Musculoskeletal

Clostridial myonecrosis (clostridial myositis/cellulitis, malignant oedema)

Clostridial myonecrosis is a syndrome of severe necrotizing soft tissue infection associated with Clostridium spp. It typically presents as peracute emphysematous soft tissue swelling in the region of an injection or wound within hours of the inciting cause. Intramuscular injection of several common drugs, including flunixin meglumine, ivermectin, omeprazole, antihistamines, phenylbutazone, dipyrone, vitamin B complex and synthetic prostaglandins, has been implicated. Disease following injection of flunixin meglumine appears over-represented and the association with wounds seems less common. Central to the aetiology is the inoculation of the organisms and the creation of anerobic foci in which the organisms can proliferate, sometimes facilitated by irritant medications. Clostridium perfringens and C. septicum are the species that have most often been reported as causative organisms, but other Clostridium species have also been implicated. Rapid identification of cases is critical, as prompt treatment can improve survival rates. Horses can develop clinical signs and die within 48 - 72 h.

Key issues

1. Clinical progression is rapid, so prompt identification of clinical cases is essential.
2. Soft tissue swelling, along with signs of systemic disease, following IM injection should raise suspicion of clostridial myonecrosis.

Diagnostics

Horses are generally febrile and have moderate to severe depression and inappetence. They are generally stiff and reluctant to move. Severe toxaemia and cardiovascular collapse can occur soon after clinical signs develop, with diffuse intravascular coagulation and acute renal failure as consequences.

Soft tissue swelling, with palpable subcutaneous emphysema, is very common, especially when disease affects the cervical region, and this generally leads to a presumptive diagnosis. When the disease affects the gluteal region, subcutaneous emphysema may be a less reliable clinical sign. The overlying skin may initially feel hot, but quickly becomes cold, tough and insensitive due to the underlying necrosis. Aspiration of fluid from the affected region, or upon myotomy/fasciotomy, reveals large parallel-sided, Gram-positive rods. Ultrasonography can be useful to identify gas shadows within deeper soft tissues and pockets of necrotic tissue to target for fasciotomy.

All horses that develop soft-tissue swellings acutely after IM, SC or inadvertent perivascular administration of drugs and have systemic signs of illness should be assessed by examining a Gram-stained smear of an aspirate from the affected area. Release of exotoxins by the bacteria causes muscle necrosis and destruction of white blood cells. Absorption of the exotoxins into the circulation causes widespread damage to the endothelium, liver and muscles, leading quickly to death.

Treatment

An aggressive approach to therapy is prudent when clostridial myonecrosis is suspected or confirmed. Medical and surgical therapy should be pursued.

Medical:

1. Antimicrobials – high doses of crystalline penicillin (benzyl penicillin) at 12,000-48,000 IU/kg IV q 4-6 h. Other beta-lactams may be used, but clinical experience suggests that high-dose crystalline penicillin is superior. Aggressive antimicrobial therapy in the first 2-3 days of therapy may improve survival rates. Therapy beyond 10 days is probably unnecessary.
2. Anti-inflammatory and analgesic medication – flunixin meglumine or phenylbutazone at standard dose rates. Opioids are probably necessary for adequate analgesia.
3. Supportive adjunctive care – plasma transfusion may be indicated, especially in cases where coagulation is delayed and prior to surgical interventions. Treatment of shock with corticosteroids has been employed in some case reports, but the efficacy of this therapy is unknown. Fluid therapy with isotonic fluids is required in most cases.

Surgical:

Fenestration of the emphysematous area is indicated to improve oxygenation, reduce swelling and facilitate debridement of necrotic tissue. This is typically performed standing with only light systemic sedation. Due to the extensive necrosis, only light local analgesia is needed. Multiple vertical incisions, approximately 2.5 cm apart, should be made through the muscles in the affected area. Exposed tissues can be irrigated and many different solutions have been advocated (hydrogen peroxide, chlorhexidine, crystalline penicillin), but there is no evidence that any one agent is more beneficial. Daily hydrotherapy should follow to keep the area clean and facilitate granulation. Owners should be warned of the significant soft tissue and skin sloughing that will probably occur over the medium to long term.

Antimicrobials used

• Crystalline penicillin (benzyl penicillin at 12,000-48,000 IU/kg IV q 4-6 h) for 3-5 days, after which more typical doses of penicillin are probably adequate. Total antimicrobial duration ~10 days.

Prognosis

In a series of 37 cases, 27 horses (73%) survived to discharge, with a median duration of hospitalisation of 12 days, although treatment was necessary following discharge in all cases. There has been speculation that survival rates may differ depending on the Clostridium species involved, but there is insufficient evidence to make such distinctions.

Further reading

• Peek SF, Semrad SD, & Perkins, GA. "Clostridial myonecrosis in horses (37 cases
• 1985–2000)." Equine veterinary journal 35.1 (2003): 86-92 (1).

