resistance in the soilborne equine and zoonotic pathogen is conferred by the (46) gene carried on the 87-kb conjugative plasmid pRErm46. Here, we investigated the conjugal transferability of pRErm46 to 14 representative bacteria likely encountered by in the environmental habitat. mating experiments demonstrated conjugation to different members of the genus as well as to and spp. at frequencies ranging from ∼10 to 10 pRErm46 transfer was also observed in mating experiments in soil and horse manure, albeit at a low frequency and after prolonged incubation at 22 to 30°C (environmental temperatures), not 37°C. All transconjugants were able to transfer pRErm46 back to Conjugation could not be detected with or spp. or several members of the more distant phylum such as , , or Thus, the pRErm46 host range appears to span several actinobacterial orders with certain host restriction within the All bacterial species that acquired pRErm46 expressed increased macrolide resistance with no significant deleterious impact on fitness, except in the case of Our results indicate that actinobacterial members of the environmental microbiota can both acquire and transmit the pRErm46 plasmid and thus potentially contribute to the maintenance and spread of (46)-mediated macrolide resistance in equine farms. This study demonstrates the efficient horizontal transfer of the conjugative plasmid pRErm46, recently identified as the cause of the emerging macrolide resistance among equine isolates of this pathogen, to and from different environmental , including a variety of rhodococci as well as and spp. The reported data support the notion that environmental microbiotas may act as reservoirs for the endemic maintenance of antimicrobial resistance in an antibiotic pressurized farm habitat.
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http://dx.doi.org/10.1128/AEM.00108-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170479PMC
April 2020

Effect of feed deprivation on daily water consumption in healthy horses.

Equine Vet J 2021 Jan 30;53(1):117-124. Epub 2020 Mar 30.

Island Whirl Equine Colic Research Laboratory, Department of Large Animal Clinical Sciences, University of Florida, College of Veterinary Medicine, Gainesville, FL, USA.

Background: Measurements of water consumed by fed healthy horses might not apply to horses that are unwilling or unable to drink or are not fed for any reason.

Objective: To examine the effects of feed deprivation on voluntary water consumption compared with fed conditions.

Study Design: In vivo experiment.

Methods: Eight healthy adult Thoroughbred geldings were used in a randomised crossover design so that each horse served as its own control for fed vs feed-deprived conditions. Water intake, bodyweight, physical findings and vital signs were measured during 4 days of feeding and 4 days of feed deprivation. Daily measurements during the trial periods were PCV, TPP, electrolytes, osmolality and triglycerides. Plasma and extracellular fluid volumes were measured in the last 8 hours of the trial periods. Data were analysed with a two-way analysis of variance with repeated measures, and statistical significance was P ≤ .05.

Results: Feed deprivation immediately and persistently reduced water consumption to ~16% of fed values, with laboratory evidence of mild dehydration on day 4.

Main Limitations: Changes in total body water and in water and electrolyte excretion or conservation through faeces and urine were not measured.

Conclusions: Feed consumption has a marked effect on water requirements in healthy horses. Because current guidelines for water needs were obtained in the fed state, they might not apply to horses that are denied feed for any reason or have reduced feed intake. This study provides new information on water consumption in horses that should apply to this essential nutrient in health and disease.
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http://dx.doi.org/10.1111/evj.13259DOI Listing
January 2021

Comparing PFGE, MLST, and WGS in monitoring the spread of macrolide and rifampin resistant Rhodococcus equi in horse production.

Vet Microbiol 2020 Mar 28;242:108571. Epub 2019 Dec 28.

Department of Large Animal Medicine, University of Georgia, Athens 30605, USA.

Background: Rhodococcus equi (R. equi) infections are endemic in many horse facilities in the United States resulting significant economic loses annually. Currently, there is no commercial vaccine available and the emergence of isolates that are resistant to the current treatment and prophylaxis using antibiotics prompts closer surveillance of this pathogen.

Objective: This study compares three different genotyping techniques, Pulsed Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST) and whole genome SNP-based phylogeny to determine the most accurate method to monitor the spread of macrolide-and-rifampin-resistant R. equi.

Methods: 16 macrolide and rifampin-resistant and 6 susceptible R. equi and their Illumina Miseq whole genome sequences were used in this study. The isolates were sub-typed by PFGE with VspI and a dendrogram based on their similarities generated. Additionally, three phylogenetic trees were constructed using CSI phylogeny on (i) whole genome sequences (WGS), (ii) in silico MLST sequences and (iii) MLST sequences obtained after PCR-amplification and Sanger sequencing.

