Invasive fungal disease of the sinus and orbit: a comparison between mucormycosis and Aspergillus.

BACKGROUND/AIMS: Invasive fungal infections of the head and neck are rare life-threatening infections where prompt diagnosis and intervention is critical for survival. The aim of this study is to determine the clinical characteristics and outcomes of invasive fungal disease of the sinus and orbit, and to compare mucormycosis and Aspergillus infection. METHODS: A retrospective review was conducted from a single tertiary care eye and ear hospital over 20 years (1994-2014). Twenty-four patients with a confirmed pathological diagnosis of invasive fungal disease of the sinus and/or orbit were identified and their medical records were reviewed. The main outcome measures were type of fungus, location of disease, mortality and visual outcome. RESULTS: Patients with orbital involvement had a higher mortality and higher likelihood of mucormycosis infection compared with those with sinus-only disease (78.6% vs 20%, p=0.01; 86% vs 30%, p=0.01, respectively). Patients with mucormycosis had a higher mortality (71%) than patients with Aspergillus (29%); however, this was not statistically significant (p=0.16). All patients with orbital involvement and/or mucormycosis infections were immunosuppressed or had inadequately controlled diabetes, and had a cranial neuropathy or ocular motility dysfunction. All five post-transplant patients with orbital infections died, while the two transplant patients with sinus infections survived. CONCLUSIONS: Patients with orbital fungal infections are more likely to be infected with mucormycosis compared with Aspergillus and have a higher mortality compared with infections sparing the orbit. History of transplant portends a dismal prognosis in orbital infections. Invasive fungal disease should be considered in any immunocompromised patient presenting with a new cranial neuropathy or ocular motility abnormality.

The Role of Adjunctive Therapies in the Management of Invasive Sino-Orbital Infection.

OBJECTIVE: Invasive sino-orbital fungal infections are life-threatening complications of immunonosupression that are difficult to treat. Currently there are no standard treatment guidelines. The most widely accepted therapy includes parenteral anti-fungal therapy and surgical debridement of sinuses with orbital exenteration, a procedure that is not only disfiguring, but may increase morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an alternative approach that provides local administration to infected tissues. The adjunct use of anti-fungal retrobulbar injections not been extensively reviewed in treating sino-orbital infection. We are reporting the multimodal approach of using L-AMB retrobulbar injections in combination with sinus debridement, intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the management of sino-orbital infection. METHOD & RESULTS: Review of literature of 12 cases and retrospective evaluation of one patient with sino-orbital Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and hyperbaric oxygen therapy. Clinical characteristics, radiographic features, management techniques, and clinical outcomes are described. CONCLUSION: Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric oxygen and parenteral anti-fungals in the control of sino-orbital fungal infections.

Successful treatment of rhino-orbital mucormycosis with posaconazole and hyperbaric oxygen therapy.

Mucormycosis is a rare, but invasive infection caused by ubiquitous molds. Amphotericin B and surgery have been known to help improve the outcome. Sporadic case reports support the use of posaconazole in adults. We report a toddler with acute lymphoblastic leukemia who acquired rhino-orbital mucormycosis caused by Rhizopus species at the end of induction chemotherapy. She was successfully treated with multiple surgical debridements, amphotericin B, posaconazole and hyperbaric oxygen therapy. In conclusion, mucormycosis is a serious infection that requires aggressive surgical and medical therapy. To the best of our knowledge the use of posaconazole combined with hyperbaric oxygen therapy has not been reported in a toddler with leukemia and invasive Rhizopus sp. infection. This approach was found to be safe and effective in our patient.

Rhizopus microsporus var. rhizopodiformis sinus-orbital zygomycosis in an immunosuppressed patient: successful treatment with posaconazole after a complicated clinical course.

A case of sinus-orbital Rhizopus microsporus var. rhizopodiformis infection in a patient with graft versus host disease following allogeneic blood stem cell transplantation is reported. Commercially available pea straw compost used for gardening was suspected to be the source of the infection. After an initial relapse, treatment with surgical debridement, liposomal amphotericin B and posaconazole was successful.

