Cryptococcal Meningitis: Diagnosis and Management Update (original) (raw)
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Recent advances in managing HIV-associated cryptococcal meningitis
F1000Research
The recent development of highly sensitive and specific point-of-care tests has made it possible to diagnose HIV-associated cryptococcal meningitis within minutes. However, diagnostic advances have not been matched by new antifungal drugs and treatment still relies on old off-patent drugs: amphotericin B, flucytosine and fluconazole. Cryptococcal meningitis treatment is divided in three phases: induction, consolidation and maintenance. The induction phase, aimed at drastically reducing cerebrospinal fluid fungal burden, is key for patient survival. The major challenge in cryptococcal meningitis management has been the optimisation of induction phase treatment using the limited number of available medications, and major progress has recently been made. In this review, we summarise data from key trials which form the basis of current treatment recommendations for HIV-associated cryptococcal meningitis.
Neurobehavioral HIV Medicine, 2012
Cryptococcal meningitis has emerged as one of the most frequent and deadly opportunistic infections in patients with human immunodeficiency virus (HIV). Cryptococcosis has become the most common cause of adult meningitis in many parts of Africa, where it now rivals tuberculosis in all-cause mortality. While expanding access to antiretroviral therapy in many resource-limited settings has led to improvements in long-term prognosis, early mortality from HIV-associated cryptococcal meningitis remains unacceptably high. Successful management of cryptococcal meningitis is often hindered by unsatisfactory antifungal regimens or by poor control of elevated cerebrospinal fluid pressures. Immune reconstitution inflammatory syndrome also frequently complicates cryptococcal meningitis in patients with acquired immune deficiency syndrome (AIDS) initiating antiretroviral therapy, and the optimal timing of antiretroviral therapy remains unclear. The optimal initial regimen of amphotericin B and flucytosine is difficult to administer and is often not available in resource-limited settings, where cryptococcal meningitis is most prevalent. Fluid and electrolyte coadministration with amphotericin B is essential to minimizing iatrogenic comorbidities. Fortunately, several new approaches have been leading the way toward improving care for cryptococcal meningitis patients in resource-limited settings. Innovative trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different induction regimens. Universal cryptococcal antigen screening of AIDS patients, combined with new point-of-care testing, has the potential to improve the early diagnosis of cryptococcal meningitis markedly in resource-limited settings.
Initial treatment of cryptococcal meningitis in AIDS
The Southeast Asian journal of tropical medicine and public health, 2005
The comparison of initial treatment with amphotericin B (0.7 mg/kg/d) plus rifampin (600 mg/d) with amphotericin B (0.7 mg/kg/d) alone for 2 weeks, both followed by fluconazole (400 mg/ d) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS by an open- randomized, controlled, prospective clinical trial is reported. Twenty patients were enrolled in each group. There were no significant differences between the groups in regard to a negative CSF culture for Cryptococcus neoformans in the 2nd and 10th weeks of treatment, time until normal body temperature after treatment, number of patients who died, and persistence of high CSF pressure after completion of treatment. Elevated intracranial pressure was an important factor associated with the patients who died. These results indicate that the combination of amphotericin B plus rifampin is not superior to amphotericin B alone.
Expert review of anti-infective therapy, 2017
Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.
Treatment of Cryptococcal Meningitis in KwaZulu-Natal, South Africa
PLoS ONE, 2010
Background: Cryptococcal meningitis (CM) remains a leading cause of death for HIV-infected individuals in sub-Saharan Africa. Improved treatment strategies are needed if individuals are to benefit from the increasing availability of antiretroviral therapy. We investigated the factors associated with mortality in routine care in KwaZulu-Natal, South Africa.
Faculty of 1000 evaluation for Combination antifungal therapy for cryptococcal meningitis
F1000 - Post-publication peer review of the biomedical literature, 2013
BACKGROUND-Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS-We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS-A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P = 0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P = 0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P = 0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P = 0.13). amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log 10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log 10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.
Southern African Journal of Hiv Medicine, 2013
Six years after the first Society guidelines were published, cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among HIV-infected adults in South Africa. Several important developments have spurred the publication of updated guidelines to manage this common fungal opportunistic infection. Recommendations described here include: (1) screening and pre-emptive treatment; (2) laboratory diagnosis and monitoring; (3) management of a first episode of CM; (4) amphotericin B deoxycholate toxicity prevention, monitoring and management; (5) timing of antiretroviral therapy among patients with CM; (6) management of raised intracranial pressure; (7) management of relapse episodes of CM.
Cochrane Database Syst …, 2008
Background Despite the advent and increasingly wide availability of antiretroviral therapy, cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with HIV infection in resource-limited settings. The ideal management of CM remains unclear. The aim of this review is to assess the evidence for deciding on which antifungal regimen to use as well as other modalities of management to utilise especially resource poor settings in order to achieve the best possible outcome and enable an individual with CM to survive their acute illness and benefit from antiretroviral therapy. Objectives To determine the most effective initial and consolidation treatment strategy for CM in HIV infected adults. Search methods The Cochrane HIV/AIDS group search strategy was used. Key words in the search included, meningitis, cryptococcus neoformans, treatment, trial, human immunodeficiency virus, acquired immunodeficiency syndrome, antifungal agents, amphotericin, flucytosine, fluconazole, azole, lumbar puncture, cerebrospinal fluid (CSF) pressure and acetazolamide. Selection criteria Randomised of HIV-infected adults with a first episode of CM diagnosed on CSF examination, by India ink staining, CSF culture or cryptococcal antigen testing. Data collection and analysis Data were extracted using standardised forms and analysed using Rev Man 4.2.7 software. Main results Six studies are included in the review. Five of the studies compared antifungal treatments and one study addressed lowering intracranial pressure. This study was stopped early due to excess adverse effects. The results of the other five studies as summarised as follows. 1 Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings (Review)