Ostrosky-Zeichner, L., Casadevall, A., Galgiani, J. N., Odds, F. C., & Rex, J. H. (2010). An insight into the antifungal pipeline: selected new molecules and beyond. Nature reviews. Drug discovery, 9(9), 719-27.
Invasive fungal infections are increasing in incidence and are associated with substantial mortality. Improved diagnostics and the availability of new antifungals have revolutionized the field of medical mycology in the past decades. This Review focuses on recent developments in the antifungal pipeline, concentrating on promising candidates such as new azoles, polyenes and echinocandins, as well as agents such as nikkomycin Z and the sordarins. Developments in vaccines and antibody-based immunotherapy are also discussed. Few therapeutic products are currently in active development, and progression of therapeutic agents with fungus-specific mechanisms of action is of key importance.
Bennett, J. E., Powers, J., Walsh, T., Viscoli, C., de Pauw, B., Dismukes, W., Galgiani, J., Glauser, M., Herbrecht, R., Kauffman, C., Lee, J., Pappas, P., Rex, J., & Verweij, P. (2003). Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 36(Suppl 3), S117-22.
There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever.
Shubitz, L. F., Roy, M. E., Nix, D. E., & Galgiani, J. N. (2013). Efficacy of Nikkomycin Z for respiratory coccidioidomycosis in naturally infected dogs. Medical mycology, 51(7), 747-54.
Nikkomycin Z (NikZ) is a chitin synthase inhibitor with antifungal efficacy against Coccidioides spp. and other endemic fungi. Dogs suffer a rate and range of natural coccidioidomycosis similar to humans and were considered an excellent model for initially testing NikZ against naturally acquired disease. Twelve dogs with coccidioidal pneumonia that had been present for an average of three months were treated with 250 mg (5-15 kg) or 500 mg (> 15-30 kg) twice daily for 60 days. Nine dogs completed the course of treatment and seven dogs had improvement in disease based on radiographs, clinicopathological parameters, physical examination findings, and subjective assessment by owners; three dogs had resolution or near resolution of disease. Based on this small study, NikZ shows efficacy to treat naturally acquired coccidioidomycosis and merits further development for trials in humans.
Rex, J. H., Pfaller, M. A., Galgiani, J. N., Bartlett, M. S., EspinelIngroff, A., Ghannoum, M. A., Lancaster, M., Odds, F. C., Rinaldi, M. G., Walsh, T. J., & Barry, A. L. (1997). Development of interpretive breakpoints for antifungal susceptibility testing: Conceptual framework and analysis of in vitro in vivo correlation data for fluconazole, itraconazole, and Candida infections. CLINICAL INFECTIOUS DISEASES, 24(2), 235-247.
Wack, E. E., Ampel, N. M., Sunenshine, R. H., & Galgiani, J. N. (2015). The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 61(5), 787-91.
A skin test that detects dermal hypersensitivity in persons with past infection with Coccidioides species is again available for clinical use. Nearly all of the clinical studies with similar materials were published prior to the 1990s, and as a result, many practicing physicians will be unfamiliar with how skin testing for coccidioidomycosis might be useful in patient management or as a research tool. We review clinical and epidemiological studies with past skin test antigens, the composition of past and current skin test preparations with particular attention to differences in the preservatives, and how the current preparation could be used today.
