• Osteomyelitis septic arthritis Lomentospora prolificans voriconazole paediatric

• Scedosporium apiospermum
• amphotericin B cholesterol sulfate lipid complex
• metagenomic next-generation sequencing
• near-drowning
• voriconazole

• funding

• fungal disease

• Antifungal Agents/therapeutic use
• Antifungal Agents/pharmacokinetics
• Antifungal Agents/pharmacology
• Humans
• Invasive Fungal Infections/drug therapy
• Invasive Fungal Infections/microbiology
• Drug Resistance, Fungal
• Fungi/drug effects
• Animals
• Treatment Outcome

• Aspergillus
• DMI fungicides
• Fusarium
• Rhizopus
• cross-resistance
• emerging fungal pathogens
• resistance markers
• trans-kingdom pathogens

• amphotericin B
• drug resistance
• genetic speciation
• micafungin
• multiple
• scedosporium
• voriconazole

• Humans
• Antifungal Agents/pharmacology
• Antifungal Agents/therapeutic use
• Voriconazole/therapeutic use
• Scedosporium
• Retrospective Studies
• Taiwan/epidemiology
• Ascomycota

• Candida species
• antifungal susceptibility testing
• antifungals
• drug combinations

• Chemical composition
• Prunus mahaleb l.
• antifungal
• candida species
• indifferent effect

• Antifungal Agents/pharmacology
• Candida albicans
• Fatty Acids/pharmacology
• Fluconazole/pharmacology
• Linoleic Acid/pharmacology
• Microbial Sensitivity Tests
• Oleic Acid/pharmacology
• Plant Oils/pharmacology
• Prunus
• alpha-Linolenic Acid/pharmacology

• Bliss independence
• Candida
• Loewe additivity
• antagonism
• antifungal drugs
• pharmacodynamic interactions
• synergy

Scedosporium apiospermum (S. apiospermum) is a clinically rare and aggressive fungus mainly found in contaminated water, wetlands, decaying plants, stagnant water, and potted plants in hospitals. The lung, bone, joint, eye, brain, skin, and other sites are easily infected, and there is a marked risk of misdiagnosis. There have been few case reports of infection by S. apiospermum of the lumbar vertebrae; most reports have focused on infection of the lung.

An otherwise healthy 60-year-old man presented with a 4-mo history of lumbosacral pain, stooping, and limited walking. The symptoms were significantly aggravated 10 d prior to hospitalization, and radiating pain in the back of his left lower leg developed, which was so severe that he could not walk. Movement of the lumbar spine was significantly limited, anterior flexion was about 30°; backward extension, right and left lateral curvature, and rotational mobility were about 10°; tenderness of the spinous processes of the lumbar 3-5 vertebrae was evident, and the muscle strength of both lower limbs was grade IV. Imaging suggested bony destruction of the lumbar 3, 4, and 5 vertebrae and sacral 1 vertebra; in addition, the corresponding intervertebral spaces were narrowed and the lumbar 5 vertebra was posteriorly displaced and unstable. Lumbar vertebral infection was also noted, and the possibility of lumbar tuberculosis was considered. We first performed surgical intervention on the lesioned lumbar vertebrae, cleared the infected lesion, and performed stable fixation of the lesioned vertebral body using a lumbar internal fixation device, which restored the stability of the lumbar vertebrae. Cytological and pathological examination of the lesioned tissue removed during surgery confirmed S. apiospermum infection of the lumbar vertebrae; on this basis, the patient was administered voriconazole. At the 6-mo follow-up, efficacy was significant, no drug-related side effects were observed, and imaging examination showed no evidence of recurrence.

S. apiospermum infection can occur in immunocompetent individuals with no history of near drowning. Voriconazole is effective for the treatment of S. apiospermum infection of the lumbar vertebrae for which it is suitable as the first-line therapy.

• Scedosporium apiospermum
• Lumbar vertebrae
• Fungal infection
• Treatment
• Voriconazole
• Case report

• Lomentospora prolificans
• fusariosis
• invasive mould disease
• mucormycosis
• non-Aspergillus mould
• scedosporiosis

• Amorolfine
• Antifungal
• Fusarium species
• Synergistic
• Voriconazole

• Ibrexafungerp
• candidiasis
• fungerps
• triterpenoid class
• β-(1,3)-d-glucan

Scedosporium apiospermum is ubiquitous in the environment and is considered an emerging infection. Immunocompromised hosts can have a wide spectrum of diseases ranging from cutaneous to disseminated disease that may involve pulmonary, central nervous system, or bone. Disseminated disease in immunocompetent hosts is uncommon. Treatment of deep-seated infections is challenging because of the limited susceptibility of the Scedosporium species to all current antifungal drugs. We report a case of Scedosporidium apiospermum fungemia with a presumed pulmonary involvement in an immunocompetent patient. The fungemia was successfully treated with oral voriconazole and terbinafine.

