Insights in Antifungal Drug Discovery
Françoise Gay-Andrieu
Georgetown University Medical Center, Washington, DC, 20057
Nantes Atlantique Universities, EA1155-IICiMed Nantes, France
Search for more papers by this authorJared May
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorDongmei Li
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorNuo Sun
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorHui Chen
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorRichard Calderone
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorDeepu Alex
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorFrançoise Gay-Andrieu
Georgetown University Medical Center, Washington, DC, 20057
Nantes Atlantique Universities, EA1155-IICiMed Nantes, France
Search for more papers by this authorJared May
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorDongmei Li
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorNuo Sun
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorHui Chen
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorRichard Calderone
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorDeepu Alex
Georgetown University Medical Center, Washington, DC, 20057
Search for more papers by this authorRichard A. Calderone
Georgetown University Medical Center, Washington, DC
Search for more papers by this authorCornelius J. Clancy
Department of Medicine, Infectious Diseases Division, University of Pittsburgh, Pittsburgh, PA
Search for more papers by this authorSummary
This chapter is divided into two sections. The first section focuses on clinical perspectives, especially of global candidiasis. The second section discusses antifungal drug discovery by offering two different but interacting approaches: traditional, or classical, and genomic. A large study was recently published on a 10.5-year surveillance of susceptibility of Candida species to fluconazole and voriconazole. This study reported a slight trend toward an increasing resistance, in some regions, of NAC species like Candida tropicalis and Candida parapsilosis. In human immunodeficiency virus (HIV)/AIDS patients especially, mucosal candidiasis, or oropharyngeal candidiasis (OPC), remains one of the most common types of infection throughout the world, but especially in both adult and pediatric age groups in developing countries. Information on the incidence of vulvovaginal candidiasis (VVC) is incomplete as it is not reportable. However, the estimate is that VVC caused by Candida species affects about 70 to 75% of young women of childbearing age (most frequent); 40 to 50% of these individuals will have a recurrence, and 5 to 8% will develop recurrent VVC, defined as four or more episodes per year. Systemic candidiasis and bloodstream infections (BSI) also qualify as global infectious diseases. An increased incidence of invasive candidiasis (IC), aspergillosis, and zygomycosis has been reported in tertiary care facilities in India. The currently used echinocandins (caspofungin, micafungin, and anidulafungin) are still relatively new, and studies relating to their in vivo efficacy are ongoing.
References
- Ameen, M., and R. Arenas 2009. Developments in the management of mycetomas. Clin. Exp. Dermatol. 34: 1–7.
- Arikan, S., and J. H. Rex 2001. Nystatin LF (Aronex/Abbott). Curr. Opin. Investig. Drugs 2: 488–495.
- Arita, A., X. Zhou, T. P. Ellen, X. Liu, J. Bai, J. P. Rooney, A. Kurtz, C. B. Klein, W. Dai, T. J. Begley, and M. Costa 2009. A genome-wide deletion mutant screen identifies pathways affected by nickel sulfate in Saccharomyces cerevisiae . BMC Genomics 10: 524.
- Baetz, K., L. McHardy, K. Gable, T. Tarling, D. Reberioux, J. Bryan, R. J. Andersen, T. Dunn, P. Hieter, and M. Roberge 2004. Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action. Proc. Natl. Acad. Sci. USA 101: 4525–4530.
- Batova, M., V. Klobucnikova, Z. Oblasova, J. Gregan, P. Zahradnik, I. Hapala, J. Subik, and C. Schuller 2010. Chemogenomic and transcriptome analysis identifies mode of action of the chemosensitizing agent CTBT (7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine). BMC Genomics 11: 153.
- Bennett, J. E. 2009. The changing face of febrile neutropenia—from monotherapy to moulds to mucositis. Management of mycoses in neutropenic patients: a brief history, 1960–2008. J. Antimicrob. Chemother. 63 (Suppl. 1): i23–i26.
- Blignaut, E. 2007. Oral candidiasis and oral yeast carriage among institutionalised South African paediatric HIV/ AIDS patients. Mycopathologia 163: 67–73.
- Boechk, M., and K. Marr 2002. Infection in hematopoietic stem cell transplantation, p. 527–571. In R. H. Rubin and L. S. Young (ed.), Clinical Approach to Infection in the Compromised Host. Kluwer Academic/Plenum, New York, NY.
- Bonifaz, A., D. Vazquez-Gonzalez, and A. M. Perusquia-Ortiz 2010. Subcutaneous mycoses: chromoblastomycosis, sporotrichosis and mycetoma. J. Dtsch. Dermatol. Ges. 8: 619–627; quiz, 628.
- Boucher, H. W., G. H. Talbot, J. S. Bradley, J. E. Edwards, D. Gilbert, L. B. Rice, M. Scheld, B. Spellberg, and J. Bartlett 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48: 1–12.