Results: PFGE identified 18 different genetic profiles and grouped the 22 isolates into 3 clusters independently of their susceptibilities. The phylogenetic trees built from WGS and MLST data showed similar topology, separating the isolates into 2 major clades in accordance with their susceptibility profiles (susceptible and resistant). However, only the trees generated with next generation sequencing data could detect the clonality of the resistant isolates.
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http://dx.doi.org/10.1016/j.vetmic.2019.108571DOI Listing
March 2020

Profibrotic gene transcription in renal tissues from cats with ischemia-induced chronic kidney disease.

Am J Vet Res 2020 Feb;81(2):180-189

Objective: To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD).

Sample: Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats.

Procedures: For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (), matrix metalloproteinase ()-, tissue inhibitor of metalloproteinase-1 (), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys.

Results: Ischemic kidneys had greater transcript levels of , and transforming growth factor-β1 relative to control kidneys and of relative to contralateral kidneys. Transcription of was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of , and and severity of fibrosis.

Conclusions And Clinical Relevance: Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.
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http://dx.doi.org/10.2460/ajvr.81.2.180DOI Listing
February 2020

Comparison of 2 collection methods for cerebrospinal fluid analysis from standing, sedate adult horses.

J Vet Intern Med 2020 Mar 24;34(2):972-978. Epub 2020 Jan 24.

Department of Large Animal Medicine and Surgery, University of Georgia, College of Veterinary Medicine, Georgia.

Background: Cerebrospinal fluid (CSF) analysis is an important component of the evaluation of horses with neurologic disease. Lumbosacral (LS) centesis is routine, but CSF is also collected from the space between the first and second cervical vertebrae (C1-C2).

Objectives: To compare collection times, CSF cytology results, and equine protozoal myelitis (EPM) titers of CSF collected from the C1-C2 and LS sites.

Animals: Fifteen university-owned adult horses with no evidence of neurologic disease, and 9 horses with signs of neurologic disease: 3 university-owned and 6 client-owned.

Methods: Prospective study. Cerebrospinal fluid collection from the LS space and C1-C2 space of each horse was performed in randomized order. Continuous data were analyzed using mixed-effects linear models and count data using mixed-effects negative binomial regression. Statistical significance was set at P < .05.

Results: Cerebrospinal fluid collected from the C1-C2 site had a significantly lower mean protein concentration (49 [95% CI: 43-55.8] mg/dL C1-C2 versus 52.1 [95% CI: 45.7-59.3] mg/dL LS; P = .03) and red blood cell count (6 [95% CI: 2-16] cells/μL versus 33 [95% CI: 13-81] cells/μL; P = .02). Collection time, total nucleated cell count, EPM titers, and serum:CSF EPM titer ratios were not significantly different between collection sites.

Conclusions And Clinical Importance: Cerebrospinal fluid from the C1-C2 space provides an acceptable alternative to LS CSF collection with decreased likelihood of clinically important blood contamination of samples.
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http://dx.doi.org/10.1111/jvim.15702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096653PMC
March 2020

Changing policy to treat foals with Rhodococcus equi pneumonia in the later course of disease decreases antimicrobial usage without increasing mortality rate.

Equine Vet J 2020 Jul 17;52(4):531-537. Epub 2020 Feb 17.

Large Animal Medicine, University of Georgia, Athens, Georgia, USA.

Background: There is a lack of data on the efficacy of treatment of Rhodococcus equi pneumonia in association with an optimised selection of foals.

Objectives: To evaluate whether targeted treatment protocols resulting in decreased antimicrobial use impact foal mortality rates.

Study Design: Retrospective study.

Methods: Three hundred and thirty foals with pneumonia per year were randomly selected from 2008 to 2016. All foals were examined once weekly from birth until weaning. A physical examination of the respiratory tract, body temperature, haematology and an ultrasonographic examination of the lungs was included. Sonography areas with visible consolidation were measured and added to calculate an 'abscess score' which represents the extent of pulmonary damage. All weekly medical data were analysed retrospectively.

Results: In the period from 2008 to 2011, every foal with pulmonary abscesses was treated. The treatment protocol was changed in 2012 when only foals with larger lesions were treated. Between the two time periods 2008-2011 and 2012-2016, the abscess score at the beginning of treatment increased from a median of 4-11.5 cm. From all foals that developed R equi pneumonia, 81.5% received antibiotic treatment in 2008-2011 (n = 1215) compared with 50.9% in 2012-2016 (n = 1541). The percentage of foals that died from pneumonia or R equi infections did not differ significantly between 2008-2011 and 2012-2016 (0.4% vs 0.6% respectively; P = .6).