Periorbital zygomycosis (mucormycosis) treated with posaconazole.

PURPOSE: To report on the successful treatment of periorbital zygomycosis (mucormycosis) with posaconazole, a broad-spectrum oral antifungal available for compassionate use. DESIGN: Interventional case report. METHODS: Review of a medical record. RESULTS: A 22-year-old male undergoing induction chemotherapy for acute lymphoblastic leukemia presented with periorbital cellulitis attributable to Rhizopus. The patient was initially treated with liposomal amphotericin B, surgical debridement, and reversal of immune compromise. The patient was switched to posaconazole because of amphotericin side effects and lack of improvement. He took posaconazole for five months while undergoing additional cycles of chemotherapy. Despite recurrent profound neutropenia, the periorbital infection resolved, he tolerated reconstructive procedures, and he did not develop orbital invasion. His Rhizopus isolate was highly susceptible to posaconazole in vitro. CONCLUSIONS: Drug toxicities can limit the use of amphotericin in some patients with zygomycosis. Posaconazole shows promise as an alternative antifungal agent in the treatment of periorbital zygomycosis.

Mucormycosis--early diagnosis and treatment.

OBJECTIVE: The aim of this retrospective study was to analyse the data of patients with rhino-orbital-cerebral mucormycosis for predisposing factors, diagnosis, treatment and survival rate. The role of frozen section in early diagnosis and use of nasal endoscopy in diagnosis, treatment and follow-up of patients has also been examined. DESIGN: Retrospective case series. SETTING: University Teaching Hospital. METHODS: The case notes of 9 patients with diagnosis of mucormycosis who presented from 1973 to 2001 were examined. The data for predisposing factors, signs/symptoms, histological diagnosis, radiological intervention, medical and surgical treatment and final outcome was analysed. RESULTS: There were 9 patients with mucormycoses. Early diagnosis was made by endoscopic examination and frozen section in 5 patients, which was later confirmed by histology. Treatment included parental and/or local amphotericin, hyperbaric oxygen and debridement either by endoscopic or external approach, with or without orbital exenteration. This resulted in an overall survival of 5 patients. CONCLUSION: Frozen section diagnosis allows for early therapy since successful treatment depends on systemic amphotericin, surgical debridement and treatment of underlying predisposing factors. Nasal endoscopy is useful in diagnosis, endoscopic debridement and follow up of patients.

Severe hyperphosphatemia resulting from high-dose liposomal amphotericin in a child with leukemia.

Children with acute lymphoblastic leukemia (ALL) are at risk for serious electrolyte abnormalities. The authors report their experience in managing a child with ALL who developed severe hyperphosphatemia as a consequence of a large exogenous load of phosphorus from high-dose liposomal amphotericin B. Health care providers need to recognize this potentially life-threatening complication of liposomal amphotericin B, since early detection and intervention can prevent significant morbidity.

Hyperbaric oxygen therapy in the treatment of orbital gas gangrene.

Clostridial gas gangrene (myonecrosis) is a rapidly progressive, life-threatening infection. The occurrence of clostridial gas gangrene in the orbit is uncommon. We present a case of gas gangrene in the orbit of a child, with Clostridium perfringens isolated from the wound. Our patient was successfully treated with extensive surgical débridement, anti-microbial therapy, and hyperbaric oxygen therapy. Hyperbaric oxygen is established as an adjuvant therapy of clostridial gas gangrene and has been shown to significantly reduce morbidity and mortality. To our knowledge, this is the first reported case of using hyperbaric oxygen therapy in the treatment of orbital gas gangrene.

Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities.

PURPOSE: To describe the successful management of rhino-orbital mucormycosis without the use of orbital exenteration. METHOD: Case report. RESULTS: The patient had successful eradication of the fungal infection with retention of normal vision and ocular function. CONCLUSIONS: The use of multiple treatment modalities including aggressive surgical debridement guided by intraoperative frozen section monitoring, intravenous liposomal amphotericin B, intraorbital regular amphotericin B and hyperbaric oxygen may allow complete resolution of orbital phycomycosis and spare the patient from the blindness and disfigurement associated with exenteration.

