scholarly journals Comparative Effectiveness of Induction Therapy for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis: A Network Meta-Analysis

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Jeffrey I. Campbell ◽  
Steve Kanters ◽  
John E. Bennett ◽  
Kristian Thorlund ◽  
Alexander C. Tsai ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amphotericin B ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Comparative Effectiveness ◽  
Treatment Guidelines ◽  
Meta Analysis ◽  
High Dose ◽  
Mortality Benefit ◽  
Immunodeficiency Virus

Abstract Background.  Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin-fluconazole. Methods.  We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine +triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results.  In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not ide.jpegy a benefit for combination therapy in restricted analyses in either resource-rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions.  Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virus-associated cryptococcal meningitis.

scholarly journals Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Melissa A. Rolfes ◽  
Joshua Rhein ◽  
Charlotte Schutz ◽  
Kabanda Taseera ◽  
Henry W. Nabeta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Clinical Outcomes ◽  
Antifungal Therapy ◽  
Induction Therapy ◽  
Cryptococcal Meningitis ◽  
Cox Regression ◽  
Culture Positivity ◽  
Immunodeficiency Virus ◽  
Cerebrospinal Fluid Culture

Abstract Background.  Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.  Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.  Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.  Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes.

scholarly journals High Mortality in HIV-Associated Cryptococcal Meningitis Patients Treated With Amphotericin B–Based Therapy Under Routine Care Conditions in Africa

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Raju K K Patel ◽  
Tshepo Leeme ◽  
Caitlin Azzo ◽  
Nametso Tlhako ◽  
Katlego Tsholo ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Treatment Guidelines ◽  
Routine Care ◽  
Outcome Data ◽  
High Dose ◽  
Recommended Treatment ◽  
Amphotericin B Deoxycholate ◽  
Intravenous Amphotericin

Abstract Background Cryptococcal meningitis (CM) causes 10%–20% of HIV-related deaths in Africa. Due to limited access to liposomal amphotericin and flucytosine, most African treatment guidelines recommend amphotericin B deoxycholate (AmB-d) plus high-dose fluconazole; outcomes with this treatment regimen in routine care settings have not been well described. Methods Electronic national death registry data and computerized medical records were used to retrospectively collect demographic, laboratory, and 1-year outcome data from all patients with CM between 2012 and 2014 at Botswana’s main referral hospital, when recommended treatment for CM was AmB-d 1 mg/kg/d plus fluconazole 800 mg/d for 14 days. Cumulative survival was estimated at 2 weeks, 10 weeks, and 1 year. Results There were 283 episodes of CM among 236 individuals; 69% (163/236) were male, and the median age was 36 years. All patients were HIV-infected, with a median CD4 count of 39 cells/mm3. Two hundred fifteen person-years of follow-up data were captured for the 236 CM patients. Complete outcome data were available for 233 patients (99%) at 2 weeks, 224 patients (95%) at 10 weeks, and 219 patients (93%) at 1 year. Cumulative mortality was 26% (95% confidence interval [CI], 20%–32%) at 2 weeks, 50% (95% CI, 43%–57%) at 10 weeks, and 65% (95% CI, 58%–71%) at 1 year. Conclusions Mortality rates following HIV-associated CM treated with AmB-d and fluconazole in a routine health care setting in Botswana were very high. The findings highlight the inadequacies of current antifungal treatments for HIV-associated CM and underscore the difficulties of administering and monitoring intravenous amphotericin B deoxycholate therapy in resource-poor settings.

scholarly journals Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies

2020 ◽  
Author(s):  
Elvis Temfack ◽  
Jean Joel Bigna Rim ◽  
Rene Spijker ◽  
Angela Loyse ◽  
Tom Chiller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Sensitivity And Specificity ◽  
Antifungal Therapy ◽  
Cryptococcal Meningitis ◽  
Meta Analysis ◽  
Test Accuracy ◽  
Fungal Culture ◽  
Cryptococcal Antigen ◽  
Immunodeficiency Virus

Abstract Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4–100) and 94.1% (88.3–98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2–99.6) and 99.3% (96.7–99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97–99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.

scholarly journals A case–control study of human immunodeficiency virus-negative patients with cryptococcemia and cryptococcal meningitis in a Chinese tertiary care hospital during 10 years

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098465
Author(s):  
Liling Liang ◽  
Zhixin Liang ◽  
Danyang She ◽  
Liang’an Chen
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Case Control Study ◽  
Tertiary Care ◽  
Case Control ◽  
Care Hospital ◽  
Retrospective Case ◽  
Immunodeficiency Virus ◽  
Control Study

