Clostridiosis, Enteric

Basic Information 

Definition

Enteric disease caused by infection with clostridial species, primarily Clostridium perfringens and Clostridium difficile

Synonym(s)

• •Necrotizing enterocolitis (typically associated with C. perfringens)
• •Pseudomembraneous colitis (typically associated with C. difficile)

Epidemiology

Risk Factors

Antimicrobial use

Contagion and Zoonosis

• •Occurrence is often sporadic, but outbreaks have been described on farms and in veterinary hospitals. Therefore isolation of affected horses and use of barrier precautions, such as dedicated clothes and gloves, are recommended.
• •Both C. perfringens and C. difficile are recognized enteropathogens in humans. Although direct transmission between horses and humans has not been documented, horses should be treated as if infectious and control measures implemented (barrier precautions, hand hygiene, disinfectants).

Clinical Presentation

Disease Forms/Subtypes

• •Variable signs depending on several factors, including the region of the gastrointestinal (GI) tract that is affected
• •Acute colitis most common
• •Proximal enteritis

History, Chief Complaint

• •Diarrhea is the most common complaint
• •Colic
• •Occasionally, sudden death

Physical Exam Findings

• •
  Colitis

  • •
    Diarrhea
  • •
    Anorexia, pyrexia
  • •
    Variable degrees of dehydration, toxemia, colic
• •Cases that involve only the small intestine or cecum may exhibit similar signs without diarrhea.
• •Cases that involve the proximal small intestine may present with significant reflux.

Etiology and Pathophysiology

• •Gram-positive, anaerobic bacteria in the genus Clostridium, primarily C. difficile and C. perfringens.
• •Transmission is by ingestion; disease is caused by the proliferation of toxigenic strains in the intestinal tract.
• •Toxin production results in enterocolitis.
• •
  C. difficile: primarily toxin A (enterotoxin) and toxin B (cytotoxin).

  • •
    Approximately 13% of equine isolates do not produce any toxin and are nonpathogenic; most pathogenic isolates produce both toxin A and B.
  • •
    Age influences colonization rates: subclinical carriage of C. difficile has been reported in 29% of foals younger than 14 days of age but in less than 1% of older foals and normal adults.
• •
  C. perfringens: classified into different types based on the pattern of toxin production; β-2 toxin and enterotoxin may be the most important clinically.

  • •
    A normal inhabitant of the equine GI tract found in 19% to 35% of broodmares and more than 90% of 3-day-old foals
  • •
    Type A: predominant type in normal horses and horses with diarrhea
  • •
    Type C: has been associated with severe enterocolitis, especially in foals
  • •
    Limited reports of disease associated with types B and D

FIGURE 1.

Colony morphology of Clostridium difficile on a cycloserine-cefoxitin fructose agar, a selective and differential culture medium used for isoluation of C. difficile.

(From Sellon DC, Long MT: Equine infectious diseases. St. Louis, Saunders, 2007.)

FIGURE 2.

Gram stain morphology of Clostridium difficile. Note the long, thin rods. The variable staining appearance may be encountered in cultures over 48 hours or longer.

(From Sellon DC, Long MT: Equine infectious diseases. St. Louis, Saunders, 2007.)

FIGURE 3.

Gram stain appearance of Clostridium perfringens, demonstrating the characteristic appearance of short, thick, gram-positive rods.

(From Sellon DC, Long MT: Equine infectious diseases. St. Louis, Saunders, 2007.)

Diagnosis 

Differential Diagnosis

• •Salmonellosis
• • Neorickettsia risticii (Potomac horse fever)
• •Cantharidin toxicity
• •Parasitism
• • Aeromonas, Campylobacter, and Lawsonia spp.
• •Other antibiotic-associated diarrhea
• •Sand
• •Thromboembolic disease
• •Anaphylaxis
• •Undiagnosed colitis
• •
  Additional differentials in foals

  • •
    Rotavirus, coronavirus
  • •
    Foal heat diarrhea
  • •
    Cryptosporidiosis
  • •
    Associated with septicemia
  • •
    Secondary lactose intolerance

FIGURE 4.

Clostridium difficile colitis. Note the widespread petechial and ecchymotic hemorrhages consistent with disseminated intravascular coagulation.

(From Sellon DC, Long MT: Equine infectious diseases. St. Louis, Saunders, 2007.)