Invasive rhinosino-orbital aspergillosis with precipitous visual loss.

OBJECTIVE: To describe the clinicopathological and radiologic features in five cases of primary and secondary orbital aspergillosis. DESIGN: Case series. SETTING: Ophthalmology department of a university hospital. PATIENTS: Five patients over 65 years of age with invasive rhinosino-orbital aspergillosis. RESULTS: Presenting features were abrupt onset of proptosis, ophthalmoplegia and blepharoptosis with precipitous visual loss. All had debilitating periorbital pain or headache, but none had orbital inflammatory signs or appeared "toxic." Predisposing causes included alcoholism, low-dose prednisone therapy and insulin-dependent diabetes mellitus. One patient, suspected of having mucormycosis based on tissue biopsy and results of potassium hydroxide preparations, harboured Aspergillus fumigatus, which grew on culture. Secondary bacterial infections developed in three patients. Three patients died from their disease despite aggressive surgical treatment, including exenteration and sinus extirpation. The one patient with primary orbital aspergillosis survived after exenteration. CONCLUSIONS: Sinonasal aspergillosis with orbital extension and primary orbital aspergillosis have a precipitous clinical course that mimics that of mucormycosis and may be fatal despite early exenteration. Computed tomography and magnetic resonance imaging of the sinuses, orbit and head provide complementary diagnostic signs. While results of potassium hydroxide preparations and tissue biopsy guide treatment of fungal infection, definitive diagnosis requires fungal culture. Relatively good vision may be associated with massive orbital and secondary intracranial extension.

Survival factors in rhino-orbital-cerebral mucormycosis.

Mucormycosis is a highly aggressive fungal infection affecting diabetic, immunocompromised, and, occasionally, healthy patients. This infection is associated with significant mortality. We have reviewed 208 cases in the literature since 1970, 139 of which were presented in sufficient detail to assess prognostic factors, and added data from six of our patients. The histories of these 145 patients were analyzed for the following variables: 1) underlying conditions associated with mucormycotic infections; 2) incidence of ocular and orbital signs and symptoms; 3) incidence of nonocular signs and symptoms; 4) interval from symptom onset to treatment; and 5) the pattern of sinus involvement seen on imaging studies and noted at the time of surgery. Factors related to a lower survival rate include: 1) delayed diagnosis and treatment; 2) hemiparesis or hemiplegia; 3) bilateral sinus involvement; 4) leukemia; 5) renal disease; and 6) treatment with deferoxamine. The association of facial necrosis with a poor prognosis fell just short of statistical significance, but appears clinically important. This is the first review that documents the heretofore intuitive claim that early diagnosis is necessary to cure this disease. Standard treatment with amphotericin B and aggressive surgery are reviewed and adjunctive therapeutic modalities are discussed, including local amphotericin B irrigation, hyperbaric oxygen, and optimizing the immunosuppressive regimen in transplant patients. Hyperbaric oxygen was found to have a favorable effect on prognosis. In addition, possible treatment options for patients with declining renal function are reviewed.

Adjunctive hyperbaric oxygen in the treatment of bilateral cerebro-rhino-orbital mucormycosis.

Survival is uncommon in bilateral cerebro-rhino-orbital mucormycosis treated surgically and medically. A 66-year-old man in previously good health had bilateral cerebro-rhino-orbital mucormycosis and newly diagnosed nonketotic diabetes mellitus at initial examination. Total loss of vision, proptosis, and ophthalmoplegia of both eyes were present. The patient was treated with aggressive surgical and medical therapies that included bilateral orbital exenteration, intravenous and local amphotericin B, hyperbaric oxygen, and control of the diabetes mellitus. One and one-half years after onset of the illness, the patient is alert and clinically stable. The importance of prompt diagnosis and aggressive treatment of this disease is emphasized by this case. Additionally, we suggest that adjunctive hyperbaric oxygen is a reasonable modality in the treatment of this often fatal disease.