Is there any documentation concerning irrigation with Fungizone (amphotericin B) and Diflucan (fluc

Fråga: Is there any documentation concerning irrigation with Fungizone (amphotericin B) and Diflucan (fluconazole)?

A patient who underwent by-pass surgery developed a fungal infection post-surgically in the wound.

Sammanfattning: There is documentation concerning local antifungal treatment with amphotericin B irrigation. Doses from 5 or 10 mg initially into the pleural cavity have been suggested. The solution has to be properly prepared or it could precipitate. The choice between systemic and/or local treatment is a delicate clinical matter.

Svar: An old article, which describes a group of 15 patients with Candida endocarditis, emphasizes that medical or surgical treatment alone result in a mortality of approximately 80 per cent while combined treatment result in 20 per cent mortality (1).

A more recent case report describes a patient with massive hemoptysis, secondary to an intracavitary aspergilloma (2). This patient was successfully treated by computed tomography-guided placement of a Cope-loop catheter with daily instillation of amphotericin B and cavitary irrigation. Over a 15-day period, this regimen resulted in cessation of hemoptysis and radiographic resolution of the aspergilloma. No complications were encountered.

An information package was, provided by the manufacturer of amphotericin B (3). In a case report the authors recommend the use of amphotericin in the treatment of mycotic empyema. Amphotericin was infused directly into the pleural cavity, first at 10 mg daily, rising to 15 mg and then 25 mg, after thoracocentesis and washing of the pleural cavity with 5 per cent glucose solution. Local treatment was continued for about a month, daily at first, then on alternate days. Finally, when the fluid had become sterile, local treatment was given every 3-4 days, until the pleural complication was completely resolved (4).

Six patients with pulmonary aspergillomas were treated with percutaneous instillation of intracavitary amphotericin B. It was diluted in 10-15 ml 5 per cent Dextrose and injected percutaneously using fluoroscopic guidance. Daily dose was initially 5 mg, then 10, 20, 30, 40 and 50 mg. Thereafter 50 mg was instilled two or three times a week (total 500 mg). Two patients had percutaneous catheters for the administration. Four patients received the full course and improved clinically; negative cultures were found in three (5).

There are many studies found in Medline that compare oral treatment and local irrigation in fungal urinary tract infections. The most recent article compares the efficacy and safety of oral fluconazole with bladder irrigation with amphotericin B in a randomized trial with 109 hospitalized elderly patients. The bladder irrigation was performed with amphotericin B > 10000 cfu/mL or urine. Two days after completion of treatment, funguria was eradicated in 96 per cent of the patients treated with amphotericin B and 73 per cent of those treated with fluconazole (p<.05). However, one month after study enrollment, the mortality rate associated with all causes was greater among patients who were treated with amphotericin B bladder irrigation than among those who received oral fluconazole therapy (41 per cent versus 22 per cent, respectively). This finding suggests that local therapy may be associated with poorer survival. The proportion of patients without funguria at 1 month after study enrollment was similar in the two groups (6).

According to a pharmaceutical expert (7), it is crucial to prepare the solution properly. Amphotericin B could be solved in enough amount (approximately 1.0 mg drug per liter) glucose or water, but will precipitate with saline. For further information see (3) "Practical guidelines for preparing and administering amphotericin B".

We have found no specific information about irrigation with fluconazole. Fluconazole is to be solved in saline, thus it cannot be mixed with amphotericin B. 1 Turnier E, Kay JH, Bernstein S, Mendez AM, Zubiate P. Surgical treatment of Candida endocarditis. Chest 1975; 67: 262-268 2 Klein JS, Fang K, Chang MC. Percutaneous transcatheter treatment of an intracavitary aspergilloma. Cardiovasc Intervent Radiol 1993; 16: 321-324 3 Via Eva Lena Hellmin, Bristol-Myers Squibb AB, Pharmaceutical Group, Regulatory Affairs 4 Sartori F et al. Sulla terapia degli empiemi sostenuti da miceti. Chirurgia Italiana 1968; 20: 861 5 Hargis JL et al. Intracavitary amphotericin B in the treatment of symptomatic pulmonary aspergillomas. Am J Med 1980; 68: 389 6 Jacobs LG, Skidmore EA, Freeman K, Lipschultz D, Fox N. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis 1996; 23: 30-35 7 Personal communication (KH) 981027 with Örjan Ericsson, MSPharm, PhD, Sjukhusapoteket, Huddinge University Hospital