Micafungin Enhances Neutrophil Fungicidal Functions against Candida Pseudohyphae

We evaluated the effect of the combination of micafungin and polymorphonuclear leukocytes (PMN) against hyphae of Candida albicans and Candida dubliniensis. Micafungin enhanced the PMN oxidative burst dose dependently. The combination was synergistic (C. albicans) or additive (C. dubliniensis); when PMN were pretreated with granulocyte-macrophage colony-stimulating factor, the combination was more effective

Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum

Scedosporium prolificans and Scedosporium apiospermum are resistant to most antifungal agents and cause refractory pulmonary and disseminated infections. The combined effects of deoxycholate amphotericin B, amphotericin B lipid complex and liposomal amphotericin B with human polymorphonuclear leucocytes(PMNs) in damaging hyphae of these fungi were evaluated by XTT assay. Amphotericin B lipid complex displayed a significant additive effect with PMNs against both Scedosporium species (22% for S. prolificans and 81% for S. apiospermum; P < 0.04). None of the formulations adversely affected the PMN antifungal activity. These findings may be important in designing better strategies for management of infections due to these organisms

Antifungal activity of human polymorphonuclear and mononuclear phagocytes against non-fumigatus Aspergillus species

Human phagocytic defenses against non-fumigatus aspergilli were compared with those against Aspergillus fumigatus. Monocyte-derived macrophages exhibited lower phagocytic capacities against non-fumigatus aspergilli, particularly A. nidulans and A. niger, compared with A fumigatus (P < 0.05). Non-opsonized hyphae suppressed oxidative burst (as measured by superoxide anion production) of polymorphonuclear leukocytes (PMNs). Further, these cells responded with less vigorous oxidative burst to serum-opsonized hyphae of non-fumigatus Aspergillus species, particularly A. flavus and A. terreus, compared with A. fumigatus (P ≤ 0.05). Similarly, PMNs induced less hyphal damage assessed by XTT colorimetric assay to non-fumigatus species, particularly A. flavus and A. nidulans, compared with A. fumigatus (P < 0.05). Thus, non-fumigatus aspergilli are generally more resistant to mononuclear and polymorphonuclear phagocytes than A. fumigatus, a finding which should be considered during management of invasive aspergillosis caused by these species

Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity

The balance of arginine metabolism via nitric oxide synthase (NOS) or arginase is an important determinant of the inflammatory response of murine macrophages and dendritic cells. Here we analyzed the expression of the isoform arginase I in human myeloid cells. Using healthy donors and patients with arginase I deficiency, we found that in human leukocytes arginase I is constitutively expressed only in granulocytes and is not modulated by a variety of proinflammatory and anti-inflammatory stimuli in vitro. We demonstrate that arginase I is localized in azurophil granules of neutrophils and constitutes a novel antimicrobial effector pathway, likely through arginine depletion in the phagolysosome. Our findings demonstrate important differences between murine and human leukocytes with respect to regulation and function of arginine metabolism via arginase

Comparative In Vitro Activities Of Posaconazole, Voriconazole, Itraconazole, And Amphotericin B Against Aspergillus And Rhizopus, And Synergy Testing For Rhizopus

We compared the in vitro activities of posaconazole, voriconazole, itraconazole, and amphotericin B against clinical isolates of Aspergillus spp. and Rhizopus spp., and explored the in vitro interaction between posaconazole and amphotericin B against Rhizopus spp. Clinical strains of 82 Aspergillus spp. (43 Aspergillus fumigatus, 29 A. flavus, 7 A. niger, 2 A. terreus, 1 A. nidulans) and 11 Rhizopus oryzae isolates were tested in accordance with CLSI M38-A microdilution guidelines. In vitro activity of posaconazole against Aspergillus spp. was also investigated with the Etest. The combination of posaconazole and amphotericin B against R. oryzae isolates was investigated by the checkerboard methodology. Voriconazole was the most active drug in vitro against Aspergillus spp., followed by posaconazole, itraconazole, and amphotericin B, in order of decreasing activity. In studies with R. oryzae isolates, posaconazole was found to be the most potent drug followed by itraconazole and amphotericin B. Voriconazole had no meaningful activity against Rhizopus. Posaconazole Etest MICs (g/ml) with Aspergillus spp. were found to be considerably lower than those obtained with the CLSI microdilution method (4-9 and 3-7 two-fold lower than CLSI MICs at 24 and 48 h, respectively). The interaction between posaconazole and amphotericin B was indifferent for all R. oryzae isolates tested; importantly no antagonism was observed.WoSScopu