• Fungemia
• Scedosporium apiospermum

In the fungal pathogen Aspergillus fumigatus, resistance to azole antifungals is often linked to mutations in CYP51A, a gene that encodes the azole antifungal drug target lanosterol 14α-demethylase. The aim of this study was to investigate whether similar changes could be associated with azole resistance in a Malaysian Fusarium solani species complex (FSSC) isolate collection. Most (11 of 15) clinical FSSC isolates were Neocosmospora keratoplastica and the majority (6 of 10) of environmental isolates were Neocosmospora suttoniana strains. All 25 FSSC isolates had high minimum inhibitory concentrations (MICs) for itraconazole and posaconazole, low MICs for amphotericin B, and various (1 to >32 mg/l) voriconazole susceptibilities. There was a tight association between a 23 bp CYP51A promoter deletion and high (>32 mg/l) voriconazole MICs; of 19 FSSC strains sequenced, nine isolates had voriconazole MICs > 32 mg/l, and they all contained the 23 bp CYP51A promoter deletion, although it was absent in the ten remaining isolates with low (≤12 mg/l) voriconazole MICs. Surprisingly, this association between voriconazole resistance and the 23 bp CYP51A promoter deletion held true across species boundaries. It was randomly distributed within and across species boundaries and both types of FSSC isolates were found among environmental and clinical isolates. Three randomly selected N. keratoplastica isolates with low (≤8 mg/l) voriconazole MICs had significantly lower (1.3–7.5 times) CYP51A mRNA expression levels than three randomly selected N. keratoplastica isolates with high (>32 mg/l) voriconazole MICs. CYP51A expression levels, however, were equally strongly induced (~6,500-fold) by voriconazole in two representative strains reaching levels, after 80 min of induction, that were comparable to those of CYP51B. Our results suggest that FSSC isolates with high voriconazole MICs have a 23 bp CYP51A promoter deletion that provides a potentially useful marker for voriconazole resistance in FSSC isolates. Early detection of possible voriconazole resistance is critical for choosing the correct treatment option for patients with invasive fusariosis.

• Cyp51A
• FSSC
• Fusarium
• Neocosmospora
• azole
• sterol regulatory element

• Cancer
• Children
• Fusarium spp.
• Nosocomial infection

• Aspergillus fumigatus
• In vitro interactions
• Micafungin
• Voriconazole

• Scedosporium
• bone marrow transplant
• genitourinary
• kidney
• opportunistic infection
• transplantation
• urinary

• Scedosporium
• cystic fibrosis
• lung transplantation
• scedosporiosis

• Model organisms
• Molecular mechanisms
• Multidrug resistance (MDR)
• Primary antifungal resistance

• Aspergillosis
• echinocandin
• isavuconazole
• mucormycosis
• polyene
• triazole

Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents.

• Corticosteroid
• GM-CSF
• Immunocompromised
• Scedosporium
• Synergy

• Chronic granulomatous disease
• Emericella nidulans var. echinulata
• Micafungin
• Rasamsonia piperina
• Voriconazole

Disseminated scedosporiosis is rare in dogs and is usually reported in German Shepherds with suspected heritable immunodeficiency. This is the first report of disseminated scedosporiosis due to Scedosporium prolificans in a Labrador retriever dog that was receiving immunosuppressive drug therapy for treatment of immune-mediated haemolytic anaemia. Despite cessation of immunosuppressive medications and an initial response to aggressive treatment with voriconazole and terbinafine the dog developed progressive disease with neurological signs necessitating euthanasia six months from diagnosis.

•

Disseminated scedosporiosis due to Scedosporium prolificans is described in a dog.

• Canine
• Invasive fungal infection
• Scedosporiosis

• Brain abscess
• Immunocompetent
• Scedosporium
• Silicosis

Invasive aspergillosis is a serious complication of solid organ transplantation. An early diagnosis is hampered by the lack of reliable serum markers and, even if appropriately diagnosed and treated with current antifungal agents, has a high mortality rate. We report a case of invasive pulmonary and cerebral aspergillosis in a renal transplant patient treated with IFN-γ in conjunction with combination anti-fungal therapy for six weeks in whom complete resolution of the fungal infection was achieved. Renal function remained intact throughout the treatment period. Surveillance CT scans of the chest and head showed resolution of prior disease but revealed a new left upper lobe mass four months after completion of treatment with IFN-γ. Biopsy of the lesion was positive for primary lung adenocarcinoma, for which she underwent left upper lobe resection. The pathology report confirmed clear surgical margins and lymph nodes and no evidence of fungal hyphae. IFN-γ should be considered early in the management of invasive aspergillosis in renal transplant patients. To date, allograft rejection has not been encountered.