Septic synovial structures

Synovial structures can become infected by direct inoculation following a wound, by iatrogenic introduction with intra-synovial injections or by haematogenous spread. Although haematogenous spread is more common in foals, it can occur in adult horses. Early diagnosis and aggressive treatment with lavage and appropriate antimicrobial therapy is critically important, as chronic disease is associated with higher mortality. The most common bacterial isolates from wounds are Enterobacter spp., Staphylococcus spp., Streptococcus spp. and Pseudomonas spp., but infections are often mixed and can involve anaerobic bacteria. Iatrogenic infections are often caused by Staphylococcus spp.. Studies of the efficacy of addition of prophylactic antimicrobials (such as amikacin) to intra-articular medications (such as corticosteroids) have not demonstrated a reduction in joint sepsis, so this prophylactic use is not recommended. Aseptic joint preparation and adequate injection technique are sufficient to prevent sepsis (3). Polysulphated glycosaminoglycans (PSGAGs) are the only exception to this, with the current recommendation being to use concurrent intra-articular antimicrobials to reduce the risk of infection (4).

Although the use of intra-articular antimicrobials for treatment of joint sepsis is widespread, there are important clinical knowledge gaps about the appropriate intra-articular doses to use, the potential for contribution to the development of antimicrobial resistance with overuse, and whether there are long-term adverse side effects of the cytotoxicity of local antimicrobial treatment for cartilage. The intraarticular administration of amikacin can induce dose-dependent increases in cartilage degradation products and biomarkers of inflammation. It is thought that concurrent administration of other medications, such as hyaluronic acid, may mitigate antimicrobial-induced cytotoxicity (5).

Intravenous regional limb perfusions (IVRLP) are used to treat distal limb infections by isolating the limb from the systemic circulation with a tourniquet and infusing a high concentration of an antimicrobial intravenously. The antimicrobial diffuses passively into all tissues throughout the isolated region until the tourniquet is removed, after approximately 20 min. Ceftiofur sodium administered at a dose of 2 g diluted in 60 mL of sterile saline as an IVRLP maintained regional plasma concentrations above MIC (1 µg/mL) for 12 h, and subcutaneous tissue concentrations above MIC for 24 h, but bone concentrations were only above MIC until immediately after tourniquet removal (6). Inflamed joints have been shown to have increased concentrations of amikacin after IVRLP, when a 5 mg/kg dose (one-third of the systemic dose) was diluted in 60 mL of sterile saline, and the concentrations reached the recommended Cmax-to-MIC ratio of 8 (MIC of 16 µg/mL) in most inflamed joints, but not in normal joints (7). There are many published reports describing variations in this technique, including the dose used, the dose volume and the concentration of perfusate, the dosing interval, the type, method and duration of tourniquet application (with or without an Esmarch bandage) and whether the technique is performed standing or under general anaesthesia, so the optimal method for performing IVRLP has not been established and the apparent clinical benefits of the technique are often difficult to confirm and quantify (8). For detailed recommendations on intra-synovial and intra-venous regional perfusion, see the next section (Section 12).

Key issues

1. Early detection of a septic synovial structure and prompt treatment are crucial to a successful outcome.
2. Collection of synovial fluid for cytology and culture and sensitivity testing is very important and ideally should be performed prior to initiation of antimicrobial therapy.
3. Lavage of synovial structures is associated with better outcomes.

Diagnostics

Horses with septic synovial structures are generally febrile and non-weight-bearing lame in the affected leg, with effusion into the infected synovial structure. Synovial fluid analysis reveals an elevated nucleated cell count (> 2.5 x 10⁹/L), with a neutrophilia (> 80%) and an elevated protein concentration (> 25 g/L). Synovial fluid should be submitted for culture and susceptibility testing.

Treatment

1. Needle lavage of the affected joint can be done standing, or via arthroscopy under general anaesthesia.
2. Arthroscopy allows visualisation of the joint and may enable determination of a more accurate prognosis, and enable debridement of infected tissue.
3. Broad spectrum antimicrobial therapy is indicated until culture results are available.
4. Intra-articular administration and regional limb perfusions have been used to deliver increased concentrations of antimicrobials to synovial structures. Concentration dependant antimicrobial drugs (aminoglycosides) are the best choice, as high concentration-to-MIC ratios can be achieved, which enhances bacterial killing, and these drugs are also amenable to once daily administration due to the presence of a post-antibiotic effect.

Antimicrobials used

• Procaine penicillin (22 000 IU/kg IM q 12 h) and gentamicin (6.6 mg/kg IV q 24 h) until resolution of lameness.
• Intra-articular administration (gentamicin at 150 -500 mg; amikacin at 250 -1000 mg) q 24 h until resolution of lameness.
• Intravenous regional limb perfusion (gentamicin at 500 – 1000 mg; amikacin at 500 – 2000 mg) q 24 h until resolution of lameness.

Prognosis

Fair to good with early detection and prompt treatment of infection. In recent studies 84% and 90% survived to discharge (mean duration of antimicrobial therapy is 12 days), but only 54% and 65% returned to function (9, 10).