Drug development challenges and strategies to address emerging and resistant fungal pathogens

References

• Clancy CJ, Nguyen MH. Emergence of Candida auris: an international call to arms. Clin Infect Dis. 2017;64(2):141–143.
   PubMed Web of Science ®Google Scholar
• Larkin E, Hager C, Chandra J, et al. The emerging Candida auris: characterization of growth phenotype, virulence factors, antifungal activity, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation. Antimicrob Agents Chem. 2017.
   PubMedGoogle Scholar
• Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64(2):134–140.
   PubMed Web of Science ®Google Scholar
• Osherov N, Kontoyiannis DP. The anti-aspergillus drug pipeline: is the glass half full or empty? Med Mycol. 2016;55:118-124.
   PubMed Web of Science ®Google Scholar
• Bagshaw E, Kuessner D, Posthumus J, et al. The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK. Future Microbiol. 2017.
   PubMedGoogle Scholar
• Chang CC, Slavin MA, Chen SC. New developments and directions in the clinical application of the echinocandins. Arch Toxicol. 2017.
   Web of Science ®Google Scholar
• Seyedmousavi S, Rafati H, Ilkit M, et al. Systemic antifungal agents: current status and projected future developments. Methods Mol Biol. 2017;1508:107–139.
   PubMedGoogle Scholar
• Kontoyiannis DP, Yang H, Song J, et al. Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study. BMC Infect Dis. 2016;16(1):730.
   PubMed Web of Science ®Google Scholar
• Ben-Ami R, Lewis RE, Raad II, et al. Phaeohyphomycosis in a tertiary care cancer center. Clin Infect Dis. 2009;48(8):1033–1041.
   PubMed Web of Science ®Google Scholar
• Calvo B, Melo AS, Perozo-Mena A, et al. First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia. J Infect. 2016;73(4):369–374.
   PubMed Web of Science ®Google Scholar
• Chowdhary A, Voss A, Meis JF. Multidrug-resistant Candida auris: ‘new kid on the block’ in hospital-associated infections? J Hosp Infect. 2016;94(3):209–212.
   PubMed Web of Science ®Google Scholar
• Emara M, Ahmad S, Khan Z, et al. Candida auris candidemia in Kuwait, 2014. Emerg Infect Dis. 2015;21(6):1091–1092.
   PubMed Web of Science ®Google Scholar
• Griggs RC, Batshaw M, Dunkle M, et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009;96(1):20–26.
   PubMed Web of Science ®Google Scholar
• Augustine EF, Adams HR, Mink JW. Clinical trials in rare disease: challenges and opportunities. J Child Neurol. 2013;28(9):1142–1150.
   PubMed Web of Science ®Google Scholar
• America IDSo. Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis. 2011;52(Suppl 5):S397–428.
   PubMedGoogle Scholar
• Alvarez-Moreno C, Lavergne RA, Hagen F, et al. Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia. Sci Rep. 2017;7:45631.
   PubMed Web of Science ®Google Scholar
• Biswas C, Chen SC, Halliday C, et al. Identification of genetic markers of resistance to echinocandins, azoles and 5-fluorocytosine in Candida glabrata by next generation sequencing: a feasibility study. Clin Microbiol Infect. 2017;64:110-120.
   Google Scholar
• Barnes RA. Early diagnosis of fungal infection in immunocompromised patients. J Antimicrob Chemother. 2008;61(Suppl 1):i3–6.
   PubMed Web of Science ®Google Scholar
• Marti Aguado D, Ballester MP, Bosca Watts MM. Invasive pulmonary aspergillosis in an immunocompromised patient with severe ulcerative colitis. Rev Esp Enferm Dig. 2017;109:45-64.
   Google Scholar
• Coria P, Urízar C, Alba A, et al. The water supply of a pediatric hospital as a possible source of an outbreak of diarrhea due to Microsporidium spp. in immunocompromised patients. Rev Chilena Infectol. 2016;33(4):373–379.
   PubMed Web of Science ®Google Scholar
• Petrikkos G, Skiada A, Lortholary O, et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012;54(Suppl 1):S23–34.
   PubMed Web of Science ®Google Scholar
• Wold WS, Toth K. New drug on the horizon for treating adenovirus. Expert Opin Pharmacother. 2015;16(14):2095–2099.
   PubMed Web of Science ®Google Scholar
• Kerr DS. Review of clinical trials for mitochondrial disorders: 1997–2012. Neurotherapeutics. 2013;10(2):307–319.
   PubMed Web of Science ®Google Scholar
• Kontoyiannis DP, Wessel VC, Bodey GP, et al. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000;30(6):851–856.