Main Limitations: There was some lack of clarity in old data because this was a retrospective study; therefore, some foals had to be excluded from data analysis.

Conclusions: Alteration of treatment criteria, to exclude antibiotic treatment of foals with smaller lesions, has significantly decreased the number of foals being treated without a significant increase in mortality from R equi pneumonia.
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http://dx.doi.org/10.1111/evj.13219DOI Listing
July 2020

Efficacy of the combination of doxycycline and azithromycin for the treatment of foals with mild to moderate bronchopneumonia.

Equine Vet J 2020 Jul 17;52(4):613-619. Epub 2020 Feb 17.

Veterinary Medical Center, University of Georgia, Athens, GA, USA.

Background: Given the importance of rifampin in treatment protocols for tuberculosis in people, its use in veterinary medicine is under increasing scrutiny in some countries and alternatives might be needed in the near future.

Objectives: This study was set up to evaluate whether azithromycin combined with doxycycline is effective for the treatment of bronchopneumonia in foals and noninferior to the combination of azithromycin and rifampin.

Study Design: This is a controlled, randomised and double-blinded clinical trial. Two hundred and forty foals on a farm endemic for infections caused by Rhodococcus equi were involved.

Methods: Foals with ultrasonographic pulmonary lesions (lesion score 10-15 cm) were allocated to 3 groups: azithromycin-doxycycline orally (n = 81); azithromycin-rifampin orally (n = 81); or untreated controls (n = 78). Physical examination and thoracic ultrasonography were performed by individuals unaware of treatment group assignment. Foals that worsened were considered treatment failures and removed from the study.

Results: The proportion of foals that recovered was significantly higher for foals treated with azithromycin-doxycycline (80 of 81) or azithromycin-rifampin (81 of 81) compared with that of control foals (57 of 78). The difference in the percentage of efficacy of azithromycin-rifampin vs azithromycin-doxycycline was 1.2% (90% CI = -0.78% to 3.5%) which did not cross the predetermined noninferiority limit of 10%. Therefore, azithromycin-doxycycline was noninferior to azithromycin-rifampin within the predetermined noninferiority limit.

Main Limitations: The study was performed on a single farm, and recovery rates may differ in other locations.

Conclusion: Azithromycin-doxycycline was noninferior to azithromycin-rifampin for the treatment of bronchopneumonia in this farm.
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http://dx.doi.org/10.1111/evj.13211DOI Listing
July 2020

Clonal Confinement of a Highly Mobile Resistance Element Driven by Combination Therapy in Rhodococcus equi.

mBio 2019 10 15;10(5). Epub 2019 Oct 15.

Microbial Pathogenesis Group, Infection Medicine, Edinburgh Medical School (Biomedical Sciences), University of Edinburgh, Edinburgh, United Kingdom

Antibiotic use has been linked to changes in the population structure of human pathogens and the clonal expansion of multidrug-resistant (MDR) strains among healthcare- and community-acquired infections. Here we present a compelling example in a veterinary pathogen, , the causative agent of a severe pulmonary infection affecting foals worldwide. We show that the (46) gene responsible for emerging macrolide resistance among equine isolates in the United States is part of a 6.9-kb transposable element, Tn, actively mobilized by an IS family transposase. Tn is carried on an 87-kb conjugative plasmid, pRErm46, transferable between strains at frequencies up to 10 The (46) gene becomes stabilized in by pRErm46's apparent fitness neutrality and wholesale Tn transposition onto the host genome. This includes the conjugally exchangeable pVAPA virulence plasmid, enabling the possibility of cotransfer of two essential traits for survival in macrolide-treated foals in a single mating event. Despite its high horizontal transfer potential, phylogenomic analyses show that (46) is paradoxically confined to a specific clone, 2287. 2287 also carries a unique mutation conferring high-level resistance to rifampin, systematically administered together with macrolides against rhodococcal pneumonia on equine farms. Our data illustrate that under sustained combination therapy, several independent "founder" genetic events are concurrently required for resistance, limiting not only its emergence but also, crucially, horizontal spread, ultimately determining multiresistance clonality. MDR clades arise upon acquisition of resistance traits, but the determinants of their clonal expansion remain largely undefined. Taking advantage of the unique features of infection control in equine farms, involving the same dual antibiotic treatment since the 1980s (a macrolide and rifampin), this study sheds light into the determinants of multiresistance clonality and the importance of combination therapy in limiting the dissemination of mobile resistance elements. Clinically effective therapeutic alternatives against foal pneumonia are currently lacking, and the identified macrolide-rifampin MDR clone 2287 has serious implications. Still at early stages of evolution and local spread, 2287 may disseminate globally, posing a significant threat to the equine industry and, also, public health due to the risk of zoonotic transmission. The characterization of the 2287 clone and its resistance determinants will enable targeted surveillance and control interventions to tackle the emergence of MDR .
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http://dx.doi.org/10.1128/mBio.02260-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794481PMC
October 2019

Pharmacokinetics of tulathromycin following administration to stocker cattle with remote delivery devices.