- Bougnoux, M. E., G. Kac, P. Aegerter, C. d'Enfert, J. Y. Fagon, and CandiRea Study Group 2008. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med. 34: 292–299.
- Bredel, M., and E. Jacoby 2004. Chemogenomics: an emerging strategy for rapid target and drug discovery. Nat. Rev. Genet. 5: 262–275.
- Bromuro, C., M. Romano, P. Chiani, F. Berti, M. Tontini, D. Proietti, E. Mori, A. Torosantucci, P. Costantino, R. Rappuoli, and A. Cassone 2010. Beta-glucan-CRM197 conjugates as candidates antifungal vaccines. Vaccine 28: 2615–2623.
- Cabib, E. 1991. Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins. Antimicrob. Agents Chemother. 35: 170–173.
- Cagnoni, P. J., T. J. Walsh, M. M. Prendergast, D. Bodensteiner, S. Hiemenz, R. N. Greenberg, C. A. Arndt, M. Schuster, N. Seibel, V. Yeldandi, and K. B. Tong 2000. Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J. Clin. Oncol. 18: 2476–2483.
- Canton, E., J. Peman, A. Valentin, A. Espinel-Ingroff, and M. Gobernado 2009. In vitro activities of echinocandins against Candida krusei determined by three methods: MIC and minimal fungicidal concentration measurements and time-kill studies. Antimicrob. Agents Chemother. 53: 3108–3111.
- Caston-Osorio, J. J., A. Rivero, and J. Torre-Cisneros 2008. Epidemiology of invasive fungal infection. Int. J. Antimicrob. Agents 32 (Suppl. 2): S103–S109.
- Cegelski, L., G. R. Marshall, G. R. Eldridge, and S. J. Hultgren 2008. The biology and future prospects of anti-virulence therapies. Nat. Rev. Microbiol. 6: 17–27.
- Chakrabarti, A., S. S. Chatterjee, and M. R. Shivaprakash 2008. Overview of opportunistic fungal infections in India. Nippon Ishinkin Gakkai Zasshi 49: 165–172.
- Chakraborty, N., A. Mukherjee, S. Santra, R. N. Sarkar, D. Banerjee, S. K. Guha, S. Chakraborty, and S. K. Bhattacharyya 2008. Current trends of opportunistic infections among HIV-seropositive patients from Eastern India. Jpn. J. Infect. Dis. 61: 49–53.
- Delmas, G., S. Park, Z. W. Chen, F. Tan, R. Kashiwazaki, L. Zarif, and D. S. Perlin 2002. Efficacy of orally delivered cochleates containing amphotericin B in a murine model of aspergillosis. Antimicrob. Agents Chemother. 46: 2704–2707.
- De Pauw, B., T. J. Walsh, J. P. Donnelly, D. A. Stevens, J. E. Edwards, T. Calandra, P. G. Pappas, J. Maertens, O. Lortholary, C. A. Kauffman, D. W. Denning, T. F. Patterson, G. Maschmeyer, J. Bille, W. E. Dismukes, R. Herbrecht, W. W. Hope, C. C. Kibbler, B. J. Kullberg, K. A. Marr, P. Munoz, F. C. Odds, J. R. Perfect, A. Restrepo, M. Ruhnke, B. H. Segal, J. D. Sobel, T. C. Sorrell, C. Viscoli, J. R. Wingard, T. Zaoutis, J. E. Bennett, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 2008. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin. Infect. Dis. 46: 1813–1821.
- Dominguez, J. M., and J. J. Martin 1998. Identification of elongation factor 2 as the essential protein targeted by sordarins in Candida albicans . Antimicrob. Agents Chemother. 42: 2279–2283.
- Drewry, D. H., and S. S. Young 1999. Approaches to the design of combinatorial libraries. Chemom. Intell. Lab. Syst. 48: 1–20.
- Espinel-Ingroff, A. 2009. Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005–2009). Rev. Iberoam. Micol. 26: 15–22.
- Fidel, P. L., Jr. 2006. Candida-host interactions in HIV disease: relationships in oropharyngeal candidiasis. Adv. Dent. Res. 19: 80–84.
- Fricker-Hidalgo, H., B. Lebeau, H. Pelloux, and R. Grillot 2004. Use of the BACTEC 9240 System with Mycosis-IC/F blood culture bottles for detection of fungemia. J. Clin. Microbiol. 42: 1855–1856. (Author's reply, 42: 1855–1856.)
- Gagne, J. J., and N. I. Goldfarb 2007. Candidemia in the in-patient setting: treatment options and economics. Expert Opin. Pharmacother. 8: 1643–1650.
- Garcia-Effron, G., S. K. Katiyar, S. Park, T. D. Edlind, and D. S. Perlin 2008. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob. Agents Chemother. 52: 2305–2312.
