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Early mycological treatment failure in AIDS-associated cryptococcal meningitis
P A Robinson1, M Bauer, M A Leal
1Department of Medicine, University of Southern California School of Medicine, USA.
Abstract:
Cryptococcal meningitis causes significant morbidity and mortality in persons with AIDS. Of 236 AIDS patients treated with amphotericin B plus flucytosine, 29 (12%) died within 2 weeks and 62 (26%) died before 10 weeks. Just 129 (55%) of 236 patients were alive with negative cerebrospinal fluid (CSF) cultures at 10 weeks. Multivariate analyses identified that titer of cryptococcal antigen in CSF, serum albumin level, and CD4 cell count, together with dose of amphotericin B, had the strongest joint association with failure to achieve negative CSF cultures by day 14. Among patients with similar CSF cryptococcal antigen titers, CD4 cell counts, and serum albumin levels, the odds of failure at week 10 for those without negative CSF cultures by day 14 was five times that for those with negative CSF cultures by day 14 (odds ratio, 5.0; 95% confidence interval, 2.2-10.9). Prognosis is dismal for patients with AIDS-related cryptococcal meningitis. Multivariate analyses identified three components that, along with initial treatment, have the strongest joint association with early outcome. Clearly, more effective initial therapy and patient management strategies that address immune function and nutritional status are needed to improve outcomes of this disease.
Insights
Cryptococcal meningitis in AIDS patients has a poor prognosis, with over 40% mortality within 10 weeks. Factors like CSF antigen, albumin, and CD4 count impact treatment outcomes.
Area of Science:
- Infectious Diseases
- Immunology
- Clinical Medicine
Background:
- Cryptococcal meningitis is a severe opportunistic infection in individuals with Acquired Immunodeficiency Syndrome (AIDS).
- High morbidity and mortality rates are associated with cryptococcal meningitis in AIDS patients, despite treatment.
Purpose of the Study:
- To evaluate the outcomes of cryptococcal meningitis treatment in AIDS patients using amphotericin B plus flucytosine.
- To identify factors associated with treatment failure and early mortality.
Main Methods:
- A cohort of 236 AIDS patients with cryptococcal meningitis treated with amphotericin B and flucytosine was analyzed.
- Multivariate analyses were performed to identify predictors of treatment failure, defined by negative cerebrospinal fluid (CSF) cultures by day 14 and survival at 10 weeks.
Main Results:
- 12% of patients died within 2 weeks, and 26% died before 10 weeks; only 55% had negative CSF cultures at 10 weeks.
- CSF cryptococcal antigen titer, serum albumin, and CD4 cell count were strongly associated with failure to achieve negative CSF cultures by day 14.
- Patients without negative CSF cultures by day 14 had a fivefold increased odds of failure at 10 weeks (OR, 5.0; 95% CI, 2.2-10.9).
Conclusions:
- The prognosis for AIDS-related cryptococcal meningitis remains poor.
- Initial treatment, CSF antigen levels, immune status (CD4 count), and nutritional status (albumin) are key determinants of early outcomes.
- Improved initial therapies and management strategies addressing immune function and nutritional status are crucial to enhance patient outcomes.