Integrated analysis of gut metabolome, microbiome, and exfoliome data in an equine model of intestinal injury.

BACKGROUND: The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions. METHODS: Twenty horses were randomly assigned to 1 of 2 groups (n = 10): control (placebo paste) or NSAID (phenylbutazone 4.4 mg/kg orally once daily for 9 days). Fecal samples were collected on days 0 and 10 and analyzed with respect to microbiota (16S rDNA gene sequencing), metabolomic (untargeted metabolites), and host exfoliated cell transcriptomic (exfoliome) changes. Data were analyzed and integrated using a variety of computational techniques, and underlying regulatory mechanisms were inferred from features that were commonly identified by all computational approaches. RESULTS: Phenylbutazone induced alterations in the microbiota, metabolome, and host transcriptome. Data integration identified correlation of specific bacterial genera with expression of several genes and metabolites that were linked to oxidative stress. Concomitant microbiota and metabolite changes resulted in the initiation of endoplasmic reticulum stress and unfolded protein response within the intestinal mucosa. CONCLUSIONS: Results of integrative analysis identified an important role for oxidative stress, and subsequent cell signaling responses, in a large animal model of GI inflammation. The computational approaches for combining non-invasive platforms for unbiased assessment of host GI responses (e.g., exfoliomics) with metabolomic and microbiota changes have broad application for the field of gastroenterology. Video Abstract.

A Common Practice of Widespread Antimicrobial Use in Horse Production Promotes Multi-Drug Resistance.

The practice of prophylactic administration of a macrolide antimicrobial with rifampin (MaR) to apparently healthy foals with pulmonary lesions identified by thoracic ultrasonography (i.e., subclinically pneumonic foals) is common in the United States. The practice has been associated epidemiologically with emergence of R. equi resistant to MaR. Here, we report direct evidence of multi-drug resistance among foals treated with MaR. In silico and in vitro analysis of the fecal microbiome and resistome of 38 subclinically pneumonic foals treated with either MaR (n = 19) or gallium maltolate (GaM; n = 19) and 19 untreated controls was performed. Treatment with MaR, but not GaM, significantly decreased fecal microbiota abundance and diversity, and expanded the abundance and diversity of antimicrobial resistance genes in feces. Soil plots experimentally infected with Rhodococcus equi (R. equi) and treated with MaR selected for MaR-resistant R. equi, whereas MaR-susceptible R. equi out-competed resistant isolates in GaM-treated or untreated plots. Our results indicate that MaR use promotes multi-drug resistance in R. equi and commensals that are shed into their environment where they can persist and potentially infect or colonize horses and other animals.

Identification of macrolide- and rifampicin-resistant Rhodococcus equi in environmental samples from equine breeding farms in central Kentucky during 2018.

Rhodococcus equi causes severe pneumonia in foals and is most often recognized in people as an opportunistic pathogen. Longitudinal studies examining antimicrobial-resistant R. equi from environmental samples are lacking. We hypothesized that antimicrobial-resistant R. equi would be detectable in the ground (pasture soil or stall bedding) and air at breeding farms with previous documentation of foals infected with resistant isolates, and that concentrations of resistant isolates would increase over time during the foaling season. In this prospective cohort study, ground and air samples were collected from stalls and paddocks in January, March, May and July of 2018 at 10 horse-breeding farms with history of foal pneumonia attributed to macrolide- or Rifampicin-resistant R. equi. Environmental samples were cultured in the presence and absence of macrolides and Rifampicin to select for resistant organisms. Data were analyzed with linear mixed-effects and Hurdle models. Concentrations of total R. equi in bedding or air of stalls were significantly (P < 0.05) higher in January than other months. The proportion of resistant R. equi in soil samples from paddocks was significantly (P < 0.05) higher than stall bedding during all months. For each month, air samples from paddocks had a significantly (P < 0.05) higher proportion of resistant isolates than those from stalls. Fifty-five percent of resistant soil isolates and 34% of resistant air isolates were considered virulent by identification of the vapA gene. Concentrations of resistant R. equi isolates did not increase over time during the foaling season. Antimicrobial-resistant R. equi can persist in the environment at farms with a history of pneumonia caused by resistant R. equi infections, and exposure to resistant isolates in paddocks and stalls appears stable during the foaling season. Resistant isolates in the environment not only pose a risk for disease but also can serve as a repository for dissemination of resistance genes.

