Hyaline molds: Difference between revisions

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* Filamentous fungi that do ''not'' have melanin present in the fungal cells (although the spores may be coloured).
* Filamentous fungi that do ''not'' have melanin present in the fungal cells (although the spores may be coloured).
* Common genera include:

== ''Aspergillus'' species ==
** [[Aspergillus]]
** [[Fusarium]]

** [[Penicillium]]
=== Epidemiology ===
**[[Scedosporium]]

*Other genera include:
* ''Aspergillus'' is a ubiquitous fungus present worldwide, most commonly found in soil, air, water, and decaying vegetation. Risk factors for invasive disease include prolonged neutropenia (such as after induction chemotherapy), hematopoietic stem cell transplantation, graft-vs-host disease (especially with intensified therapy), solid-organ transplant (especially lung), anti-TNF-alpha immunosuppression, and CMV reactivation. Outbreaks have happened after construction.
**[[Acremonium]]

**[[Arthrinium]]
=== Pathogenesis ===
**[[Beauveria]]

**[[Chrysosporium]]
* Conidia are inhaled into the lungs and alveoli, where, if not cleared, the conidia can germinate and start to invade. The normal host defense involves ciliary clearance of the conidia, destruction of the conidia by pulmonary macrophages, or destruction of the hyphal form by PMNs.
**[[Geotrichum]]
** ''A. fumigatus'' has smaller conidia and may be more likely to reach the alveoli, which may explain the increased pathogenicity.
**[[Gliocladium]]
* Opsonization and complement may also be important.
**[[Malbranchea]]
* T-cell response is also important, with a Th-1 response being more favourable than Th-2.
**[[Paecilomyces]]
* Hydrocortisone appears to be a growth factor.
**[[Pestalotiopsis]]

**[[Purpureocillium]]
=== Spectrum of Disease ===
**[[Rasamsonia]]

**[[Sarocladium]]
* Colonization and superficial infections
**[[Scedosporium]]
** Pulmonary aspergilloma
**[[Scopulariopsis]]
** Otomycosis
**[[Sepedonium]]
** Onychomycosis
**[[Trichoderma]]
** Keratitis
**[[Trichothecium roseum]]
* Allergic syndromes
**[[Verticillium]]
** Allergic bronchopulmonary aspergillosis (ABPA)
** Allergic fungal rhinosinusitis
* Invasive aspergillosis, also a spectrum
** Chronic cavitary pulmonary aspergillosis (CCPA)
** Chronic necrotizing pulmonary aspergillosis
** Invasive pulmonary aspergillosis
* Other rare syndromes
** Ulcerative tracheobronchitis
** Invasive fungal rhinosinusitis
** Hematogenous dissemination to any organ
*** Cerebral aspergillosis
*** Osteomyelitis
*** SSTI

=== Non-culture diagnostic methods ===

* '''Serology''' for aspergillus antibodies exists, but is unhelpful, since it is a ubiquitous mold
* '''Galactomannan (GM):''' in serum or bronchoalveolar lavage (maybe CSF)
** Release by the fungal cell wall during growth
** Cutoff of 0.5 has 80% Sn and Sp (higher Sp and lower Sn at higher threshold)
*** Up to 90% in HSCT patients (serum)
*** Lower sensitivity in SOT
*** BAL fluid has higher sensitivity
** Can do it in CSF as well
** False-positives with piptazo and other beta-lactams (but may not still be the case)
** No longer useful in surveillance now that we use mold-active antifungal prophylaxis (per IDSA)
* '''1,3-beta-D-glucan''' (BDG): can detect ''Candida'' and ''Pneumocystis'' as well, so less specific. May be useful in combination with GM.
** Utility in invasive fungal infections: from [https://doi.org/10.1371/journal.pone.0131602 a systematic review in 2015], it is about 80% sensitive and 85% specific for IFI. Identified ''Candida'' and ''Aspergillus''. In [https://doi.org/10.1016/j.jinf.2014.04.008 a retrospective review from 2014], it had similar specific and inferior sensitivity compared to GM.
** Combination serologies: GM (BAL) Sn 43-56% and Sp 97%; BDG (blood) Sn 56-65% and Sp 97%; combination of ''either'' test positive Sn 78-92%% and Sp 93%, while PCR did not have any additional benefit ([https://doi.org/10.1016/j.cmi.2016.06.021 source]).
* '''Fungal PCR''' possible, but not routinely done; may not be helpful since the fungus is ubiquitous and wouldn’t differentiate invasive disease vs. colonization.
* '''Microarray DNA''':
* Microbiologic diagnostics are often combined with imaging to diagnose probable invasive fungal infection.

