9 Equine Neonatal Septicemia

• Equine Neonatal Septicemia is the focus

Objectives

• Identify differential diagnoses for recumbent foals.
• Determine predisposing causes and causative organisms of neonatal foal septicemia.
• Perform and assess diagnostics in septicemic foal suspects.
• Implement a treatment plan for septic foals, with specific antibiotic choices.
• Monitor for sequelae.

Case 1: Quarter Horse Filly

• A Quarter Horse filly was found recumbent in a field.
• The mare had foaled overnight at approximately 326 days of gestation.
• The placenta was attached, and the foal was unresponsive and cold to the touch.

Differential Diagnoses for Recumbent Foal

• Potential diagnoses include septicemia, hypoglycemia, hypothermia, and hypoxia.
• Neonatal encephalopathy, neurologic disease, and neonatal isoerythrolysis should be considered.
• Muscle weakness and trauma are possible diagnoses, sometimes, foals experience multiple problems.

Definitions

• Sepsis and septicemia both refer to systemic inflammatory response syndrome (SIRS).
• SIRS stems from circulating microorganisms or their products.
• SIRS involves alterations in body temperature, heart rate, respiratory rate, and leukogram parameters.
• Bacteremia is the presence of viable circulating bacteria.

Neonatal Septicemia Equation

• Neonatal Septicemia = Sepsis: SIRS + Pathogen Challenge.
• Sepsis is the leading cause of death in foals younger than 7 days.
• SIRS elicits clinical signs of sepsis.

Predisposing Factors

• Maternal factors such as in utero infection are predisposing factors.
• Fetal factors include failure of transfer of passive immunity.
• Farm management and gestational age/length are also factors.
• Immunodeficiency leading to postnatal infection is also a predisposing factor.

Routes of Infection

• Infection can occur in utero or post-natally.
• Post-natal routes include umbilical remnants, the gastrointestinal tract, and the respiratory tract.

Failure of Transfer of Passive Immunity

• Failure occurs due to maternal or foal factors.
• Foals typically require 1-2 L of good quality colostrum.
• Environmental challenges must be considered.
• Treatment requires colostrum if less than 6-12 hours have passed or IV plasma.

Causative Organisms

• Gram-negative bacteria are most common.
• Common bacteria include E. coli, Salmonella, Actinobacillus equuli, Klebsiella spp, Enterobacter spp, and Pseudomonas spp.
• Gram-positive bacteria include Enterococcus, Streptococcus, and Staphylococcus spp.
• Uncommon fungal organisms to be aware of include Candida albicans.

Pathophysiology

• Pathogen exposure can lead to bacteremia and clinical signs of SIRS.
• Pathogens can seed different organ systems, leading to sequelae.
• Pathogen virulence is an important factor.
• IgG is not the only protective factor against pathogens in a foal's immune system.

Clinical Signs

• Clinical signs include decreased milk intake, lethargy, and depression.
• Progressing to recumbency, maternal disinterest, diarrhea and dehydration can be apparent.
• Temperature may be febrile or hypothermic if in shock.
• Specific foci of infection may cause diarrhea or uveitis.
• Clinical signs may also include joint effusion, lameness, physeal swelling, seizures or respiratory distress.
• Subcutaneous abscesses, patent urachus, and omphalitis are also signs.

Physical Exam

• Assess both the foal and the mare.
• Look for evidence of maternal illness and udder fill.
• Examine the placenta for abnormalities.

Physical Exam Findings

• Dehydration, tachypnea, and tachycardia can be observed.
• Mucous membranes may be hyperemic, injected, or have petechiae; inner pinna or coronary bands may show.
• Sclera may be hyperemic and injected, and the foal may have uveitis.
• Hypovolemia and abnormalities consistent with specific foci of infection are findings.

Case 1: Physical Exam

• The foal was laterally recumbent and obtunded, with no suckle reflex and little to absent muscle tone.
• The temperature was too low to register, the heart rate was 92 bpm, and the respiratory rate was 36 brpm.
• The foal had cold extremities, prolonged CRT, tacky, injected mucous membranes and sclera.
• Entropion OU, dirt and debris OU, and an obvious corneal ulcer OD were present.
• The foal had a domed head, floppy ears and eponychium present on all feet.

