amphotericin-b and Cerebrospinal-Fluid-Otorrhea

Otogenic skull base osteomyelitis (SBO) of fungal etiology is a very rare but life-threatening complication of inflammatory processes of the ear. The authors present a case of otogenic SBO caused by Aspergillus flavus in a 65-year-old man with a fatal course. Because of the encountered difficulties with the proper diagnosis and treatment, the authors reviewed the literature on the subject.

Topics: Aged; Amphotericin B; Antifungal Agents; Cavernous Sinus; Cerebrospinal Fluid Otorrhea; Fatal Outcome; Humans; Injections, Intravenous; Magnetic Resonance Imaging; Male; Neuroaspergillosis; Osteomyelitis; Paracentesis; Skull Base

Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered.. We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole.. The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups.. Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Retroviral Agents; Antifungal Agents; Cause of Death; Cerebrospinal Fluid Otorrhea; Drug Administration Schedule; Female; Humans; Leukocyte Count; Male; Meningitis, Cryptococcal; South Africa; Survival Analysis; Uganda