Novel lipoprotein density profiling in laminitic, obese, and healthy horses.

Lipoproteins are water-miscible macromolecules enabling the transport of lipids in blood. In humans, altered proportions of lipoproteins are used to detect and classify metabolic diseases. Obesity and obesity-related comorbidities are common in horses. The pathophysiology of obesity is poorly understood and likely multifactorial. Development of new diagnostic tests to identify horses at risk of developing obesity to implement preventative measures is critical; however, a necessary first step to accomplish this goal is to improve our understanding of the pathophysiology of disease. Thus, the objective of this study was to characterize and compare lipoprotein profiles of horses with normal and excess body conditions, with and without laminitis using a novel method of continuous lipoprotein density profiling (CLPDP). Comparisons were made between 4 groups of horses: (1) laminitic, obese horses (n = 66); (2) laminitic, nonobese horses (n = 35); (3) nonlaminitic, obese horses (n = 41); and (4) nonlaminitic, nonobese horses (n = 95). Lipoprotein profiling, including evaluation of triglyceride-rich lipoprotein (TRL), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) was performed using CLPDP, and all 4 groups were compared. A significant difference was observed among groups for the subfractions TRL, LDL1, LDL2, HDL2b, HDL2a, HDL3a, HDL3b, HDL3c, and total HDL. This is the first known description of CLPDP to characterize equine lipid profiles and holds promise as a useful method for lipid characterization of horses.

Regular brief interruptions to sitting after a high-energy evening meal attenuate glycemic excursions in overweight/obese adults.

BACKGROUND AND AIMS: Modern Western lifestyles are characterized by consumption of approximately 45% of total daily energy intake at the evening meal, followed by prolonged sitting while watching television (TV), which may deleteriously impact glycemic control. After a high-energy evening meal (dinner), we examined whether regular, brief activity bouts during TV commercial breaks could acutely lower postprandial glucose and insulin responses in overweight/obese adults, compared to prolonged uninterrupted sitting. METHODS AND RESULTS: Nine overweight/obese adults (29.7 ± 4.06 kg m-2; aged 32 ± 3 years; 5 male) completed two laboratory-based conditions of three and a half hours: prolonged sitting during TV viewing (SIT); and, prolonged sitting interrupted every 20 min with 3 min of light-intensity body-weight resistance activities (active commercial breaks; ACBs). Venous postprandial glucose and insulin responses to dinner were calculated as positive incremental area under the curve (iAUC) from baseline. Interstitial glucose was measured using a continuous glucose monitor and quantified as total AUC (tAUC). Compared to SIT, plasma glucose iAUC was reduced by 33% [3.4 ± 1.0 vs 5.1 ± 1.0 (mean ± SEM) mmol h·L-1, p = 0.019] and plasma insulin iAUC by 41% (813 ± 224 vs 1373 ± 224, p = 0.033 pmol h·L-1) for the ACB condition. During the ACB condition there was a significant reduction in interstitial glucose tAUC (24.4 ± 5.2 vs 26.9 ± 5.2 mmol h·L-1, p < 0.001), but this did not persist beyond the laboratory observation period. CONCLUSIONS: Regular brief light-intensity activity bouts can attenuate glycemic responses during television viewing time following a high-energy evening meal in overweight/obese adults.

Prevalence of Rhodococcus equi from the nasal cavity of 1010 apparently healthy horses.

BACKGROUND: Rhodococcus equi is an important cause of foal pneumonia. While its isolation from different sources has been widely evaluated, there is a need to better understand the R. equi epidemiology from samples of the nasal cavity of healthy horses. OBJECTIVES: To determine the prevalence of R. equi from the nasal cavity of healthy horses, along with its virulence profile, antimicrobial susceptibility and environmental variables associated. STUDY DESIGN: Cross-sectional study. METHODS: Swabs from the nasal cavity of 1010 apparently healthy horses from 341 farms were submitted for bacteriological analyses. The identity and virulence profile of the R. equi isolates were assessed by multiplex PCR; antimicrobial susceptibility was determined by the disk-diffusion method. The occurrence of R. equi was calculated at the level of both animal and farm. The association of seven specific environmental factors with R. equi isolation was assessed using logistic regression and by a spatial scan statistical method to determine the presence of local clusters. RESULTS: Antimicrobial-sensitive R. equi was isolated from 10 (1%) of 1010 horses ranging between 3 and 29 years old. Ten farms (3%) had at least one positive horse. Only one R. equi isolate (10%) was classified as virulent. Red-Yellow Argisol (PVA/PV) soils were significantly associated with R. equi isolation (odds ratio (OR) 8.02; CI95% , 1.98-32.50, P = 0.01), and areas with well-drained soil were less likely to be test positive (OR 0.85; CI95% , 0.76-0.96, P = 0.03). MAIN LIMITATIONS: The use of culture-based method instead of PCR-based assay and the lack of soil sampling. CONCLUSIONS: Antimicrobial-sensitive R. equi may be considered a minor part of the normal bacterial flora in the nasal cavity of healthy and immunologically functional horses breeding on pasture. Further studies are warranted to determine if soils rich in iron and well-drained are, in fact, associated with the occurrence of R. equi.

