The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports

Jeong, Wirawan; Keighley, Caitlin; Wolfe, Rory; Lee, Wee Leng; Slavin, Monica A; Kong, David C M; Chen, S.C.-A.

doi:10.1016/j.cmi.2018.07.011

Cited by 706 publications

(876 citation statements)

References 39 publications

(53 reference statements)

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“…This species is isolated primarily in patients with pulmonary or disseminated disease, which is why cutaneous manifestations are unusual. In our case, the most common alternative hypotheses were suspected initially: catastrophic cholesterol crystal embolism following coronarography, calciphylaxis due to a long history of dialysis, or heparin‐related cutaneous necrosis.…”

Section: Discussionmentioning

confidence: 99%

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Early necrotic skin lesions after a ABO‐incompatible kidney transplantation: The threat of Cunninghamella Spp.

Béllière

Rolland

Tournier

et al. 2019

Transplant Infectious Dis

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A 49-year-old man underwent ABO-incompatible kidney transplantation with a living donor. At day 33 post-transplantation, he presented with undiagnosed epilepsy with generalized tonic-clonic seizures. At day 44 post-transplantation, he developed left-sided pneumonia attributed to Aspergillus fumigatus and treatment with liposomal amphotericin B was initiated. At day 51 post-transplantation, necrotic skin lesions appeared. DNA sequencing in a fresh cutaneous biopsy finally identified Cunninghamella Spp., a member of the order Mucorales. Unfortunately, the necrotic lesions spread, and the patient died at day 60 post-transplantation. This case report highlights the infectious risk related to ABO-incompatible kidney transplantation and suggests a requirement for rapid identification of every skin lesion, even in the early phases of immunosuppression. K E Y W O R D S ABO-incompatible kidney transplantation, Cunninghamella, mucormycosis, necrotic skin lesions

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Section: Discussionmentioning

confidence: 99%

“…It is consistent with the high mortality associated with Cunninghamella Spp infections, which is significantly higher than for those caused by other Mucorales. The global mortality rate for Mucorales infections is around 50% …”

Section: Discussionmentioning

confidence: 99%

Early necrotic skin lesions after a ABO‐incompatible kidney transplantation: The threat of Cunninghamella Spp.

Béllière

Rolland

Tournier

et al. 2019

Transplant Infectious Dis

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“…Currently, they have been known to be the second or third most common agent responsible for invasive fungal infections in most countries (Oliver et al ). They represent the second filamentous fungal agent of infections in patients with haematological malignancies, bone marrow and solid organs transplanted patients (Cornely et al ; Jeong et al ). The rise in the incidence of invasive mucormycosis in recent years had become a matter of concern worldwide (Yamazaki et al ; Roden et al ; Vaezi et al ).…”

Section: Introductionmentioning

confidence: 99%

“…It is due to growing patient populations with severe immune disorders or uncontrolled metabolic diseases (Pang et al ). Rhizopus arrhizus is the most common organism isolated from patients with mucormycosis and is responsible for 70% to 80% of all infections cases (Roden et al ; Skiada et al ; Jeong et al ). Currently, this species have been divided into two varieties based on organic acid production: R. arrhizus var.…”

Section: Introductionmentioning

confidence: 99%

Microsatellite analysis of the population structure in Rhizopus arrhizus

et al. 2020

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Objectives Rhizopus arrhizus is recognized as an emergent agent of superficial and invasive mucormycosis. Despite an increasing number of these infections, the molecular epidemiology of Rhizopus species has not been well studied. Materials and methods In this study, 43 R. arrhizus strains (25 environmental and 18 clinical isolates) were genotyped using six novel panels of microsatellite markers. Results Upon the analysis of 43 isolates, 4–8 distinct alleles were detected for each marker. The discriminatory power for the individual markers ranged from 0·522 to 0·830. The combination of all six markers yielded 33 different haplotypes with a high degree of discrimination (0·989 D value). A four‐marker combination were selected as the most parsimonious panel achieving D > 0·95. One clinical isolate and one environmental isolate shared the same genotype suggesting the possible nosocomial outbreak of mucormycosis in hospitalized patients. We have noted that the strains isolated from cutaneous mucormycosis were different from the strains isolated from rhino‐orbito‐cerebral mucormycosis. Then, the hypothesis of particular tropism of infectious strains for a given site is not excluded. The standardized indices of association IA and rBarD were significantly different from zero (P < 0·01), suggesting a prevailing clonal reproduction. The environmental population was significantly differentiated from clinical populations (Fst = 0·2249). Conclusions Microsatellite typing method described in our study showed an excellent degree of discriminatory power. It is a promising tool for illuminating the molecular epidemiology of R. arrhizus species, including strain relatedness and transmission pathways.

