TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY

Background: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV)...

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Main Authors: Rola Husni, Remie Chrabieh, Rita Wilson Dib, Jose Vazquez, MD, Thaís Guimarães, Ana Fernández, Rita Khoury, Lina Asmar, Georges Khazen, Nadia Lara Samaha, Issam Raad, Ray Hachem
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Language:English
Published: PAGEPress Publications 2021-04-01
Series:Mediterranean Journal of Hematology and Infectious Diseases
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Online Access:https://mjhid.org/3214/index.php/mjhid/article/view/4578
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author Rola Husni
Remie Chrabieh
Rita Wilson Dib
Jose Vazquez, MD
Thaís Guimarães
Ana Fernández
Rita Khoury
Lina Asmar
Georges Khazen
Nadia Lara Samaha
Issam Raad
Ray Hachem
author_facet Rola Husni
Remie Chrabieh
Rita Wilson Dib
Jose Vazquez, MD
Thaís Guimarães
Ana Fernández
Rita Khoury
Lina Asmar
Georges Khazen
Nadia Lara Samaha
Issam Raad
Ray Hachem
author_sort Rola Husni
collection DOAJ
description Background: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival. Method: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon ,Spain and the United States, to assess the duration of IV therapy and appropriate time to step down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down. Results: Candida albicans contributed to 45% bloodstream infection versus 55% infection caused Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. There were 45 patients who were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step down was 5 days. Patients who had a stepdown had more successful outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1-4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75). Conclusion: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.
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spelling doaj-art-8081e9da87eb4ed1b10dd1074bdc4bd32025-01-02T10:37:19ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062021-04-01131TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDYRola HusniRemie ChrabiehRita Wilson DibJose Vazquez, MDThaís GuimarãesAna FernándezRita KhouryLina AsmarGeorges KhazenNadia Lara SamahaIssam RaadRay Hachem0Anderson Cancer CenterBackground: Candida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival. Method: We performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon ,Spain and the United States, to assess the duration of IV therapy and appropriate time to step down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down. Results: Candida albicans contributed to 45% bloodstream infection versus 55% infection caused Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. There were 45 patients who were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step down was 5 days. Patients who had a stepdown had more successful outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1-4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75). Conclusion: Our data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.https://mjhid.org/3214/index.php/mjhid/article/view/4578Candida infectionNeutropeniaBloodstream Infections
spellingShingle Rola Husni
Remie Chrabieh
Rita Wilson Dib
Jose Vazquez, MD
Thaís Guimarães
Ana Fernández
Rita Khoury
Lina Asmar
Georges Khazen
Nadia Lara Samaha
Issam Raad
Ray Hachem
TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
Mediterranean Journal of Hematology and Infectious Diseases
Candida infection
Neutropenia
Bloodstream Infections
title TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
title_full TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
title_fullStr TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
title_full_unstemmed TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
title_short TIMING FOR STEP-DOWN THERAPY OF CANDIDEMIA IN NON-NEUTROPENIC PATIENTS: AN INTERNATIONAL MULTI-CENTER STUDY
title_sort timing for step down therapy of candidemia in non neutropenic patients an international multi center study
topic Candida infection
Neutropenia
Bloodstream Infections
url https://mjhid.org/3214/index.php/mjhid/article/view/4578
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