Objective This study aimed to characterize patients with cryptococcemia and compare the clinical features of cryptococcemia and cryptococcal meningitis. Methods This was a retrospective, case–control study. We retrospectively identified blood cultures with Cryptococcus spp. growth. Controls were hospitalized patients who suffered from cryptococcal meningitis, but did not experience cryptococcemia. Controls and cases were matched by admission date, age, sex, and body weight. Clinical information was analyzed by two independent reviewers. Results Eight patients with cryptococcemia and eight patients with cryptococcal meningitis were included. They were all negative for human immunodeficiency virus. The most common underlying disease was primary nephrotic syndrome. All patients presented with fever. The incidence of headache, nausea/vomiting, seizures, and cough/expectoration was significantly lower in patients with cryptococcemia than in those with cryptococcal meningitis. All clinical strains of Cryptococcus, except for one, were sensitive to fluconazole, voriconazole, itraconazole, amphotericin B, and flucytosine in vitro. The rate of receiving an amphotericin B-containing regimen was significantly higher in patients with cryptococcal meningitis than in those with cryptococcemia. In-hospital mortality was significantly higher in cryptococcemia cases compared with cryptococcal meningitis cases. Conclusion Cryptococcemia is an unusual infection characterized by a high mortality. Cryptococcemia requires early identification and prompt antifungal therapy.

scholarly journals Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus–Associated Cryptococcal Meningitis

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Charlotte Schutz ◽  
David R. Boulware ◽  
Katherine Huppler-Hullsiek ◽  
Maximilian von Hohenberg ◽  
Joshua Rhein ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Acute Kidney Injury ◽  
Amphotericin B ◽  
Cryptococcal Meningitis ◽  
Kidney Injury ◽  
Cox Proportional Hazards ◽  
Cd4 Count ◽  
Urine Ngal ◽  
Urine Protein ◽  
Immunodeficiency Virus

Abstract Background Cryptococcus is the most common etiology of adult meningitis in Africa. Amphotericin B deoxycholate remains paramount to treatment, despite toxicities, including acute kidney injury (AKI). We assessed the ability of the following urine markers to predict AKI in patients who received amphotericin B: urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein. Methods One hundred and thirty human immunodeficiency virus (HIV)–infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models. Results Participants were 48% female with a median age of 35 years, a median CD4 count of 21 cells/μL, and 44% died within 12 months. Incident AKI occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] = 2.8; P < .001). Development of AKI was associated with female sex (P = .04) and with higher CD4 count (49 vs 14 cells/μL; P < .01). Urine protein level in the highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04; aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile independently predicted AKI (aHR = 1.65; P = .04). Conclusions Acute kidney injury occurred in 42% of patients, and AKI was associated with mortality. Urine biomarkers, specifically urine protein, may be useful for antecedent prediction of amphotericin-associated AKI but need further evaluation.

scholarly journals Re-Appraisal of Effective, and Tolerable Induction Regimens for Managing Cryptococcal Meningitis in HIV-Infected Adults: A Systematic Review and Network Meta-Analysis

2020 ◽  
Author(s):  
Chang-Hua chen ◽  
Hua Li ◽  
Hsien-Meng Chen ◽  
Yu-Min Chen ◽  
Yu-Jun Chang ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Cryptococcal Meningitis ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
High Dose ◽  
Randomized Controlled ◽  
Immunodeficiency Virus ◽  
Amphotericin B Deoxycholate ◽  
Induction Regimen ◽  
A Current

Abstract Cryptococcal meningitis (CM) has become the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of one-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV-CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV-CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2,642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + High dose azole (Azole_H) (OR = 1.1*10− 12, 95% CIs = 1.3*10− 41 to 0.06) comparing to AmphB + 5-FC. Azole_H was possibly associated with the lowest late-mortality rate (OR = 0.27, 95% CIs = 0.08 to 0.99). The current NMA provides evidence that AmphB + 5-FC + Azole_H are superior to all the investigated treatments for induction regimen in HIV-CM patients.

scholarly journals Effect of high-dose fluconazole on QT interval in patients with human immunodeficiency virus (HIV)-associated cryptococcal meningitis

2009 ◽  
Vol 34 (5) ◽  
pp. 494-496 ◽  
Author(s):  
Weerawat Manosuthi ◽  
Somnuek Sungkanuparph ◽  
Thanomsak Anekthananon ◽  
Khuanchai Supparatpinyo ◽  
Tracy L. Nolen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cryptococcal Meningitis ◽  
Qt Interval ◽  
High Dose ◽  
Immunodeficiency Virus
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