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“…The most common manifestation of disease is rhino-orbito-cerebral mucormycosis, which is often seen in patients with predisposing factors such as immunosuppression or diabetes (4). Rates of mucormycosis are increasing worldwide, due in part to an increase in the prevalence of predisposing factors (4, 5). As the causative fungi are ubiquitous in the soil, outbreaks are often caused by exposure to environmental sources, ranging widely from environmental disasters such as tornadoes to contaminated hospital linen (6-8).…”

Section: Introductionmentioning

confidence: 99%

Drug-resistant epimutants exhibit organ-specific stability and induction during murine infections caused by the human fungal pathogenMucor circinelloides

Chang

Heitman

2019

Preprint

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The environmentally ubiquitous fungus Mucor circinelloides is a primary cause of the emerging disease mucormycosis. Mucor infection is notable for causing high morbidity and mortality, especially in immunosuppressed patients, while being inherently resistant to the majority of clinically available antifungal drugs. A new, RNAi-dependent, and reversible epigenetic mechanism of antifungal resistance – epimutation - was recently discovered in M. circinelloides. However, the effects of epimutation in a host-pathogen setting were unknown. We employed a systemic, intravenous murine model of Mucor infection to elucidate the potential impact of epimutation in vivo. Infection with an epimutant strain resistant to the antifungal agents FK506 and rapamycin revealed that the epimutant-induced drug resistance was stable in vivo in a variety of different organs and tissues. Reversion of the epimutant-induced drug resistance was observed to be more rapid in isolates from the brain, as compared to those recovered from the liver, spleen, kidney, or lungs. Importantly, infection with a wild-type strain of Mucor led to increased rates of epimutation after strains were recovered from organs and exposed to FK506 stress in vitro. Once again, this effect was more pronounced in strains recovered from the brain than from other organs. In summary, we report the rapid induction and reversion of RNAi-dependent drug resistance after in vivo passage through a murine model, with pronounced impact in strains recovered from brain. Defining the role played by epimutation in drug resistance and infection advances our understanding of Mucor and other fungal pathogens, and may have implications for antifungal therapy.IMPORTANCEThe emerging fungal pathogen Mucor circinelloides causes a severe infection, mucormycosis, which leads to considerable morbidity and mortality. Treatment of Mucor infection is challenging because Mucor is inherently resistant to nearly all clinical antifungal agents. An RNAi-dependent and reversible mechanism of antifungal resistance, epimutation, was recently described in Mucor. Epimutation has not been studied in vivo and it was unclear whether it would contribute to antifungal resistance observed clinically. We demonstrate that epimutation can be both induced and reverted after in vivo passage through a mouse model; rates of both induction and reversion are higher after brain infection than after infection of other organs (liver, spleen, kidneys, or lungs). Elucidating the roles played by epimutation in drug resistance and infection will improve our understanding of Mucor and other fungal pathogens, and may have implications for antifungal treatment.

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The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports

Abstract: Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.

Cited by 706 publications

References 39 publications

Early necrotic skin lesions after a ABO‐incompatible kidney transplantation: The threat of Cunninghamella Spp.

Early necrotic skin lesions after a ABO‐incompatible kidney transplantation: The threat of Cunninghamella Spp.

Microsatellite analysis of the population structure in Rhizopus arrhizus

Drug-resistant epimutants exhibit organ-specific stability and induction during murine infections caused by the human fungal pathogenMucor circinelloides

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