   PubMed Web of Science ®Google Scholar
• Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2):81–89.
   PubMed Web of Science ®Google Scholar
• Haug CJ. From patient to patient – sharing the data from clinical trials. N Engl J Med. 2016.
   Web of Science ®Google Scholar
• Bai JP, Barrett JS, Burckart GJ, et al. Strategic biomarkers for drug development in treating rare diseases and diseases in neonates and infants. Aaps J. 2013;15(2):447–454.
   PubMed Web of Science ®Google Scholar
• Sussex J, Rollet P, Garau M, et al. A pilot study of multicriteria decision analysis for valuing orphan medicines. Value Health. 2013;16(8):1163–1169.
   PubMed Web of Science ®Google Scholar
• Putzeist M, Mantel-Teeuwisse AK, Wied CC, et al. Drug development for exceptionally rare metabolic diseases: challenging but not impossible. Orphanet J Rare Dis. 2013;8:179.
   PubMed Web of Science ®Google Scholar
• Ambrose PG, Hammel JP, Bhavnani SM, et al. Frequentist and Bayesian pharmacometric-based approaches to facilitate critically needed new antibiotic development: overcoming lies, damn lies, and statistics. Antimicrob Agents Chem. 2012;56(3):1466–1470.
   PubMed Web of Science ®Google Scholar
• Patel A, Ozsahin M, Mirimanoff RO, et al. The Rare Cancer Network: achievements from 1993 to 2012. Rare Tumors. 2012;4(3):e35.
   Google Scholar
• Powers JH. Issues in clinical trials of prophylaxis of fungal infections. Clin Infect Dis. 2004;39(Suppl 4):S211–7.
   Google Scholar
• Wilson DT, Dimondi VP, Johnson SW, et al. Role of isavuconazole in the treatment of invasive fungal infections. Ther Clin Risk Manag. 2016;12:1197–1206.
   PubMed Web of Science ®Google Scholar
• Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2016;102:433-444.
   PubMedGoogle Scholar
• Cornely OA, Duarte RF, Haider S, et al. Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease. J Antimicrob Chemother. 2016;71(6):1747.
   PubMed Web of Science ®Google Scholar
• McCarthy M, Rosengart A, Schuetz AN, et al. Mold infections of the central nervous system. N Engl J Med. 2014;371(2):150–160.
   PubMed Web of Science ®Google Scholar
• Kinder BW, Sherman AC, Young LR, et al. Predictors for clinical trial participation in the rare lung disease lymphangioleiomyomatosis. Respir Med. 2010;104(4):578–583.
   PubMed Web of Science ®Google Scholar
• Park S, Kim K, Jang JH, et al. Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients. J Infect. 2016;73:496-505.
   PubMed Web of Science ®Google Scholar
• Kim TH, Kweon OJ, Kim HR, et al. Identification of uncommon Candida species using commercial identification systems. J Microbiol Biotechnol. 2016;26(12):2206–2213.
   PubMed Web of Science ®Google Scholar
• Schelenz S, Hagen F, Rhodes JL, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:35.
   PubMed Web of Science ®Google Scholar
• Ruiz Gaitán AC, Moret A, López Hontangas JL, et al. Nosocomial fungemia by Candida auris: first four reported cases in continental Europe. Rev Iberoam Micol. 2017;34(1):23–27.
   PubMed Web of Science ®Google Scholar
• Mahajan R, Gupta K. Adaptive design clinical trials: methodology, challenges and prospect. Indian J Pharmacol. 2010;42(4):201–207.
   PubMed Web of Science ®Google Scholar
• Krams M, Burman CF, Dragalin V, et al. Adaptive designs in clinical drug development: opportunities, challenges, and scope reflections following PhRMA’s November 2006 workshop. J Biopharm Stat. 2007;17(6):957–964.
   PubMed Web of Science ®Google Scholar
• Kairalla JA, Coffey CS, Thomann MA, et al. Adaptive trial designs: a review of barriers and opportunities. Trials. 2012;13:145.
   PubMed Web of Science ®Google Scholar
• Shirley M. Olaratumab: first global approval. Drugs. 2017;77(1):107–112.
   PubMed Web of Science ®Google Scholar
• Kesselheim AS, Wang B, Franklin JM, et al. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study. Bmj. 2015;351:h4633.
   PubMedGoogle Scholar
• Wells KB. Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. Am J Psychiatry. 1999;156(1):5–10.
   PubMed Web of Science ®Google Scholar
• Gale EA. Lessons from the glitazones: a story of drug development. Lancet. 2001;357(9271):1870–1875.
