Aspergillosis prevention

Marr KA, Boeckh M, Carter RA, et al. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004 39 797-802. Masur H, Kaplan JE, Holmes KK, et al. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Clin Infect Dis 2000 30 S29-S65. 

The use of prophylactic antifungal therapy to prevent primary infection or reactivation of aspergillosis during subsequent courses of chemotherapy is controversial. 

Caspofungin Blocks 3-glucan synthase Prevents synthesis of fungal cell wall Fungicidal Candida sp also used in aspergillosis IV only duration, 11-15 h Toxicity Minor gastrointestinal effects, flushing Interactions Increases cyclosporine levels (avoid combination)... 

Caspofungin is indicated for treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies such as amphotericin B. The use of prophylactic antifungal therapy to prevent primary infection or reactivation of aspergillosis during subsequent courses of chemotherapy is controversial. 

Erjavec Z, Woolthuis GM, de Vries-Hospers HG, Sluiter WJ, Daenen SM, de Pauw B, Halie MR. Tolerance and efficacy of amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haema-tological patients. Eur J Clin Microbiol Infect Dis 1997 16(5) 364-8. 

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. 

The management of a pharmacokinetic interaction of voriconazole with everolimus has been described in a 65-year-old man who underwent orthotopic liver transplantation complicated by intestinal perforation, sepsis, and acute renal insufficiency [32 ]. He received intravenous fluconazole 400 mg followed by 100 mg/day and oral everolimus 0.75 mg bd the steady-state Cmin of everolimus was satisfactory. On day 72 after transplantation, because of invasive aspergillosis, antifungal therapy was switched to intravenous voriconazole 400 mg bd on the first day followed by 200 mg bd to prevent drug toxicity the dosage of... 

Rhame FS. Prevention of nosocomial aspergillosis. J Hosp Infect 1991 18 466-472. 

---