Coccidioidomycosis treatment

Ketoconazole (KC) as the first systemlcally-active azole antifungal has been the subject of a number of reviews including the general management of fungal disease,and its efficacy in superficial and systemic infections 0 it was the subject of a number of papers at a recent symposium, The use of KC in the treatment of coccidioidomycosis has been recently reviewed in detail, 2 gjid parallel reviews of the indications for coccidioidomycosis treatment in general, 5 and the use of AMB and miconazole (MC) 5 in particular have been presented. 

A marked improvement is generally noted after 4—8 weeks of treatment. Treatment is often continued until a total dose of 3 g is reached. In the case of coccidioidomycosis, for example, treatment with 0.4—0.8 mg/kg/d may last months. The polyene is adrninistered intrathecaHy to treat Coccidioides meningitis. However, the results are only moderate. It is very important to check renal and hepatic function during treatment with amphotericin B. 

The patient s serum titer for coccidioidomycosis returns as greater than 1 32. Based on the information presented, select an appropriate treatment plan for the patient s coccidioidomycosis. 

Specific antifungals (and their usual dosages) for the treatment of coccidioidomycosis include amphotericin B IV (0.5 to 1.5 mg/kg/day), ketocona-zole (400 mg orally daily), IV or oral fluconazole (usually 400 to 800 mg daily, although dosages as high as 1,200 mg/day have been utilized without complications), and itraconazole (200 to 300 mg orally twice daily as either capsules or solution). If itraconazole is used, measurement of serum concentrations may be helpful to ascertain whether oral bioavailability is adequate. 

Amphotericin B is generally preferred as initial therapy in patients with rapidly progressive disease, whereas azoles are generally preferred in patients with subacute or chronic presentations. Lipid formulations of amphotericin B have not been extensively studied for coccidioidomycosis but can offer a means of giving more drug with less toxicity. Treatments for primary respiratory disease (mainly symptomatic patients) are 3- to 6-month courses of therapy. 

Use only to treat severe systemic fungal disease Coccidioidomycosis, candidiasis, cryptococcosis, pseudoallescheriosis (petriellidiosis, allescheriosis), paracoccidioidomycosis, and for the treatment of chronic mucocutaneous candidiasis. 

Itraconazole is most useful in the long-term suppressive treatment of disseminated histoplasmosis in AIDS and in the oral treatment of nonmeningeal, non-life-threatening blastomycosis. It appears to be the drug of choice for all forms of sporotrichosis except meningitis and may have a lower relapse rate in the treatment of disseminated coccidioidomycosis than does fluconazole. 

Unlabeled Uses Treatment of coccidioidomycosis, cryptococcosis, fungal pneumonia, onychomycosis, ringworm of the hand, septicemia... 

The spectrum of action of azole medications is broad, including many Candida species, C neofbrmans, the endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), the dermatophytes, and, in the case of itraconazole and voriconazole, even aspergillus infections. They are also useful in the treatment of intrinsically amphotericin-resistant organisms such as P boydii. 

Indications Treatment of the following systemic fungal infections Candidiasis Chronic mucocutaneous candidiasis Oral thrush Candiduria Blastomycosis Coccidioidomycosis Histoplasmosis Chromomycosis Paracoccidioidomycosis... 

Antifungal spectrum It is the drug of choice for Cryptococcus neoformans. for candidemia, and for coccidioidomycosis. Fluconazole has also been shown to be useful in the treatment of blastomycosis, candidiasis, and histoplasmosis. These infections are characterized by a high rate of relapse, and fluconazole has proved effective in chronic ambulatory treatment. 

Itraconazole [it ra KON a zole] is a recent addition to the azole family of antifungal agents. Like fluconazole it is a synthetic triazole, and it also lacks the endocrinologic side effects of ketoconazole. Its mode of action is the same as that of the other azoles. Itraconazole is now the drug of choice for the treatment of blastomycosis. Unlike ketoconazole, it is effective in AIDS-associated histoplasmosis. However, current studies show that it may also be effective in the treatment of aspergillosis, candidemia, coccidioidomycosis, and cryptococcosis. Thus it has a broad antifungal spectrum. 