Use of Serial Quantitative PCR of the vapA Gene of Rhodococcus equi in Feces for Early Detection of R. equi Pneumonia in Foals.

BACKGROUND: Current screening tests for Rhodococcus equi pneumonia in foals lack adequate accuracy for clinical use. Real-time, quantitative PCR (qPCR) for virulent R. equi in feces has not been systematically evaluated as a screening test. OBJECTIVE: The objective of this study was to evaluate the accuracy of qPCR for vapA in serially collected fecal samples as a screening test for R. equi pneumonia in foals. ANIMALS: One hundred and twenty-five foals born in 2011 at a ranch in Texas. METHODS: Fecal samples were collected concurrently with thoracic ultrasonography (TUS) screening examinations at ages 3, 5, and 7 weeks. Affected (pneumonic) foals (n = 25) were matched by age and date-of-birth to unaffected (n = 25) and subclinical (ie, having thoracic TUS lesions but no clinical signs of pneumonia) foals (n = 75). DNA was extracted from feces using commercial kits and concentration of virulent R. equi in feces was determined by qPCR. RESULTS: Subsequently affected foals had significantly greater concentrations of vapA in feces than foals that did not develop pneumonia (unaffected and subclinical foals) at 5 and 7 weeks of age. Accuracy of fecal qPCR, however, was poor as a screening test to differentiate foals that would develop clinical signs of pneumonia from those that would remain free of clinical signs (including foals with subclinical pulmonary lesions attributed to R. equi) using receiver operating characteristic (ROC) methods. CONCLUSIONS AND CLINICAL IMPORTANCE: In the population studied, serial qPCR on feces lacked adequate accuracy as a screening test for clinical R. equi foal pneumonia.

Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia.

BACKGROUND: Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. HYPOTHESIS: Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. ANIMALS: Ten foals with experimentally induced R. equi pneumonia. METHODS: Pilot treatment trial. Foals with pneumonia induced by intrabronchial instillation of R. equi were randomly allocated to receive either clarithromycin combined with rifampin (CLR + RIF) PO or LG IV, and followed by daily physical examinations and weekly thoracic ultrasonography and serum creatinine concentration determinations until the resolution of clinical signs. Treatment success was defined as the resolution of clinical signs and ultrasonographically identified pulmonary abscesses. RESULTS: All 10 foals were successfully treated. Two of 5 foals treated with LG developed azotemia within 1 week; LG was discontinued and treatment switched to CLR + RIF for these foals. None of the CLR + RIF treated foals developed azotemia. CONCLUSIONS AND CLINICAL IMPORTANCE: Liposomal gentamicin IV can be effective for treatment of R. equi pneumonia, but nephrotoxicity indicates that an alternative dosing interval or route (such as nebulization) will be needed before LG is adequately safe for clinical use. Larger comparative trials will be needed to evaluate the relative efficacy of a safer LG dosage regimen.

Retrospective analysis of factors associated with outcome of proximal interphalangeal joint arthrodesis in 82 horses including Warmblood and Thoroughbred sport horses and Quarter Horses (1992-2014).