Case 1: Minimum Database

• PCV/TP were 38% (rr 32-44) and 4.9 g/dl (rr 6-8.0).
• Blood glucose was 45 mg/dl (rr 70-118).
• An IgG Snap Test was submitted for CBC and biochemical profile.

Case 1: Blood Work Abnormalities

• WBC was 1900 (L; 4600-8500/ul).
• Neutrophils were 1200 (L; 2200-5500/ul) with a mild toxic change.
• Lymphocytes were 500 (L; 1400-4000/ul).
• Creatinine was 15.9 (H; 1.0-1.9 mg/dl).
• Globulin was 1.3 (L; 2.6-4.2 g/dl).

Diagnosis of Sepsis

• Consistent historical data, clinical signs, and physical exam findings are necessary.
• Clinicopathologic findings including IgG levels are important.
• Blood cultures and sepsis scores are also part of the diagnostic process.

Clinicopathologic Findings

• Leukopenia, neutropenia, left shift, and toxic changes to neutrophils can be observed.
• Hyperfibrinogenemia may indicate in utero infection if elevated within the first 1-2 days of life.
• Elevated serum amyloid A (SAA) is another indicator.
• Additional findings include hypoglycemia, azotemia, hyperbilirubinemia, acidemia, and hyperlactatemia.

Coagulation Abnormalities

• Thrombocytopenia, decreased antithrombin III, prolonged PT and APTT can be noted.
• Elevated FDP and D-dimers are also coagulation abnormalities.

Blood Culture

• Blood culture is the gold standard for diagnosis.
• The procedure requires both aerobic and anaerobic culture.
• It aids in the identification of the organism.
• Blood cultures direct antimicrobial therapy and identify resistance.
• Collection is from a large vein (jugular, cephalic, saphenous), and needs sterile preparation in blood culture media.

Sepsis Score

• The scoring system predicts sepsis, with blood cultures returning delayed results and low sensitivity.
• Prior antimicrobial therapy and low circulating bacterial numbers are challenges when assessing.
• A score >12 indicates sensitivity of 93% and specificity of 88%.
• Newer evidence finds a score of >7

Case 1: Sepsis Score

• The sepsis score for Case 1 was 15.

Treatment

• Treatment involves antimicrobial and anti-endotoxin therapy.
• Cardiovascular and nutritional support are necessary.
• Supportive care and reverse isolation are important.

Antimicrobial Therapy

• Broad spectrum antibiotics with gram-negative coverage are imperative.
• Typically, aminoglycoside plus beta-lactam antibiotics are used.
• Monitor renal status.
• Do not delay antibiotics for blood culture.
• Duration should last at least 2 weeks, or 4 weeks if localizing signs are apparent.

Anti-Endotoxin Therapy

• Flunixin, pentoxifylline, polymyxin B, and plasma are options.

Cardiovascular Support

• Address signs of hypovolemia, septic shock, and hypotension, which warrant resuscitation.
• Monitor carefully for volume overload during maintenance.
• Options include colloids, FTPI, oncotic support, coagulation abnormalities, and anti-endotoxin.
• Pressor agents are also viable to consider.

Crystalloids

• Administer 100-120 ml/kg/day to foals for maintenance.
• Use a sodium-restricting fluid rate.
• Recumbent neonatal foals for maintenance needs only: 100 ml/kg for first 10 kg.
• Use 50 ml/kg for the next 10 kg; 25 ml/kg will cover the remaining body weight in kg.

Plasma

• Administer ~20-40 ml/kg for FTPI; 1-2 L for a 50 kg foal.
• Plasma is antigenic, so use initial infusion rates at 0.5 ml/kg over 10-20 minutes.
• Monitor for adverse reactions, administering the remainder at rates up to 40 ml/kg/h.
• Recheck IgG levels, recognizing that they may decrease following transfusion due to catabolism.

Nutritional Support

• Enteral nutrition via a nasoesophageal feeding tube is an option.
• Provide frequent feedings, starting slow at ~10% of BW.
• The goal = 25% of body weight daily.
• Parenteral nutrition can be partial or total and should determine caloric needs.

