Tuberculosis: a spectre has returned.

UNLABELLED: The recommendations for the treatment of sporotrichosis were derived primarily from multicenter, nonrandomized treatment trials, small retrospective series, and case reports; no randomized, comparative treatment trials have been reported. Most cases of sporotrichosis are non life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. The treatment of choice for fixed cutaneous or lymphocutaneous sporotrichosis is itraconazole for 36 months. The preferred treatment for osteoarticular sporotrichosis also is itraconazole, but therapy must be continued for at least 12 months. Pulmonary sporotrichosis responds poorly to treatment. Severe infection requires treatment with amphotericin B; mild to moderate infection can be treated with itraconazole. Meningeal and disseminated forms of sporotrichosis are rare and usually require treatment with amphotericin B. AIDS patients most often have disseminated infection and require life-long suppressive therapy with itraconazole after initial use of amphotericin B. OVERVIEW: Sporotrichosis is caused by the dimorphic fungus Sporothrix schenckii, which is found throughout the world in decaying vegetation, sphagnum moss, and soil. The usual mode of infection is by cutaneous inoculation of the organism. Pulmonary and disseminated forms of infection, although uncommon, can occur when S. schenckii conidia are inhaled. Infections are most often sporadic and usually associated with trauma during the course of outdoor work. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos. Outbreaks have been well-described and often are traced back to activities that involved contaminated sphagnum moss, hay, or wood. Most cases of sporotrichosis are localized to the skin and subcutaneous tissues. Dissemination to osteoarticular structures and viscera is uncommon and appears to occur more often in patients who have a history of alcohol abuse or immunosuppression, especially AIDS. Spontaneous resolution of sporotrichosis is rare, and treatment is required for most patients. Although sporotrichosis localized to skin and subcutaneous tissues is readily treated, management of osteoarticular, other localized visceral, and disseminated forms of sporotrichosis is difficult. OBJECTIVE: The objective of these guidelines is to provide recommendations for the treatment of various forms of sporotrichosis. OUTCOMES: The desired outcomes of treatment include eradication of S. schenckii from tissues, resolution of symptoms and signs of active infection, and return of function of involved organs. In persons with AIDS, eradication of the organism may not be possible, but clinical resolution should be attained and subsequently maintained with suppressive antifungal therapy. EVIDENCE: The English-language literature on the treatment of sporotrichosis was reviewed. Although randomized, blinded, controlled treatment trials were sought, none were found to have been performed for the treatment of sporotrichosis. Therefore, most weight was placed on those reports that were derived from multicenter trials of specific treatment modalities for sporotrichosis. Small series from a single institution and individual case reports were accorded less importance. VALUES: The highest value was placed on clinical efficacy and the ability of the antifungal regimen to eradicate the organism, but safety, tolerability, and cost of therapy were also valued. BENEFITS AND COSTS: The benefits of successfully treating sporotrichosis accrue primarily for the patient. Because this infection is not spread from person-to-person, public health aspects of treatment are of minor importance. Most forms of sporotrichosis are not life-threatening; thus, therapy is aimed at decreasing morbidity, improving quality of life, and allowing the patient to return to occupational and familial pursuits. (ABSTRACT TRUNCATED)

AIDS-Related Opportunistic Infections↗

PubMed2000

Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America.

An 8-person subcommittee of the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group evaluated available data on the treatment of cryptococcal disease. Opinion regarding optimal treatment was based on personal experience and information in the literature. The relative strength of each recommendation was graded according to the type and degree of evidence available to support the recommendation, in keeping with previously published guidelines by the Infectious Diseases Society of America (IDSA). The panel conferred in person (on 2 occasions), by conference call, and through written reviews of each draft of the manuscript. The choice of treatment for disease caused by Cryptococcus neoformans depends on both the anatomic sites of involvement and the host's immune status. For immunocompetent hosts with isolated pulmonary disease, careful observation may be warranted; in the case of symptomatic infection, indicated treatment is fluconazole, 200-400 mg/day for 36 months. For those individuals with non-CNS-isolated cryptococcemia, a positive serum cryptococcal antigen titer >1:8, or urinary tract or cutaneous disease, recommended treatment is oral azole therapy (fluconazole) for 36 months. In each case, careful assessment of the CNS is required to rule out occult meningitis. For those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/day for 6-12 months) is an acceptable alternative. For patients with more severe disease, treatment with amphotericin B (0.5-1 mg/kg/d) may be necessary for 6-10 weeks. For otherwise healthy hosts with CNS disease, standard therapy consists of amphotericin B, 0.7-1 mg/kg/d, plus flucytosine, 100 mg/kg/d, for 6-10 weeks. An alternative to this regimen is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 2 weeks, followed by fluconazole (400 mg/day) for a minimum of 10 weeks. Fluconazole "consolidation" therapy may be continued for as along as 6-12 months, depending on the clinical status of the patient. HIV-negative, immunocompromised hosts should be treated in the same fashion as those with CNS disease, regardless of the site of involvement. Cryptococcal disease that develops in patients with HIV infection always warrants therapy. For those patients with HIV who present with isolated pulmonary or urinary tract disease, fluconazole at 200-400 mg/d is indicated. Although the ultimate impact from highly active antiretroviral therapy (HAART) is currently unclear, it is recommended that all HIV-infected individuals continue maintenance therapy for life. Among those individuals who are unable to tolerate fluconazole, itraconazole (200-400 mg/d) is an acceptable alternative. For patients with more severe disease, a combination of fluconazole (400 mg/d) plus flucytosine (100-150 mg/d) may be used for 10 weeks, followed by fluconazole maintenance therapy. Among patients with HIV infection and cryptococcal meningitis, induction therapy with amphotericin B (0.7-1 mg/kg/d) plus flucytosine (100 mg/kg/d for 2 weeks) followed by fluconazole (400 mg/d) for a minimum of 10 weeks is the treatment of choice. After 10 weeks of therapy, the fluconazole dosage may be reduced to 200 mg/d, depending on the patient's clinical status. Fluconazole should be continued for life. An alternative regimen for AIDS-associated cryptococcal meningitis is amphotericin B (0.7-1 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 6-10 weeks, followed by fluconazole maintenance therapy. Induction therapy beginning with an azole alone is generally discouraged. Lipid formulations of amphotericin B can be substituted for amphotericin B for patients whose renal function is impaired. Fluconazole (400-800 mg/d) plus flucytosine (100-150 mg/kg/d) for 6 weeks is an alternative to the use of amphotericin B, although toxicity with this regimen is high. In all cases of cryptococcal meningitis, careful attention to the management of intracranial pressure is imperative to assure optimal c

AIDS-Related Opportunistic Infections↗