   PubMed Web of Science ®Google Scholar
• Horning SJ, Haber DA, Selig WK, et al. Developing standards for breakthrough therapy designation in oncology. Clin Cancer Res. 2013;19(16):4297–4304.
   PubMed Web of Science ®Google Scholar
• Kakkis ED, O’Donovan M, Cox G, et al. Recommendations for the development of rare disease drugs using the accelerated approval pathway and for qualifying biomarkers as primary endpoints. Orphanet J Rare Dis. 2015;10:16.
   PubMed Web of Science ®Google Scholar
• Salvatore CM, Chen TK, Toussi SS, et al. (1→3)-β-d-glucan in cerebrospinal fluid as a biomarker for candida and aspergillus infections of the central nervous system in pediatric patients. J Pediatric Infect Dis Soc. 2016;5(3):277–286.
   PubMed Web of Science ®Google Scholar
• Maertens J, Buvé K, Theunissen K, et al. Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients. Cancer. 2009;115(2):355–362.
   PubMed Web of Science ®Google Scholar
• Ciani O, Buyse M, Drummond M, et al. Time to review the role of surrogate end points in health policy: state of the art and the way forward. Value Health. 2017;20(3):487–495.
   PubMed Web of Science ®Google Scholar
• Ciociola AA, Cohen LB, Kulkarni P. Gastroenterology F-RMCotACo. How drugs are developed and approved by the FDA: current process and future directions. Am J Gastroenterol. 2014;109(5):620–623.
   PubMed Web of Science ®Google Scholar
• Leon AC, Davis LL, Kraemer HC. The role and interpretation of pilot studies in clinical research. J Psychiatr Res. 2011;45(5):626–629.
   PubMed Web of Science ®Google Scholar
• Tan SB, Dear KB, Bruzzi P, et al. Strategy for randomised clinical trials in rare cancers. Bmj. 2003;327(7405):47–49.
   PubMed Web of Science ®Google Scholar
• Luce BR, Connor JT, Broglio KR, et al. Using Bayesian adaptive trial designs for comparative effectiveness research: a virtual trial execution. Ann Intern Med. 2016;165:431-438.
   PubMed Web of Science ®Google Scholar
• Jacob L, Uvarova M, Boulet S, et al. Evaluation of a multi-arm multi-stage Bayesian design for phase II drug selection trials - an example in hemato-oncology. BMC Med Res Methodol. 2016;16(1):67.
   PubMed Web of Science ®Google Scholar
• Billingham L, Malottki K, Steven N. Research methods to change clinical practice for patients with rare cancers. Lancet Oncol. 2016;17(2):e70–80.
   PubMed Web of Science ®Google Scholar
• Bolignano D, Nagler EV, Van Biesen W, et al. Providing guidance in the dark: rare renal diseases and the challenge to improve the quality of evidence. Nephrol Dial Transplant. 2014;29(9):1628–1632.
   PubMed Web of Science ®Google Scholar
• Kaufman L, Gore K, Zandee JC. Data standardization, pharmaceutical drug development, and the 3Rs. Ilar J. 2016;57(2):109–119.
   PubMed Web of Science ®Google Scholar
• Longo DL, Drazen JM. Data sharing. N Engl J Med. 2016;374(3):276–277.
   PubMed Web of Science ®Google Scholar
• Lamarca R, Herrera D. Beyond “data sharing”. Med Clin (Barc). 2015;144(12):548–549.
   PubMed Web of Science ®Google Scholar
• Stephenson D, Hu MT, Romero K, et al. Precompetitive data sharing as a catalyst to address unmet needs in Parkinson’s disease. J Parkinsons Dis. 2015;5(3):581–594.
   PubMedGoogle Scholar
• Bierer BE, Li R, Barnes M, et al. A global, neutral platform for sharing trial data. N Engl J Med. 2016.
   PubMed Web of Science ®Google Scholar
• Merson L, Gaye O, Guerin PJ. Avoiding data dumpsters – toward equitable and useful data sharing. N Engl J Med. 2016.
   Web of Science ®Google Scholar
• Ben-Ami R, Berman J, Novikov A, et al. Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg Infect Dis. 2017;23:1.
   PubMed Web of Science ®Google Scholar
• Mizusawa M, Miller H, Green R, et al. Can multidrug-resistant Candida auris be reliably identified in clinical microbiology laboratories? J Clin Microbiol. 2017;55(2):638–640.
