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.

Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates.

BACKGROUND: The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated. OBJECTIVES: To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals. ANIMALS: Two-hundred and seventy-three ill foals and 25 healthy control foals. METHODS: Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis. RESULTS: One-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study. CONCLUSIONS AND CLINICAL IMPORTANCE: The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis.

Factors associated with equine shedding of multi-drug-resistant Salmonella enterica and its impact on health outcomes.

BACKGROUND: Salmonella enterica is an important cause of healthcare-associated infections in veterinary hospitals - with outbreaks of multi-drug resistant (MDR) Salmonella among equine cases resulting in high case fatality rates and substantial financial cost. OBJECTIVES: Study objectives were to 1) investigate factors associated with shedding of MDR-Salmonella enterica and 2) evaluate the effect shedding may have on health outcomes of previously hospitalised horses and their stablemates. STUDY DESIGN: Retrospective case-control study with prospective cohort study. METHODS: Analysis of medical records (N = 373; 94 culture positive, 279 culture negative) was undertaken to determine factors associated with shedding of MDR-Salmonella. Additionally, a follow-up study was conducted to assess long-term outcomes associated with shedding among previously hospitalised horses and their stablemates. Data regarding exposures of interest were collected retrospectively from medical records. Information on long-term outcomes was obtained by phone interview of owners. Multivariable regression techniques were used to investigate factors associated with shedding and subsequent health outcomes. RESULTS: Horses experiencing diarrhoea during hospitalisation were more likely to shed Salmonella (OR 1.88; 95% CI 1.02, 3.45) compared with horses without diarrhoea, but isolates tended to be susceptible strains. Antimicrobial therapy during hospitalisation was not associated with shedding or recovery of MDR strains. Shedding did not increase long-term risk for non-survival, colic or abnormal faeces after hospital discharge; nor increase risk for hospitalisation or occurrence of abnormal faeces in stablemates. MAIN LIMITATIONS: Data collection was reliant upon the quality of medical records and owner recall, which may have led to information bias. The study population was derived from central Kentucky and may differ from horse populations in other regions. CONCLUSIONS AND CLINICAL IMPORTANCE: In general, Salmonella shedding was not associated with decreased average survival times or impacts to health of stablemates, perhaps due to owner implemented biosecurity precautions. Regardless, recently hospitalised horses should be segregated after discharge, in addition to employing rigorous hygiene practices. The Summary is available in Spanish - see Supporting Information.

Sales performance and athletic outcome in young Thoroughbreds with pericarditis.

BACKGROUND: Pericarditis is a sporadic, but important cause of critical illness in horses of all ages. There is limited information on whether Thoroughbred horses that survive pericarditis are able to reach athletic potential. OBJECTIVES: To determine how pericarditis affected horses that had the disease as young animals with regard to selling price in public sales and the ability to race successfully. STUDY DESIGN: Retrospective case series. METHODS: Medical records were searched to identify pericarditis cases. Signalment and month of diagnosis were noted and Thoroughbreds with ultrasonographically confirmed pericarditis that presented from 2 months to 3 years old were identified. For this subgroup data on sales and racing performed were obtained from publicly available databases to determine long-term survival and post-treatment outcomes from these horses and their unaffected half-siblings. RESULTS: Horses that survived pericarditis as young animals may recover growth and maturation rates quickly enough to reach expected sales prices at public sales for horses of racing age and recovered horses can have successful racing careers. MAIN LIMITATIONS: The number of horses in this case series was not sufficient to enable statistical comparisons between affected horses and unaffected half-siblings, but description of sales prices and race earnings nevertheless yields information about the chances for affected young horses to achieve their intended purposes. CONCLUSIONS: Young Thoroughbreds with pericarditis warrant treatment and can sell and have successful racing careers.

Factors Associated with Survival in 97 Horses with Septic Pleuropneumonia.

BACKGROUND: Septic pleuropneumonia is a common cause of morbidity and mortality in horses, but there is limited data available regarding factors associated with survival. HYPOTHESIS/OBJECTIVES: To identify factors predictive of survival in horses with septic pleuropneumonia. ANIMALS: A total of 97 horses with septic pleuropneumonia at 2 referral institutions. METHODS: A retrospective study was performed. A diagnosis of septic pleuropneumonia was based on the presence of sepsis, pleural effusion, and positive bacterial culture from tracheal aspiration (TA) or pleural fluid (PF). RESULTS: Thirty-one percent of horses had a recent history of travel. Clinical signs included lethargy (78%), tachycardia (75%), tachypnea (60%), fever (43%), prolonged capillary refill time (22%), and ventral edema (14%). The most common clinicopathologic abnormality was hyperfibrinogenemia (79%). Increased serum creatinine concentration at presentation was negatively associated with survival (OR, 5.13; CI, 1.88-14.01; P = .001) and return to work (OR, 6.46; CI, 1.10-37.92; P = .034). Eighty-four TA and 67 PF samples were submitted for culture, 98 and 84% of which were positive, respectively. The most common isolate was Streptococcus equi subsp zooepidemicus. Tracheal aspirates were more sensitive than PF for bacterial growth, but some organisms isolated from PF were not isolated from TA. Thoracotomy was positively associated with survival (OR, 0.13; CI, 0.01-0.83; P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased serum creatinine concentration is a negative prognostic indicator and is likely a reflection of dehydration. Submission of TA and PF is recommended. Thoracotomy should be considered as a treatment for pleuropneumonia.