REASONS FOR PERFORMING STUDY: Outcomes associated with arthrodesis of the proximal interphalangeal (PIP) joint in Quarter Horses used for Western performance activities are well documented but little is known regarding outcomes for other types of horses. OBJECTIVES: To identify factors associated with outcomes, including breed and activity, after arthrodesis of the PIP joint in Warmbloods, Thoroughbreds and Quarter Horses. STUDY DESIGN: Retrospective case series. METHODS: Surgical case records of 82 Quarter Horses principally engaged in Western performance and Thoroughbred or Warmblood breeds principally engaged in showing, showjumping and dressage, with arthrodesis of the PIP joint were reviewed. Arthrodesis was performed with either 3 transarticular cortex bone screws placed in lag fashion, a dynamic compression plate (DCP) with 2 transarticular cortex bone screws placed in lag fashion, or a locking compression plate (LCP) with 2 transarticular cortex bone screws placed in lag fashion. Demographic data, clinical presentation, radiographic findings, surgical technique, post operative treatment and complications were recorded. Long-term follow-up was obtained for all 82 horses. RESULTS: Osteoarthritis of the PIP joint was the most common presenting condition requiring arthrodesis, which was performed with either the 3 screw technique (n = 41), DCP fixation (n = 22), or LCP fixation (n = 19). Post operatively, 23/31 (74%) Warmbloods/Thoroughbreds and 44/51 (87%) Quarter Horses achieved successful outcomes. Thirteen of 23 (57%) Warmbloods/Thoroughbreds and 24 of 38 (63%) Quarter Horses, used for athletic performance, returned to successful competition. Within this subgroup of horses engaged in high-level activity, regardless of breed type, horses undergoing hindlimb arthrodesis were significantly more likely to return to successful competition (73%; 33/45) than those with forelimb arthrodesis (25%; 4/16, P = 0.002). CONCLUSIONS: Arthrodesis of the PIP joint in Warmbloods/Thoroughbreds and Quarter Horses results in a favourable outcome for return to their intended use and athletic competition.

Estimating the Sensitivity and Specificity of Real-Time Quantitative PCR of Fecal Samples for Diagnosis of Rhodococcus equi Pneumonia in Foals.

BACKGROUND: Real-time, quantitative PCR (qPCR) methods for detecting Rhodococcus equi in feces have been developed as a noninvasive, rapid diagnostic test for R. equi pneumonia, but have not been evaluated in a large population of foals. OBJECTIVE: The objective of this study was to evaluate the clinical utility of fecal PCR as a diagnostic test for R. equi pneumonia in foals using receiver operating characteristic (ROC) methods. ANIMALS: 186 foals born in 2011 at an R. equi-endemic ranch in Texas. METHODS: Fecal samples were collected at the time of onset of clinical signs for pneumonic foals (n = 31). Foals with pneumonia were matched by age and birth date to healthy (n = 31) and subclinical (n = 124) control foals; fecal samples were collected from these controls. DNA was extracted from feces using commercial kits and concentration of virulent R. equi in feces was determined by qPCR. RESULTS: Concentration of R. equi in feces differed significantly (P < .05) among groups. The area under the ROC curve for fecal qPCR for diagnosis of R. equi pneumonia was 89% (95% CI, 83-99), with a sensitivity of 94% and specificity of 72%. CONCLUSIONS AND CLINICAL IMPORTANCE: qPCR of feces can be useful as an alternative to tracheobronchial aspiration for the diagnosis of R. equi in foals with clinical signs of pneumonia. Caution should be used in extrapolating results of this study to other populations because fecal concentration of R. equi might vary by geographic location or management practices.

Genetic Susceptibility to Rhodococcus equi.

Rhodococcus equi pneumonia is a major cause of morbidity and mortality in neonatal foals. Much effort has been made to identify preventative measures and new treatments for R. equi with limited success. With a growing focus in the medical community on understanding the genetic basis of disease susceptibility, investigators have begun to evaluate the interaction of the genetics of the foal with R. equi. This review describes past efforts to understand the genetic basis underlying R. equi susceptibility and tolerance. It also highlights the genetic technology available to study horses and describes the use of this technology in investigating R. equi. This review provides readers with a foundational understanding of candidate gene approaches, single nucleotide polymorphism-based, and copy number variant-based genome-wide association studies, and next generation sequencing (both DNA and RNA).

