HIV-Associated Cryptococcal Meningitis Patients Treated with Amphotericin B Deoxycholate Plus Flucytosine under Routine Care Conditions in a Referral Center in São Paulo, Brazil

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.

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Poster 516 Spinal Cord Injuries in a Referral Center in São Paulo, Brazil

PM&R ◽

10.1016/j.pmrj.2012.09.1118 ◽

2012 ◽

Vol 4 ◽

pp. S367-S367

Author(s):

Roberto D. Rached ◽

Daniel R. Souza ◽

Chen C. Yuan

Keyword(s):

Spinal Cord ◽

Spinal Cord Injuries ◽

Sao Paulo ◽

São Paulo ◽

Referral Center

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Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02526-17 ◽

2018 ◽

Vol 62 (7) ◽

Cited By ~ 4

Author(s):

Katharine E. Stott ◽

Justin Beardsley ◽

Sarah Whalley ◽

Freddie Mukasa Kibengo ◽

Nguyen Thi Hoang Mai ◽

...

Keyword(s):

Amphotericin B ◽

Rate Constant ◽

Cryptococcal Meningitis ◽

Drug Exposure ◽

Meta Analysis ◽

Central Compartment ◽

Order Rate Constant ◽

Peripheral Compartment ◽

First Order ◽

Amphotericin B Deoxycholate

ABSTRACT There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis. A PK study was conducted in n = 42 patients receiving DAmB (1 mg/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) × weight + 0.67 (0.01) liters/h; volume, 0.82 (0.80) × weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h−1; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h−1. The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC144–168) resulted in median (interquartile range) values of 5.83 mg · h/liter (4.66 to 8.55), 10.16 mg · h/liter (8.07 to 14.55), and 14.51 mg · h/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.

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Randomized Comparison of Amphotericin B Deoxycholate Dissolved in Dextrose or Intralipid for the Treatment of AIDS-Associated Cryptococcal Meningitis

Clinical Infectious Diseases ◽

10.1093/clinids/23.3.556 ◽

1996 ◽

Vol 23 (3) ◽

pp. 556-562 ◽

Cited By ~ 32

Author(s):

V. Joly ◽

P. Aubry ◽

A. Ndayiragide ◽

I. Carriere ◽

E. Kawa ◽

...

Keyword(s):

Amphotericin B ◽

Cryptococcal Meningitis ◽

Amphotericin B Deoxycholate

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Aids-related progressive multifocal leukoencephalopathy: a retrospective study in a referral center in São Paulo, Brazil

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652008000400004 ◽

2008 ◽

Vol 50 (4) ◽

pp. 209-212 ◽

Cited By ~ 21

Author(s):

José E. Vidal ◽

Augusto C. Penalva de Oliveira ◽

Maria Cristina D. S. Fink ◽

Cláudio S. Pannuti ◽

J. Roberto Trujillo

Keyword(s):

Progressive Multifocal Leukoencephalopathy ◽

Opportunistic Infections ◽

Neurological Diseases ◽

Clinical Manifestations ◽

Sao Paulo ◽

São Paulo ◽

Referral Center ◽

Acquired Immunodeficiency ◽

Few Data ◽

Immunodeficiency Syndrome

Few data are available about progressive multifocal leukoencephalopathy (PML) in patients with acquired immunodeficiency syndrome (AIDS) from Brazil. The objectives of this study were to describe the main features of patients with PML and estimate its frequency among AIDS patients with central nervous system (CNS) opportunistic diseases admitted to the Instituto de Infectologia Emílio Ribas, São Paulo, Brazil, from April 2003 to April 2004. A retrospective and descriptive study was performed. Twelve (6%) cases of PML were identified among 219 patients with neurological diseases. The median age of patients with PML was 36 years and nine (75%) were men. Nine (75%) patients were not on antiretroviral therapy at admission. The most common clinical manifestations were: focal weakness (75%), speech disturbances (58%), visual disturbances (42%), cognitive dysfunction (42%), and impaired coordination (42%). The median CD4+ T-cell count was 45 cells/µL. Eight (67%) of 12 patients were laboratory-confirmed with PML and four (33%) were possible cases. Eleven (92%) presented classic PML and only one case had immune reconstitution inflammatory syndrome (IRIS)-related PML. In four (33%) patients, PML was the first AIDS-defining illness. During hospitalization, three patients (25%) died as a result of nosocomial pneumonia and nine (75%) were discharged to home. Cases of PML were only exceeded by cases of cerebral toxoplasmosis, cryptococcal meningoencephalitis, and CNS tuberculosis, the three more frequent neurologic opportunistic infections in Brazil. The results of this study suggest that PML is not an uncommon HIV-related neurologic disorder in a referral center in Brazil.

