Mucormycosis complicating lower limb crash injury in a multiple traumatised patient: an unusual case

Abstract

Necrotising skin and soft tissues infections are most commonly bacterial in origin. However, saprophytic fungi of the class Zygomycetes, family Mucoraceae, can cause highly aggressive infections (mucormycoses) mainly in immunocompromised patients. Severe trauma is one of the major risk factors for mucormycosis. Fungal traumatic wound infection is an unusual complication associated with crash limb injury. This report describes a case of serious necrotising soft tissue infection caused by Mucor sp following primary fungal environmental wound contamination in a multiply injured patient. Despite undelayed diagnosis and proper treatment (surgical debridement and limb amputation, amphotericin B therapy) the patient presented a fatal outcome.

BACKGROUND

Mucormycosis is an angioinvasive infection with high mortality and it is caused by saprophytic ubiquitous fungi of the order Mucorales.^1–4 Most frequently mucormycosis occurs in immunocompromised patients^1,2,5–7; in immunocompetent patients without underlying disease develops rarely: about 4% of infections.^2,4,5 Fungal wound infections are extremely rare.³ We present an unusual case of severe necrotising soft tissue infection following primary fungal environmental wound contamination in a multiply injured patient.

CASE PRESENTATION

A 40-year-old, previously healthy, woman was admitted to the regional hospital after a car crash accident. She suffered severe, multiple trauma: serious craniocerebral injury with cerebral contusion and open basal cranial fracture, abdominal cavity trauma and severe lower limb injuries with an open right femur fracture and comminuted open left lower leg fracture. x Rays (fig 1) and abdominal ultrasonography were performed. Initial surgical treatment was implemented: multiple wounds, also of the lower limb, were primarily sutured in a municipal hospital, and the lower limbs were temporarily immobilised in plaster splints. The patient was transferred to the trauma surgery department for further diagnosis and treatment. Due to traumatic shock on admission, diagnostic peritoneal lavage was performed with a positive result. Laparotomy revealed multifocal minor omental and peritoneal lacerations with active bleeding. Haemostasis was achieved. At the same time, neurosurgical procedure was performed: anterior cranial fossa reconstruction. Because of the general condition of the patient and very high risk of longer anaesthesia, external stabilisation was not put in place. Instead, skeletal traction and plaster splint were used to stabilise the fracture. After the surgery the patient was admitted to the intensive care clinic, and intubated with controlled mechanical ventilation. Wide-spectrum empirical antibiotics were administered intravenously: cefoperazone 3×1.0, amikacin 3×0.5, and metronidazole 3×0.5. On the third postoperative day the patient was extubated, with full consciousness, and returned to our clinic. The next day the wound region became painful, oedematous, with a serosanguineous exudate. Fluid samples were obtained and sent for microbiological examination. Multiresistant Enterococcus faecium strain susceptible only to glycopeptides (vancomycin, teicoplanin) was grown. On the fifth postoperative day the patient became febrile (38.6°C), and the white blood cell count was 15.6×10⁹/l. The antibiotic therapy was modified: piperacillin 2×2.0 and vancomycin 2×1.0 were introduced. The next day the wound was surgically opened, and necrotic tissue and an ichor-like exudate were observed. Due to prior clinical observations, an anaerobic clostridial infection was suspected. Clinical specimen (“borderline” tissue fragments, exudate) were taken for microbiological analysis. Enterococcus faecium and Mucor sp were cultured. Mucor sp was grown on Sabouraud dextrose agar. On the eighth day the patient’s body temperature rose to 39°C, and the white blood cell count was 18.2×10⁹/l. The local extremity condition worsened with rapidly progressive skin and subcutaneous tissue necrosis surrounded by massive inflammatory infiltrate (fig 2). Surgical intervention with extensive debridement of the necrotic tissue was performed (fig 3). Acinetobacter baumannii, Enterococcus faecium and Mucor sp were isolated from the debrided tissues. Microscopically, typical non-septate and irregularly branched fungal hyphae were found (fig 4). On histopathology, haemorrhagic necrosis of muscle and fascia layers, thrombotic changes in blood vessels, and inflammatory response with a mixture of neutrophils and granulomas, were observed. Local dressings with antiseptic agents (povidone-iodine, chlorhexidine solution) were changed every day. Antibiotic therapy was modified due to the findings: netilmycin 2×0.2 was introduced and also antifungal therapy with liposomal amphotericin B in doses of 3.0 mg/kg/day intravenous was implemented. The wound was surgically debrided and dressings with disinfectants were changed each day. Amphotericin B therapy was continued 12 days; from the fifth day of therapy there was no fungal isolation from the wound. On day 21 after hospital admittance, the patient’s general condition and conscious state progressively deteriorated with acute circulatory and respiratory derangement. The patient was transferred to the intensive care clinic; bilateral pneumonia and pulmonary oedema due to myocardial ischaemia were diagnosed. After 12 days of amphotericin B therapy, complete eradication of Mucor sp infection was achieved. Unfortunately, the wound became infected with a multiresistant hospital strain of Staphylococcus aureus (MRSA). Despite continuous microbiological monitoring and proper antibiogram-guided antibiotic therapy, the patient developed severe staphylococcal sepsis originating from the infected lower limb. On the 32nd day of hospitalisation, a femoral limb amputation procedure was performed. The patient died on the 50th day after trauma. Biological samples taken at autopsy revealed growth of S aureus (MRSA) and Gram-negative rods.

