• 8
    May
  • Fluconazole in the Treatment of Persistent Coccidioidomycosis: MATERIALS AND METHODS

Patients were enrolled in this study at the University of California San Diego Medical Center and the VA Medical Center from July 1986 to March 1987. Participation in the study was offered to all known patients who had a diagnosis of coccidioidomycosis proven by culture or histology, and who had persistent pulmonary or disseminated infection. Patients with primary pulmonary coccidi­oidomycosis were excluded. Some patients had previously failed to respond to or reactivated following treatment with amphotericin В or ketoconazole. All patients had either pulmonary infection for more than a year or disseminated disease with cultures positive for С immitis or spherules seen on biopsy in conjunction with serum complement-fixation antibodies against Сimmitis antigens. Patients with immunosuppressive disease, hepatitis, or pregnancy were excluded.

Patients

Fourteen patients met the criteria to be enrolled in this series. The age range was 25 to 83 years; all patients but one were older than 30 years, and four were over 60 years old. There were ten men and four women. Nine patients were white, three were hispanic, and one each was black and American Indian. Coccidioidal infection was confined to the lungs in four patients, was extrapulmonary in seven patients, and involved both in three patients. The pulmonary involvement consisted of a single chronic cavity in two patients, chronic fibrocavitary disease in two patients, or hilar and mediastinal adenopathy (one patient also had an infiltrate) with dissemination to soft tissue in three patients. No patient had primary pneumonia, which is often self-limited. The sites of extrapulmonary dissemina­tion were multiple in most cases and were as follows: skin or soft tissue, five patients; visceral organs, five patients; lymph nodes, four patients; and bone or synovium, two patients. Soft tissue involvement was adjacent to cutaneous lesions in five patients and to surgical wounds in two patients. In one case, there was infection of a deep wound following nephrectomy for renal cell carcinoma. The involved visceral organ was the liver in one, the peritoneum in two, and the epididymis in two patients. Of the two patients with skeletal involvement, one had several bony lesions, and one had synovitis of the knee.
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Treatment

Patients were started on 50 mg of fluconazole per day. If there was not a satisfactory clinical response in two weeks to ten months, the dosage was increased to 100 mg/day. In each case the medication was administered once per day in the morning. Patients were examined at least monthly. Patients were questioned about side effects, compliance, and symptoms; their remaining capsules were counted. Monthly laboratory studies included the following: com­plete blood cell count with leukocyte, differential, and platelet counts; prothrombin time; partial thromboplastin time; SCOT; SCPT; LDH; alkaline phosphatase; bilirubin; blood urea nitrogen; serum creatinine; and urinalysis, including microscopic examination and serologic studies which were performed at either the University of California, Davis, or the VA Medical Center, San Diego.

Evaluation of the response to treatment included analysis of the clinical response, the radiographic response, the serologic response, and the ability to recover the organism from infected tissue. A semiquantitative system, previously developed to measure progress under drug treatment, was used to record the severity of involve­ment at the bedside (by the clinical score) and radiographically (by radiographic score). Clinical scoring by the presence of symptoms was as follows:

Fever

1

Pain

1

Productive cough

1

Hemoptysis

1

Swelling

1

Pleural rub

1

Pulmonary radiographic scoring was as follows:

Size

Less than
5
cm

1

Less than right
upper lobe zone

2

More than above

3

Distribution

Unilateral

1

Bilateral

2

Miliary

3

Cavitation

1

Hilar adenopathy

1

Mediastinal
adenopathy

2

Small effusion

1

Large eflusion

2

To determine the radiographic score, add scores for size and distribution and for any additional intrathoracic abnormalities.) Failure to respond is defined as persistent positive cultures for С immitis or the development of new coccidioidal lesions. Treatment was discontinued if the patient either failed to respond to the 100- mg/day dosage, or had complete clinical resolution or stability with negative culture. pharmacy uk

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