Cryptococcal meningitis in AIDS occurring despite systemic antifungal therapy

1992 ◽  
Vol 24 (1) ◽  
pp. 107-108 ◽  
Author(s):  
R.J. Coker ◽  
D. Moulopoulos ◽  
J. Main ◽  
S.M. Murphy ◽  
A.J. Pinching ◽  
...  
2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Melissa A. Rolfes ◽  
Joshua Rhein ◽  
Charlotte Schutz ◽  
Kabanda Taseera ◽  
Henry W. Nabeta ◽  
...  

Abstract Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.


1994 ◽  
Vol 28 (2) ◽  
pp. 261-270 ◽  
Author(s):  
Thaddeus H. Grasela ◽  
Mary T. Pasko ◽  
S. Diane Goodwin ◽  
Cynthia A. Walawander ◽  
Nicole Blackwelder ◽  
...  

OBJECTIVE: To evaluatethe prescribing patternsof antifungal agents in the hospital setting after the introduction of fluconazole, a new broad-spectrum bis-triazole antifungal agent. Also comparedare the prescribing patterns of antifungal agents prior to (phase I) and following (phase II) fluconazole marketing. DESIGN: A prospective cohort of hospitalized patients prescribed topical or systemic antifungal agents. Data were collected from December 1990 to April 1991. SETTING: Fifty-seven hospitals ranging in size from 100 to more than 500 beds. Sixty-three percentare affiliated with medical schools. PATIENTS: Participating pharmacists consecutively identified 15 patients receiving systemic antifungal therapy and 5 patients receiving topical antifungal therapy. INTERVENTIONS: Observational data on patient antifungal therapy, risk factors for fungal infections, comorbidities, concurrent medications, and culture data were collected. MEASURES: Differences in prescribing patterns before and after the marketing of fluconazole were assessed using t-tests and chi-square tests. RESULTS: Of 818 patients studied, 615 (75.2 percent) received systemic antifungal therapy. Five hundred forty-six patients received a single antifungal agent; 348 (63.7 percent) received fluconazole, 105 (19.2 percent) received ketoconazole, 92 (16.8 percent) received amphotericin B, and 1 (0.2 percent) received flucytosine. Sixty-nine patients received two or more systemic agents either concurrently or consecutively. The use of parenteral amphotericin B, alone or in combination with flucytosine and/or an azole, declined from 56.8 percent in the phase I study to 24.2 percent in the current study. The use of parenteral therapy also declined from 56.8 to 40.2 percent. Ketoconazole was used in more than 90 percent of the oral and esophageal infections in the phase I study, but its use declined to only 33 percent in this study. Fluconazole was used most frequently across all sites of presumed or documented infections, with the exception of fungemia. Of the presumed or proven systemic or blood infections, amphotericin B was used alone or in combination in 48.4 percent of the patients and fluconazole was used exclusively in 39.0 percent of the patients. Fluconazole was used more often than amphotericin B (22 vs. 3 patients, respectively) for prophylaxis of systemic infections. The overall use of antifungal prophylaxis also increased from the phase I (9.5 percent) to phase II (13.7 percent). CONCLUSIONS: The introduction of fluconazole had a major impact on the prescribing patterns of antifungal therapy. Although amphotericin B remained the preferred agent for treatment of suspected or proven systemic, central nervous system, or blood infections, use of fluconazole for these indications approached nearly 40 percent. Further studies are needed to address the role of fluconazole in the prophylaxis and treatment of systemic mycoses.


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