- Gavalda, J., O. Len, R. San Juan, J. M. Aguado, J. Fortun, C. Lumbreras, A. Moreno, P. Munoz, M. Blanes, A. Ramos, G. Rufi, M. Gurgui, J. Torre-Cisneros, M. Montejo, M. Cuenca-Estrella, J. L. Rodriguez-Tudela, A. Pahissa, and RESITRA (Spanish Network for Research on Infection in Transplantation). 2005. Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clin. Infect. Dis. 41: 52–59.
- Ghannoum, M. A., H. G. Kim, and L. Long 2007. Efficacy of aminocandin in the treatment of immunocompetent mice with haematogenously disseminated fluconazole-resistant candidiasis. J. Antimicrob. Chemother. 59: 556–559.
- Giaever, G., A. M. Chu, L. Ni, C. Connelly, L. Riles, S. Veronneau, S. Dow, A. Lucau-Danila, K. Anderson, B. Andre, A. P. Arkin, A. Astromoff, M. El-Bakkoury, R. Bangham, R. Benito, S. Brachat, S. Campanaro, M. Curtiss, K. Davis, A. Deutschbauer, K. D. Entian, P. Flaherty, F. Foury, D. J. Garfinkel, M. Gerstein, D. Gotte, U. Guldener, J. H. Hegemann, S. Hempel, Z. Herman, D. F. Jaramillo, D. E. Kelly, S. L. Kelly, P. Kotter, D. LaBonte, D. C. Lamb, N. Lan, H. Liang, H. Liao, L. Liu, C. Luo, M. Lussier, R. Mao, P. Menard, S. L. Ooi, J. L. Revuelta, C. J. Roberts, M. Rose, P. Ross-Macdonald, B. Scherens, G. Schimmack, B. Shafer, D. D. Shoemaker, S. Sookhai-Mahadeo, R. K. Storms, J. N. Strathern, G. Valle, M. Voet, G. Volckaert, C. Y. Wang, T. R. Ward, J. Wilhelmy, E. A. Winzeler, Y. Yang, G. Yen, E. Youngman, K. Yu, H. Bussey, J. D. Boeke, M. Snyder, P. Philippsen, R. W. Davis, and M. Johnston 2002. Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387–391.
- Giaever, G., P. Flaherty, J. Kumm, M. Proctor, C. Nislow, D. F. Jaramillo, A. M. Chu, M. I. Jordan, A. P. Arkin, and R. W. Davis 2004. Chemogenomic profiling: identifying the functional interactions of small molecules in yeast. Proc. Natl. Acad. Sci. USA 101: 793–798.
- Groll, A. H., P. M. Shah, C. Mentzel, M. Schneider, G. Just-Nuebling, and K. Huebner 1996. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 33: 23–32.
- Guillon, R., F. Giraud, C. Loge, M. Le Borgne, C. Picot, F. Pagniez, and P. Le Pape 2009. Design of new antifungal agents: synthesis and evaluation of 1-[(1H-indol-5-ylmethyl)amino]-2-phenyl-3-(1H-1,2,4-triazol-1-yl) propan-2- ols. Bioorg. Med. Chem. Lett. 19: 5833–5836.
- Guillon, R., C. Loge, F. Pagniez, V. Ferchaud-Roucher, M. Duflos, C. Picot, and P. L. Pape 2010. Synthesis and in vitro antifungal evaluation of 2-(2,4-difluorophenyl)-1--[(1H-indol-3-ylmethyl)methylamino]-3-(1H-1,2,4-tr iazol-1-yl)propan-2-ols. J. Enzyme Inhib. Med. Chem. 26: 261–269.
- Hachem, R., H. Hanna, D. Kontoyiannis, Y. Jiang, and I. Raad 2008. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer 112: 2493–2499.
- Hamza, O. J., M. I. Matee, M. J. Moshi, E. N. Simon, F. Mugusi, F. H. Mikx, W. H. Helderman, A. J. Rijs, A. J. van der Ven, and P. E. Verweij 2008. Species distribution and in vitro antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis. BMC Microbiol. 8: 135.
- Hanadate, T., M. Tomishima, N. Shiraishi, D. Tanabe, H. Morikawa, D. Barrett, S. Matsumoto, K. Ohtomo, and K. Maki 2009. FR290581, a novel sordarin derivative: synthesis and antifungal activity. Bioorg. Med. Chem. Lett. 19: 1465–1468.
- Harbarth, S., C. Ruef, P. Francioli, A. Widmer, and D. Pittet 1999. Nosocomial infections in Swiss university hospitals: a multi-centre survey and review of the published experience. Swiss-Noso Network. Schweiz. Med. Wochenschr. 129: 1521–1528.
- Hasenoehrl, A., T. Galic, G. Ergovic, N. Marsic, M. Skerlev, J. Mittendorf, U. Geschke, A. Schmidt, and W. Schoenfeld 2006. In vitro activity and in vivo efficacy of icofungipen (PLD-118), a novel oral antifungal agent, against the pathogenic yeast Candida albicans . Antimicrob. Agents Chemother. 50: 3011–3018.