Quantitative magnetic resonance imaging in a naturally occurring canine model of spinal cord injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To analyze magnetic resonance imaging (MRI) evaluator agreement in dogs with spinal cord injury (SCI) caused by intervertebral disk herniation (IVDH) using semiautomated and manual lesion segmentation and to analyze the associations between MRI and functional outcome. SETTING: United States of America. METHODS: T2-weighted MRIs from dogs with SCI resulting from thoracolumbar IVDH were identified from a database. Evaluators categorized MRIs on the basis of the presence or absence of a T2-hyperintense spinal cord lesion in axial and sagittal images. A semiautomated segmentation algorithm was developed and used to estimate the lesion volume. Agreement between evaluators and between semiautomated and manual segmentation was analyzed. The relationships of qualitative and quantitative MRIs with behavioral functional outcome were analyzed. RESULTS: Axial images more commonly depicted lesions compared with sagittal images. Lesions in axial images had more consistent associations with functional outcome compared with sagittal images. There was imperfect qualitative agreement, and lesion volume estimation was imprecise. However, there was improved precision using semiautomated segmentation compared with manual segmentation. CONCLUSION: Lesion volume estimation in dogs with naturally occurring SCI caused by IVDH is challenging, and axial images have important advantages compared with sagittal images. The semiautomated segmentation algorithm described herein shows promise but may require further refinement.

Amikacin resistance in Staphylococcus pseudintermedius isolated from dogs.

Staphylococcus pseudintermedius is the most common microorganism isolated from canine pyoderma and postoperative wound infections. The prevalence of methicillin-resistant S. pseudintermedius (MRSP) has increased, and recently, isolates that are resistant not only to methicillin but also to other classes of antibiotic drugs, including aminoglycosides, have become common. A total of 422 S. pseudintermedius isolates collected from 413 dogs were analyzed for amikacin and methicillin resistance using broth microdilution and disk diffusion testing. Methicillin-resistant isolates were significantly (P < 0.0001) more likely to be resistant to amikacin (37%, 31/84) than were methicillin-susceptible isolates (7%, 22/338). Additionally, resistance to non-ß-lactam antibiotics was significantly associated with resistance to amikacin irrespective of methicillin resistance. Among the 422 isolates, 32 that tested positive for amikacin resistance by broth microdilution or disk diffusion testing were investigated further for the presence of aminoglycoside-modifying enzyme genes using multiplex PCR. Of these isolates, 66% (21/32) were methicillin resistant. In contrast to previous studies of Staphylococcus aureus, the most prevalent gene detected was aph(3')-IIIa found in 75% (24/32) of isolates followed by aac(6')/aph(2") and ant(4')-Ia in 12% (4/32) and 3% (1/32), respectively. Understanding the differences in antimicrobial resistance gene carriage between different species of Staphylococcus may improve antimicrobial drug selection for clinical therapy and provide insights into how resistance develops in S. pseudintermedius.

In vitro susceptibility of equine-obtained isolates of Corynebacterium pseudotuberculosis to gallium maltolate and 20 other antimicrobial agents.

This study's objective was to determine the in vitro antimicrobial activities of gallium maltolate (GaM) and 20 other antimicrobial agents against clinical equine isolates of Corynebacterium pseudotuberculosis. The growth of cultured isolates was not inhibited by any concentration of GaM. MIC data revealed susceptibility to commonly used antimicrobials.

Relationship of mixed bacterial infection to prognosis in foals with pneumonia caused by Rhodococcus equi.

BACKGROUND: Isolation of multiple bacterial species is common in foals with Rhodococcus equi pneumonia. HYPOTHESIS: There is no association between isolation of other microorganisms and outcome. ANIMALS: 155 foals with pneumonia caused by R. equi. METHODS: Case records of foals diagnosed with R. equi pneumonia based on culture of the respiratory tract were reviewed at 2 referral hospitals (University of Florida [UF] and Texas A&M University [TAMU]). RESULTS: R. equi was cultured from a tracheobronchial aspirate (TBA) in 115 foals and from lung tissue in 38 foals. Survival was significantly higher at UF (71%; 70/99) than at TAMU (50%; 28/56). R. equi was significantly more likely to grow in pure cultures from samples obtained from foals at UF (55%; 54/99) than from foals at TAMU (23%; 13/56). Microorganisms cultured with R. equi included Gram-positive bacteria in 40, Gram-negative bacteria in 41, and fungi in 23 foals. The most common bacteria isolated were beta-hemolytic streptococci (n = 26) and Escherichia coli (n = 18). Mixed infections were significantly more likely to be encountered in TBA than in lung tissue. Only foals from which R. equi was cultured from a TBA were included in the analysis for association between mixed infection and outcome. After adjusting for the effect of hospital using multivariate logistic regression, mixed culture, mixed bacterial culture, Gram-positive bacteria, beta-hemolytic streptococci, Gram-negative bacteria, enteric Gram-negative bacteria, nonenteric Gram-negative bacteria, and fungi were not significantly associated with outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: Isolation of multiple bacteria or fungi from a TBA along with R. equi does not negatively impact prognosis.

