<i>Scedosporium prolificans</i>
            Osteomyelitis in an Immunocompetent Child Treated with Voriconazole and Caspofungin, as Well as Locally Applied Polyhexamethylene Biguanide

Steinbach, William J.; Schell, Wiley A.; Miller, Jackie L.; Perfect, John R.

doi:10.1128/jcm.41.8.3981-3985.2003

Cited by 95 publications

(62 citation statements)

References 55 publications

(26 reference statements)

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“…The combination of voriconazole with micafungin and amphotericin B was found to be synergistic in vitro against S. prolificans, though double combinations also lowered individual MICs (637). Other reports suggest synergy against S. prolificans with voriconazole and caspofungin or with micafungin and amphotericin B (160,716,821). Importantly, antagonism was not observed with any of these combinations.…”

Section: Antifungal Combinationsmentioning

confidence: 90%

“…There are relatively few case reports of isolated osteoarticular infections due to dematiaceous fungi, perhaps reflecting the significant trauma often required for implantation into these deeper tissues, though some cases did not have noticeable trauma. S. prolificans is the most common cause, with all except two cases occurring in young children (166,299,325,406,453,474,716,718). In addition to surgery, various antifungal therapies have been employed, with three cases using the combination of voriconazole and terbinafine with success (166,299,406).…”

Section: Phaeohyphomycosismentioning

confidence: 99%

“…In addition to surgery, various antifungal therapies have been employed, with three cases using the combination of voriconazole and terbinafine with success (166,299,406). Unusual therapies have also been tried, including irrigation with polyhexamethylbiguanide and oral therapy with miltefosine (406,716). Whether these actually improved the likelihood of a clinical response is unknown.…”

Section: Phaeohyphomycosismentioning

confidence: 99%

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Melanized Fungi in Human Disease

2010

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SUMMARY Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.

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Section: Antifungal Combinationsmentioning

confidence: 90%

Section: Phaeohyphomycosismentioning

confidence: 99%

Section: Phaeohyphomycosismentioning

confidence: 99%

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Melanized Fungi in Human Disease

2010

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“…We also assessed whether flocculation was affected by changes in pH by culture of the skn7 mutant in DMEM equilibrated to various pH levels (pH 5 to 8.5). These assays were, in part, predicated on conditions and principles suggested in previous reports (6,43). Flocculation of the skn7 mutant was not observed upon gross ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification and Characterization of anSKN7Homologue inCryptococcus neoformans

et al. 2005

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Cryptococcus neoformans is an encapsulated fungal pathogen that primarily infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis. The capacity of C. neoformans to subvert host defenses and disseminate by intracellular parasitism of alveolar macrophages in the immune-compromised host has led to studies to evaluate genes associated with C. neoformans resistance to oxidative stress. In the present study, we identify and characterize a C. neoformans homologue to SKN7, a transcription factor in Saccharomyces cerevisiae that regulates the oxidative stress response, cell cycle, and cell wall biosynthesis. To examine the contribution of SKN7 in the pathogenesis of fungal infections, we created skn7 mutants via targeted disruption. The skn7 mutants were observed to be more susceptible to reactive oxygen species in vitro and were significantly less virulent than the wild-type strain and a reconstituted strain as measured by cumulative survival in the mouse inhalational model. The Skn7 protein was observed to be important for expression of thioredoxin reductase in response to oxidative challenge. Interestingly, skn7 mutants were also observed to flocculate following in vitro culture, a novel phenotype not observed in skn7 mutants derived from other fungi. These findings demonstrate that SKN7 contributes to the virulence composite but is not required for pathogenicity in C. neoformans. In addition, flocculation of C. neoformans skn7 mutants suggests a potentially unique function of SKN7 not previously observed in other cryptococcal strains or skn7 mutants.Cryptococcus neoformans, the etiological agent of cryptococcosis, is an encapsulated fungal pathogen that infects the central nervous system of immunocompromised individuals, causing life-threatening meningoencephalitis (31). Cryptococcosis occurs in approximately 5 to 25% of AIDS patients worldwide (37), and studies have shown that 2.8% of organ transplant recipients can develop C. neoformans infections, resulting in an overall death rate of 42% (16). Although highly active antiretroviral therapy has contributed to a significant decrease in the incidence of cryptococcosis in AIDS patients in developed countries (2), increases in organ transplant recipients and patients undergoing extensive corticosteroid therapy forecast a rise of cryptococcosis in other high-risk populations. In medically advanced countries the acute mortality rate is between 10 and 25% (37), and conventional antifungal agents are often excessively toxic, lack potent fungicidal properties, or are being rendered less effective by the emergence of drug-resistant strains. Therefore, continued studies are needed to identify novel targets for the development of drugs or vaccines to combat cryptococcal infections.Obligate aerobic microorganisms, such as C. neoformans, are under persistent exposure to endogenous oxidative stress caused by the incomplete reduction of oxygen to water, which yields reactive oxygen species (ROS) such as H 2 O 2 , the hydrox...

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“…Fungal osteomyelitis following a traumatic injury is typically due to contamination of the wound with soil containing fungi such as Fusarium spp. (12,18), Scedosporium prolificans (19,20), or Pseudallescheria boydii (6,11,13,14). The clinical and radiological presentation of fungal osteomyelitis differs little from that of osteomyelitis caused by bacteria.…”

mentioning

confidence: 97%