Antifungal Triazoles and Polymorphonuclear Leukocytes Synergize To Cause Increased Hyphal Damage to<i>Scedosporium prolificans</i>and<i>Scedosporium apiospermum</i>

Gil-Lamaignere, Cristina; Roilides, Emmanuel; Mosquera, Juan Alejandro Neira; Maloukou, Avgi; Walsh, Thomas J.

doi:10.1128/aac.46.7.2234-2237.2002

Cited by 56 publications

(33 citation statements)

References 42 publications

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“…Of note, the synergistic activity has been observed at low concentrations of the antifungals. This finding may be of particular importance, especially in immunocompromised patients, when a triazole reaches its trough level in plasma where such synergy may prevent fungal regrowth (152). Regardless of the mechanisms behind these collaborative effects, the findings from these studies would support the concomitant administration of antifungals and PMN transfusions to persistently neutropenic patients with invasive scedosporiosis.…”

Section: Immunotherapymentioning

confidence: 79%

“…Triazoles (itraconazole, voriconazole, and posaconazole) have additive antifungal activities in combination with PMNs against S. apiospermum. Voriconazole plus posaconazole demonstrated synergistic interactions with PMNs against S. prolificans (152). In a murine model of Scedosporium infection, Ortoneda and colleagues (325) demonstrated that liposomal amphotericin B plus G-CSF improved survival over that with liposomal amphotericin B or amphotericin B deoxycholate.…”

Section: Immunotherapymentioning

confidence: 99%

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Infections Caused byScedosporiumspp

et al. 2008

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SUMMARY Scedosporium spp. are increasingly recognized as causes of resistant life-threatening infections in immunocompromised patients. Scedosporium spp. also cause a wide spectrum of conditions, including mycetoma, saprobic involvement and colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. Invasive scedosporium infections are also associated with central nervous infection following near-drowning accidents. The most common sites of infection are the lungs, sinuses, bones, joints, eyes, and brain. Scedosporium apiospermum and Scedosporium prolificans are the two principal medically important species of this genus. Pseudallescheria boydii, the teleomorph of S. apiospermum, is recognized by the presence of cleistothecia. Recent advances in molecular taxonomy have advanced the understanding of the genus Scedosporium and have demonstrated a wider range of species than heretofore recognized. Studies of the pathogenesis of and immune response to Scedosporium spp. underscore the importance of innate host defenses in protection against these organisms. Microbiological diagnosis of Scedosporium spp. currently depends upon culture and morphological characterization. Molecular tools for clinical microbiological detection of Scedosporium spp. are currently investigational. Infections caused by S. apiospermum and P. boydii in patients and animals may respond to antifungal triazoles. By comparison, infections caused by S. prolificans seldom respond to medical therapy alone. Surgery and reversal of immunosuppression may be the only effective therapeutic options for infections caused by S. prolificans.

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Section: Immunotherapymentioning

confidence: 79%

Section: Immunotherapymentioning

confidence: 99%

Infections Caused byScedosporiumspp

et al. 2008

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“…These studies suggested that immunomodulators may be acting via neutrophils (Th1 response) or monocytes (inducing tumor necrosis factor and macrophage inflammatory protein 1␣). In separate studies, VORI, POSA, and ITRA enhanced the antifungal functions of human PMNs against hyphae of S. prolificans and S. apiospermium (81). Similarly, AmB lipid complex plus PMN displayed a significant additive effect against both Scedosporium species (22% for S. prolificans and 81% for S. apiospermum; P Ͻ 0.04) (80).…”

Section: Antifungals Combined With Immunomodulatorsmentioning

confidence: 87%

Combination Treatment of Invasive Fungal Infections

et al. 2005

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The persistence of high morbidity and mortality from systemic fungal infections despite the availability of novel antifungals points to the need for effective treatment strategies. Treatment of invasive fungal infections is often hampered by drug toxicity, tolerability, and specificity issues, and added complications often arise due to the lack of diagnostic tests and to treatment complexities. Combination therapy has been suggested as a possible approach to improve treatment outcome. In this article, we undertake a historical review of studies of combination therapy and also focus on recent studies involving newly approved antifungal agents. The limitations surrounding antifungal combinations include nonuniform interpretation criteria, inability to predict the likelihood of clinical success, strain variability, and variations in pharmacodynamic/pharmacokinetic properties of antifungals used in combination. The issue of antagonism between polyenes and azoles is beginning to be addressed, but data regarding other drug combinations are not adequate for us to draw definite conclusions. However, recent data have identified potentially useful combinations. Standardization of assay methods and adoption of common interpretive criteria are essential to avoid discrepancies between different in vitro studies. Larger clinical trials are needed to assess whether combination therapy improves survival and treatment outcome in the most seriously debilitated patients afflicted with life-threatening fungal infections

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“…Importantly, antagonism was not observed with any of these combinations. Gil-Lamaignere et al showed a synergistic effect of voriconazole or posaconazole with neutrophils in vitro against hyphae of S. prolificans (285). Older literature also suggests synergy with ketoconazole and 5-FC for a variety of dematiaceous fungi (152).…”

Section: Antifungal Combinationsmentioning

confidence: 99%

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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Antifungal Triazoles and Polymorphonuclear Leukocytes Synergize To Cause Increased Hyphal Damage toScedosporium prolificansandScedosporium apiospermum

Cited by 56 publications

References 42 publications

Infections Caused byScedosporiumspp

Infections Caused byScedosporiumspp

Combination Treatment of Invasive Fungal Infections

Melanized Fungi in Human Disease

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