=== Identification of ''Aspergillus'' spp. ===

[[File:media/image12.png]]

* Identification is done based on macroscopic appearance, microscopic features (especially of the fruiting body), and sometimes with special tests.
* Complexes cannot be differentiated phenotypically, but rather need molecular methods
** May have cryptic species that are more resistant.
** Fumigatus: fumigatus, lentulus, udagawae
** Ustus: '''''A. calidoustus''''' (inherent resistance to ampho B)
** Niger: tubingensis and niger
** Versicolor: versicolor and sydowii

{|
! '''Species'''
! '''Colonies'''
! '''Head'''
! '''Conidiophore'''
! '''Phialides'''
! '''Other'''
|-
| ''A. flavus''
| Yellow green, yellow, brownish
| [[File:media/image11.png]]
| Rough colourless
| Uniseriate and biseriate
| Sclerotia sometimes present
|-
| ''A. fumigatus'' complex
| Grey-green, blue green, yellowish
| [[File:media/image5.png]]
| Smooth, colourless or greenish
| Uniseriate
| Good growth at 48ºC
|-
| ''A. glaucus''
| Green and yellow, yellowish, brown
| [[File:media/image2.png]]
| Smooth, colourless
| Uniseriate
| Yellow to orange cleistothecia present
|-
| ''A. nidulans''
| Green buff, purplish red, olive
| [[File:media/image8.png]]
| Smooth, brown
| Biseriate
| Round hülle cells and cleistothecia with purple ascospores usually present
|-
| ''A. niger''
| Black, white, yellowish
| [[File:media/image1.png]]
| Smooth, colourless or brown
| Biseriate
|
|-
| ''A. terreus''
| Brown cinnamon, yellowish brown
| [[File:media/image4.png]]
| Smooth, colourless
| Biseriate
| Round, solitary aleurioconidia produced directly on hyphae
|-
| ''A. ustus''
| Light brown, grayish brown, yellowish brown
|
| Smooth, brown
| Biseriate
| Long, brown-walled conidiophores, small vesicles, rough-walled conidia
|-
| ''A. versicolor''
| White, buff, yellow, pink, pale green, white, yellow, purplish red
|
| Smooth, colourless
| Biseriate
| Round hülle cells sometimes present
|}

=== Antifungal resistance ===

* '''Antifungal mechanisms'''
** '''Polyenes''' (amphotericin): binds ergosterol to create pores within the cell membrane.
** '''Triazoles''' (except fluconazole): inhibit sterol synthesis of ergosterol by disrupting 14-alpha demethylase. The mechanisms of resistance are myriad: modification of target enzymes, an increased expression of drug efflux mechanisms, an overexpression of target enzymes, an incorporation of exogenous cholesterol, an overexpression of HSP90 and of a sterole-regulatory element binding protein.
** '''Echinocandins''' (the fungins): disrupt synthesis of beta-glucan in the cell wall by inhibiting 1,3-beta glucan synthase.
* '''Resistance patterns'''
** All species are resistant to fluconazole. Historically, amphotericin has been the most reliable anti-''Aspergillus'' antifungal; now, voriconazole is the standard.
** Resistance to amphotericin is seen in ''A. terreus'', ''A. flavus'', and other less common species.
** ''A. niger'' has variable susceptibility to azoles. There is increasing ''A. fumigatus'' resistance to azoles, with reports being most common from Europe. ''A. calidoustus'' (within ''A. ustus'' complex) is a growing cause, with late presentation, intrinsic antifungal resistance, and high mortality.

