Mucormycosis in immunocompetent patient resulting in extensive maxillary sequestration

Venkatesh, Deepak; Dandagi, Satyajit; Chandrappa, Pramod Redder; Hema, K.

doi:10.4103/jomfp.jomfp_163_17

Cited by 36 publications

(29 citation statements)

References 11 publications

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“…[48][49][50][51]65 Mucormycosis rarely affects immunocompetent persons, 16 but cutaneous, rhino-orbital, and (occasionally) disseminated infections have been reported following local cutaneous or soft tissue trauma. 7,[95][96][97][98] A recent meta-analysis of 600 publications from 2000 to 2017 comprising 851 cases of mucormycosis worldwide cited the following risk factors: DM (40%); trauma (33%); HemeM (32%); diabetic ketoacidosis (20%); neutropenia (20%); no underlying disease (18%); SOTR (14%); burns (11%); and natural disasters (5%). 20 In Asia, DM is the most common risk factor for mucormycosis, 20,67,99 whereas organ transplants and HemeM are more common in Europe and North America.…”

Section: Risk Factors For Mucormycosismentioning

confidence: 99%

“…7 A black eschar may result as blood vessels become thrombosed and tissue infarction occurs. 98 Mucorales stain poorly with Gram stain; Grocott-Gomori methenamine silver is the preferred stain. 23 In tissue specimens, Mucorales have broad (10-20 μm in diameter) nonseptate ribbon-like hyphae with branches occurring at right angles 132 (►Fig.…”

Section: Diagnosis Changes In Diagnosis and Treatmentmentioning

confidence: 99%

“…15,70,74 Dental procedures in patients with poorly controlled DM may be a risk factor for ROCM. 158,159 Destructive infections of the mandible 160 or maxilla 98,161 may extend from dental infections. 159 Signs and symptoms may include fever, headache, facial pain, nasal congestion, swelling of periorbital tissues, and dark nasal or palatine mucosa eschar.…”

Section: Rhino-orbital-cerebral Mucormycosismentioning

confidence: 99%

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Mucormycosis

Reid

Lynch

Fishbein

et al. 2020

Semin Respir Crit Care Med

158

108

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Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result from ingestion of contaminated food, inhalation of spores into the nares or lungs, or inoculation into disrupted skin or wounds. In developed countries, mucormycosis occurs primarily in severely immunocompromised hosts (e.g., those with hematological malignancies, organ transplantation, neutropenia, autoimmune disorders, or other impairments in immunity). Only 6 to 10% of cases occur in subjects with no underlying disease. In contrast, in developing countries, most cases of mucormycosis occur in persons with poorly controlled diabetes mellitus or in immunocompetent subjects following trauma. Mucormycosis exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis, and infarction of tissue. Mortality associated with invasive mucormycosis is high (> 30–50%), with 90% mortality associated with disseminated disease. Mortality rates are much lower, though still significant (10–30%), among patients with localized cutaneous disease.The diagnosis of mucormycosis relies upon histopathology and culture. Blood tests are of limited diagnostic value. Even with disseminated disease, blood cultures are usually negative. Mucorales have a distinct histological appearance, with irregular, nonseptate hyphae that branch at right angles. Cultures and/or polymerase chain reaction (PCR) are important to identify the genera.Based on anatomic localization, mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal (GI), (5) disseminated, and (6) mucormycosis of uncommon sites. Among diabetics, ROCM is the most common clinical presentation, whereas lung involvement is uncommon. In contrast, among organ transplant recipients or patients with hematological malignancies (HemeM), pulmonary and disseminated diseases are most common. Mucormycosis can progress rapidly, and delay in initiation of treatment by even a few days markedly worsens outcomes.Due to the rarity of mucormycosis, randomized controlled therapeutic trials have not been performed. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but the newer triazoles, posaconazole (POSA) and isavuconazole (ISAV) (the active component of the prodrug isavuconazonium sulfate), may be effective in patients refractory to or intolerant of LFAB. Early surgical debridement or excision plays an important adjunctive role. Additional studies are required to assess the optimal duration of therapy as well as the specific roles of LFAB and the triazoles in the treatment of mucormycosis.

