Micafungin Breakthrough Fungemia in Patients with Hematological Disorders

Kimura, Muneyoshi; Araoka, Hideki; Yamamoto, Hisashi; Nakamura, Shigeki; Nagi, Minoru; Yamagoe, Satoshi; Miyazaki, Yoshitsugu; Ogura, Sho; Mitsuki, Takashi; Yuasa, Mitsuhiro; Kaji, Daisuke; Kageyama, Kosei; Nishida, Aya; Taya, Yuki; Shimazu, Hiroshi; Ishiwata, Kiichi; Takagi, Shinsuke; Yamamoto, Go; Asano‐Mori, Yuki; Uchida, Naoyuki; Wake, Atsushi; Taniguchi, Shuichi; Yoneyama, Akio

doi:10.1128/aac.02183-17

Cited by 27 publications

(19 citation statements)

References 38 publications

(40 reference statements)

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“…C. parapsilosis displays reduced susceptibility in vitro to echinocandins (297)(298)(299), and the yeast can cause infection in the setting of echinocandin administration (300)(301)(302)(303)(304)(305). Notably, caspofungin MICs for C. parapsilosis are higher than for other Candida species, with MIC 50 values typically ranging from 0.85 to 2 g/ml (186,271,275,306,307).…”

Section: Antifungal Susceptibility and Resistancementioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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SUMMARY Patients with suppressed immunity are at the highest risk for hospital-acquired infections. Among these, invasive candidiasis is the most prevalent systemic fungal nosocomial infection. Over recent decades, the combined prevalence of non-albicans Candida species outranked Candida albicans infections in several geographical regions worldwide, highlighting the need to understand their pathobiology in order to develop effective treatment and to prevent future outbreaks. Candida parapsilosis is the second or third most frequently isolated Candida species from patients. Besides being highly prevalent, its biology differs markedly from that of C. albicans, which may be associated with C. parapsilosis’ increased incidence. Differences in virulence, regulatory and antifungal drug resistance mechanisms, and the patient groups at risk indicate that conclusions drawn from C. albicans pathobiology cannot be simply extrapolated to C. parapsilosis. Such species-specific characteristics may also influence their recognition and elimination by the host and the efficacy of antifungal drugs. Due to the availability of high-throughput, state-of-the-art experimental tools and molecular genetic methods adapted to C. parapsilosis, genome and transcriptome studies are now available that greatly contribute to our understanding of what makes this species a threat. In this review, we summarize 10 years of findings on C. parapsilosis pathogenesis, including the species’ genetic properties, transcriptome studies, host responses, and molecular mechanisms of virulence. Antifungal susceptibility studies and clinician perspectives are discussed. We also present regional incidence reports in order to provide an updated worldwide epidemiology summary.

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Section: Antifungal Susceptibility and Resistancementioning

confidence: 99%

Candida parapsilosis: from Genes to the Bedside

et al. 2019

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“…Trichosporon species has become a critical life-threatening opportunistic pathogen that causes B-IFI during exposure to antifungals. 238 Also, with higher use of wide-spectrum triazoles as prophylaxis in high-risk patients, infection with multidrug-resistant (MDR) Trichosporon species was reported. 239 A recent study reported a series of 68 cases who developed breakthrough Trichosporon species infections.…”

Section: Trichosporonosismentioning

confidence: 99%

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

Shariati¹,

Moradabadi²,

Chegini³

et al. 2020

IDR

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In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes.

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“…The difference in the timing of the administration may account for the difference in ED 50 values. T. asahii exhibits natural resistance to candin antifungals such as micafungin, and strains resistant to azole antifungals such as fluconazole and amphotericin B have also been clinically isolated [12][13][14] . New antifungal drugs might be obtained by in vivo screening using a silkworm infection model with a multidrug-resistant T. asahii strain.…”

Section: Discussionmentioning

confidence: 99%

A novel silkworm infection model with fluorescence imaging using transgenic Trichosporon asahii expressing eGFP

Matsumoto

Yamazaki

Yamasaki

et al. 2020

Sci Rep

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Trichosporon asahii is a pathogenic fungus that causes deep mycosis in patients with neutropenia. Establishing an experimental animal model for quantitatively evaluating pathogenicity and developing a genetic recombination technology will help to elucidate the infection mechanism of T. asahii and promote the development of antifungal drugs. Here we established a silkworm infection model with a transgenic T. asahii strain expressing eGFP. Injecting T. asahii into silkworms eventually killed the silkworms. Moreover, the administration of antifungal agents, such as amphotericin B, fluconazole, and voriconazole, prolonged the survival time of silkworms infected with T. asahii. A transgenic T. asahii strain expressing eGFP was obtained using a gene recombination method with Agrobacterium tumefaciens. The T. asahii strain expressing eGFP showed hyphal formation in the silkworm hemolymph. Both hyphal growth and the inhibition of hyphal growth by the administration of antifungal agents were quantitatively estimated by monitoring fluorescence. Our findings suggest that a silkworm infection model using T. asahii expressing eGFP is useful for evaluating both the pathogenicity of T. asahii and the efficacy of antifungal drugs. Trichosporon asahii is a basidiomycetous yeast widely distributed in the environment 1-4 , and commonly isolated from human blood, sputum, skin, feces, and urine 5-8. T. asahii is a pathogenic fungus that causes severe deep mycosis in patients with neutropenia 8-10. Whereas the mortality rate of deep mycosis caused by Candida albicans is approximately 40%, that caused by T. asahii is approximately 80%, and the prognosis is poor 11. T. asahii is resistant to echinocandin antifungal drugs and causes severe infections in patients treated with micafungin 12. Moreover, strains resistant to amphotericin B and azole antifungal drugs such as fluconazole have been isolated from patients 13,14. Therefore, T. asahii has become a serious clinical problem as a pathogenic fungus that causes systemic infection in immunocompromised hosts 8. T. asahii forms hyphae, which are branching filamentous structures 14. In pathogenic fungi that form hyphae such as Candida albicans, hyphal formation is crucial for the host epithelial cell damage and biofilm formation that are involved in infections 15. As with C. albicans, T. asahii makes treatment difficult by forming a biofilm on devices such as catheters 14,16. Hyphal growth of T. asahii in blood vessels causes necrotic thrombi, and may contribute to infection 17. The molecular mechanisms of infection caused by T. asahii, however, remain unclear. Establishing a simple animal experimental system for systemic infection with hyphal formation of T. asahii and developing genetic recombination technology in T. asahii will contribute to elucidate the infection mechanism. The silkworm, an invertebrate, is a useful experimental animal for evaluating the pathogenicity of pathogenic microorganisms and the therapeutic effects of antibacterial, antifungal, and antiviral drugs 18-22. Silkw...

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Micafungin Breakthrough Fungemia in Patients with Hematological Disorders

Cited by 27 publications

References 38 publications

Candida parapsilosis: from Genes to the Bedside

Candida parapsilosis: from Genes to the Bedside

<p>An Overview of the Management of the Most Important Invasive Fungal Infections in Patients with Blood Malignancies</p>

A novel silkworm infection model with fluorescence imaging using transgenic Trichosporon asahii expressing eGFP

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