Plasma C-reactive protein and haptoglobin concentrations in critically ill neonatal foals.

BACKGROUND: Accurate diagnostic markers for sepsis in neonatal foals are needed. Plasma C-reactive protein concentration (p[CRP]) and haptoglobin concentration (p[Hp]) are well-established biomarkers of infection in humans, but studies are lacking in foals. HYPOTHESES: p[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival. ANIMALS: Eighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1 week of age. METHODS: Multicenter, prospective observational clinical study. Venous blood was collected at admission from septic and sick nonseptic foals and from clinically healthy foals at 24 h of age. A diagnosis of sepsis was made based on positive blood culture or a sepsis score >11, and p[CRP] and p[Hp] were measured by using ELISA tests. Data were analyzed by using the Mann-Whitney U-test and forward stepwise multivariable linear regression. P < .05 was considered significant. RESULTS: Plasma [CRP] was positively associated with age, serum globulin, adrenomedullin, and bilirubin concentrations, aspartate aminotransferase activity, glutamyl-transferase activity, band neutrophil count, and rectal temperature, and was increased in foals with toxic neutrophils, enterocolitis, colic, rib fractures and septic arthritis. Surprisingly, p[Hp] was lower in septic foals than in sick nonseptic foals. Neither p[CRP] or p[Hp] was predictive of survival in critically ill foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma [CRP] increases with inflammation in neonatal foals but is not indicative of sepsis. Single time point, admission sampling of p[CRP] and p[Hp] do not appear to be useful biomarkers for sepsis in foals.

Validation of IgG cut-off values and their association with survival in neonatal foals.

REASONS FOR PERFORMING STUDY: Serum immunoglobulin (IgG) assessment in neonatal foals is considered standard care in equine hospitals to determine immunity and overall health. However, cut-off values of IgG to predict complete or partial failure of transfer of passive immunity (FTPI) were developed 30 years ago and are largely empirical with little prospective or statistical data to support their use or association with outcome. OBJECTIVES: To critically evaluate the traditional cut-off values of IgG in the assessment of FTPI (IgG < 8 g/l), determine the association between various degrees of FTPI and likelihood of nonsurvival and examine whether FTPI can be predicted by serum total protein (TP), albumin and globulin in hospitalised foals. STUDY DESIGN: Multicentre, cross-sectional study. METHODS: We evaluated clinicopathological variables in 597 foals ≤ 7 days old from 3 equine hospitals including serum IgG, fibrinogen, TP and albumin concentrations. Foals were divided into 3 groups by diagnosis: healthy, sick nonseptic and septic. The aforementioned variables in addition to globulin concentrations were evaluated in a subset of 118 foals. Univariate, multivariate and multinomial logistic regression were used to compute odds ratios for nonsurvival in these foals. RESULTS: Our findings support use of the traditional cut-off value of > 8 g/l as adequate transfer of passive immunity (ATPI). Odds of nonsurvival increased in proportion to lower IgG concentrations. Higher TP concentrations were associated with lower likelihood of FTPI; however, higher albumin concentrations were associated with a greater likelihood of FTPI. A regression equation was created to predict IgG in foals using serum proteins. CONCLUSIONS: Serum IgG values of <8 g/l in hospitalised foals were proportionally associated with mortality. We recommend immediate assessment of IgG concentrations in hospitalised foals and those with FTPI should receive prompt immunotherapy. The summary is available in Chinese - see Supporting information.

Plasma adrenomedullin concentrations in critically ill neonatal foals.

