GENERAL MEASURES 99% of acute primary histoplasmosis resolve spontaneously; symptomatic treatment only
DRUG(S) OF CHOICE
. Disseminated histoplasmosis
. Amphotericin B - test dose is 1 mg followed by 0.25 mg/kg/dose, which may be slowly increased to 0.5
mg/kg/dose. Cumulative dose to 1-2 gm (at least 35 mg/kg is indicated).
. Ketoconazole or itraconazole for mild disease
- Ketoconazole: Induction therapy with 400 mg/day for 3 days, then maintenance therapy 200 mg or 400 mg a day
- Itraconazole: Induction therapy with 200 mg twice a day for 3 days, then 200 mg once or twice daily
. AIDS patients
. Itraconazole for mild disease: Induction therapy with 600 mg/day for 3 days, then 400 mg/day. Drug of choice for primary and maintenance therapy is itraconazole. Ketoconazole is not effective in AIDSrelated
histoplasmosis. Maintenance therapy with itraconazole 400 mg/day or amphotericin-B 50-100 mg weekly (1 mg/kg).
. Chronic cavitary histoplasmosis
. Amphotericin-B for severe or moderately severe disease, 2.0-2.5 g cumulative
. Ketoconazole or itraconazole for mild disease
- Ketoconazole: Induction therapy with 400 mg/day for 3 days, then maintenance therapy 200 mg or 400 mg/day
- Itraconazole: Induction therapy with 200 mg twice daily for 3 days, then 200 mg once or twice daily
. Acute pulmonary histoplasmosis
. Amphotericin B for severe or moderately severe disease; test dose is 1 mg followed by 0.25 mg/kg/dose
which may be slowly increased to 0.5 mg/kg/dose. Cumulative dose at least 35 mg/kg.
. Ketoconazole or itraconazole for mild disease
- Ketoconazole: Induction therapy with 400 mg/day for 3 days, then maintenance therapy 200 mg or 400 mg/day
- Itraconazole: Induction therapy with 200 mg twice daily for 3 days, then 200 mg once or twice daily
. Duration of treatment
. Optimal duration of treatment with antifungals has not been established
. Disseminated histoplasmosis - 6 months course
. Chronic cavitary histoplasmosis - at least 12 months course with stable CXR fi ndings over 3-6 months
. Acute pulmonary histoplasmosis - 2-3 month course
. AIDS-related or relapsed - chronic, lifelong, maintenance therapy
. Mediastinal granuloma
. Can mimic fi brosing mediastinitis, may respond to treatment with amphotericin B
. Fibrosing mediastinitis
. Has no active infection present and is not treatable
Contraindications: No contraindications to treatment in patients with progressive cavitary disease or
disseminated histoplasmosis. The latter has a mortality rate of 80% if untreated.
Precautions:
. Amphotericin B
. Dosage probably does not need to be adjusted for creatinine clearance
. It is nephrotoxic. Renal function must be monitored closely. Monitor electrolytes, especially potassium and magnesium.
. Rigors can be prevented by pre-infusion meperidine. Fever and chills can be diminished by pre-infusion
dose of acetaminophen plus diphenhydramine.
. Ketoconazole
. Is associated with gastrointestinal upset
. May inhibit testosterone synthesis and should be used with caution in patients with underlying hepatic
dysfunction
ALTERNATIVE DRUGS
β’ Fluconazole has not been approved for histoplasmosis therapy. Fluconazole is undergoing investigational studies in its use for chronic pulmonary and disseminated histoplasmosis. Preliminarily, fl uconazole doses of 400 mg/day or higher may be necessary for therapeutic outcome.
β’ Liposomal amphotericin may be used if amphotericin nephrotoxicity encountered
PATIENT MONITORING Renal function and liver chemistries every 1-2 months for chronic therapy patients; chest x-ray to evaluate therapy response at regular intervals
PREVENTION/AVOIDANCE Maintenance therapy is required in AIDS
POSSIBLE COMPLICATIONS
β’ Bronchial, tracheal or esophageal obstruction secondary to adenopathy, broncholithiasis
β’ Pulmonary, splenic and hepatic calcifi cations, rarely pericarditis, pleurisy or effusion
β’ CNS histoplasmosis (rare): Chronic meningitis or intracranial histoplasmosis
β’ Endocarditis involving aortic or mitral valves
β’ Pericardial effusions (sterile exudates) not thought to be secondary to hematogenous spread
β’ Fibrosing mediastinitis can cause stenosis of vascular and bronchial structures within the mediastinum
causing pulmonary hypertension, superior vena cava syndrome and bronchial obstruction
β’ Acute renal failure and hepatic dysfunction secondary to medications
β’ Amphotericin induced hypokalemia
β’ Relapse occurring in the immunocompromised or inadequately treated patient with disseminated histoplasmosis
EXPECTED COURSE/PROGNOSIS
β’ Primary histoplasmosis - 99% resolve spontaneously
β’ The prognosis for chronic cavitary pulmonary histoplasmosis is determined by the loss of lung parenchyma
and pulmonary function
β’ Treatment of disseminated disease in AIDS/non-AIDS cases does improve outcome with ketoconazole having > 80% success rate and amphotericin B being 60-100% successful. Despite maintenance therapy, AIDS patients, have 10-50% relapse rate.