- Hector, R. F., B. L. Zimmer, and D. Pappagianis 1990. Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis. Antimicrob. Agents Chemother. 34: 587–593.
- Hiemenz, J. W., and T. J. Walsh 1996. Lipid formulations of amphotericin B: recent progress and future directions. Clin. Infect. Dis. 22 (Suppl. 2): S133–S144.
- Hillenmeyer, M. E., E. Fung, J. Wildenhain, S. E. Pierce, S. Hoon, W. Lee, M. Proctor, R. P. St. Onge, M. Tyers, D. Koller, R. B. Altman, R. W. Davis, C. Nislow, and G. Giaever 2008. The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science 320: 362–365.
- Hodgetts, S., L. Nooney, R. Al-Akeel, A. Curry, S. Awad, R. Matthews, and J. Burnie 2008. Efungumab and caspofungin: pre-clinical data supporting synergy. J. Antimicrob. Chemother. 61: 1132–1139.
- Horn, D. L., D. Neofytos, E. J. Anaissie, J. A. Fishman, W. J. Steinbach, A. J. Olyaei, K. A. Marr, M. A. Pfaller, C. H. Chang, and K. M. Webster 2009. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis. 48: 1695–1703.
- Ibrahim, A. S., B. J. Spellberg, V. Avanesian, Y. Fu, and J. E. Edwards, Jr. 2006. The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is broadly active against disseminated candidiasis. Infect. Immun. 74: 3039–3041.
- Infectious Diseases Society of America. 2010. The 10 × ‘20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis. 50: 1081–1083.
- Jabra-Rizk, M. A., W. A. Falkler, Jr., C. O. Enwonwu, D. I. Onwujekwe, Jr., W. G. Merz, and T. F. Meiller 2001. Prevalence of yeast among children in Nigeria and the United States. Oral Microbiol. Immunol. 16: 383–385.
- Jiang, B., D. Xu, J. Allocco, C. Parish, J. Davison, K. Veil-lette, S. Sillaots, W. Hu, R. Rodriguez-Suarez, S. Trosok, L. Zhang, Y. Li, F. Rahkhoodaee, T. Ransom, N. Martel, H. Wang, D. Gauvin, J. Wiltsie, D. Wisniewski, S. Sa-lowe, J. N. Kahn, M. J. Hsu, R. Giacobbe, G. Abruzzo, A. Flattery, C. Gill, P. Youngman, K. Wilson, G. Bills, G. Platas, F. Pelaez, M. T. Diez, S. Kauffman, J. Becker, G. Harris, P. Liberator, and T. Roemer 2008. PAP inhibitor with in vivo efficacy identified by Candida albicans genetic profiling of natural products. Chem. Biol. 15: 363–374.
- Jung, S. H., D. H. Lim, S. H. Jung, J. E. Lee, K. S. Jeong, H. Seong, and B. C. Shin 2009. Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics. Eur. J. Pharm. Sci. 37: 313–320.
- Justice, M. C., M. J. Hsu, B. Tse, T. Ku, J. Balkovec, D. Schmatz, and J. Nielsen 1998. Elongation factor 2 as a novel target for selective inhibition of fungal protein synthesis. J. Biol. Chem. 273: 3148–3151.
- Kakeya, H., Y. Miyazaki, H. Senda, T. Kobayashi, M. Seki, K. Izumikawa, K. Yanagihara, Y. Yamamoto, T. Tashiro, and S. Kohno 2008. Efficacy of SPK-843, a novel polyene antifungal, in comparison with amphotericin B, liposomal amphotericin B, and micafungin against murine pulmonary aspergillosis. Antimicrob. Agents Chemother. 52: 1868–1870.
- Kamai, Y., M. Kakuta, T. Shibayama, T. Fukuoka, and S. Kuwahara 2005. Antifungal activities of R-135853, a sordarin derivative, in experimental candidiasis in mice. Anti-microb. Agents Chemother. 49: 52–56.
- Kang, T. H., E. I. Hwang, B. S. Yun, K. D. Park, B. M. Kwon, C. S. Shin, and S. U. Kim 2007. Inhibition of chitin synthases and antifungal activities by 2‵-benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and its derivatives. Biol. Pharm. Bull. 30: 598–602.
- Kang, T. H., E. I. Hwang, B. S. Yun, C. S. Shin, and S. U. Kim 2008. Chitin synthase 2 inhibitory activity of O-methyl pisiferic acid and 8,20-dihydroxy-9(11),13-abietadien-12-one, isolated from Chamaecyparis pisifera . Biol. Pharm. Bull. 31: 755–759.
- Kitamura, A., K. Someya, M. Hata, R. Nakajima, and M. Takemura 2009. Discovery of a small-molecule inhibitor of β-1,6-glucan synthesis. Antimicrob. Agents Chemother. 53: 670–677.
