B Spellberg

..These factors may be useful in defining enrollment randomization stratification critieria for future clinical trials, and in supporting clinical care of patients with mucormycosis...

..The optimal structure of an internal medicine ward team at a teaching hospital is unknown. We hypothesized that increasing the ratio of attendings to housestaff would result in an enhanced perceived educational experience for residents...

..To determine the safety of combination deferasirox plus LAmB therapy for mucormycosis, a multicentred, placebo-controlled, double-blinded clinical trial was conducted...

..It is critical that sponsors step forward with funding to conduct these clinical trials to determine whether outcomes from these devastating infections can be improved...

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..A number of candidate vaccines are in development, raising the promise that effective vaccines against S. aureus will become available in the not-so-distant future. Possible development programs for such vaccines are discussed...

..However, wild-card patent extension legislation is highly controversial due to concerns regarding its societal cost...

..With continued development, this strategy to recapitulate neutrophil functions has the potential to serve as an effective alternative to granulocyte transfusions...

..glabrata or C. krusei. Central venous catheters should be removed from all patients who have disseminated candidiasis, if feasible, and antifungal therapy should be administered to all patients who have candidemia or proven candidiasis...

..These data have significant implications for the development and interpretation of vaccine surrogate markers...

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..These data provide the foundation for cross-kingdom vaccine development against S. aureus and Candida, which collectively cause 200,000 bloodstream infections resulting in >/=40,000 to 50,000 deaths annually in the United States alone...

..In the absence of placebo-controlled trials, we sought to define the magnitude of efficacy of antimicrobial agents and resulting noninferiority margins for studies of complicated skin and skin-structure infection (SSSI)...

..Prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis...

..Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis...

..The rAls3p-N vaccine is a promising new vaccine candidate for further exploration to prevent systemic and mucosal candidal infections...

..With further refinements, activated HL-60 cells have the potential to overcome the technical barriers to neutrophil transfusions...

..Large-scale, prospective, randomized clinical trials are needed to define optimal management strategies for mucormycosis...

..However, despite decades of use, little is known about the physiological characteristics of the host in this model, and the cause of death remains unclear...

..We now report marked efficacy with subcutaneous rAls1p-N vaccination. Efficacy is retained in neutropenic and corticosteroid-treated mice. The rAls1p-N vaccine is a promising candidate for the prevention of invasive candidiasis...

..The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement...

..05) but did not improve organ clearance. In addition, prophylactic combination therapy was not more effective than prophylactic ABLC alone...

..aureus and C. albicans from tissues. Thus, vaccine-mediated adaptive immunity can protect against both infections by targeting microbes for destruction by innate effectors...

..Caspofungin at 1 but not 5 mg/kg/day mediated surprising improvements in survival during active fusariosis, despite lack of reduction in fungal burden. Further studies are warranted...

..These results suggest a unique susceptibility of patients with DKA to mucormycosis and provide a foundation for the development of new therapeutic interventions for these deadly infections...

..Furthermore, the results provide in vivo confirmation that hyphal formation by C. albicans induces type 2 or IL-10-dominant host responses in tissues...

..001) and mice treated with 0.5 mg of AmB per kg b.i.d. (P = 0.047). These data indicate that high-dose LAmB is more effective than AmB in treating murine disseminated zygomycosis...

..Thus, protein binding, by itself, may not predict the efficacy of some vaccines with aluminum adjuvants...

..Donors reacted to diverse immunodominant epitopes. Thus, facile humoral and cellular assays can monitor immune responses to the rAls3p-N vaccine in planned clinical trials...

..We sought to determine the potential for combination therapy with the iron chelator deferasirox + liposomal amphotericin B (LAmB) to improve the outcome of murine IPA compared with LAmB monotherapy...

..Continued investigation into the use of triple therapy against mucormycosis and aspergillosis is warranted...

..Invasive fungal infections cause considerable morbidity and mortality in neutropenic patients. White blood cell transfusions are a promising treatment for such infections, but technical barriers have prevented their widespread use...