Initial Database

• •
  Clinicopathologic abnormalities: nonspecific; consistent with dehydration and endotoxemia from diarrhea and mucosal damage

  • •
    Leukopenia, neutropenia
  • •
    Elevated packed cell volume (PCV), variable total protein (TP); hypoproteinemia often develops
  • •
    Acid-base and electrolyte abnormalities consistent with diarrhea
• •Although clostridial diarrhea in neonatal foals is not generally associated with failure of passive transfer, it is recommended to evaluate affected foals for antibody concentration and the presence of septicemia.
• •Abdominal ultrasonography may reveal ileus or a thickened intestinal wall; occasionally, intramural gas is seen (may also be seen radiographically in foals).

Advanced or Confirmatory Testing

• •Culture: not diagnostic by itself because of the presence of nonpathogenic isolates and the presence in some normal horses, especially with C. perfringens; culture samples should be handled anaerobically.
• •
  C. difficile toxin detection in feces (toxins stable in refrigerated or frozen samples)

  • •
    Cell cytotoxicity assay (toxin B): Considered the gold standard but not available in some laboratories
  • •
    Enzyme immunoassays (EIA) to detect toxin A or B: Rapid and frequently used, but sensitivity and specificity in horses are not well established
  • •
    Polymerase chain reaction for toxin genes after culture
• •
  C. perfringens

  • •
    Genotyping of isolates to determine the strain and, identify specific toxin genes
  • •
    Detection of toxin in feces: Commercial EIA for enterotoxin; sensitivity and specificity in horses are not known

Treatment 

Therapeutic Goal(s)

• •Resolution of enterocolitis
• •Maintenance of physiologic homeostasis of water and electrolyte balance
• •Amelioration of clinical effects of systemic inflammatory response syndrome

Acute General Treatment

• •
  Specific antimicrobial therapy: Drug choice is most often based on historical information because antimicrobial sensitivity testing for Clostridium spp. is not routine in many laboratories. However, antimicrobial resistance has been documented in Clostridium spp., and sensitivity testing is recommended in refractory cases.

  • •
    Metronidazole (15 mg/kg PO q8h): Generally considered the drug of choice; resistance has been identified infrequently
  • •
    Vancomycin has been used in cases with metronidazole resistance; consider use carefully because of the importance of vancomycin in the treatment of resistant bacteria in human medicine
  • •
    Zinc bacitracin is effective against C. perfringens but resistance is common in C. difficile
• •Di-tri-octahedral smectite (BioSponge, Platinum Performance, Belton, CA.) adsorbs clostridial toxins and endotoxin in vitro.
• • Saccharomyces boulardii (25 g PO q12h) may be useful in the management of horses with acute enterocolitis.
• •
  Supportive care for diarrhea

  • •
    Treatment for dehydration and electrolyte and acid-base abnormalities
  • •
    Treatment for associated systemic inflammatory response syndrome (endotoxemia).
  • •
    Broad-spectrum systemic antibiotic therapy in horses with colitis is controversial.

    • ▪
      Sometimes used to prophylactically control potential bacteremia from translocation of bacteria across the damaged intestinal mucosa.
    • ▪
      If diarrhea developed while the horse is on antibiotics, discontinuing or changing those antibiotics is suggested.

Possible Complications

• •Laminitis
• •Thrombophlebitis
• •Peritonitis

Recommended Monitoring

• •Attitude, vital parameters, diarrhea
• •PCV, TP
• •Hydration status, renal function
• •Acid-base and electrolyte abnormalities

Prognosis and Outcome 

• •Prognosis is variable depending on the strain and host factors.
• •A mortality rate of up to 42% has been reported with C. difficile; prognosis may be worse in adults than foals.
• •Prognosis is guarded in foals with C. perfringens, especially type C; the mortality rate is approximately 50%.

Pearls & Considerations 

Comments

Enteric clostridiosis is an important cause of enterocolitis in horses, accounting for approximately 40% of cases in some studies.

Prevention

• •Careful use of antimicrobials.
• •Clostridial spores are often present in the environment; good management practices, including regular cleaning and disinfection of stalls and equipment, will limit the environmental burden.
• •There is no approved vaccine for horses. Anecdotally, vaccines approved in other species for the prevention of C. perfringens–associated disease have been used in horses; no data currently support their use.

Client Education

Clients should be made aware of the risk of antibiotic-associated diarrhea and should be counseled to call their veterinarian if diarrhea occurs.