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Section: Risk Factors For Mucormycosismentioning

confidence: 99%

Section: Diagnosis Changes In Diagnosis and Treatmentmentioning

confidence: 99%

Section: Rhino-orbital-cerebral Mucormycosismentioning

confidence: 99%

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Mucormycosis

Reid

Lynch

Fishbein

et al. 2020

Semin Respir Crit Care Med

158

108

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“…It shows extraction paves path for entry of fungi (microbes). It usually begins in nasal mucosa or palate and extends to the paranasal sinuses, spreading via the angular, lacrimal, and ethmoid vessels as well as by direct extension from the sinuses into the retro-orbital region and then brain [7]. Once fungus enters the blood stream they can disseminate to other organs such as cerebrum or lungs which can be fatal for the patient.…”

Section: Discussionmentioning

confidence: 99%

Rhino- Orbito Cerebral Mucormycosis – Uncontrolled, Untimely and Unsaved

Mathew¹,

R²,

Kumar³

et al. 2019

SJM

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“…Over the past decades, there has been a global and ongoing rise in the incidence of mucormycosis, primarily due to the increasing number of diabetic patients and increased use of immunosuppressive drugs (5)(6)(7)(8)(9)(10). Mucormycosis is also on the rise in immunocompetent individuals (11)(12)(13)(14). Mucorales species grow as molds in the environment and produce sporangiospores that can enter the host via inhalation resulting in pulmonary infection, through the skin due to trauma resulting in cutaneous infections, or through the nasal passages resulting in rhinocerebral infections (15)(16)(17).…”

mentioning

confidence: 99%

A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides

Vellanki

Billmyre

Lorenzen

et al. 2020

mBio

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Mucormycosis is an emerging lethal fungal infection in immunocompromised patients. Mucor circinelloides is a causal agent of mucormycosis and serves as a model system to understand genetics in Mucorales. Calcineurin is a conserved virulence factor in many pathogenic fungi, and calcineurin inhibition or deletion of the calcineurin regulatory subunit (CnbR) in Mucor results in a shift from hyphal to yeast growth. We analyzed 36 calcineurin inhibitor-resistant or bypass mutants that exhibited hyphal growth in the presence of calcineurin inhibitors or in the yeast-locked cnbRΔ mutant background without carrying any mutations in known calcineurin components. We found that a majority of the mutants had altered sequence in a gene, named here bycA (bypass of calcineurin). bycA encodes an amino acid permease. We verified that both the bycAΔ single mutant and the bycAΔ cnbRΔ double mutant are resistant to calcineurin inhibitor FK506, thereby demonstrating a novel mechanism of resistance against calcineurin inhibitors. We also found that the level of expression of bycA was significantly higher in the wild-type strain treated with FK506 and in the cnbRΔ mutants but was significantly lower in the wild-type strain without FK506 treatment. These findings suggest that bycA is a negative regulator of hyphal growth and/or a positive regulator of yeast growth in Mucor and that calcineurin suppresses expression of the bycA gene at the mRNA level to promote hyphal growth. BycA is involved in the Mucor hypha-yeast transition as our data demonstrate positive correlations among bycA expression, protein kinase A activity, and Mucor yeast growth. Also, calcineurin, independently of its role in morphogenesis, contributes to virulence traits, including phagosome maturation blockade, host cell damages, and proangiogenic growth factor induction during interactions with hosts. IMPORTANCE Mucor is intrinsically resistant to most known antifungals, which makes mucormycosis treatment challenging. Calcineurin is a serine/threonine phosphatase that is widely conserved across eukaryotes. When calcineurin function is inhibited in Mucor, growth shifts to a less virulent yeast growth form, which makes calcineurin an attractive target for development of new antifungal drugs. Previously, we identified two distinct mechanisms through which Mucor can become resistant to calcineurin inhibitors involving Mendelian mutations in the gene for FKBP12, including mechanisms corresponding to calcineurin A or B subunits and epimutations silencing the FKBP12 gene. Here, we identified a third novel mechanism where loss-of-function mutations in the amino acid permease corresponding to the bycA gene contribute to resistance against calcineurin inhibitors. When calcineurin activity is absent, BycA can activate protein kinase A (PKA) to promote yeast growth via a cAMP-independent pathway. Our data also show that calcineurin activity contributes to host-pathogen interactions primarily in the pathogenesis of Mucor.

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Mucormycosis in immunocompetent patient resulting in extensive maxillary sequestration

Cited by 36 publications

References 11 publications

Mucormycosis

Mucormycosis

Rhino- Orbito Cerebral Mucormycosis – Uncontrolled, Untimely and Unsaved

A Novel Resistance Pathway for Calcineurin Inhibitors in the Human-Pathogenic Mucorales Mucor circinelloides

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