-
Views
-
Cite
Cite
Cornelius J. Clancy, M. Hong Nguyen, Reply to Antinori, Clinical Infectious Diseases, Volume 43, Issue 7, 1 October 2006, Pages 949–950, https://doi.org/10.1086/507553
Close - Share Icon Share
Extract
To THE EDITOR—We thank Dr. Antinori [1] for highlighting the frequency with which cryptococcal meningitis among non-HIV-infected patients is treated with suboptimal antifungal regimens. We agree that amphotericin B in combination with flucytosine is the optimal initial regimen among this population. Although the duration of combination therapy has not been defined in the era of azole agents [2], the current recommendations of the Infectious Diseases Society of America call for a ⩾2-week induction period [3]. Among patients who have a clinical and microbiological response to induction therapy, consolidation therapy for an additional 8–10 weeks with fluconazole can be considered. Data from randomized trials conducted before the HIV era support at least 4–6 weeks of therapy with amphotericin B and flucytosine [4, 5]. Initial therapy with a fluconazole-containing regimen, even among “low-risk” patients, is discouraged [3] on the basis of the poor outcome observed in a pilot study [6].
Furthermore, the observations of Dr. Antinori [1] and the findings of our study [7] are notable in the face of reports demonstrating that management of elevated intracranial pressure during cryptococcal meningitis often does not correspond to recommended practice [3, 8, 9]. Clearly, the infectious diseases community needs to do a better job of educating our colleagues about the recognition and treatment of this disease. At the same time, our experience suggests that more-timely diagnosis, appropriate antifungal therapy, and control of intracranial pressure will not ensure improved outcomes for all nonimmunosuppressed patients. As we reported, 2 (40%) of 5 patients treated with amphotericin B and flucytosine died; moreover, the conditions of 3 (33%) of 9 patients paradoxically worsened on receipt of antifungal therapy, despite initial clinical and laboratory improvement and the sterilization of CSF [7]. This worsening was accompanied by brain edema, cortical and laminar necrosis, new areas of leptomeningeal enhancement, cerebral infarcts, and the development of cystic lesions, suggesting that the host inflammatory response contributed to the pathogenesis of disease [7]. In this regard, our findings are consistent with the recently proposed damage-response framework of infectious diseases [10, 11].