J Anim Sci 2019 Nov;97(11):4482-4487

Department of Pathobiology and Population Medicine, Mississippi State University, Mississippi State, MS.

Remote delivery devices (RDD) are used by some to administer antimicrobials (AM) to cattle when treatment by manual injection is logistically difficult. However, it is not clear that the pharmacokinetics (PK) of AM administered by RDD is comparable to that for AM administered by injection; thus, it is not certain that cattle treated by RDD experience equivalent AM effect. Fifteen crossbred beef steers (body weight [BW] = 302.5 ± 21.7 kg) were used in a three-way crossover study to determine the PK of tulathromycin following administration with RDD in the BQA injection triangle. Cattle were treated by each of three methods at 2.5 mg of tulathromycin per kg of BW with a 60 d washout period between treatments: 1) subcutaneous injection of tulathromycin (SC), 2) treatment by RDD delivered by air pump projector (AIR, Pneudart, Model 178B) at 4.5 m distance, and 3) treatment by RDD delivered by CO2-powered projector at 7.5 m (CO2, Pneudart, Model 176B). Blood was collected prior to injection and at various points up to 552 h post-administration, pharmacokinetic data were analyzed as a mixed model using animal as a random effect and method of administration, order of administration, and their interaction as fixed effects. Plasma creatine kinase (CK) was measured before treatment and at 24 h after treatment to determine the degree of muscle injury resulting from each treatment. Three darts administered by AIR did not discharge (20%; 95% CI = 4% to 48%); and results from these steers were excluded from analysis. Maximum plasma concentration (718, 702.6, and 755.5 µg/mL for SC, AIR, and CO2, respectively) and area under the concentration-time curve (17,885, 17,423, and 18,796 µg • h/mL for SC, AIR and CO, respectively) were similar and not significantly different between methods of administration. There was an effect of time (P = 0.0002), period (P = 0.0001), and interaction between method of administration and study period (P = 0.0210) on plasma concentration of CK. However, method of treatment (P = 0.6091), interaction between method and time (P = 0.6972), interaction between period and time (P = 0.6153), and 3-way interaction between method, period and time (P = 0.6804) were not different. Results suggest that PK of tulathromycin following delivery by RDD can be similar to subcutaneous injection; however, failure of RDD to discharge after delivery by some types of projectors can cause an important proportion of cattle to fail to receive drug as expected.
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http://dx.doi.org/10.1093/jas/skz311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827394PMC
November 2019

Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA.

Vet Microbiol 2019 Aug 10;235:243-247. Epub 2019 Jul 10.

Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

The combination of a macrolide and rifampicin has been the mainstay of therapy in foals with Rhodococcus equi pneumonia for decades. Recent studies suggest that mass antimicrobial treatment of subclinically affected foals over time has selected for antimicrobial resistance. Our objective was to estimate the prevalence of R. equi strains resistant to macrolides and rifampicin at horse breeding farms in Kentucky. A hundred breeding farms in Kentucky were surveyed and R. equi were cultured from soil samples. Data were analyzed with logistic regression and generalized linear modeling (P < 0.05). Seventy-six percent (76%) of farms yielded resistant R. equi, and resistance to macrolides and rifampicin was associated with their use at farms. The present study is the first to report the prevalence and distribution of resistant isolates in the environment of farms in Kentucky, USA. Collectively, previous reports and the data presented herein provide irrefutable evidence of emerging antimicrobial resistance in R. equi with alarming prevalence. Widespread dissemination and maintenance of resistance genes in the environment where many other pathogenic bacteria exist is a concern for both animal and human health.
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http://dx.doi.org/10.1016/j.vetmic.2019.07.010DOI Listing
August 2019

Effect of Macrolide and Rifampin Resistance on Fitness of during Intramacrophage Replication and .

Infect Immun 2019 10 19;87(10). Epub 2019 Sep 19.

Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.

