Aspergillosis, treatment

The glucan synthase inhibitor caspofungin (intravenous formulation) is new on the market for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other therapies. During the clinical trials fever, infused vein complications, nausea, vomiting and in combination with cyclosporin mild transient hepatic side effects were observed. Interaction with tacrolismius and with potential inducer or mixed inducer/inhibitors of drug clearance was also seen. 

Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med 2006 173 707-717. 

Caspofungin is indicated for treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies such as amphotericin B. 

Posaconazole, launched last year in the UK, is the newest member of the azole class of antifungal agents to reach the market. It is indicated for the treatment and prophylaxis of a range of invasive fungal infections, including aspergillosis,... 

Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik J-A, Wingard JR, Patterson TF. (2008) Treatment of aspergillosis Clinical practice guidelines of the infectious diseases society of America. Clin Infect Dis 46 327-360. 

Lipid-based formuiations - For use in patients refractory to conventional amphotericin B deoxycholate therapy or where renal impairment or unacceptable toxicity precludes the use of the deoxycholate formulation for the treatment of invasive fungal infections (lipid complex) for the treatment of invasive aspergillosis (cholesteryl) for the treatment of infections caused by... 

Invasive aspergillosis For the treatment of invasive aspergillosis. In clinical trials, the majority of isolates recovered were Aspergillus fumigatus. There were a small... 

For the treatment of blastomycosis, histoplasmosis, and aspergillosis, itraconazole can be given as oral capsules or IV. The safety and efficacy of the injection administered for more than 14 days are not known. 

Invasive aspergillosis For the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (ie, amphotericin B, lipid formulations of amphotericin B, itraconazole). Caspofungin has not been studied as initial therapy for invasive aspergillosis. 

Owing to its inferior pharmacokinetic profile, voriconazole is dosed twice daily i.v. doses of 6 mg/kg are used on the first day, followed by 200 mg orally or continued i.v. dosing at 4 mg/kg. Voriconazole is recommended for the treatment of adults with invasive aspergillosis and can be used for rare infections caused by Fusarium spp. and Scedosporium apiospermum, where treatment with other agents has failed. Its primary use is in immunocompromised patients with progressive, life-threatening infections. 

If it is decided to treat an upper RTI in general 5-7 days treatment suffices. In lower RTI generally 10-14 days are recommended. Two to three weeks of treatment is advised for Staphylococcus aureus, Legionella pneumophila. Pseudomonas aeruginosa, Pneumocystis jiroveci (formerly carinii) and severe aspiration-pneumonia. Tuberculosis, actinomycosis, nocardiosis, aspergillosis, melioidosis and anaerobic lung abscesses require many months of treatment. 

Amphotericin B remains the drug of choice in the treatment of invasive aspergillosis, locally invasive mucormycosis, and many disseminated fungal infections occurring in immunocompromised hosts (the patient population most at risk for serious fungal infections). For example, the febrile neutropenic oncology patient with persistent fever despite empirical antibacterial therapy is best treated with amphotericin B for possible Candida spp. sepsis. 

Blastomycosis, histoplasmosis, sporotrichosis, paracoccidioidomycosis, and chromomycosis are better treated with itraconazole than ketoconazole, although ketoconazole remains an alternative agent. Ketoconazole is ineffective in the treatment of cryptococcosis, aspergillosis, and mucormycosis. Candidemia is best treated with fluconazole or amphotericin B. 

Voriconazole is similar to itraconazole in its spectrum of action, having excellent activity against Candida sp (including fluconazole-resistant species such as C krusei) and the dimorphic fungi. Voriconazole is less toxic than amphotericin and is the treatment of choice for invasive aspergillosis. 

Fatal aspergillosis with a thyroid gland abscess occurred in a 74-year-old man after treatment with prednisolone for polymyalgia rheumatica (338). 

Amphotericin B In vivo—mice In vivo—mice In vivo—mice Treatment of pulmonary and systemic Cryptococcus neoformans infections Prophylaxis of pulmonary aspergillosis Pharmacokinetics, effect of lipid composition [91] [92] [93]... 

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. 

Many of the clinical studies conducted so far have examined the efficacy of micafungin as a prophylaxis and treatment for mycoses. One of representative studies on the treatment of invasive aspergillosis (IA) is summarised below.16... 

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