BACKGROUND: Bacterial sepsis remains a leading cause of morbidity and mortality in neonatal foals, but accurate diagnostic and prognostic markers are lacking. Adrenomedullin (AM) is a polypeptide with diverse biologic effects on the cardiovascular system that increases in septic humans and laboratory animals. HYPOTHESES: Plasma AM concentration (p[AM]) is increased in septic neonatal foals compared to sick nonseptic and healthy control foals, and p[AM] is predictive of survival in septic neonatal foals. ANIMALS: Ninety critically ill (42 septic, 48 sick nonseptic) and 61 healthy foals <1 week of age. METHODS: A prospective observational clinical study was performed. Venous blood was collected from critically ill foals at admission and from healthy foals at 24 hours of age. Critically ill foals were categorized as septic or sick nonseptic based on blood culture results and sepsis score. Plasma [AM] was measured by using a commercially available ELISA for horses. Data were analyzed by using the Mann-Whitney U-test and P < .05 was considered significant. RESULTS: Plasma [AM] was not significantly different between septic and sick nonseptic foals (P = .71), but critically ill foals had significantly increased p[AM] compared to healthy controls (P < .0001). In critically ill foals, p[AM] was not predictive of survival (P = .051). A p[AM] cutoff concentration of 0.041 ng/mL provided a test sensitivity of 91% and specificity of 54% to predict illness. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma [AM] shows promise as a marker of health in neonatal foals, but p[AM] increases nonspecifically during perinatal illnesses and is not necessarily associated with sepsis.

Infectious agents associated with diarrhoea in neonatal foals in central Kentucky: a comprehensive molecular study.

REASONS FOR PERFORMING STUDY: Diarrhoea caused by infectious agents is common in foals but there is no comprehensive molecular work-up of the relative prevalence of common agents and appearance of coinfections. OBJECTIVES: To determine the prevalence of 9 infectious agents in gastrointestinal (GI)-diseased and healthy foals with ages ranging from 1 to 20 weeks of age and to what degree coinfections are associated with clinical signs of GI disease. STUDY DESIGN: Retrospective controlled observational study. METHODS: The population consisted of 88 Thoroughbred foals aged 2 days to 17 weeks born on 32 different studfarms in Kentucky. Healthy (n = 37) and GI-diseased (n = 51) foals were identified based on clinical presentation. Faecal samples were analysed for 9 infectious agents by real-time PCR: equine rotavirus, equine coronavirus, Clostridium difficile toxins A & B, Neorickettsia risticii, Clostridium perfringens alpha toxin, Lawsonia intracellularis, Rhodococcus equi, Cryptosporidium spp., and Salmonella spp. Salmonella was also cultured from overnight selenite enrichment broth. RESULTS: The prevalence of infectious pathogens under study was between 0% (Lawsonia intracellularis) and 34.6% (equine rotavirus). The overall prevalence for any infectious agent was 63.2% in the GI-diseased group and 43.2% in the healthy group. Coinfections were significantly more frequent in the sick group (15 monoinfections vs. 22 coinfections) than in the healthy group (12 vs. 4, respectively, P = 0.0002). Six of the 8 infectious agents were associated with the GI-diseased group, the other 2 were not (equine coronavirus and R. equi). CONCLUSIONS: The use of panels rather than individual tests in combination with quantitative toxin gene analysis enables detection of coinfections significantly associated with risk of disease. Several infectious diseases previously not tested for or considered unimportant were found at high prevalence and require further investigation.

Somatotropic axis resistance and ghrelin in critically ill foals.

REASONS FOR PERFORMING STUDY: Resistance to the somatotropic axis and increases in ghrelin concentrations have been documented in critically ill human patients, but limited information exists in healthy or sick foals. OBJECTIVES: To investigate components of the somatotropic axis (ghrelin, growth hormone and insulin-like growth factor-1 [IGF-1]) with regard to energy metabolism (glucose and triglycerides), severity of disease and survival in critically ill equine neonates. It was hypothesised that ghrelin and growth hormone would increase and IGF-1 would decrease in proportion to severity of disease, supporting somatotropic axis resistance, which would be associated with severity of disease and mortality in sick foals. STUDY DESIGN: Prospective multicentre cross-sectional study. METHODS: Blood samples were collected at admission from 44 septic, 62 sick nonseptic (SNS) and 19 healthy foals, all aged <7 days. Foals with positive blood cultures or sepsis scores ≥12 were considered septic, foals with sepsis scores of 5-11 were classified as SNS. Data were analysed by nonparametric methods and multivariate logistic regression. RESULTS: Septic foals had higher ghrelin, growth hormone and triglyceride and lower IGF-1 and glucose concentrations than healthy foals (P<0.01). Sick nonseptic foals had higher growth hormone and triglycerides and lower IGF-1 concentrations than healthy foals (P<0.05). Growth hormone:IGF-1 ratio was higher in septic and SNS foals than healthy foals (P<0.05). Hormone concentrations were not different between septic nonsurvivors (n = 14) and survivors (n = 30), but the growth hormone:IGF-1 ratio was lower in nonsurvivors (P = 0.043). CONCLUSIONS: Somatotropic axis resistance, characterised by a high growth hormone:IGF-1 ratio, was frequent in sick foals, associated with the energy status (hypoglycaemia, hypertriglyceridaemia) and with mortality in septic foals. POTENTIAL RELEVANCE: A functional somatotropic axis appears to be important for foal survival during sepsis. Somatotropic resistance is likely to contribute to severity of disease, a catabolic state and likelihood of recovery.