   PubMed Web of Science ®Google Scholar
• Vallabhaneni S, Kallen A, Tsay S, et al. Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus – United States, May 2013–August 2016. Am J Transplant. 2017;17(1):296–299.
   PubMed Web of Science ®Google Scholar
• Jumbe NL, Murray JC, Kern S. Data sharing and inductive learning – toward healthy birth, growth, and development. N Engl J Med. 2016;374(25):2415–2417.
   PubMed Web of Science ®Google Scholar
• Goudar SS, Stolka KB, Koso-Thomas M, et al. Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings. Reprod Health. 2015;12(Suppl 2):S2.
   Google Scholar
• Leclerc JM, Laberge N, Marion J. Metrics survey of industry-sponsored clinical trials in Canada and comparator jurisdictions between 2005 and 2010. Healthc Policy. 2012;8(2):88–104.
   PubMedGoogle Scholar
• Berthon-Jones N, Courtney-Vega K, Donaldson A, et al. Assessing site performance in the Altair study, a multinational clinical trial. Trials. 2015;16:138.
   PubMed Web of Science ®Google Scholar
• Haffner ME. Adopting orphan drugs – two dozen years of treating rare diseases. N Engl J Med. 2006;354(5):445–447.
   PubMed Web of Science ®Google Scholar
• Orphan Drug Act, Pub. L. No. 97–414 (1983).
   Google Scholar
• Orphan Drug Act, Pub. L. No. 97–414 (1984 as amended).
   Google Scholar
• El Dib R, Gomaa H, Ortiz A, et al. Enzyme replacement therapy for Anderson-Fabry disease: a complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies. Plos One. 2017;12(3):e0173358.
   PubMed Web of Science ®Google Scholar
• Minoura H, Iwai M, Taniuchi Y, et al. Pharmacological and clinical profile of nitisinone (Orfadin(®) capsules): a therapeutic agent for hereditary tyrosinemia type 1. Nihon Yakurigaku Zasshi. 2015;146(6):342–348.
   PubMedGoogle Scholar
• Kaufmann KB, Büning H, Galy A, et al. Gene therapy on the move. EMBO Mol Med. 2013;5(11):1642–1661.
   PubMed Web of Science ®Google Scholar
• Aiuti A, Cattaneo F, Galimberti S, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009;360(5):447–458.
   PubMed Web of Science ®Google Scholar
• Kainer MA, Reagan DR, Nguyen DB, et al. Fungal infections associated with contaminated methylprednisolone in Tennessee. N Engl J Med. 2012.
   Web of Science ®Google Scholar
• Farmakiotis D, Shirazi F, Zhao Y, et al. Methylprednisolone enhances the growth of Exserohilum rostratum in vitro, attenuates spontaneous apoptosis, and increases mortality rates in immunocompetent Drosophila flies. J Infect Dis. 2014;210(9):1471–1475.
   PubMed Web of Science ®Google Scholar
• Kontoyiannis DP, Perlin DS, Roilides E, et al. What can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis? Clin Infect Dis. 2013;57(6):853–859.
   PubMed Web of Science ®Google Scholar
• Katragkou A, Pana ZD, Perlin DS, et al. Exserohilum infections: review of 48 cases before the 2012 United States outbreak. Med Mycol. 2014;52(4):376–386.
   PubMed Web of Science ®Google Scholar
• Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348(24):2416–2422.
   PubMed Web of Science ®Google Scholar
• Lagakos SW. Clinical trials and rare diseases. N Engl J Med. 2003;348(24):2455–2456.
   PubMed Web of Science ®Google Scholar
• Guo J, Kelton CM, Guo JJ. Recent developments, utilization, and spending trends for Pompe disease therapies. Am Health Drug Benefits. 2012;5(3):182–189.
   PubMedGoogle Scholar
• Austin SL, Chiou A, Sun B, et al. Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for a patient presenting with a PRKAG2 mutation. Mol Genet Metab. 2017;120(1–2):96–100.
   PubMed Web of Science ®Google Scholar
• Chan J, Desai AK, Kazi ZB, et al. The emerging phenotype of late-onset Pompe disease: a systematic literature review. Mol Genet Metab. 2017;120(3):163–172.
   PubMed Web of Science ®Google Scholar
• Stepien KM, Hendriksz CJ, Roberts M, et al. Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5 years. Mol Genet Metab. 2016;117(4):413–418.
   PubMed Web of Science ®Google Scholar
• Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–837.
   PubMed Web of Science ®Google Scholar
• Donnelley MA, Zhu ES, Thompson GR. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections. Infect Drug Resist. 2016;9:79–86.
   PubMed Web of Science ®Google Scholar
• Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–653.