Figure 1.

x Ray examination.

Figure 2.

Local extremity condition with rapidly progressive skin and subcutaneous tissue necrosis surrounded by massive inflammatory infiltrate.

Figure 3.

Wound condition after surgical debridement.

Figure 4.

Fungal hyphae in direct microscopic examination (H&E, ×400).

DISCUSSION

Mucormycosis is an opportunistic infection caused by fungi of the class Zygomycetes, family Mucoraceae.^1–4 The genera that are most often recovered and play a role as human pathogens are: Mucor, Rhisopus, Rhisomucor and Absidia.^1,2,4,7 Mucorales are common saprophytes found in soil and decaying organic vegetable matter.^1,3,5 Mucormycosis develops mainly in debilitated hosts: 70% cases are related to diabetes mellitus (types 1 and 2); other major risk factors for mucormycosis are: neutropenia, AIDS, haematological malignancy, pharmacological immunosupression (antineoplastic chemotherapy, corticosteroid and antirejection therapy), bone marrow and peripheral blood stem cell transplantation, solid organ transplantation, deferoxamine therapy for iron or aluminium overload or iron overload itself, severe burns, severe multiple trauma, malnutrition (pellagra and kwashiorkor), anaemia, gastroenteritis, diarrhoea, hepatitis, glomerulonephritis, acute tubular necrosis, liver cirrhosis, amoebiasis, septicaemia, uraemia, typhoid fever, congenital heart disease and intravenous drug abuse.^1,2,4,5,7 Mucormycosis is generally the third most common invasive fungal infection (after aspergillosis and candidiasis), with 8.3–13% of infections occurring in haematology patients²; and it is the second most common infection caused by filamentous fungi (after aspergillosis).¹ The clinical importance of mucormycosis is rising significantly.² There are five major clinical presentations of mucormycosis: rhino-orbito-cerebral, pulmonary, disseminated, cutaneous and gastrointestinal.^1–4,7 Other rare presentations of mucormycosis are: osteomyelitis, endocarditis, and infection of prosthetic valves, Dacron vascular grafts, and autologous venous grafts.⁷ Cutaneous mucormycosis is the form of infection least likely to be related to underlying disease: only 26% of cases of cutaneous mucormycosis are associated with diabetes mellitus, and 16% with haematological malignancy.¹ Mucormycosis with cutaneous involvement has the lowest mortality (16%) compared with other clinical manifestations for which the mortality varies from 67% to 100%.^2,5 Fungi can enter the human through inhalation, ingestion or percutaneous inoculation; environmental contamination of tissues happens in traumatic skin lesions and burns.^1–7 Cutaneous mucormycosis can develop after surgery, soiled trauma, in injured survivors from natural disasters (eg, the tsunami disaster in Asia in 2004, the volcanic eruption in Columbia in 1985), after motor vehicle accidents, bone fractures, tibial pin placement, intravenous lines, insect bites, cactus spine injuries, abrasions, lacerations, in biopsy sites or allergen patch sites, after use of contaminated adhesive or elasticised dressings (Elastoplast), wooden spatulas as splints in neonates, cosmetic clay with mashed vegetables and intramuscular injections.^1–7 Implanted fungal elements produce superficial or deep-seated infection affecting the dermis and subcutaneous layer.^1,2,6 Mucorales have a strong ability to invade blood vessels with endothelial damage (vasculotropism) and to cause thrombosis, infarction, local tissue destruction and purulent inflammation.^1,3–7 Skin disorders can manifest as pustules, blisters, nodules, necrotic haemorrhagic ulcerations surrounded by local erythema, ecthyma gangrenosum-like lesions or necrotising cellulitis around the wound with minimal response to standard antibiotic therapy.^1–3,5,6 The course of infection is usually gangrenous and rapidly progressive with extensive tissue necrosis.^1,2,5,6 Necrotising bacterial infections such as clostridial cellulitis or fasciitis should be excluded in the differential diagnosis.⁶