The soil-dwelling, saprophytic actinomycete is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in the incidence of macrolide- and rifampin-resistant isolates has been documented. Previously, our laboratory demonstrated decreased fitness of strains that were resistant to macrolides, rifampin, or both, resulting in impaired growth in iron-restricted media and in soil. The objective of this study was to examine the effect of macrolide and/or rifampin resistance on intracellular replication of in equine pulmonary macrophages and in an mouse infection model in the presence and absence of antibiotics. In equine macrophages, the macrolide-resistant strain did not increase in bacterial numbers over time and the dual macrolide- and rifampin-resistant strain exhibited decreased proliferation compared to the susceptible isolate. In the mouse model, in the absence of antibiotics, the susceptible isolate outcompeted the macrolide- or rifampin-resistant strains.
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http://dx.doi.org/10.1128/IAI.00281-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759311PMC
October 2019

The effect of age on foal monocyte-derived dendritic cell (MoDC) maturation and function after exposure to killed bacteria.

Vet Immunol Immunopathol 2019 Apr 9;210:38-45. Epub 2019 Mar 9.

From the Department of Large Animal Medicine, 2200 College Station Road, University of Georgia College of Veterinary Medicine, Athens, GA, 30602, USA. Electronic address:

Neonatal foals are uniquely susceptible to certain infections early in life. Dendritic cells (DC) are vital in the transition between the innate and adaptive immune response to infection, but DC biology in foals is not fully characterized. Monocyte-derived DC represent a suitable in vitro model similar to DC that differentiate from monocytes recruited from circulation. We hypothesized that foal monocyte-derived DC (MoDC) would exhibit age-dependent phenotypic and functional differences compared to adult horse MoDC. MoDC generated from 9 horses (collected once) and from 8 foals (collected at 1, 7, and 30 days-of-age) were exposed to killed whole cell Escherichia coli or Staphylococcus aureus bacteria. MoDC expression of MHC class II (MHC class-II), CD86, and CD14 were measured by flow cytometry, and supernatant cytokine concentrations of IL-4, IL-17, IFN-γ, and IL-10 were quantified with a validated immunoassay. The percentage of MoDC expressing MHC class-II and CD86 was lower and CD14 was higher for cells generated from 1-day-old foals compared to cells generated from adult horses (P < 0.0001). Bacterial exposure increased the percentage of cells expressing CD86 at all ages (P < 0.0001). Bacteria-exposed MoDC from 1-day-old foals produced significantly less IL-4, IL-17, and IFN-γ than adult MoDC produced in response to bacterial exposure (P ≤ 0.04). Following bacterial exposure, foal MoDC phenotype and cytokine secretion were different than those of mature horses. These differences could reduce the ability of foals to generate a protective immune response against bacterial infection.
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http://dx.doi.org/10.1016/j.vetimm.2018.11.020DOI Listing
April 2019

The pharmacokinetics and pharmacodynamics of intravenous hydromorphone in horses.

Vet Anaesth Analg 2019 May 22;46(3):395-404. Epub 2018 Nov 22.

Department of Large Animal Medicine, University of Georgia College of Veterinary Medicine, Athens, GA, USA.

Objective: Describe the pharmacokinetics and pharmacodynamics of intravenous hydromorphone in healthy horses.

Study Design: Masked, randomized, cross-over, Latin square design.

Animals: A group of eight healthy adult horses METHODS: Horses were administered each of four treatments with an 8 day washout. Treatments groups included intravenous hydromorphone 0.02 mg kg (LD), 0.04 mg kg (MD), 0.08 mg kg (HD) and saline (P). Blood samples for hydromorphone analysis were obtained for 24 hours after treatment. Plasma hydromorphone was quantified and pharmacokinetic parameters were determined using non-compartmental analysis. Pharmacodynamic data collected for 24 hours after treatment included thermal nociceptive threshold, heart rate (HR), respiratory rate (f) and rectal temperature, and analyzed using mixed-effects linear models.

Results: Mean (± standard deviation) hydromorphone terminal half-life (t), systemic clearance and apparent volume of distribution at steady state (Vd) were 18.1 ± 18.6, 34.0 ± 12.8, and 41.3 ± 32.5 minutes, 66.6 ± 5.3, 550.0 ± 76.4, and 92.7 ± 13.9 mL kg minute, and 1118 ± 369, 1460 ± 325 and 2242 ± 950 mL kg for treatments LD, MD and HD, respectively. Thermal threshold increased significantly compared to baseline for all treatments for up to 12 hours. HR was elevated above baseline in treatments LD, MD and HD, extending to 30, 15 and 105 minutes after treatment, respectively. Respiratory rate was elevated above baseline in treatments MD and HD from 30 to 195 minutes and from 45 to 480 minutes after treatment, respectively. Temperature was elevated above baseline in treatment HD until 255 minutes after treatment.