- Knaus, W. A., D. P. Wagner, E. A. Draper, J. E. Zimmerman, M. Bergner, P. G. Bastos, C. A. Sirio, D. J. Murphy, T. Lotring, and A. Damiano 1991. The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest 100: 1619–1636.
- Kontoyiannis, D. P., K. A. Marr, B. J. Park, B. D. Alexander, E. J. Anaissie, T. J. Walsh, J. Ito, D. R. Andes, J. W. Baddley, J. M. Brown, L. M. Brumble, A. G. Freifeld, S. Hadley, L. A. Herwaldt, C. A. Kauffman, K. Knapp, G. M. Lyon, V. A. Morrison, G. Papanicolaou, T. F. Patterson, T. M. Perl, M. G. Schuster, R. Walker, K. A. Wannemuehler, J. R. Wingard, T. M. Chiller, and P. G. Pappas 2010. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin. Infect. Dis. 50: 1091–1100.
- Krcmery, V., and A. J. Barnes 2002. Non-albicans Candida spp. causing fungaemia: pathogenicity and antifungal resistance. J. Hosp. Infect. 50: 243–260.
- Lass-Florl, C. 2009. The changing face of epidemiology of invasive fungal disease in Europe. Mycoses 52: 197–205.
- Lehrnbecher, T., C. Frank, K. Engels, S. Kriener, A. H. Groll, and D. Schwabe 2010. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 61: 259–265.
- Lewis, R. E. 2007. Pharmacodynamic implications for use of antifungal agents. Curr. Opin. Pharmacol. 7: 491–497.
- Li, D., O. A. Agrellos, and R. Calderone 2010. Histidine kinases keep fungi safe and vigorous. Curr. Opin. Microbiol. 13: 424–430.
- Li, J. W., and J. C. Vederas 2009. Drug discovery and natural products: end of an era or an endless frontier? Science 325: 161–165.
- Liu, T. T., R. E. Lee, K. S. Barker, R. E. Lee, L. Wei, R. Homayouni, and P. D. Rogers 2005. Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans . Antimicrob. Agents Chemother. 49: 2226–2236.
- Lortholary, O., D. W. Denning, and B. Dupont 1999. Endemic mycoses: a treatment update. J. Antimicrob. Chemother. 43: 321–331.
- Lortholary, O., M. Desnos-Ollivier, K. Sitbon, A. Fontanet, S. Bretagne, F. Dromer, and the French Mycosis Study Group. 2011. Recent exposure to caspofungin or fluconazole influences the epidemiology of candidemia: a prospective multicenter study involving 2,441 patients. Antimicrob. Agents Chemother. 55: 532–538.
- Micol, R., A. Tajahmady, O. Lortholary, S. Balkan, C. Quillet, J. P. Dousset, H. Chanroeun, Y. Madec, A. Fontanet, and Y. Yazdanpanah 2010. Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia. PLoS One 5: e13856.
- Miller, L. G., R. A. Hajjeh, and J. E. Edwards, Jr. 2001. Estimating the cost of nosocomial candidemia in the United States. Clin. Infect. Dis. 32: 1110.
- Mitsuyama, J., N. Nomura, K. Hashimoto, E. Yamada, H. Nishikawa, M. Kaeriyama, A. Kimura, Y. Todo, and H. Narita 2008. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine. Antimicrob. Agents Chemother. 52: 1318–1324.
- Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65: 55–63.
- Nadagir, S. D., S. K. Chunchanur, L. H. Halesh, K. Yasmeen, M. R. Chandrasekhar, and B. S. Patil 2008. Significance of isolation and drug susceptibility testing of non-Candida albicans species causing oropharyngeal candidiasis in HIV patients. Southeast Asian J. Trop. Med. Public Health 39: 492–495.
- Nakamata, K., T. Kurita, M. S. Bhuiyan, K. Sato, Y. Noda, and K. Yoda 2007. KEG1/YFR042w encodes a novel Kre6-binding endoplasmic reticulum membrane protein responsible for beta-1,6-glucan synthesis in Saccharomyces cerevisiae . J. Biol. Chem. 282: 34315–34324.
- Neofytos, D., D. Horn, E. Anaissie, W. Steinbach, A. Olyaei, J. Fishman, M. Pfaller, C. Chang, K. Webster, and K. Marr 2009. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin. Infect. Dis. 48: 265–273.
- Niimi, M., N. A. Firth, and R. D. Cannon 2010. Antifungal drug resistance of oral fungi. Odontology 98: 15–25.
-
Nishikaku, A.,
A. Melo, and A. Colombo
2010. Geographic trends in invasive candidiasis. Curr. Fungal Infect.
4:
210–218.
