Scedosporiosis is the general name for any

mycosis Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common ti ...

- i.e., fungal infection - caused by a

fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...

from the genus

Scedosporium ''Scedosporium'' is a genus of fungi in the family Microascaceae. The genus shed the alternative name '' Pseudallescheria'' as the " One Fungus, One Name" principle overtook the previous dual naming system, which had a distinct names for the an ...

. Current population-based studies suggest ''

Scedosporium prolificans ''Lomentospora prolificans'' is an emerging opportunistic fungal pathogen that causes a wide variety of infections in immunologically normal and immunosuppressed people and animals. It is resistant to most antifungal drugs and infections are often ...

'' (also known and recently more commonly referred to as ''Lomentospora prolificans'') and ''

Scedosporium apiospermum ''Pseudallescheria boydii'' is a species of fungus classified in the Ascomycota. It is associated with some forms of eumycetoma/ maduromycosis and is the causative agent of pseudallescheriasis. Typically found in stagnant and polluted water, it ...

'' to be among the most common infecting agents from the genus, although infections caused by other members thereof are not unheard of. The latter is an asexual form (anamorph) of another fungus, '' Pseudallescheria boydii''. The former is a “black yeast” (aka dematiaceous fungus), currently not characterized as well, although both of them have been described as saprophytes. The fungi of this

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biological classification, genus com ...

are more and more recognized as significant human pathogens. ''S. apiospermum'' is described as an emerging and even an “underrated” opportunistic pathogen. It was reported in a 2003 US study that Scedosporiosis had been associated with 25% of all non-''

Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Miche ...

'' fungal infections for

organ transplant Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...

patients. In a similar 2005 study scedosporal infections caused a 58%

mortality rate Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of de ...

for transplant recipients affected with it. Among the patients with

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...

, it is the second most common fungal infection. Moreover, a certain difficulty has been reported with correctly identifying the pathogen as, for example, scedosporal infections are in some cases almost indistinguishable from infections with other

filamentous fungi A mold () or mould () is one of the structures certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not ...

, like the already-mentioned ''Aspergillus'' – this difficulty could have potentially contributed to the “underrating” of the pathogen. All of this, along with the wide resistance possessed by the pathogens to the

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...

therapies currently in medical use, presents the increased interest for researchers to further study the scedoporal infections and develop treatments.

Background

First detectable description of a scedosporal disease arises in 1911 where ''S. apiospermum'' was identified as a cause of human

mycetoma Mycetoma is a chronic infection in the skin caused by either bacteria (actinomycetoma) or fungi (eumycetoma), typically resulting in a triad of painless firm skin lumps, the formation of weeping sinuses, and a discharge that contains grains. 80% ...

– a deep fungal subcutaneous infection. ''S. apiospermum'' is, indeed, not a recently discovered human pathogen and data about it have been aggregated over a period of more than 120 years. ''S. prolificans'', on the other hand, was discovered more recently, in 1974, under the name ''L. prolificans''. There has been a series of name changes for both ''S. apiospermum'' and its teleomorph ''P. boydii''. It has also been reported that at different timepoints, both, at some point, have been referred to as ''Petriellidium boydii'', ''Allescheria boydii'', ''Pseudallescheria sheari'' and ''Monosporium apiospermum'. S. prolificans'', likewise, went through a name change, and in the most recent literature, the original name ''L. prolificans'' is generally preferred as proposed by Lackner et al. in 2014. The risk of misidentification of the fungi for other infecting agents is, as previously mentioned, extant and significant as a given treatment will be differently applicable to different fungal infections, especially considering resistance patterns. In 2002, a corneal disease case was reported wherein '' Acrophialophora fusispora'' was mistaken for ''S. prolifcans''. The identification performed by the researchers based on the specifics of the pathogen’s

morphology Morphology, from the Greek and meaning "study of shape", may refer to: Disciplines * Morphology (archaeology), study of the shapes or forms of artifacts * Morphology (astronomy), study of the shape of astronomical objects such as nebulae, galaxies ...

was shown to be erroneous. In the correction to that particular case, a distinction was suggested based on the arrangement of cells and shape and color of

conidia A conidium ( ; ), sometimes termed an asexual chlamydospore or chlamydoconidium (), is an asexual, non-motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also called mitospores due to the ...

, however, in practice, difficulties therein still can persist. ''S. apiospermum'' was found to be resistant to a wide range of the known antifungal drugs, displaying high

minimal inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only ...

values to

amphotericin B Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...

isavuconazole Isavuconazonium sulfate, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis. The most common side effects include abnormal liver tests, ...

and

posaconazole Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication. It was approved for medical use in the United States in September 2006, and is available as a generic medication. Medical uses Posaconazole is u ...

, and is, to different extents, susceptible to

voriconazole Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by '' ...

micafungin Micafungin, sold under the brand name Mycamine, is an echinochandin antifungal medication used to treat and prevent invasive fungal infections including candidemia, abscesses, and esophageal candidiasis. It inhibits the production of beta-1,3- ...

and

anidulafungin Anidulafungin (International nonproprietary name, INN) (trade names Eraxis, Ecalta) is a Semisynthesis, semisynthetic echinocandin used as an antifungal medication, antifungal drug. It was previously known as LY303366. It may also have applicatio ...

. ''S. prolificans'' was found to be consistently resistant to all of these drugs and the effectiveness of voriconazole against it ''in vitro'' is limited. Interestingly, it was recently established that the growth ''S. prolificans'' can be inhibited by non-mucoid strains of ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...

''.

Infection

Both ''S. apiospermum'' and ''S. prolificans'' are capable of causing a wide range of infections, both in immunocompromised and immunocompetent individuals. Infections arising therefrom can be both localized and disseminated. It was reported that solid organ transplant and

hematopoietic stem cell transplant Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...

patients are a significant proportion of those at risk of ''Scedosporium'' mycoses.