Conclusions: Hydromorphone exhibited a short t, rapid clearance and large Vd in horses. It also provided a dose-dependent increase in thermal threshold with associated increases in HR, f and rectal temperature.

Clinical Relevance: Hydromorphone 0.04 mg kg provided clinically relevant thermal antinociception with minimal adverse effects.
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http://dx.doi.org/10.1016/j.vaa.2018.11.001DOI Listing
May 2019

Effect of Macrolide and Rifampin Resistance on the Fitness of Rhodococcus equi.

Appl Environ Microbiol 2019 04 22;85(7). Epub 2019 Mar 22.

Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.

is a leading cause of severe pneumonia in foals. Standard treatment is dual antimicrobial therapy with a macrolide and rifampin, but the emergence of macrolide- and rifampin-resistant isolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness of Three unique isogenic sets were created, each consisting of four strains, as follows: a susceptible parent isolate, strains resistant to macrolides or rifampin, and a dual macrolide- and rifampin-resistant strain. Each isogenic set's bacterial growth curve was generated in enriched medium, minimal medium (MM), and minimal medium without iron (MM-I). Bacterial survival in soil was analyzed over 12 months at -20°C, 4°C, 25°C, and 37°C, and the ability of these strains to retain antimicrobial resistance during sequential subculturing was determined. Insertion of the mobile element conferring macrolide resistance had minimal effect on growth. However, two of three mutations conferring rifampin resistance resulted in a decreased growth rate in MM. In soil, macrolide- or rifampin-resistant strains exhibited limited growth compared to that of the susceptible isolate at all temperatures except -20°C. During subculturing, macrolide resistance was lost over time, and two of three mutations reverted to the wild-type form. The growth of rifampin-resistant colonies is delayed under nutrient restriction. In soil, possession of rifampin or macrolide resistance results in decreased fitness. Both macrolide and rifampin resistance can be lost after repeated subculturing. This work advances our understanding of the opportunistic environmental pathogen , a disease agent affecting horses and immunocompromised people. is one of the most common causes of severe pneumonia in young horses. For decades, the standard treatment for pneumonia in horses has been dual antimicrobial therapy with a macrolide and rifampin; effective alternatives to this combination are lacking. The World Health Organization classifies these antimicrobial agents as critically important for human medicine. Widespread macrolide and rifampin resistance in isolates is a major emerging problem for the horse-breeding industry and might also adversely impact human health if resistant strains infect people or transfer resistance mechanisms to other pathogens. This study details the impact of antimicrobial resistance on fitness, a vital step for understanding the ecology and epidemiology of resistant isolates, and will support development of novel strategies to combat antimicrobial resistance.
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http://dx.doi.org/10.1128/AEM.02665-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585491PMC
April 2019

Investigation of effects of omeprazole on the fecal and gastric microbiota of healthy adult horses.

Am J Vet Res 2019 Jan;80(1):79-86

OBJECTIVE To determine the effects of oral omeprazole administration on the fecal and gastric microbiota of healthy adult horses. ANIMALS 12 healthy adult research horses. PROCEDURES Horses were randomly assigned to receive omeprazole paste (4 mg/kg, PO, q 24 h) or a sham (control) treatment (tap water [20 mL, PO, q 24 h]) for 28 days. Fecal and gastric fluid samples were collected prior to the first treatment (day 0), and on days 7, 28, 35, and 56. Sample DNA was extracted, and bacterial 16S rRNA gene sequences were amplified and sequenced to characterize α and β diversity and differential expression of the fecal and gastric microbiota. Data were analyzed by visual examination and by statistical methods. RESULTS Composition and diversity of the fecal microbiota did not differ significantly between treatment groups or over time. Substantial variation in gastric fluid results within groups and over time precluded meaningful interpretation of the microbiota in those samples. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that omeprazole administration had no effect on fecal microbiota composition and diversity in this group of healthy adult horses. Small sample size limited power to detect a difference if one existed; however, qualitative graphic examination supported that any difference would likely have been small and of limited clinical importance. Adequate data to evaluate potential effects on the gastric microbiota were not obtained. Investigations are needed to determine the effects of omeprazole in horses with systemic disease or horses receiving other medical treatments.
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http://dx.doi.org/10.2460/ajvr.80.1.79DOI Listing
January 2019

Emergence of Resistance to Macrolides and Rifampin in Clinical Isolates of Rhodococcus equi from Foals in Central Kentucky, 1995 to 2017.