Supportive Care

• Supportive care is especially vital if the foal is recumbent.
• Provide padding and monitor for corneal ulcers, staining eyes daily and protecting them.
• Facilitate thermoregulation, urination, and defecation, as well as feeding and oxygen tubes, and sternal recumbency.

Case 1: Treatments

• Warming measures included the placement on an IV catheter, IV fluids, and IV antibiotics.
• Ceftiofur sodium and Aminoglycoside were provided.
• A nasoesophageal tube was placed once the body temperature was >99F.
• Mare’s colostrum was provided once body temperature >99F, continuing with mare’s milk q 1h.
• An Umbilical dip with dilute chlorhexidine was performed.
• Treatment included temporary tacking of lower eyelids OU and triple antibiotic ophthalmic ointment OU.

Sequelae of Sepsis

• Address diagnostics and treatments for various foci of infection.
• Sequelae include respiratory, gastrointestinal, neurologic systems and umbilical remnants issues.
• Septic arthritis and osteomyelitis are considerations.
• Presentation with localized infections should warrant examination for sepsis.

Sequelae: Respiratory Disease

• Respiratory disease is very common.
• Observed incidence in septic foals: 28-50%.
• Respiratory can stem from in utero aspiration, meconium aspiration, and hematogenous spread.
• Diagnosis is made with a respiratory exam, thoracic ultrasound and radiographs, and arterial blood-gas.
• Treat with antimicrobial therapy, oxygen supplementation, and potentially mechanical ventilation.

Sequelae: Diarrhea/Enteritis

• Commonly reported, with an incidence in septic foals of 16-38%.
• 50% of diarrheic foals are bacteremic.

Sequelae: Umbilical Remnant

• Omphalitis is a common source of continual bacterial shedding.
• Diagnose using a physical exam and ultrasonographic evaluation, understanding that external signs are not always present.
• Serial ultrasonographic evaluation is used to monitor.
• Treat with antibiotics or surgical resection if persistent.
• Sequelae can include patent urachus and uroperitoneum.

Sequelae: Neurologic System

• Meningitis is a potential sequelae.
• Meningitis presents with clinical signs of seizures and somnolence.
• CSF analysis revealing neutrophilic pleocytosis +/- bacteria aids diagnosis.
• Treatment involves 3rd-4th generation cephalosporins.
• Expect a poor to grave prognosis.

Sequelae: Septic Arthritis and Osteomyelitis

• Early clinical signs include joint effusion, periarticular swelling, heat, pain on palpation, and restricted movement.
• Lameness is expected.
• Diagnose with synovial fluid analysis with cytology and culture, and radiographs.
• Treat with systemic and local antibiotics and lavage of synovial structure +/- surgical intervention.

Prognosis for Sepsis

• Survival rates recently are 45-55%; ranging from 32-72%.
• Early detection and aggressive therapy give the best prognosis.

Prevention

• Maintain a clean foaling environment, cleaning between mares and the stall once to twice daily.
• Reduce potential bacterial load introduced during udder seeking.
• Clean and dry the mare.
• Attend foaling and ensure Gl intake of good quality colostrum.
• Confirm adequate transfer of passive immunity and ensure appropriate umbilical care.
• Closely monitor foals and treat suspects quickly, as well as focusing on client education.

Objectives revisited

• Identify differential diagnoses for recumbent foals.
• Identify signs of neonatal encephalopathy.
• Implement a treatment plan based on pathophysiology.
• Diagnose neonatal isoerythrolysis (NI) and implement a treatment and prevention plan.

Case 2: Clydesdale Colt

• A Clydesdale colt was born to a mare with placentitis, requiring no assistance during foaling.
• The foal was stained with meconium at parturition, breathing at 38 brpm and heart rate of 68 bpm.

Case 2: Physical Exam at Birth

• The exam revealed injected mucous membranes with a good suckle reflex.
• Mild crackles cranioventrally in bilateral lung fields were noted, as well as to weak, uncoordinated movements and an enlarged umbilicus.

Case 2: Problems

• Placentitis in the dam is a risk factor for sepsis and neonatal encephalopathy (NE).
• Meconium staining indicates fetal distress and a risk factor for NE.
• Possible meconium aspiration with crackles on auscultation is a problem.
• Injected mucous membranes indicate sepsis
• Weakness is non-specific, but may indicate sepsis or NE.
• The enlarged umbilicus is an entry point for and source of continued infection.