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Patient-Perceived Barriers to Accessing Cleft Care at a Tertiary Referral Center in São Paulo, Brazil

The Cleft Palate-Craniofacial Journal ◽

10.1177/1055665618796018 ◽

2018 ◽

Vol 56 (5) ◽

pp. 639-645 ◽

Cited By ~ 1

Author(s):

Ananda Ise ◽

Camila Menezes ◽

Joao Batista Neto ◽

Saurab Saluja ◽

Julia R. Amundson ◽

...

Keyword(s):

Access To Care ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Sao Paulo ◽

Perceived Barriers ◽

Treatment Result ◽

São Paulo ◽

Orofacial Clefts ◽

Middle Income ◽

Referral Center

Background: In low- and middle-income countries, poor access to care can result in delayed surgical repair of orofacial clefts leading to poor functional outcomes. Even in Brazil, an upper middle-income country with free comprehensive cleft care, delayed repair of orofacial clefts commonly occurs. This study aims to assess patient-perceived barriers to cleft care at a referral center in São Paulo. Methods: A 29-item questionnaire assessing the barriers to care was administered to 101 consecutive patients (or their guardians) undergoing orofacial cleft surgery in the Plastic Surgery Department in Hospital das Clínicas, in São Paulo, Brazil, between February 2016 and January 2017. Results: A total of 54.4% of patients had their first surgery beyond the recommended time frame of 6 months for a cleft lip or cleft lip and palate and 18 months for a cleft palate. There was a greater proportion of isolated cleft palates in the delayed group (66.7% vs 33.3%). Almost all patients had a timely diagnosis, but delays occurred from diagnosis to repair. The mean number of barriers reported for each patient was 3.8. The most frequently cited barriers related to lack of access to care include (1) lack of hospitals available to perform the surgery (54%) and (2) lack of availability of doctors (51%). Conclusion: Delays from diagnosis to treatment result in patients receiving delayed primary repairs. The commonest patient-perceived barriers are related to a lack of access to cleft care, which may represent a lack of awareness of available services.

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Ambulatory induction phase treatment of cryptococcal meningitis in HIV integrated primary care clinics, Yangon, Myanmar

BMC Infectious Diseases ◽

10.1186/s12879-021-06049-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Clare E. Warrell ◽

Catriona Macrae ◽

Alistair R. D. McLean ◽

Edmund Wilkins ◽

Elizabeth A. Ashley ◽

...

Keyword(s):

Primary Care ◽

Amphotericin B ◽

Cryptococcal Meningitis ◽

Integrated Primary Care ◽

Induction Treatment ◽

Induction Phase ◽

Retrospective Case ◽

Primary Care Clinics ◽

Amphotericin B Deoxycholate ◽

One Year

Abstract Background Cryptococcal meningitis (CM) is a common HIV-associated opportunistic-infection worldwide. Existing literature focusses on hospital-based outcomes of induction treatment. This paper reviews outpatient management in integrated primary care clinics in Yangon. Method This retrospective case note review analyses a Myanmar HIV-positive patient cohort managed using ambulatory induction-phase treatment with intravenous amphotericin-B-deoxycholate (0.7–1.0 mg/kg) and oral fluconazole (800 mg orally/day). Results Seventy-six patients were diagnosed between 2010 and 2017. The median age of patients diagnosed was 35 years, 63% were male and 33 (45%) were on concurrent treatment for tuberculosis. The median CD4 count was 60 at the time of diagnosis. Amphotericin-B-deoxycholate infusions precipitated 56 episodes of toxicity, namely hypokalaemia, nephrotoxicity, anaemia, febrile reactions, phlebitis, observed in 44 patients (58%). One-year survival (86%) was higher than existing hospital-based treatment studies. Conclusion Ambulation of patients in this cohort saved 1029 hospital bed days and had better survival outcomes when compared to hospital-based studies in other resource constrained settings.

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Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v14i2.82 ◽

2013 ◽

Vol 14 (2) ◽

pp. 76-86 ◽

Cited By ~ 17

Author(s):

The Southern African HIV Clinicians Society

Keyword(s):

South Africa ◽

Antiretroviral Therapy ◽

Intracranial Pressure ◽

Amphotericin B ◽

Opportunistic Infection ◽

Cryptococcal Meningitis ◽

Laboratory Diagnosis ◽

First Episode ◽

Raised Intracranial Pressure ◽

Amphotericin B Deoxycholate

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.

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