Antimicrob Agents Chemother 2019 01 21;63(1). Epub 2018 Dec 21.

Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, Kentucky, USA.

The objective of this study was to determine the prevalence of strains resistant to macrolides and rifampin over time in clinical samples from foals submitted to diagnostic laboratories in central Kentucky. We performed a retrospective observational study of all clinical samples from foals that were submitted to veterinary diagnostic laboratories in Kentucky between January 1995 and December 2017. Samples were included if the bacterium was cultured and tested for susceptibility to erythromycin or rifampin. susceptibility testing to erythromycin was available for 2,169 isolates of , while susceptibility testing to both erythromycin and rifampin was available for 1,681 isolates. Rifampin resistance was first detected in 2000, and erythromycin resistance was first detected in 2004. Between 1995 and 2006, the proportion of resistant isolates of was 0.7% for erythromycin and 2.3% for rifampin. There was a significant ( < 0.001) increase in the proportion of resistant between 2007 and 2017, with 13.6% of isolates being resistant to erythromycin and 16.1% being resistant to rifampin. Between 2007 and 2017, isolates of resistant to erythromycin or rifampin were significantly less likely to be isolated from feces than from the respiratory tract, other soft tissues, or musculoskeletal infections. The considerable increase in the prevalence of isolates of resistant to macrolides and rifampin since 2007 is of concern for both human and animal health.
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http://dx.doi.org/10.1128/AAC.01714-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325176PMC
January 2019

Fecal shedding of Rhodococcus equi in mares and foals after experimental infection of foals and effect of composting on concentrations of R. equi in contaminated bedding.

Vet Microbiol 2018 Sep 21;223:42-46. Epub 2018 Jul 21.

Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

Rhodococcus equi, a soil saprophyte, is a common cause of pneumonia in foals and a frequent opportunistic pathogen in immunosuppressed people. Because it is widespread in the environment, R. equi can be detected in the feces of most horses. However, the exact timing and rate of shedding relative to infection is unknown. The objectives of this study were to quantify shedding of R. equi in mares and foals after experimental infection of foals with 2 different inocula and to determine the effect of composting on concentrations of R. equi in contaminated bedding. Foals were infected intratracheally with virulent R. equi using inocula of 1 × 10 CFU/mL (n = 16) or 1 × 10 CFU/mL (n = 12) at 23 ± 2 days (range 21 to 27 days) of age. Fecal samples were collected from mares and foals prior to infection and on days 3, 7, and 14 post-infection for quantitative culture of total and virulent R. equi. Waste from the horses was composted for 7 days. Concentrations of total and virulent R. equi in foal feces were significantly higher on day 14 post-infection compared to day 0, regardless of inoculum size. Concentration of total R. equi in mare feces was significantly higher on days 3, 7 and 14 compared to day 0 regardless of inoculum size, whereas shedding of virulent R. equi only increased on day 14 post-infection. Composting for 7 days significantly decreased concentrations of total R. equi and virulent R. equi by an average of 1.08 ± 0.21 and 0.59 ± 0.26 log CFU/g, respectively.
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http://dx.doi.org/10.1016/j.vetmic.2018.07.017DOI Listing
September 2018

Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi.

PLoS Pathog 2018 07 19;14(7):e1007160. Epub 2018 Jul 19.

Harvard Medical School, Brigham & Women's Hospital, Boston, MA, United States of America.

Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equi, that causes granulomatous pneumonia in horse foals, we devised and tested an experimental system relying solely on antibody-mediated protection against this host-specific etiologic agent. Immunity was induced by vaccinating pregnant mares 6 and 3 weeks prior to predicted parturition with a conjugate vaccine targeting the highly conserved microbial surface polysaccharide, poly-N-acetyl glucosamine (PNAG). We ascertained antibody was transferred to foals via colostrum, the only means for foals to acquire maternal antibody. Horses lack transplacental antibody transfer. Next, a randomized, controlled, blinded challenge was conducted by inoculating at ~4 weeks of age ~10(6) cfu of R. equi via intrabronchial challenge. Eleven of 12 (91%) foals born to immune mares did not develop clinical R. equi pneumonia, whereas 6 of 7 (86%) foals born to unvaccinated controls developed pneumonia (P = 0.0017). In a confirmatory passive immunization study, infusion of PNAG-hyperimmune plasma protected 100% of 5 foals against R. equi pneumonia whereas all 4 recipients of normal horse plasma developed clinical disease (P = 0.0079). Antibodies to PNAG mediated killing of extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms depended on antibody recognition of surface expression of PNAG on infected cells, along with complement deposition and PMN-assisted lysis of infected macrophages. Peripheral blood mononuclear cells from immune and protected foals released higher levels of interferon-γ in response to PNAG compared to controls, indicating vaccination also induced an antibody-dependent cellular release of this critical immune cytokine. Overall, antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against diseases caused by intracellular bacterial pathogens.
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http://dx.doi.org/10.1371/journal.ppat.1007160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053243PMC
July 2018

Accuracy of an oscillometric blood pressure monitor in anesthetized pigs.

