Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients. Cryptococcal meningitis is an important cause of central nervous system disease and death in patients with AIDS. Although the introduction of amphotericin B has greatly improved the prognosis of patients with cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing. The discovery of the additive effects of amphotericin B and flucytosine in cryptococcosis resulted in some improvement in efficacy and reduction in amphotericin B-related toxicity. However, approximately 30% of patients with cryptococcal meningitis still fail to respond to therapy. Ketoconazole has not proved useful in treating cryptococcal meningitis. Accumulating evidence suggests that the antifungal triazoles fluconazole, itraconazole, and SCH 39304 represent an advance in the treatment of cryptococcal meningitis, particularly in AIDS patients. Preliminary clinical trials in patients with and without AIDS have indicated that fluconazole and intraconazole are effective and well tolerated as either initial or maintenance therapy. Two large comparative trials of fluconazole and amphotericin B in patients with cryptococcal meningitis (mostly those with AIDS) are under way.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Evaluation of immunological infertility.

To evaluate the frequency with which immunological factors are associated with infertility, 92 couples with unexplained infertility were studied by using assays to detect anti-sperm antibodies (ASA), human leukocyte antigen tissue types (HLA), lymphocytotoxic antibodies (LCA), and inhibitors of mixed lymphocyte culture (MLC) and mouse blastocyst assay (MBA). Seventy-three of the women had blood assayed for antiphospholipid antibodies (APA). The frequencies of APA, ASA, LCA, inhibitors of MLC and MBA, as well as HLA associations previously reported to be related to infertility (B locus blanks, single DQ locus in offspring, greater than 1 DR sharing between mates) among 92 infertile couples were compared with those observed among 41 fertile control couples. No significant differences in the frequencies of APA, ASA, MBA, and HLA associations between fertile and infertile couples were observed. Fertile couples demonstrated the presence of wife anti-husband LCA and MLC inhibitors more frequently than did infertile couples (51% vs. 8%, P = 0.0001 and 29% vs. 4%, P = 0.002, respectively). While APA, ASA, HLA tissue typing, LCA, and MLC and MBA have been previously reported as being markers of autoimmune and alloimmune responses relating to reproductive outcome, the current data suggest that more specific markers are necessary to diagnose immunological components of infertility.

Adult↗

PubMedDate not supplied

Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients.

OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.

Acquired Immunodeficiency Syndrome↗