Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on Posaconazole Prophylaxis

Kang, Seung Hun; Kim, Hyun Seon; Bae, Myoung Nam; Kim, Jihye; Yoo, Ji Myong; Lee, Kwan Yong; Lee, Dong Gun; Kim, Hee-Je

doi:10.3947/ic.2015.47.1.49

Cited by 17 publications

(19 citation statements)

References 20 publications

(29 reference statements)

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“…Austria reported an incidence of breakthrough IFD was 13%, despite administering posaconazole to all patients during neutropenia, as well as increasing rates of infection with Mucorales and other rare fungal pathogens [15]. Breakthrough fungal infection during antifungal prophylaxis is problematic due to rare mold infection, few available treatment drug, and poor outcome [16][17][18]. Moreover, the emergence of antifungalresistant strains, which could seriously compromise successful IFD treatment, represents an increasing problem worldwide [19].…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Choi

Cho

Yoon

et al. 2017

Biology of Blood and Marrow Transplantation

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Incidence, epidemiology, and risk factors of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients can vary from different cohorts and countries. Therefore, we performed a nationwide study to establish a proper antifungal prophylaxis strategies based on risk stratifications of IFDs after all-HSCT in Korea (RISK study). This was a multicenter, retrospective, and observational study in Korea. All consecutive adult patients who received allo-HSCT in 2013 were included. The 12-month cumulative incidence of proven/probable IFDs (PP-IFDs) was calculated during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT. Cox proportional hazard regression analysis was performed to identify risk factors for PP-IFDs at each phase. A total 521 allo-HSCT cases in 518 patients were analyzed. Overall cumulative incidence of PP-IFDs were 4.09% (95% confidence interval [CI], 2.38 to 5.81), 7.38% (95% CI, 5.09 to 9.67), and 15.36% (95% CI, 12.04 to 18.68) at the early, late and very phases, respectively. In multiple Cox regression analysis, variables were associated with PP-IFDs in each period were identified. Variables associated with early phase include underlying pulmonary diseases, underlying nonmalignant stable or chronic disease at allo-HSCT, unrelated or family mismatched donor, and prolonged neutropenia. Variables associated with the late phase include high ferritin level at the time point of allo-HSCT, use of secondary immunosuppressive agents due to refractory graft-versus-host disease (GVHD), and cytomegalovirus reactivation. For the very late phase, variables were secondary neutropenia, severe chronic GVHD, and use of TNF-alpha inhibitor for refractory GVHD. This study revealed the high cumulative incidence of IFDs in Korean allo-HSCT recipients, which have distinct risk factors in each phase after allo-HSCT. Our findings indicate that tailored antifungal prophylaxis is necessary for high-risk patients. Clinicians should consider using mold-active antifungal prophylaxis in allo-HSCT recipients who have high risks at different treatment period.

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Section: Discussionmentioning

confidence: 99%

Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Choi

Cho

Yoon

et al. 2017

Biology of Blood and Marrow Transplantation

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“…13,21 Recently, an increase in breakthrough invasive mucormycosis has been reported among large numbers of patients treated with voriconazole or echinocandin for prophylaxis. [22][23][24] In our cohort, we also had a case of proven mucormycosis 25 and one of possible mucormycosis, which comprised 15% (2/13) of the proven/probable/ possible IFIs that developed during posaconazole prophylaxis. In this anti-mould prophylaxis era, several treatment options for EAFT have been suggested, which have to be considered in context of the possibility of yeast or mould infection.…”

Section: Discussionmentioning

confidence: 99%

Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single‐centre retrospective study in Korea and clinical considerations

Cho

Lee

Choi

et al. 2015

Mycoses

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SummaryPosaconazole was introduced as the primary antifungal prophylaxis (PAP) in acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) patients during remission induction chemotherapy. Data on breakthrough invasive fungal infections (IFIs) from various centres are essential, as there are several considerations in treating IFIs in the posaconazole era. The aim of this study was to evaluate the effectiveness of posaconazole PAP and identify characteristics of IFIs at a single centre in Korea. We retrospectively reviewed consecutive patients with AML/MDS undergoing remission induction chemotherapy between December 2010 and November 2013. Of the 424 patients, 140 received posaconazole and 284 received fluconazole prophylaxis. The incidence of breakthrough proven/probable IFIs (15.5% vs. 2.9%, P < 0.001) and empirical antifungal treatment (EAFT) (45.8% vs. 12.9%, P < 0.001) decreased in the posaconazole group compared to the fluconazole group. In the posaconazole PAP group, two cases of breakthrough mucormycosis were noted among 13 proven/probable/possible IFI cases (15.4%). Overall and IFI-related mortality was 12.1% and 1.9% respectively. Fungusfree survival was significantly higher in the posaconazole group (74.7% vs. 87.1%, P = 0.028). Breakthrough IFIs and EAFT decreased significantly after posaconazole PAP. The benefit in fungus-free survival was noted with posaconazole PAP. Clinicians should be vigilant to identify non-Aspergillus IFIs with active diagnostic effort.

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“…Breakthrough invasive mucormycosis has been observed in patients receiving voriconazole or echinocandins (Kontoyiannis et al, 2005;Trifilio et al, 2007), and also for posaconazole (Kang et al, 2015;Mousset et al, 2010), showing reduced sensitivity of some Mucorales species (Almyroudis et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species

Springer

Goldenberger

Schmidt

et al. 2016

Journal of Medical Microbiology

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PCR-based detection of Mucorales species could improve diagnosis of suspected invasive fungal infection, leading to a better patient outcome. This study describes two independent probe-based real-time PCR tests for detection of clinically relevant Mucorales, targeting specific fragments of the 18S and the 28S rRNA genes. Both assays have a short turnaround time, allow fast, specific and very sensitive detection of clinically relevant Mucorales and have the potential to be used as quantitative tests. They were validated on various clinical samples (fresh and formalin-fixed paraffin-embedded specimens, mainly biopsies, n517). The assays should be used as add-on tools to complement standard techniques; a combined approach of both real-time PCR assays has 100 % sensitivity. Genus identification by subsequent sequencing is possible for amplicons of the 18S PCR assay. In conclusion, combination of the two independent Mucorales assays described in this study, 18S and 28S, detected all clinical samples associated with proven Mucorales infection (n510). Reliable and specific identification of Mucorales is a prerequisite for successful antifungal therapy as these fungi show intrinsic resistance to voriconazole and caspofungin.

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Fatal Breakthrough Mucormycosis in an Acute Myelogenous Leukemia Patient while on Posaconazole Prophylaxis

Cited by 17 publications

References 20 publications

Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Epidemiology and Risk Factors for Invasive Fungal Diseases among Allogeneic Hematopoietic Stem Cell Transplant Recipients in Korea: Results of “RISK” Study

Posaconazole for primary antifungal prophylaxis in patients with acute myeloid leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a single‐centre retrospective study in Korea and clinical considerations

Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species

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