10.1007/s12281-010-0033-7 Google Scholar
- Nomura, K., K. Kawasugi, and T. Morimoto 2006. Cost-effectiveness analysis of antifungal treatment for patients on chemotherapy. Eur. J. Cancer Care (Engl.) 15: 44–50.
- Odds, F. C., A. J. Brown, and N. A. Gow 2003. Antifungal agents: mechanisms of action. Trends Microbiol. 11: 272–279.
- Oh, J., E. Fung, U. Schlecht, R. W. Davis, G. Giaever, R. P. St. Onge, A. Deutschbauer, and C. Nislow 2010. Gene annotation and drug target discovery in Candida albicans with a tagged transposon mutant collection. PLoS Pathog. 6: e1001140.
- Okome-Nkoumou, M., M. E. Mbounja-Loclo, and M. Kombila 2000. Spectrum of opportunistic infections in subjects infected with HIV at Libreville, Gabon. Sante 10: 329–337. (In French.)
- Olaechea, P. M., M. Palomar, C. Leon-Gil, F. Alvarez-Lerma, R. Jorda, J. Nolla-Salas, M. A. Leon-Regidor, and EPCAN Study Group. 2004. Economic impact of Candida colonization and Candida infection in the critically ill patient. Eur. J. Clin. Microbiol. Infect. Dis. 23: 323–330.
- Ostrosky-Zeichner, L., A. Casadevall, J. N. Galgiani, F. C. Odds, and J. H. Rex 2010. An insight into the antifungal pipeline: selected new molecules and beyond. Nat. Rev. Drug Discov. 9: 719–727.
- Pachl, J., P. Svoboda, F. Jacobs, K. Vandewoude, B. van der Hoven, P. Spronk, G. Masterson, M. Malbrain, M. Aoun, J. Garbino, J. Takala, L. Drgona, J. Burnie, R. Matthews, and Mycograb Invasive Candidiasis Study Group. 2006. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin. Infect. Dis. 42: 1404–1413.
- Pappas, P. G., B. D. Alexander, D. R. Andes, S. Hadley, C. A. Kauffman, A. Freifeld, E. J. Anaissie, L. M. Brumble, L. Herwaldt, J. Ito, D. P. Kontoyiannis, G. M. Lyon, K. A. Marr, V. A. Morrison, B. J. Park, T. F. Patterson, T. M. Perl, R. A. Oster, M. G. Schuster, R. Walker, T. J. Walsh, K. A. Wannemuehler, and T. M. Chiller 2010. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin. Infect. Dis. 50: 1101–1111.
- Pappas, P. G., C. A. Kauffman, D. Andes, D. K. Benjamin, Jr., T. F. Calandra, J. E. Edwards, Jr., S. G. Filler, J. F. Fisher, B. J. Kullberg, L. Ostrosky-Zeichner, A. C. Reboli, J. H. Rex, T. J. Walsh, J. D. Sobel, and Infectious Diseases Society of America. 2009. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 48: 503–535.
- Parish, C. A., S. K. Smith, K. Calati, D. Zink, K. Wilson, T. Roemer, B. Jiang, D. Xu, G. Bills, G. Platas, F. Pelaez, M. T. Diez, N. Tsou, A. E. McKeown, R. G. Ball, M. A. Powles, L. Yeung, P. Liberator, and G. Harris 2008. Isolation and structure elucidation of parnafungins, antifungal natural products that inhibit mRNA polyadenylation. J. Am. Chem. Soc. 130: 7060–7066.
- Peman, J., and R. Zaragoza 2010. Current diagnostic approaches to invasive candidiasis in critical care settings. Mycoses 53: 424–433.
- Pfaller, M. A., L. Boyken, R. J. Hollis, S. A. Messer, S. Tendolkar, and D. J. Diekema 2006. In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance. J. Clin. Microbiol. 44: 760–763.
- Pfaller, M. A., M. Castanheira, S. A. Messer, G. J. Moet, and R. N. Jones 2010. Variation in Candida spp. distribution and antifungal resistance rates among bloodstream infection isolates by patient age: report from the SENTRY Antimicrobial Surveillance Program (2008–2009). Diagn. Microbiol. Infect. Dis. 68: 278–283.
- Pfaller, M. A., and D. J. Diekema 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20: 133–163.
- Pfaller, M. A., D. J. Diekema, D. L. Gibbs, V. A. Newell, H. Bijie, D. Dzierzanowska, N. N. Klimko, V. Letscher-Bru, M. Lisalova, K. Muehlethaler, C. Rennison, M. Zaidi, and Global Antifungal Surveillance Group. 2009. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J. Clin. Microbiol. 47: 117–123.
- Pfaller, M. A., D. J. Diekema, D. L. Gibbs, V. A. Newell, D. Ellis, V. Tullio, A. Rodloff, W. Fu, T. A. Ling, and the Global Antifungal Surveillance Group. 2010. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J. Clin. Microbiol. 48: 1366–1377.
