Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.

BACKGROUND: Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODS: We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTS: A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. CONCLUSIONS: One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509 .).

Renal abscess with Capnocytophaga canimorsus infection from a dog bite.

We present a case of renal abscess caused by Capnocytophaga canimorsus infection in a previously healthy middle-aged man. He presented with sepsis and an acute kidney injury, and although not identified on his initial assessment, he had sustained a dog bite 5 days prior to hospital admission. The patient developed left loin pain and imaging investigation revealed a renal abscess. Gram stain showed a gram-negative bacillus and C. canimorsus was identified by 16S PCR from these samples along with aspirate from the abscess. The patient responded to treatment with carbapenems but required a prolonged course. His clinical condition was further complicated by a pleural effusion and the development of fatigue symptoms consistent with a post-infection chronic fatigue syndrome. We present this case which we believe to be the first documented case of C. canimorsus causing renal abscess. We discuss the challenges relating to investigation, management and the importance of detailed diagnostic exposure histories in sepsis of unknown origin.

Effect of oral fluconazole 1200 mg/day on QT interval in African adults with HIV-associated cryptococcal meningitis.

: We assessed the effect of fluconazole 1200 mg/day on the QT interval in cryptococcal meningitis patients. Mean corrected QT (QTc) change from baseline to day 7 was 10.1 ms (IQR: -28 to 46 ms) in the fluconazole treatment group and -12.6 ms (IQR: -39 to 13.5 ms) in those not taking fluconazole (P = 0.04). No significant increase in QTc measurements over 500 ms was observed with fluconazole. Nevertheless, it remains important to correct any electrolyte imbalance and avoid concomitant drugs that may increase QTc.