..albicans, mediating resistance to phagocyte killing. Hyr1p is a promising target for vaccine or other immunological or small molecule intervention to improve the outcomes of disseminated candidiasis...

..oryzae. Thus, FTR1 is a virulence factor for R. oryzae, and anti-Ftr1p passive immunotherapy deserves further evaluation as a strategy to improve outcomes of deadly mucormycosis...

..Other iron chelators, including deferiprone, which do not deliver iron to R. oryzae have been described. We therefore sought to determine whether iron-chelation therapy with deferiprone would effectively treat mucormycosis...

..oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against zygomycosis merits further investigation...

..The fact that dead R. oryzae damage human endothelial cells may, in part, explain the lack of efficacy of fungicidal agents during clinical disease...

..The efficacy of combination echinocandin-polyene therapy for mucormycosis is a class effect...

..ABLC was as effective as LAmB in neutropenic but not DKA mice. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models...

..Iron acquisition is a critical step in the causative organisms' pathogenetic mechanism. Therefore, abrogation of fungal iron acquisition is a promising therapeutic strategy to impact clinical outcomes for this deadly disease...

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..In conclusion, mucormycosis causes considerable cost to the US health care system. Targeted deployment of a niche vaccine could decrease infection rates and mortality from mucormycosis in a cost-effective manner...

..Combination therapy was no better than LAmB alone, and posaconazole monotherapy did not improve survival or reduce fungal burden versus placebo...

..g., caspofungin) are ineffective against mucormycosis. However, on the basis of preclinical data, we recently began treating rhino-orbital-cerebral mucormycosis (ROCM) with combination polyene-caspofungin therapy...

..These data demonstrate that we have cloned the gene encoding a R. oryzae high affinity iron permease and the putative rFtr1p is involved in assimilation of iron from iron-depleted environments...

..Nevertheless, the mortality of nosocomial fungal infections remains high, and new therapeutic and preventative strategies are needed...

..In areas in which community-associated MRSA infection is endemic, empirical treatment of suspected necrotizing fasciitis should include antibiotics predictably active against this pathogen...

..In this review, we summarize current knowledge about non-Aspergillus mold infections of the chest, with a focus on risk factors, clinical features, diagnosis, and treatment...

..In such cases, administration of antimicrobial chemotherapy and exogenous cytokines restores systemic balance, which allows successful immune responses to clear the infection...

..aureus infections who have risk factors for acquisition of MRSA. However, there are no prospective data examining this approach...

..Despite the critical need for new antimicrobial agents, the development of these agents is declining. Solutions encouraging and facilitating the development of new antimicrobial agents are needed...

..Immun. 73:6191-6193, 2005). Here we show that the rAls1p-N vaccine also improves survival of outbred mice from disseminated candidiasis and that it is active against multiple virulent strains of C. albicans and non-C. albicans spp...

..albicans and emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis...

..As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted...

..Finally, these data validate the use of a conditional overexpression/suppression genetic strategy to identify candidal virulence factors...

..PNS 398/2590 (Rev. 11/07) Page - Continuation Format Page ..

..For these reasons, the potential for adrenergic antagonism to act as an effective immunotherapy is highly meritorious of investigation in this training application. ..

..Completion of the proposed studies will enable us to create a safe and effective strategy to overcome the barriers to white blood cell transfusions, revolutionizing the treatment of infections in cancer patients. ..

..The insights into fundamental immunological mechanisms of protection against S. aureus will also be of extreme importance to the development of other vaccine candidates targeting S. aureus in the future. ..

..Completion of the proposed studies will enable us to create a safe and effective strategy to overcome the barriers to white blood cell transfusions, revolutionizing the treatment of infections in cancer patients. ..

..PNS 398/2590 (Rev. 11/07) Page - Continuation Format Page ..

..The insights into fundamental immunological mechanisms of protection against S. aureus will also be of extreme importance to the development of other vaccine candidates targeting S. aureus in the future. ..

..The insights into fundamental immunological mechanisms of protection against S. aureus will also be of extreme importance to the development of other vaccine candidates targeting S. aureus in the future. ..