Treatment with histamine-type 2 receptor antagonists and omeprazole increase the risk of diarrhoea in neonatal foals treated in intensive care units.

REASONS FOR PERFORMING STUDY: The use of anti-ulcer medication in the neonatal intensive care unit (ICU) is common due to the concern for development of catastrophic gastric ulcerdisease. In man, however, the use of acid-suppressive medication has been shown in some studies to be a substantial riskfactorfor the development of Clostridium difficile-associated diarrhoea (CDAD), bacteraemia and neonatal sepsis. OBJECTIVE: The purpose of the study reported herein is to evaluate the influence of anti-ulcer medications on the development of diarrhoea in the neonatalfoal. HYPOTHESIS: The use of anti-ulcer medication does not alter the incidence of diarrhoea in foals treated in an ICU. METHODS: The records of 1710 foals from 6 different equine hospitals were examined and the use of anti-ulcer drugs was recorded. The presence of in-hospital acquired diarrhoea, CDAD, Clostridium perfringens-associated diarrhoea, neonatal sepsis and salmonellosis were documented. In addition, the presence of gastric ulceration, duration of hospital stay and short-term outcome were examined. RESULTS: The use of anti-ulcer medications increased the odds of in-hospital diarrhoea by 2.0 (95% CI 1.4-2.9; P < 0.0001), relative to the use of no anti-ulcer medication. There was no significant association of anti-ulcer medication with CDAD (P = 0.3189) (OR 2.0; 95% CI 0.4-9.5). Further, results indicated that decreased prevalence of gastric ulceration was not associated with use of anti-ulcer drugs among foals in the study for which these data were known (P = 0.5522). CONCLUSIONS: Use of anti-ulcer drugs increases the odds of developing diarrhoea, and may not reduce the incidence of gastric ulceration in hospitalised equine neonates. POTENTIAL RELEVANCE: The use of anti-ulcer drugs in neonatal foals being treated in a hospital setting should be carefully evaluated on an individual basis to determine if such use is warranted.

Association of adrenocorticotrophin and cortisol concentrations with peripheral blood leukocyte cytokine gene expression in septic and nonseptic neonatal foals.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) is influenced by the proinflammatory cytokines IL-6, IL-1ß, and TNF-α in critically ill humans. Information about the association of cytokines with the HPA axis in neonatal foals is lacking. HYPOTHESIS/OBJECTIVES: The objectives were to describe for hospitalized septic and nonseptic foals (1) temporal changes in blood concentrations of ACTH, and cortisol, and leukocyte cytokine gene expression, and (2) coassociation of these HPA axis hormones with blood leukocyte cytokine gene expression. ANIMALS: Hospitalized septic foals (N = 15) and hospitalized nonseptic foals (N = 11). METHODS: Blood samples, obtained from study foals at admission (T = 0), and 24 (T = 1), 48 (T = 2), 72 (T = 3), and 96 (T = 4) hours after admission, were processed to isolate RNA from leukocytes and to harvest plasma and serum for hormone assays. Plasma ACTH and serum cortisol concentrations were determined by radioimmunoassay. Leukocyte mRNA expression of IL-1ß IL-6, IL-8, IL-10, and TNF-α was determined using RT-PCR. RESULTS: Cortisol concentrations were greater (P < .05) in foals at admission than at other time points. The expressions of IL-8 and IL-10 mRNA were lower (P < .05) at each time point in septic than in nonseptic foals. Among septic foals, ACTH was positively associated (P = .0026) with IL-6 mRNA expression. CONCLUSIONS: Sepsis influences secretion of the HPA axis hormones and expression of cytokines in foals. A positive association with the HPA axis and IL-6 expression was detected. The clinical importance of these findings requires additional study.

Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals.

Rhodococcus equi, a gram-positive facultative intracellular pathogen, is one of the most common causes of pneumonia in foals. Although R. equi can be cultured from the environment of virtually all horse farms, the clinical disease in foals is endemic at some farms, sporadic at others, and unrecognized at many. On farms where the disease is endemic, costs associated with morbidity and mortality attributable to R. equi may be very high. The purpose of this consensus statement is to provide recommendations regarding the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals.