
In the “olden days,” which some of us might remember, any sick foal was considered septic until proven otherwise. Since then, many advances have been made in diagnosing sepsis. Still, experts agree that diagnosis remains anything but straightforward.
According to Daniela Espinosa Seoane, MVZ, an MSc candidate at the University of Guelph (Canada) and associate veterinarian at McKee-Pownall Equine Services in Ontario, foal sepsis is most often attributable to failure of passive transfer of immunity and bacterial infection shortly after birth.
“Sepsis is a leading cause of foal morbidity and mortality,” she says. “Clinical signs of sepsis can initially be subtle and vary depending on which body system(s) are impacted by the organisms. Foals commonly present with one or more of the following: “lethargy, decreased nursing activity, omphalophlebitis, pneumonia, enterocolitis, and/or septic arthritis.”
Early, sensitive, and specific identification of the causative agent is key to treatment success, says Espinosa Seoane.
“An antibiotic treatment is most effective when the therapy is selected based on bacterial culture and antimicrobial susceptibility testing,” she adds.
This sentiment was echoed in a recent study (Wilkins et al. 2025) co-authored by David Wong, DVM, MS, DACVIM, DACVECC, Veterinary Clinical Sciences Department Chair at Iowa State University. “There is an urgent need to identify rapid, practical, and accurate diagnostic tests for infection in newborn foals in order to rapidly initiate treatment,” he stated.
In this article we’ll review how practitioners have traditionally defined sepsis, what experts are currently recommending for the new definition, a brief description of sepsis treatment and outcomes, as well as what researchers are studying to better diagnose and manage sick foals.
Diagnosing Sepsis: Then and Now
The Dorothy Russell Havemeyer Working Group on Consensus Definition of Foal Sepsis defined the condition at their 2018 meeting as, “The presence of documented or suspected infection combined with the presence of the systemic inflammatory response syndrome (SIRS).” They also noted that a positive blood culture alone could not diagnose sepsis without evidence of systemic inflammation.
They defined SIRS in foals as a generalized inflammatory state with at least two of the following four parameters outside the normal range:
- Rectal temperature.
- Heart rate.
- Respiratory rate.
- White blood cell (WBC) count, number of band neutrophils.
- Venous L-lactate.
- Venous blood glucose.
More specifically, at least one of the two abnormal values must be abnormal rectal temperature or WBC count.
“At a follow-up meeting in 2024 and in light of a change in definition of sepsis in the human literature, the definition of sepsis was altered to no longer include SIRS,” explains Wong.
“As we reviewed the literature in people with sepsis, it became apparent that the SIRS criteria were very broad, with numerous other causes outside of infection that could result in positive SIRS status,” he continues. “This sentiment was supported by a retrospective study published by Dr. Peter Constable (Wilkins et al. 2025) in which the presence of infection in critically ill foals was not predicted by SIRS indices based on data from 1,068 critically ill foals.”
Now the group defines a diagnosis of sepsis in a foal if it meets the following two criteria:
- A life-threatening condition involving proven or suspected infection.
- Systemic manifestations of infection.
Proven infection is based on positive blood culture or culture from two different sites, and infection is suspected when foals exhibit neutropenia with left shift. Specific to neutrophils, the Havemeyer Working Group highlighted the importance of a cytologic examination of the blood sample to evaluate slides for evidence of toxic changes.
“The Havemeyer Working Group is currently developing and testing a scoring system to identify systemic manifestations of infection,” says Wong. “This scoring system is akin to the Sequential Organ Failure Assessment (SOFA) score used in critically ill people.”
Blood L-lactate, a biomarker of tissue hypoxia, is a strong indicator of response to treatment and the single most useful prognostic indicator of outcome. In contrast, serum amyloid A (SAA) was not helpful in the initial diagnosis of sepsis. It could, however, have clinical utility evaluating trends over time.
Removing SIRS From the Definition of Foal Sepsis
In their 2025 study, Wilkins et al. evaluated newborn foals ≤ 3 days of age presenting to one of 16 veterinary hospitals primarily located in the United States but also in Australia, England, and Italy. Medical records were reviewed to extract physical examination findings (including those considered in SIRS criteria described by the 2018 Dorothy Russel Havemeyer report) and blood culture results.
Results showed that of the 496 (46%) blood cultures obtained from 1,068 foals, 134 (27%) were positive. Infection at a nonblood site was reported in 655 foals, including 455 foals that had blood culture performed. Infections were identified at nonblood sites on physical examination in 45 (9.9%) of the 455 foals.
The dataset included 455 foals: 164 (36%) with infection identified on blood culture or physical examination and 291 with no infection detected.
Using the criteria presented above, the researchers diagnosed SIRS in 431 (69.9%) of the 455 foals.
The percentage of foals with SIRS and an infection (73.1%) did not differ from the percentage of foals with SIRS and no evidence of infection (71.3%). Additional uni- and multivariate analyses were conducted, and the results refuted the hypothesis that SIRS could predict infection and mortality in critically ill foals.
Treating Sepsis and Antibiotic Selection
“A neonatal foal with sepsis can present with varying levels of illness ranging from mild lethargy and decreased nursing to stupor and prolonged recumbency,” explains Wong. “A cornerstone of treatment in all foals with sepsis is prompt administration of antimicrobials; other therapies such as intravenous administration of fluids, supplemental nutritional support, excellent nursing care, and close monitoring may be required.”
He adds that because sepsis cannot be rapidly proven (blood culture results can take two or more days), empiric antimicrobials should be routinely administered to critically ill newborn foals.
Espinosa Seoane and colleagues acknowledge that antimicrobial therapy should not be delayed pending culture results. But in light of the recent push for improved antimicrobial stewardship, how do you select the best empiric antimicrobial?
“Initiation of antibiotic treatment while waiting for bacterial culture results is needed,” says Espinosa Seoane. “The clinician needs to evaluate data from anamnesis, physical examination, and laboratory tests to discern possible causative organisms. And if possible, they need to try to differentiate Gram-negative from Gram-positive bacteria. In the practice setting, either private practice or hospital, consider susceptibility patterns from previously admitted patients, which should ideally be from the same species, same site, same age, and same suspected bacteria. Intrinsic resistance, which is natural to all the members of a specific bactericidal taxonomic group, genus, species, or subspecies, must be considered. For example, several Gram-negative bacteria are naturally resistant to the activity of macrolides.”
The goal, she says, is to deescalate the drug’s spectrum of activity as much as possible with definite therapy to minimize the impact on commensal bacteria and slow the development of resistance.
She recommends practitioners become familiar with the World Health Organization’s list of critically important antimicrobials that categorizes drugs into four main groups ranging from the highest-priority critically important antimicrobials to important antimicrobials. Espinosa Seoane also encourages veterinary practices to develop active surveillance programs to identify the most common bacteria and their susceptibility patterns for a specific population and infection site. This allows practitioners to rely on that accumulative data over the years to select empiric antimicrobial treatment. Additionally, intrinsic resistance should be reviewed for Gram-positive and Gram-negative bacteria and exclude those antibiotics for initial treatment.
“Once an infectious species has been identified based on culture and susceptibility, then the antimicrobial can be altered, preferably to a narrow-spectrum antibiotic,” says Espinosa Seoane.
Appropriate antibiotic selection is particularly salient considering the continued emergence of multidrug-resistant strains of bacteria. In a 2025 retrospective study, Espinosa Seoane reviewed medical records from 60 septic foals with positive bacterial cultures and antimicrobial susceptibility testing. She identified a single isolate from most (62%) foals and grew multiple isolates (2 to 11) from 38% of foals. The most common isolates were Enterococcus spp., Streptococcus equi subsp. zooepidemicus, Escherichia coli, Actinobacillus equuli subsp. haemolyticus, and Staphylococcus aureus.
“We found that the rate of multidrug resistance was high,” says Espinosa Seoane. “It is concerning that the observed trends in a few studies show less susceptibility of bacteria to most used antibiotics in veterinary medicine. Without effective antibiotics, our goal to resolve infectious diseases will significantly decline and serious infections may become untreatable. This will go along with prolonged and more expensive treatment.”
Outcomes
Many reports relay survival rates ranging from 72% to 83%, including an overall survival rate of 76% reported by Wilkins et al. The foal survival rate in Espinosa Seoane’s study was 78%.
“While the survival rate is relatively high, it is difficult to predict survival in foals with sepsis, especially if owners allow adequate treatment (e.g., no financial constraints),” says Wong. “However, independent predictors for mortality were hypokinetic pulses, cold extremities, presence of seizures, blood L-lactate concentration of > 6.0 mmol/L, and increased serum potassium and total bilirubin concentrations.”
Nucleosomes as a Potential Marker for Foal Sepsis
Because sepsis can be difficult to definitively diagnose, other testing methods are desirable. Emily Birckhead, from the Agricultural, Environmental and Veterinary Sciences department at Australia’s Charles Sturt University, and colleagues stated in their recent study, “It can be difficult to detect sepsis in neonatal foals because of variable and nonspecific clinical signs and lack of a highly sensitive and specific diagnostic test.”
Based on research in humans and other animals, including adult horses, Birckhead’s research group suggested that increased plasma nucleosomes can detect sepsis in foals and could serve as a valuable adjunct test.
To test the hypothesis that nucleosome levels would be higher in septic foals, particularly those with severe sepsis, Birckhead’s team measured circulating nucleosome levels in plasma samples from clinically healthy, sick nonseptic, and septic foals. Nucleosomes were measured using a commercial validated Cell Death Detection ELISA kit. Sick foals included in this study were ≤ 35 days of age presenting to Charles Sturt University’s Veterinary Clinical Center. Samples were collected from healthy foals either owned by the University or a local stud.
Sick foals were categorized retrospectively as septic, sick nonseptic, or healthy based on data analysis.
Foals were classified as septic if they met two of the following criteria:
- Modified sepsis score of ≥ 11.
- Neonatal systemic inflammatory response syndrome (NSIRS) with a clinical concern for infection (i.e., using the old criteria).
- Five clinical or pathologic signs of systemic sepsis.
Septic foals were further classified as severe based on tissue hypoperfusion and/or organ dysfunction.
In contrast, sick nonseptic foals included animals that presented for inadequate nursing, colic, localized infection, and/or diarrhea.
Thirty-six foals met the sepsis criteria, 31 foals were sick nonseptic, and 16 foals were healthy. Twenty-four septic foals were ultimately diagnosed with severe sepsis.
On the day of study entry, nucleosome levels did not differ between the three groups of foals when considering all septic foals together. Nucleosome levels also did not correlate with length of hospitalization. However, among foals with severe sepsis, median nucleosome levels were significantly higher than the nonsevere septic, sick nonseptic, and healthy foals. Further, median nucleosome levels measured on the date of study entry were similar between surviving and nonsurviving foals and, therefore, did not predict survival.
One reason nucleosome levels did not increase in septic foals could be the differing causes of sepsis and individual immune responses. Because of the small number of cases included, the full picture of how nucleosome levels behave in septic foals, particularly over the course of disease, cannot be fully determined.
Future Directions and Concluding Thoughts
According to the 2024 Dorothy Russell Havemeyer Working Group Meeting on Consensus Definitions for Foal Sepsis report, further discussion and research are needed to develop two different scoring systems for foal sepsis.
“The first is a field scoring system that would allow veterinarians to systematically evaluate foals in the field setting and help identify those foals that may have sepsis,” says Wong. “The second scoring system is intended to identify systemic manifestations of infection and corroborate the second part of the sepsis definition (e.g., systemic manifestations of infection). This is an important point, as research in foals has noted that newborn foals can have bacteremia but not be considered septic.”
In summary, Wong says sepsis remains a common clinical problem in the neonatal foal, and veterinarians should examine all neonatal foals with a degree of caution.
“Diagnostic tests such as measuring the serum IgG concentration (e.g., partial or complete failure of passive transfer) and evaluating the total white blood cell count (e.g., leukopenia) and neutrophil count (e.g., neutropenia, left shift, toxic morphology) are helpful in raising suspicion of sepsis,” he concludes.
Related Reading
- Disease Du Jour: Neonatal Maladjustment Syndrome and Sepsis
- Neonatal Foal Care: When to Start and When to Stop
- Responsible Use of Antibiotics in Equine Reproduction
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