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Q1: What abnormality was seen on the thoracic computed tomogram?
Thoracic computed tomography demonstrated an irregular and thick walled cavity, 3 cm in diameter and a left pleural loculated collection including draining catheter on the right hand side image.
Q2: What was the diagnostic procedure?
The diagnostic procedure was thoracentesis. This yielded a highly viscous, purulent fluid, with 28 000 neutrophils × 106/l and hyphae on the smear. The culture was positive for Aspergillus fumigatus. The precipitating antibodies in the serum and the weal flare cutaneous reaction for aspergillus was positive. Based on these findings a diagnosis of aspergillus empyema was established.
Q3: What additional tests were/should be performed?
All other microbiological cultures and serological tests including mycobacteria were negative. Tuberculin test was positive (16 mm). Blood cultures were negative, sputum culture yielded a normal throat flora, and there was no evidence of an immunocompromised state. The bronchoscopic examination was normal. Abdominal ultrasonography was unremarkable.
Q4: What is the treatment?
The patient was started on intravenous liposomal amphotericin B (amph-B) (Fungizone, Bristol-Myers Squibb) therapy (50 mg/day) immediately after the microscopic examination of the pleural fluid. The pleural cavity was drained and irrigated with normal saline and povidone iodine solution through an intercostal drain every other day. A dose of 25 mg liposomal amph-B was also administered into the pleural cavity on the 10th day of intravenous therapy.
The patient improved considerably after three weeks of intravenous amph-B therapy. The intercostal drain was removed on the 20th day and treatment was changed to itraconazole 400 mg/day orally during the next nine weeks. A satisfactory improvement in both clinical symptoms and radiological findings were achieved. Six months after, control computed tomography was normal except for minimal residual pleural thickness. The patient remained well over the next year.
Aspergillus empyema is a rare clinical entity that predominantly affects patients with previous tuberculous infection, who have had thoracic surgery, or are taking cytotoxic therapy.1 Pleural invasion by Aspergillus species occurs most commonly as a late complication of thoracoplasty for tuberculosis, often in association with a bronchopleural fistula or as a complication of surgical resection.2,3 An increase in the number of critically ill or immunocompromised patients made aspergillus empyema a common manifestation of invasive pulmonary aspergillosis.4 Rarely the rupture of cavitary aspergillosis into the pleural space can produce aspergillus empyema.5 Interestingly, our patient had no history of pulmonary disease, operation, or evidence of an immunocompromised state, including HIV seropositivity, diabetes mellitus, and T or B cell abnormalities that were excluded by positive skin tests and normal immunoglobulin levels. Although he had an odontogenic infection, no pathogenic micro-organism could be grown on culture. Existence of a thick walled cavity on computed tomography suggested that empyema was a consequence of rupture of the aspergilloma cavity into the pleural space.
The treatment of aspergillus empyema differs among centres. Early administration of antifungal agents and pleural drainage are thought to be helpful in improving the outcome of patients.6 Highly viscous or purulent fluids require drainage via a chest tube.7
Amphotericin is the main drug for the treatment of most fungal infections. In 1959, it was first used systemically to treat a case of aspergillus empyema developing in a patient previously treated by pneumothorax for pulmonary tuberculosis.8 The major limitation of amph-B is its toxicity (nephrotoxicity, phlebitis, hypokalaemia, hypomagnesaemia, and anaemia) seen in nearly 80% of patients.9 Liposomal amph-B offers the potential of a less toxic intravenous alternative to amph-B. Local administration of this drug is also mentioned in the literature when the infection appears to be local like a mycetoma rather than an invasive disease.3
Itraconazole is an orally active triazole compound against Aspergillus species. Variable absorption and interpatient variation of serum levels are the main problems. The role for itraconazole in prophylaxis, primary treatment, and salvage therapy of invasive aspergillosis needs further controlled studies but seems promising.1 Preliminary uncontrolled studies showed itraconazole to be effective in the treatment of disseminated fungal infections in immunocompromised hosts.10,11 Itraconazole may also be used as maintenance therapy for susceptible strains of aspergillus after the initial treatment and clinical response to amph-B.11 Concomitant use with amph-B has a potential for antagonism and adverse drug interactions.12
A successful management with remarkable clinical and radiological improvement was achieved by pleural drainage and irrigation, intrapleural and intravenous amph-B followed by oral itraconazole therapy. Therefore, we recommend combined treatment using mechanical drainage and systemic and topical administration of antifungal agents.