{|
! Organism
! AmB
! Fluc
! Itra
! Vori
! Posa
! Anidula
! Caspo
! Mica
! Flucyt
|-
| ''Aspergillus'' spp.
| +
| –
| +
| +
| +
| +
| +
| +
| –
|-
| * A. flavus*
| ±
| –
| +
| +
| +
| +
| +
| +
| –
|-
| * A. fumigatus*
| +
| –
| +
| +
| +
| +
| +
| +
| –
|-
| * A. terreus*
| –
| –
| +
| +
| +
| +
| +
| +
| –
|-
| * A. niger*
| +
| –
| ±
| +
| +
| +
| +
| +
| –
|}

[[File:media/image6.png]]

=== Susceptibility testing ===

* '''Broth microdilution''' is the main method for determining ''Aspergillus'' susceptibility recommended by CLSI and EUCAST. Microdilution results are affected by a number of factors (shape of the microdilution well, inoculum concentration, temperature and length of incubation time), so testing must be rigorously standardized.

== ''Fusarium'' species ==

=== Epidemiology ===

* Ubiquitous, common in soil and organic debris, and a common cause of disease in plants.
* In humans, infection is rare and generally occurs after penetrating trauma.
* Disseminated and CNS disease is more common in immunocompromised hosts, including prolonged neutropenia.

=== Spectrum of disease ===

* Superficial
** Keratitis and endophthalmitis: big outbreak associated with contact lens solution back in the day
** Onychomycosis
** Skin and musculoskeletal infections (including mycetoma)
* Locally invasive
** Pneumonia
** Peritonitis associated with peritoneal dialysis
** Brain abscess
* Disseminated infection
** Fungemia: can be detected in blood culture.
** Disseminated infection

=== Identification ===

* '''Macroscopic:''' colonies grow rapidly with wooly texture (sometimes mucoid), and white, yellow, pink, purple, or pale brown surface and pale, red, violet, brown, or blue reverse.
* '''Microscopic:''' septate hyaline hyphae. Microconidia are unicellular (sometimes bicellular) and hyaline, ovoid to ellipsoid, in chains or singly from denticles. Macroconidia are curved and multicellular, with a foot cell at the base. Chlamydospores may be present.
** The macroconidia are the typical finding used to identify ''Fusarium'' spp.

=== Causes of invasive disease ===

* ''F. solani'': most common overall, and a common cause of keratitis
* ''F. oxysporum'': second-most common
* ''F. verticillioides'': third-most common
* ''F. moniliforme''
* ''F. proliferatum''
* ''F. chlamydosporum''
* ''F. anthophilum''
* ''F. dimerum''
* ''F. sacchari''

=== Treatment ===

* Remove indwelling lines.
* Treat underlying immunocompromise, if possible.
* Amphotericin B (high dose) is the antifungal of choice, although vori and posa have also been used.

== Other hyaline molds ==

=== ''Scedosporium'' spp. ===

* Epidemiology
** Found in rural soils, polluted waters, compost, cattle manure, and bird poop, as well as colonizing the respiratory tract.
** Present worldwide.
** Affects primarily the immunocompromised, though can cause localized infections in immunocompetent as well.
* Spectrum of disease
** Colonization of airways, especially in bronchiectasis
** ''Pseudallescheria boydii'' (''Scedosporium apio­spermum'') can cause mycetoma, and also pseudallescheriasis/scedosporiosis of lung, bone, joint, CNS. Rare sites of involvement include sinusitis, keratitis, endophthalmitis, skin and soft tissue infections, prostatitis, and endocarditis.
** ''Scedosporium prolificans'' usually causes localized infections in immunocompetent patients (bone and joint, eye, wounds, onychomycosis). In immunocompromised patients (e.g. neutropenia from chemotherapy), can disseminate and involve skin, lung, muscle, endophthalmitis
* Diagnosis
** With culture, though may represent colonization if recovered from a respiratory specimen.
** Colony grows rapidly, with wooly to cottony texture, a white surface that browns as it ages, and a pale reverse with brownish black zones.
** Septate, hyaline hyphae with annellide conidiophores that are simple or branched. Onidia are unicellular, obovoid, and pale brown. Sometimes has a ''Graphium'' state where conidiophores are bound together. Brown cleistothecia may be present after 2-3 weeks of incubation (looks like a pacman vomiting out conidia).
* Treatment
** ''S. apiopsermum'' is treated with voriconazole or amphotericin B. However, ''S. prolificans'' is extremely resistant to antifungals including amphotericin


[[Category:Microbiology]]
[[Category:Microbiology]]
[[Category:Fungi]]
[[Category:Filamentous fungi]]

Latest revision as of 21:23, 17 April 2022

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