- Pfaller, M. A., D. J. Diekema, and International Fungal Surveillance Participant Group. 2004. Twelve years of fluconazole in clinical practice: global trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida . Clin. Microbiol. Infect. 10 (Suppl. 1): 11–23.
- Pfaller, M. A., S. A. Messer, N. Georgopapadakou, L. A. Martell, J. M. Besterman, and D. J. Diekema 2009. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens. J. Clin. Microbiol. 47: 3797–3804.
- Pienaar, E. D., T. Young, and H. Holmes 2010. Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children. Cochrane Database Syst. Rev. 11: CD003940.
- Playford, E. G., J. Lipman, and T. C. Sorrell 2010. Prophylaxis, empirical and preemptive treatment of invasive candidiasis. Curr. Opin. Crit. Care 16: 470–474.
- Prentice, H. G., I. M. Hann, R. Herbrecht, M. Aoun, S. Kvaloy, D. Catovsky, C. R. Pinkerton, S. A. Schey, F. Jacobs, A. Oakhill, R. F. Stevens, P. J. Darbyshire, and B. E. Gibson 1997. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br. J. Haematol. 98: 711–718.
- Qin, Z., J. Zhang, B. Xu, L. Chen, Y. Wu, X. Yang, X. Shen, S. Molin, A. Danchin, H. Jiang, and D. Qu 2006. Structure-based discovery of inhibitors of the YycG histi-dine kinase: new chemical leads to combat Staphylococcus epidermidis infections. BMC Microbiol. 6: 96.
- Rentz, A. M., M. T. Halpern, and R. Bowden 1998. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin. Infect. Dis. 27: 781–788.
- Repetto, G., A. del Peso, and J. L. Zurita 2008. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat. Protoc. 3: 1125–1131.
- Rijnders, B. J., J. J. Cornelissen, L. Slobbe, M. J. Becker, J. K. Doorduijn, W. C. Hop, E. J. Ruijgrok, B. Lowenberg, A. Vulto, P. J. Lugtenburg, and S. de Marie 2008. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin. Infect. Dis. 46: 1401–1408.
- Rodriguez-Suarez, R., D. Xu, K. Veillette, J. Davison, S. Sillaots, S. Kauffman, W. Hu, J. Bowman, N. Martel, S. Trosok, H. Wang, L. Zhang, L. Y. Huang, Y. Li, F. Rahkhoodaee, T. Ransom, D. Gauvin, C. Douglas, P. Youngman, J. Becker, B. Jiang, and T. Roemer 2007. Mechanism-of-action determination of GMP synthase inhibitors and target validation in Candida albicans and Aspergillus fumigatus . Chem. Biol. 14: 1163–1175.
- Roemer, T., B. Jiang, J. Davison, T. Ketela, K. Veillette, A. Breton, F. Tandia, A. Linteau, S. Sillaots, C. Marta, N. Martel, S. Veronneau, S. Lemieux, S. Kauffman, J. Becker, R. Storms, C. Boone, and H. Bussey 2003. Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Mol. Microbiol. 50: 167–181.
- Sampaio Camargo, T. Z., A. R. Marra, C. V. Silva, M. F. Cardoso, M. D. Martino, L. F. Camargo, and L. Correa 2010. Secular trends of candidemia in a tertiary care hospital. Am. J. Infect. Control 38: 546–551.
- Santangelo, R., P. Paderu, G. Delmas, Z. W. Chen, R. Mannino, L. Zarif, and D. S. Perlin 2000. Efficacy of oral cochleate-amphotericin B in a mouse model of systemic candidiasis. Antimicrob. Agents Chemother. 44: 2356–2360.
- Seifert, H., U. Aurbach, D. Stefanik, and O. Cornely 2007. In vitro activities of isavuconazole and other antifungal agents against Candida bloodstream isolates. Anti-microb. Agents Chemother. 51: 1818–1821.
- Smith, A. M., R. Ammar, C. Nislow, and G. Giaever 2010. A survey of yeast genomic assays for drug and target discovery. Pharmacol. Ther. 127: 156–164.
- Sobel, J. D. 2007. Vulvovaginal candidosis. Lancet 369: 1961–1971.
- Sopko, R., D. Huang, N. Preston, G. Chua, B. Papp, K. Kafadar, M. Snyder, S. G. Oliver, M. Cyert, T. R. Hughes, C. Boone, and B. Andrews 2006. Mapping pathways and phenotypes by systematic gene overexpression. Mol. Cell 21: 319–330.
- Sorbera, L. A., J. Bartroli, and J. Castaner 2003. Alba-conazole. Drugs Future 28: 529–537.
- Spellberg, B. J., S. G. Filler, and J. E. Edwards, Jr. 2006. Current treatment strategies for disseminated candidiasis. Clin. Infect. Dis. 42: 244–251.