Case 2: Blood Work Immediately Post-Partum

• Segmented neutrophils numbered 3100 (Reference Interval 2200-5500/ul).
• Band neutrophils were 700 (H; 0-100/ul).
• Lymphocytes: 1500 (1500-4000/ul), and Fibrinogen at 400 (H; 100-400 mg/dl).
• Creatinine measured 4.6 (H; 1.0-1.9 mg/dl).

Case 2: Additional Diagnostics

• A blood culture sample was collected with negative results.
• Arterial blood gas revealed hypoxemia, as did a thoracic ultrasound and radiographs.
• Umbilical ultrasound was performed.

Case 2: Initial Treatments

• Antibiotics prescribed included ceftiofur sodium 10 mg/kg IV q12h.
• Gentamicin was added on Day 2 after creatinine had normalized.
• The foal received nasal insufflation of oxygen.
• A nasoesophageal feeding tube was passed.
• Dams colostrum/milk q1h (10% of BW/day initially) was added to the regimen.
• At 18 hours of age, IgG level was >800 mg/dl.

Neonatal Encephalopathy (NE)

• NE is the neonatal maladjustment syndrome, referred to as "dummy" foals.
• It is a neurologic manifestation of hypoxic-ischemic syndrome (HIS) or perinatal asphyxia syndrome (PAS).
• Reduced oxygen delivery to neuronal cells in the CNS results in neuronal injury and cerebral edema.
• The injury is typically reversible.
• Potential mechanisms include altered concentrations of neurosteroids (plasma progestagens) or inflammation.

Risk Factors for Neonatal Encephalopathy

• Maternal illness(hypoxemia, colic, cardiovascular compromise), Placentitis/placental insufficiency
• Premature placental separation, Dystocia
• Cesarean section, Induced parturition
• Post-term pregnancy (fescue toxicity).
• Some cases of NE have no issues in gestation or parturition.

Clinical Signs of Neonatal Encephalopathy

• Generalized weakness or somnolence. They show a Lack of interest in dam/ Lack of or have and abnormal suckle reflex.
• Weak tongue, Dysphagia, Bizarre vocalization and face and jaw movements can happen.
• Other symptoms include head pressing, cortical blindness, recumbency, and seizures.
• Other organs affected include GI and renal systems.

Classifications of Neonatal Encephalopathy

• Cases are classified as Mild, Moderate, or Severe.

Diagnosis of Neonatal Encephalopathy

• Diagnose through consistent clinical signs and the exclusion of other differential diagnoses.
• The exclusion of other differential diagnoses, consider history of a potential insult.
• Concurrent problems are typical.

Treatment for Neonatal Encephalopathy

• Maintain hydration and blood glucose; oxygen supplementation if hypoxemic.
• Control neurologic signs, especially seizures and administer anti-inflammatories and free radical scavengers
• Implement nursing care, including padding and nutrition to support life.

Treatment: Reduce Cerebral Edema

• Mannitol, Furosemide, and DMSO are viable.

Treatment: Control Seizures

• Diazepam/midazolam and Phenobarbital are options.

Treatment: Anti-Inflammatories and Free Radical Scavengers (Anti-Oxidants)

• Flunixin, Vitamin E, Magnesium, Block release of glutamate, Vitamin C, Thiamine and DMSO

Madigan Squeeze Technique

• It simulates emerging from birth canal to stop producing sedative neurosteroids.
• This technique is only used in the absence of sepsis and other illness.

Prognosis of Neonatal Encephalopathy

• Most foals respond within 3-5 days, with survival to discharge at 75%.
• Prognosis is poor in foals that show clinical signs at birth.

Case 2: Re-Assessment

• By 2 hours of age, foal was not able to stand, but the Suckle reflex was present and mildly weak
• Flunixin meglumine was initiated for inflammation associated with sepsis and NE.
• Vitamin E was also initiated.

Case 2: Progression

• Foal able to stand on own by 12 hours of age and was Weaned off oxygen around that time
• The foal started nursing 36 hours of age and Enteral feedings were discontinued on Day 4.

