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Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis

INTRODUCTION: The first-line combination therapy for HIV-associated cryptococcal meningitis (CM), a condition of high mortality particularly in the first two weeks of treatment, consists of amphotericin B plus flucytosine (5-FC). Given that 5-FC remains unavailable in many countries, the knowledge o...

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Autores principales: Concha-Velasco, Fátima, González-Lagos, Elsa, Seas, Carlos, Bustamante, Beatriz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371305/
https://www.ncbi.nlm.nih.gov/pubmed/28355252
http://dx.doi.org/10.1371/journal.pone.0174459
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author Concha-Velasco, Fátima
González-Lagos, Elsa
Seas, Carlos
Bustamante, Beatriz
author_facet Concha-Velasco, Fátima
González-Lagos, Elsa
Seas, Carlos
Bustamante, Beatriz
author_sort Concha-Velasco, Fátima
collection PubMed
description INTRODUCTION: The first-line combination therapy for HIV-associated cryptococcal meningitis (CM), a condition of high mortality particularly in the first two weeks of treatment, consists of amphotericin B plus flucytosine (5-FC). Given that 5-FC remains unavailable in many countries, the knowledge of factors influencing mycological clearance in patients treated with second-line therapy could contribute to effective management. OBJECTIVES: To determine the factors associated with the clearance of Cryptococcus sp. from the cerebrospinal fluid by the second week of effective antifungal therapy (early mycological clearance) in HIV-associated CM. METHODS: Retrospective cohort study based on secondary data corresponding to HIV-associated CM cases hospitalized at a tertiary health care center in Lima, Peru where 5-FC remains unavailable. Risk factors associated with early mycological clearance were analyzed by generalized linear regression models. RESULTS: From January 2000 to December 2013, 234 individuals were discharged with a diagnosis of HIV-associated CM; in 215 we retrieved the required data. The inpatient mortality was 20% (43/215), 15 of them in the first two weeks of treatment. In the final model (157 cases), adjusted for age, previous episode of CM, ART use, type of antifungal treatment, raised intracranial pressure, frequency of therapeutic lumbar punctures, baseline fungal burden and treatment period, the factors associated with early mycological clearance were: Amphotericin B deoxycholate plus fluconazole as combination therapy (RR, 1.56; 95% CI, 1.14–2.14); severe baseline intracranial pressure (≥35 cm H(2)O) (RR, 0.57; 95% CI, 0.33–0.99); and baseline fungal burden over 4.5 log(10) CFU/mL (RR, 0.61 95% CI: 0.39–0.95). CONCLUSIONS: In a setting without access to first-line therapy for CM, the combination therapy with amphotericin B deoxycholate plus fluconazole was positively associated with early mycological clearance, while high fungal burden and severe baseline intracranial pressure were negatively associated, and thus related to failure.
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spelling pubmed-53713052017-04-07 Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis Concha-Velasco, Fátima González-Lagos, Elsa Seas, Carlos Bustamante, Beatriz PLoS One Research Article INTRODUCTION: The first-line combination therapy for HIV-associated cryptococcal meningitis (CM), a condition of high mortality particularly in the first two weeks of treatment, consists of amphotericin B plus flucytosine (5-FC). Given that 5-FC remains unavailable in many countries, the knowledge of factors influencing mycological clearance in patients treated with second-line therapy could contribute to effective management. OBJECTIVES: To determine the factors associated with the clearance of Cryptococcus sp. from the cerebrospinal fluid by the second week of effective antifungal therapy (early mycological clearance) in HIV-associated CM. METHODS: Retrospective cohort study based on secondary data corresponding to HIV-associated CM cases hospitalized at a tertiary health care center in Lima, Peru where 5-FC remains unavailable. Risk factors associated with early mycological clearance were analyzed by generalized linear regression models. RESULTS: From January 2000 to December 2013, 234 individuals were discharged with a diagnosis of HIV-associated CM; in 215 we retrieved the required data. The inpatient mortality was 20% (43/215), 15 of them in the first two weeks of treatment. In the final model (157 cases), adjusted for age, previous episode of CM, ART use, type of antifungal treatment, raised intracranial pressure, frequency of therapeutic lumbar punctures, baseline fungal burden and treatment period, the factors associated with early mycological clearance were: Amphotericin B deoxycholate plus fluconazole as combination therapy (RR, 1.56; 95% CI, 1.14–2.14); severe baseline intracranial pressure (≥35 cm H(2)O) (RR, 0.57; 95% CI, 0.33–0.99); and baseline fungal burden over 4.5 log(10) CFU/mL (RR, 0.61 95% CI: 0.39–0.95). CONCLUSIONS: In a setting without access to first-line therapy for CM, the combination therapy with amphotericin B deoxycholate plus fluconazole was positively associated with early mycological clearance, while high fungal burden and severe baseline intracranial pressure were negatively associated, and thus related to failure. Public Library of Science 2017-03-29 /pmc/articles/PMC5371305/ /pubmed/28355252 http://dx.doi.org/10.1371/journal.pone.0174459 Text en © 2017 Concha-Velasco et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Concha-Velasco, Fátima
González-Lagos, Elsa
Seas, Carlos
Bustamante, Beatriz
Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title_full Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title_fullStr Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title_full_unstemmed Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title_short Factors associated with early mycological clearance in HIV-associated cryptococcal meningitis
title_sort factors associated with early mycological clearance in hiv-associated cryptococcal meningitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371305/
https://www.ncbi.nlm.nih.gov/pubmed/28355252
http://dx.doi.org/10.1371/journal.pone.0174459
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