- Spellberg, B. J., A. S. Ibrahim, V. Avanesian, Y. Fu, C. Myers, Q. T. Phan, S. G. Filler, M. R. Yeaman, and J. E. Edwards, Jr. 2006. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J. Infect. Dis. 194: 256–260.
- Tolman, J. A., N. P. Wiederhold, J. T. McConville, L. K. Najvar, R. Bocanegra, J. I. Peters, J. J. Coalson, J. R. Graybill, T. F. Patterson, and R. O. Williams III 2009. Inhaled voriconazole for prevention of invasive pulmonary aspergillosis. Antimicrob. Agents Chemother. 53: 2613–2615.
- Trofa, D., A. Gacser, and J. D. Nosanchuk 2008. Candida parapsilosis, an emerging fungal pathogen. Clin. Microbiol. Rev. 21: 606–625.
- Uppuluri, P., J. Nett, J. Heitman, and D. Andes 2008. Synergistic effect of calcineurin inhibitors and fluconazole against Candida albicans biofilms. Antimicrob. Agents Chemother. 52: 1127–1132.
- van der Meer, J. W., F. L. van de Veerdonk, L. A. Joosten, B. J. Kullberg, and M. G. Netea 2010. Severe Candida spp. infections: new insights into natural immunity. Int. J. Antimicrob. Agents 36 (Suppl. 2): S58–S62.
- van Gool, R. 2001. The cost of treating systemic fungal infections. Drugs 61 (Suppl. 1): 49–56.
- Vogel, H. G. 2007. Assays for insulin and insulin-like metabolic activity, p. 1415–1416. In H. G. Vogel (ed.), Drug Discovery and Evaluation: Pharmacological Assays, 3rd ed. Springer, New York, NY.
- Walsh, T. J., J. Hiemenz, and P. A. Pizzo 1994. Evolving risk factors for invasive fungal infections—all neutropenic patients are not the same. Clin. Infect. Dis. 18: 793–798.
- Warn, P. A., A. Sharp, G. Morrissey, and D. W. Denning 2005. Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis . J. Antimicrob. Chemother. 56: 590–593.
- Warn, P. A., A. Sharp, G. Morrissey, and D. W. Denning 2010. Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of Aspergillus fumigatus . Int. J. Anti-microb. Agents 35: 146–151.
- Weig, M., and A. J. Brown 2007. Genomics and the development of new diagnostics and anti-Candida drugs. Trends Microbiol. 15: 310–317.
-
Wertheimer, A. I.,
T. M. Santella, and H. J. Lauver
2004. Successful public/private donation programs: a review of the Diflucan Partnership Program in South Africa. J. Int. Assoc. Physicians AIDS Care
3:
74–79, 84–85.
10.1177/154510970400300302 Google Scholar
- Widmer, F., L. C. Wright, D. Obando, R. Handke, R. Ganendren, D. H. Ellis, and T. C. Sorrell 2006. Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis. Antimicrob. Agents Chemother. 50: 414–421.
- Wilson, L. S., C. M. Reyes, M. Stolpman, J. Speckman, K. Allen, and J. Beney 2002. The direct cost and incidence of systemic fungal infections. Value Health 5: 26–34.
- Xu, D., B. Jiang, T. Ketela, S. Lemieux, K. Veillette, N. Martel, J. Davison, S. Sillaots, S. Trosok, C. Bachewich, H. Bussey, P. Youngman, and T. Roemer 2007. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans . PLoS Pathog. 3: e92.
- Yamada, E., H. Nishikawa, N. Nomura, and J. Mitsuyama 2010. T-2307 shows efficacy in a murine model of Candida glabrata infection despite in vitro trailing growth phenomena. Antimicrob. Agents Chemother. 54: 3630–3634.
- Yim, N. H., E. I. Hwang, B. S. Yun, K. D. Park, J. S. Moon, S. H. Lee, N. D. Sung, and S. U. Kim 2008. Sesquiterpene furan compound CJ-01, a novel chitin synthase 2 inhibitor from Chloranthus japonicus SIEB. Biol. Pharm. Bull. 31: 1041–1044.
- Zarif, L., J. R. Graybill, D. Perlin, L. Najvar, R. Bocanegra, and R. J. Mannino 2000. Antifungal activity of amphotericin B cochleates against Candida albicans infection in a mouse model. Antimicrob. Agents Chemother. 44: 1463–1469.
- Zhang, X., P. A. Reichart, and Y. Song 2009. Oral manifestations of HIV/AIDS in China: a review. Oral Maxillofac. Surg. 13: 63–68.
- Zilberberg, M. D., M. H. Kollef, H. Arnold, A. Labelle, S. T. Micek, S. Kothari, and A. F. Shorr 2010. Inappropriate empiric antifungal therapy for candidemia in the ICU and hospital resource utilization: a retrospective cohort study. BMC Infect. Dis. 10: 150.