The diagnosis of mucormycosis is difficult and requires culture methods and microscopic examinations of clinical specimens.^1–3,5–7 Specimens are taken during surgical debridement or by deep tissue biopsy.^1–3,5–7 Wound swabs for cultures and fungal stains are not sensitive and can give misleading microbiological results.²

On microscopic examination after H&E, periodic acid–Schiff or Gomori methenamine silver nitrate staining, Mucorales present themselves as having broad (10–50 μm), irregular, ribbon-like, aseptate hyphae, with right-angle branching (angle hyphal branching varies from 45 to 90 deg).^1,2,5–7

On histopathology, angioinvasion with surrounding tissue infarction or perineural invasion (90% specimens) are observed.^1–4,6,7 A variable inflammatory response can be observed. In 50% of cases a neutrophilic inflammatory response is noted; in 25%, a mixture of neutrophils and granulomas is seen; in 5%, granulomas only are observed; and there is no inflammatory response in 20% of cases.² Histopathological examination of removed tissues is assumed to be the quickest way to early diagnosis of mucormycosis.³

Final confirmation of the diagnosis is a positive tissue culture.^1,3,5,6 Mucorales can be grown on most routine bacterial (ie, sheep blood agar, chocolate agar) and fungal culture media (ie, Sabouraud dextrose agar, potato dextrose agar) at a very wide range of temperatures: 25–55°C.^1,2,5,6 Fungal colonies are fluffy white, grey or brownish in colour.^2,5,6

Treatment of mucormycosis infection should be immediate and associated with early detection.³ It should be based on surgical intervention, application of antifungal agents, and control of a pre-existing disease or correction of predisposing factors.^1,3,4,6 Surgical intervention should be performed as aggressive, complete resection of the necrotic and infected tissues or even limb amputation.^1,3–7 The drug of choice in mucormycosis is amphotericin B (conventional, liposomal or colloidal dispersion form; 1.0–5.0 mg per kg body weight daily) administered intravenously.^1–7 Nephrotoxicity is the main limitation of doses in amphotericin B therapy.¹ As additional therapy, hyperbaric oxygen can be administered, and it has been used recently with promising results.^3,4,7

Cutaneous mucormycosis in traumatic wounds after environmental contamination is a rare but very severe complication of typical bacterial wound infections. Mucormycosis and other invasive fungal infections should be seriously considered in severely traumatised patients who have rapidly progressive wound infections despite proper antibacterial treatment and surgical debridement.

LEARNING POINTS

• Cutaneous mucormycosis in traumatic wounds after environmental contamination is a rare but very severe infectious complication.

• Mucormycosis and other invasive fungal infections should be seriously considered in severely traumatised patients who have rapidly progressive wound infections despite proper antibacterial treatment and surgical debridement.

• The drug of choice in mucormycosis is amphotericin B administered intravenously.