Localized mycosis

Localized scedosporiosis can occur in a vast range of

internal organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a ...

and in

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw ...

s and limbs. It can commonly be found on the surface of the skin in a form of white and yellow papules. Among the other most common manifestations would be mycetoma, specifically,

eumycetoma Eumycetoma, also known as Madura foot, is a persistent fungal infection of the skin and the tissues just under the skin, affecting most commonly the feet, although it can occur in hands and other body parts. It starts as a painless wet nodule ...

(a mycetoma caused by a fungus), affecting

subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...

, joints and even

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

s and

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

s, although foot or leg is a common location of such an infection. A typical cause could be an open wound or surgery and both immunocompetent and immunocompromised patients can develop the infection. Eumycetoma grows in a granular fashion, is usually painless at first and grows steadily, causing complications and even disability if left untreated.

Osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...

, particularly,

sternal The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, lungs, and major blood vessels from injury. Sh ...

and lower rib bone infection, caused by ''S. apiospermum'' was reported in a successfully cured lung transplant patient in 2016. Scedosporal eye infection, specifically,

keratitis Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...

, arises usually after an injury of the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

, both ''S. apiospermum'' and ''S. prolificans'' are known to be able to cause it. It presents itself in a form of painful lesions within the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

accompanied by symptoms like

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...

and blurred vision.

Disseminated mycosis

Severely immunocompromised patients, patients on

immunosuppressive therapy Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

, as well as those suffering from cancers including

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

, have a risk of developing an infection that would constitute a spread of the extant localized infection throughout the organism. Additional and highly significant risk factor is

neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

, found especially in leukemia patients. Disseminated infections present a significant challenge to manage and result in consistently high mortality. Some studies suggest overall mortality rates for disseminated infections to be within 58-75%. A review of 25 cases published in 2006 reported mortality rates of disseminated infections with ''S. apiospermum'' and ''S. prolificans'' to be 70 and 100%, respectively. A 2002 review of 72 cases of disseminated

phaeohyphomycosis Phaeohyphomycosis is a diverse group of fungal infections, caused by dematiaceous fungi whose morphologic characteristics in tissue include hyphae, yeast-like cells, or a combination of these. It can be associated an array of melanistic filamento ...

reported poor outcomes for the antifungal treatment using

with the overall mortality being 79% among all patients, with a likewise 100% mortality for infections by ''S. prolificans.'' The culmination of disseminated scedosporiosis would be a highly fatal infection (>90% mortality rate) of the central nervous system. This development is possible in both immunocompromised and immunodeficient individuals. Studies report the former group develops the condition after a near-drowning experience in water contaminated with the pathogen's conidia. An extreme manifestation of this highly lethal case of scedosporiosis would be a

brain abscess Brain abscess (or cerebral abscess) is an abscess caused by inflammation and collection of infected material, coming from local (ear infection, dental abscess, infection of paranasal sinuses, infection of the mastoid air cells of the temporal bone ...

. Reported as "most catastrophic", a systematic disseminated scedosporal infection happens after its infiltration of blood vessel and subsequent growth in tissues. In neutropenic patients and patients with

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

, this produces most severe case of the infection and fatality.

Treatment

Effective treatment against scedosporiosis continues to present a challenge to modern medicine - as do many other fungal infections. It is still being researched and can vary depending on the localization and type of infection. Factors like immunodeficiency can significantly hinder the chances of a successful outcome. Studies suggest Voriconazole to be effective as clinical treatment for infections caused by ''S. apiospermum''. A study of 107 patients with saw the treatment successfully working in 57% in patients infected with scedosporiosis with best effects in localized ''S. apiospermum'' skin and bone infections. A 2003 review confirms its effectiveness for treating invasive mycosis of ''S. apiospermum'' while also citing evidence for efficacy of

ravuconazole Ravuconazole (codenamed BMS-207147 and ER-30346) is a potent triazole antifungal, the development of which was discontinued in 2007. The drug has shown to have a similar spectrum of activity to voriconazole, with an increased half-life. Howev ...

. A 2007 case report likewise shows the effectiveness of voriconazole in a renal transplant patient with disseminated scedosporiosis. In cases of ''S. apiospermum''-caused mycetoma, a treatment constituting a combination of surgery and

terbinafine Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to ...

was reported to be effective in 2017. An immunocompromised patient suffering from an intense subcutaneous infection in his right leg was successfully treated using this method. ''S. prolificans'' treatment presents a more significant challenge due to its wider array of antifungal resistance. Localized limb infections might require extensive surgery or even

amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...

. A review of 162 cases of ''S. prolificans'' infection found no association with antifungal treatment (using then-currently available medications) and reduced risk of death. One study, however, argued for the efficiency of combination therapy using voriconazole and terbinafine to cure an orthopedic infection in a non-immunocompromised host without the need for a radical surgery. More resent medical advances show hope for more efficient antifungal therapies, however, as novel drugs like Ibrexafungerp - a glucan synthase inhibitor - is somewhat effective in treating ''S. prolificans'' infections. Another drug, fosmanogepix, another fungal enzyme inhibitor, showed ''in vitro'' efficacy as treatment for scedosporiosis (including ''S. prolificans''). Olorofim, a new dihydroorotate dehydrogenase inhibitor - which disrupts pyrimidine biosynthesis, - is also deserving of the reader's attention as it showed efficacy against both ''S. prolificans'' and ''S. apiospermum'' as well as other fungi known to be universally resistant to known antifungal medications.

References

External links

{{Medical resources , ICD10 = B48.7 , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 449280 Animal fungal diseases Fungal diseases