Case 2: Discharge

• Trimethoprim sulfa was prescribed

Case 3: Quarter Horse Filly

• Two-day-old QH filly presented with unknown gestational age at parturition.
• Parturition was normal, but the foal was slightly weak, prompting the owners to supervise nursing.
• The foal is now mildly lethargic and lying down more often.

Case 3: Physical Exam

• The foal presented as QAR, but was mildly lethargic.
• Temperature was 100.7 F, HR was 124 bpm, RR was 56 brpm, and Sclera and mm were slightly icteric.
• Suckle, umbilicus, and joints were WNL.

Case 3: Differentials

• Elevated recumbency and lethargy are symptoms of Neonatal isoerythrolysis, bacterial sepsis, or neurologic problems.

• Icterus/hyperbilirubinemia may stem from pre-hepatic or hepatic conditions.

Pre-Hepatic Conditions

• Pre-hepatic causes encompass hemolysis, neonatal isoerythrolysis, and anorexia.

Hepatic Problems

• Hepatic problems include sepsis, EHV-1, weak foal with hepatopathy and lymphopenia
• Additional conditions may include Tyzzer disease, or Clostridium piliforme.
• consider if Post-hepatic

Case 3: Blood Work

• IgG Snap Test >800 mg/dl
• WBC 7000 (4600-8500/ul)
• PCV 30 (L / 32-44 %)
• TP 6.8 g/dl (6-8.0)
• Bilirubin, total is 12.3 ( H /0.5-2.7 mg/dl)
• Bilirubin, direct is 0.2 (0-0.3)
• Bilirubin, indirect was 12.1 ( H/ 0.3-2.6 mg/dl)

Neonatal Isoerythrolysis

• Occurs when maternal alloantibodies destroy the foal’s RBCs after absorption from colostrum.
• Prevalence
  • Thorough breds is 1%.
  • Standardbreds is 2%.
  • Mules (donkey sire and horse dam) is 10%.

Pathophysiology of Neonatal Isoerythrolysis

• The foal inherits RBC antigen from stallion that differs from dam and Dam is previously sensitize
• The disease affects Multiparous mare. Mare produces antibodies against RBC antigen of foal.
• The Foal ingests colostrum with anti-RBC antibodies.
• Foal's RBCs coated with antibody are removed via reticuloendothelial system or intravascular hemolysis by complement.

RBC Antigens

• Aa and Qa are the Most common. Other RBC antigen is the Donkey factor.

Clinical Signs and PE Findings

• Symptoms usually show up at 24-36 hours of age
• The baby will show Progressive lethargy and weakness, Pale mucous membranes followed by icterus. Some experiences Tachypnea and labored breathing, Tachycardia and Seizure-like activity as severity worsens.

Diagnosis of Neonatal Isoerythrolysis

• Anemia with Autoagglutination can indicate Neonatal Isoerythrolysis.
• Also test for Hyperbilirubinemia, Unconjugated/indirect and thrombocytopenia.
• Perform a Coomb’s test or flow cytometry for IMHA and Cross match mare’s serum with foal’s RBC

Treatment of Neonatal Isoerythrolysis

• Treat baby foal with Exercise restriction to ensure it reduce any stress for the baby foal.
• For a more medical apporach try IV fluids, exercise Milk restriction for babies over >24 hours. The baby foal may need blood transfusion if anemia is severe For the best chances of survival, use Washed maternal RBCs.

Prevention of Neonatal Isoerythrolysis

• For future pregnancy, conduct a Screen blood type and anti-
• RBC antibody in serum of mare compared to stallion prior to parturition and perform a Jaundice foal agglutination test prior to allowing consumption of colostrum.

Case 3: Additional Diagnostics

• Blood typing and Antibody Screen revealed

Foal blood type: Aa Ca Qabc Ua, Mare and Blood type: Ab Ca Antibody Anti-Aa antibody will be found.

Case 3: Progression

Monitored PCV and physical exam was conducted before determining there wasn't a need for transfusion.

Blood Transfusion Preparation

• [(PCV want – PCVhave)/PCVdonor] x 8% BWkg = Volume L

Equine Neonatology

• Ensure a strict Attended foalings , Check for FTPI, Baseline PE and Identify problems early are crucial
• It’s crucial to Do not let the sun set on a sick neonatal foal!.