   PubMed Web of Science ®Google Scholar
• Gebremariam T, Wiederhold NP, Alqarihi A, et al. Monotherapy or combination therapy of isavuconazole and micafungin for treating murine mucormycosis. J Antimicrob Chemother. 2017;72(2):462–466.
   PubMed Web of Science ®Google Scholar
• Chitasombat MN, Kontoyiannis DP. Treatment of mucormycosis in transplant patients: role of surgery and of old and new antifungal agents. Curr Opin Infect Dis. 2016;29(4):340–345.
   PubMed Web of Science ®Google Scholar
• Denning DW, Perlin DS, Eg M, et al. Delivering on antimicrobial resistance agenda not possible without improving fungal diagnostic capabilities. Emerg Infect Dis. 2017;23:2.
   Web of Science ®Google Scholar
• Enoch DA, Yang H, Aliyu SH, et al. The changing epidemiology of invasive fungal infections. Methods Mol Biol. 2017;1508:17–65.
   PubMedGoogle Scholar
• Moriyama B, Gordon LA, McCarthy M, et al. Emerging drugs and vaccines for candidemia. Mycoses. 2014;57(12):718–733.
   PubMed Web of Science ®Google Scholar
• Wring SA, Randolph R, Park S, et al. SCY-078 A first in class orally active antifungal glucan synthesis inhibitor: pre-clinical pharmacokinetics and pharmacodynamic target in murine models of disseminated candidiasis. Antimicrob Agents Chem. 2017.
   Web of Science ®Google Scholar
• Lamoth F, Alexander BD. Antifungal activities of SCY-078 (MK-3118) and standard antifungal agents against clinical non-Aspergillus mold isolates. Antimicrob Agents Chem. 2015;59(7):4308–4311.
   PubMed Web of Science ®Google Scholar
• Lepak AJ, Marchillo K, Andes DR. Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model. Antimicrob Agents Chem. 2015;59(2):1265–1272.
   PubMed Web of Science ®Google Scholar
• Denning DW, Bromley MJ. Infectious disease. How to bolster the antifungal pipeline. Science. 2015;347(6229):1414–1416.
   PubMed Web of Science ®Google Scholar
• Morales-López SE, Parra-Giraldo CM, Ceballos-Garzón A, et al. Invasive infections with multidrug-resistant yeast Candida auris, Colombia. Emerg Infect Dis. 2017;23(1):162–164.
   PubMed Web of Science ®Google Scholar
• Bendixen RM, Morgenroth LP, Clinard KL. Engaging participants in rare disease research: a qualitative study of Duchenne muscular dystrophy. Clin Ther. 2016;38(6):1474–84.e2.
   PubMed Web of Science ®Google Scholar
• Bogaerts J, Sydes MR, Keat N, et al. Clinical trial designs for rare diseases: studies developed and discussed by the international rare cancers initiative. Eur J Cancer. 2015;51(3):271–281.
   PubMed Web of Science ®Google Scholar
• Colledge VL, Solly J. The rare disease challenge and how to promote a productive rare disease community: case study of Birt-Hogg-Dubé symposia. Orphanet J Rare Dis. 2012;7:63.
   PubMed Web of Science ®Google Scholar
• DeWard SJ, Wilson A, Bausell H, et al. Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience. J Genet Couns. 2014;23(1):20–28.
   PubMed Web of Science ®Google Scholar
• Longo DL, Drazen JM. More on data sharing. N Engl J Med. 2016;374(19):1896–1897.
   PubMed Web of Science ®Google Scholar
• Booth L, Roberts JL, Ecroyd H, et al. AR-12 inhibits multiple chaperones concomitant with stimulating autophagosome formation collectively preventing virus replication. J Cell Physiol. 2016;231(10):2286–2302.
   PubMed Web of Science ®Google Scholar
• Koselny K, Green J, DiDone L, et al. The celecoxib derivative AR-12 has broad-spectrum antifungal activity in vitro and improves the activity of fluconazole in a murine model of cryptococcosis. Antimicrob Agents Chem. 2016;60(12):7115–7127.
   PubMed Web of Science ®Google Scholar
• Arnardottir AH, Haaijer-Ruskamp FM, Straus SM, et al. Additional safety risk to exceptionally approved drugs in Europe? Br J Clin Pharmacol. 2011;72(3):490–499.
   PubMed Web of Science ®Google Scholar
• Daley GQ. Polar extremes in the clinical use of stem cells. N Engl J Med. 2017;376(11):1075–1077.
   PubMed Web of Science ®Google Scholar