Impaired cell-mediated immunity leaves the host prey to many (opportunistic) infections including candidiasis, coccidioidomycosis, cryptosporidiosis, cytomegalovirus disease, herpes simplex, histoplasmosis, Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis (with multiply-resistant organisms). Treatment of these conditions is referred to elsewhere in this text for a comprehensive review of the antinticrobial prophylaxis of opportunistic infections in patients with HIV infection, readers are referred to Kovacs Masur 2000 New England Journal of Medicine 342 1416. 

Clemons KV, Stevens DA. Comparative efficacy of amphotericin B colloidal dispersion and amphotericin B deoxycholate suspension in treatment of murine coccidioidomycosis. Antimicrob Agents Chemother 1991 35 1829-33. 

Therapy for coccidioidomycosis is difficult, and the results are unpredictable. Guidelines are available for treatment of this disease however, optimal treatment for many forms of this disease still generates debate. The efficacy of antifungal therapy for coccidioidomycosis is often less certain than that for other fungal etiologies, such as blastomycosis, histoplasmosis, or cryptococcus, even when in vitro susceptibilities and the sites of infections are similar. The refractoriness of coccidioidomycosis may relate to the ability of C. immitis spherules to release hundreds of endospores, maximally challenging host defensesFortunately, only approximately 5% of infected patients require therapy. ... 

Specific antifungals (and their usual dosages) for the treatment of coccidioidomycosis include intravenous amphotericin B (0.5 to 0.7 mg/... 

Because of the lack of prospective, controlled trials, there is continued disagreement among experts in endemic areas whether patients with coccidioidomycosis should be treated and, if so, which ones and for how long. The excellent tolerability of oral azoles has lowered the threshold for deciding to treat primary infection, and some clinicians treat all primary infections. Rationale for treating a primary self-limiting infection include the ability to lessen the morbidity associated with the acute infection and the possible ability to reduce the development of more serious complications. However, there is currently no evidence that treatment of the primary infection accomplishes either of these goals. ... 

Fluconazole is the drug of choice for treatment of coccidioidal meningitis because of much less morbidity than with intrathecal amphotericin B. In other forms of coccidioidomycosis, fluconazole is comparable to itraconazole. Fluconazole has activity against histoplasmosis, blastomycosis, sporotrichosis, and ringworm, but response is less than with equivalent doses of itraconazole. Fluconazole is not effective in the prevention or treatment of aspergillosis. As with other azoles, with the possible exception of posa-conazole, there is no activity in mucormycosis. 

Amphotericin B is the treatment of choice for mucormycosis and is used for initial treatment of cryptococcal meningitis, severe or rapidly progressing histoplasmosis, blastomycosis, coccidioidomycosis, penicilliosis mameffei, and in patients not responding to azole therapy of invasive aspergillosis, extracutaneous sporotrichosis, fusariosis, altemariosis, and trichosporonosis. Amphotericin B is given once weekly to prevent relapse in patients with AIDS who have been treated successfully for cryptococcosis or histoplasmosis. 

A later study in 8 other patients confirmed that itraconazole levels were reduced by rifampicin but the clinical outcome depended on the mycosis being treated. Four out of 5 patients responded to treatment for a Cryptococcus neoformans infection, despite undetectable itraconazole levels, apparently because in vitro there is synergy between the two drugs. In contrast, 2 patients with coccidioidomycosis failed to respond, and 2 others with eryptoeoeeosis suffered a relapse or persistenee of seborrhoeic dermatitis (possibly due to M. furfur) while taking both drugs. In a pa-... 

Two patients tatong phenytoin and two taking phenytoin with car-bamazepine either did not respond to treatment with itraconazole 400 mg daily for aspergillosis, coccidioidomycosis or cryptococcosis, or suffered a relapse. All of them had undetectable or substantially reduced serum itraconazole levels compared with other patients taking itraconazole alone. Two other patients also had very low itraconazole serum levels while taking phenytoin and phenobarbital."... 

Lopez F, Hancock EW. Nausea and malaise during treatment of coccidioidomycosis. Hasp Pract ( 997) 32, 21-2. 

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