Lab Anim 2018 Oct 20;52(5):490-496. Epub 2018 Mar 20.

2 Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, USA.

The purpose of this study is to evaluate the accuracy of an oscillometric blood pressure monitor in anesthetized pigs. Invasive blood pressure (IBP) and noninvasive blood pressure (NIBP) measurements were taken using a DRE Waveline Pro multiparameter monitor at four different time points in 17 pigs undergoing injectable anesthesia. NIBP measurements were taken on both the thoracic and pelvic limbs. Bland Altman analysis was used to assess agreement between methods and a linear mixed-effects model was used to evaluate the effect of cuff position and blood pressure on bias. Invasive systolic arterial pressure (SAP) ranged between 112 and 161 mmHg (mean ± SD: 138.8 ± 13.3; median: 139.5). Invasive diastolic arterial pressure (DAP) ranged between 60 and 104 mmHg (mean ± SD: 86.0 ± 9.1; median: 87.0). Invasive mean arterial pressure (MAP) ranged between 79 and 121 mmHg (mean ± SD: 103.2 ± 9.3; median 103.0). Only the diastolic and mean measurements obtained from the pelvic limb met criteria outlined by the American College of Internal Medicine for required accuracy of NIBP monitors. Bias was significantly higher in the thoracic limb in comparison to the pelvic limb and was significantly higher at blood pressures above median. In general, NIBP measurements underestimated IBP measurements. In conclusion, the use of the DRE Waveline Pro to assess NIBP in anesthetized pigs may be useful in monitoring trends in mean and diastolic blood pressure and is most accurate when used on the pelvic limb.
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http://dx.doi.org/10.1177/0023677218763686DOI Listing
October 2018

Development of septic polysynovitis and uveitis in foals experimentally infected with Rhodococcus equi.

PLoS One 2018 7;13(2):e0192655. Epub 2018 Feb 7.

Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of age were infected intratracheally with virulent R. equi using inocula of 1×108 CFU (high inoculum; n = 16) or 1×107 CFU (low inoculum; n = 12). Foals were monitored twice daily and necropsy was performed 14 days post-infection. Aqueous humor and synovial fluid were collected aseptically and the percentage of affected lung was calculated. The mean (± SD) percentage of affected lung was significantly higher with the high inoculum (31.8 ± 14.6%) than with the low inoculum (14.4 ± 11.4%). Fourteen of 25 foals developed uveitis and 20 of 28 foals developed polysynovitis. R. equi was cultured from the aqueous humor of 11 foals and from the synovial fluid of 14 foals. The risk of development of polysynovitis and protein concentration in the aqueous humor were significantly higher in foals that received the high inoculum. These results indicate that polysynovitis and uveitis are septic complications associated with the severity of lung disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192655PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802921PMC
April 2018

Comparison of the oral and rectal mucosal and colonic serosal microcirculations of healthy, anesthetized horses.

Can J Vet Res 2018 Jan;82(1):55-59

Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA (Kieffer, Williams, Giguère, Epstein); MedVet Medical & Cancer Centers for Pets, Chicago, Illinois, USA (Shepard).

The objectives of the study were to: i) determine baseline microvascular perfusion indices (MPI) and assess their repeatability in healthy horses under general anesthesia, and ii) compare the MPIs of 3 microvascular beds (oral mucosa, colonic serosa, and rectal mucosa). Healthy adult horses were anesthetized and sidestream dark field microscopy was used to collect video loops of the oral mucosa, rectal mucosa, and colonic serosa under normotensive conditions without cardiovascular support drugs; videos were later analyzed to produce MPIs. Baseline MPI values were determined for each site, which included the total vessel density (TVD), perfused vessel density (PVD), portion perfused vessels (PPV), and microcirculatory flow index (MFI). Differences in MPIs between microvascular beds were not statistically significant. Repeatability of the measurements varied for each MPI. In particular, the site of sampling had a profound effect on the repeatability of the PPV measurements and should be considered in future studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764044PMC
January 2018