Clinical and clinicopathological factors associated with survival in 44 horses with equine neorickettsiosis (Potomac horse Fever).

BACKGROUND: The epidemiology of equine neorickettsiosis (EN) has been extensively studied but limited clinical and clinicopathological data are available concerning naturally infected horses. HYPOTHESIS: Factors predictive of survival will be identified in horses diagnosed with EN. ANIMALS: Convenience sample of 44 horses with EN admitted to 2 referral institutions. METHODS: A retrospective study was performed. A diagnosis of EN was based on the presence of positive blood or fecal PCR. RESULTS: The most common clinical signs included diarrhea (66%), fever (50%), anorexia (45%), depression (39%), colic (39%), and lameness (18%). The median duration of hospitalization was 6 days and 73% of horses survived to discharge. Laminitis was present in 36% of horses, 88% of which were affected in all 4 feet. Serum creatinine and urea nitrogen concentrations, as well as RBC count, blood hemoglobin concentration, hematocrit, band neutrophils, serum AST activity, serum CK activity, and anion gap, were significantly (P < .05) higher in nonsurvivors. Serum chloride and sodium, concentrations as well as duration of hospitalization were significantly lower in nonsurvivors. The results of forward stepwise logistic regression indicated that blood hemoglobin concentration on admission and antimicrobial treatment with oxytetracycline were independent factors associated with survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Severity of colitis as reflected by electrolyte loss, hemoconcentration, and prerenal azotemia were predictors of survival in horses diagnosed with EN. Treatment with oxytetracycline was associated with increased survival.

Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. OBJECTIVES/HYPOTHESIS: To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. ANIMALS: A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. METHODS: Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. RESULTS: ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals.

Evaluation of the field efficacy of an avirulent live Lawsonia intracellularis vaccine in foals.

Equine proliferative enteropathy caused by Lawsonia intracellularis is an emerging disease with as yet unaddressed preventative measures. The hypothesis of this study was that vaccination will prevent clinical and sub-clinical disease. Weanling Thoroughbreds (n=202) from Central Kentucky were randomly assigned into two groups (vaccinated and non-vaccinated). Vaccinated foals received 30 mL of an avirulent, live L. intracellularis vaccine intra-rectally twice, 30 days apart. Foals were monitored for clinical disease, total solids and average weight gain until yearling age. There was an overall decreased disease incidence on the farms involved in the study that did not differ significantly between the groups. This decreased disease prevalence in the study population may be associated with the ongoing vaccine trial on these farms, as disease prevalence in Central Kentucky did not change in 2009 compared to 2008.

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.

Rhodococcus equi: clinical manifestations, virulence, and immunity.

Pneumonia is a major cause of disease and death in foals. Rhodococcus equi, a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals. This article reviews the clinical manifestations of infection caused by R. equi in foals and summarizes current knowledge regarding mechanisms of virulence of, and immunity to, R. equi. A complementary consensus statement providing recommendations for the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals can be found in the same issue of the Journal.

Serum free cortisol fraction in healthy and septic neonatal foals.

BACKGROUND: Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. HYPOTHESES: In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. ANIMALS: Fifty-one septic foals; 11 healthy foals; 6 healthy horses. METHODS: In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University-owned animals served as healthy controls. Basal and cosyntropin-stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand-binding methods, respectively. Group data were compared by ANOVA, Mann-Whitney U-tests, and receiver operator characteristic curves. Significance was set at P < .05. RESULTS: Basal % free cortisol was highest in healthy foals at birth (58 ± 8% mean ± SD), and was higher (P ≤ .004) in healthy foals of all ages (33 ± 6 to 58 ± 8%) than in adult horses (7 ± 3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P ≤ .03) in foals with shock (total = 6.2 ± 8.1 µg/dL; free = 3.5 ± 4.8 µg/dL versus total = 10.8 ± 6.0 µg/dL; free = 6.9 ± 3.3 µg/dL in foals without shock) and in nonsurvivors (total = 3.8 ± 6.9 µg/dL; free = 1.9 ± 3.9 µg/dL versus total = 9.1 ± 7.7 µg/dL; free = 5.5 ± 4.4 µg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals.