Vol 39 # 2 June 2007 - Kma.org.kw

KUWAIT MEDICAL JOURNAL June 2007Review ArticleAdvances in Therapy of Invasive MycosesZia U Khan, Eiman M MokaddasDepartment of Microbiology, Faculty of Medicine, Kuwait University, KuwaitKuwait Medical Journal 2007, 39 (2):98-106ABSTRACTIntroduction: Concurrent with the advances in medicaland transplant technologies, and emergence ofHIV/AIDS as a major public health problem, the numberand type of immunosuppressed individuals hasincreased. This has resulted in an increasing incidence ofopportunistic mycoses. To meet this challenge, the fieldof antifungal therapeutics has made unpre c e d e n t e dprogress in recent years. In this article, we have reviewedsome of the major advances that have taken place in thisarea.Methods: MEDLINE database was searched using thefollowing key words: amphotericin B, lipid formulationsof amphotericin B, triazoles, voriconazole, posaconazole,echinocandins, caspofungin, micafungin, anidulafungin,clinical trials and combination therapy since the year2000.Results: Based on the information retrieved through thesearch, the following inferences could be drawn: (i)voriconazole is as effective as amphotericin B, followedby fluconazole for the treatment of candidemia in nonne u t ropenic patients with fewer side effects, (ii)caspofungin is better tolerated and is as effective asamphotericin B in treating invasive candidiasis and thusmay be preferred in patients with renal impairment, (iii)caspofungin or amphotericin B is still a preferred therapyfor candidemia in neutropenic and critically ill patients,and (iv) voriconazole has replaced amphotericin B insome centers as the drug of choice for treating invasiveaspergillosis including patients with CNS involvement.Conclusions: With the introduction of new antifungalagents, the options for treating invasive mycoses haveconsiderably expanded with improved therapeuticoutcomes. Attention is now being focused to evaluateefficacy of these agents in combination therapy.KEYWORDS: anidulafungin, caspofungin, lipid formulations of amphotericin B, micafungin, posaconazole, voriconazoleINTRODUCTIONInvasive mycoses pose a major diagnostic andtherapeutic challenge. They have emerged asimportant causes of morbidity and mortality amongim m u n o c o m p romised patients, particularly infectingthose who have undergone bone marrow or organtransplantation, or become infected with acquiredimmunodeficiency syndro m e [ 1 , 2 ] . Absence ofspecific signs and symptoms and limitations ofspecificity and sensitivity of the currently availablediagnostic tests make early diagnosis difficult, thusdelaying timely initiation of appropriate antifungalt h e r a p y. Together with the pro g ress made inmedical and transplant technologies, the numberand diversity of immunosuppressed individualshas increased, and so are the types of fungalpathogens infecting them. In fact, some of themould infections that infect the immunosu p p ressed population today were not evendescribed as pathogens 20 or 30 years ago [3,4] . In thiscontext, Professor Howard A. Buechner [5] , as earlyas 1971, wrote that “—-the role of the fungus ise m e rging with frightening rapidity and thephysician who formerly had merely a noddingacquaintance with these disorders will soon findthemselves compelled to take a more active role intheir early detection and proper treatment”. Tomeet these growing complications of modernmedicine, the field of antifungal drug research hasmade considerable pro g ress. Fluconazole anditraconazole, introduced in 1980s, were the firstalternatives to amphotericin B with activity againstC a n d i d a and A s p e rg i l l u s species, re s p e c t i v e l y [6, 7] .Fluconazole continues to be a first line therapyoption for invasive candidiasis in non-neutropenicpatients, besides its well recognized prophylacticuse in selected high-risk patients [7, 8] . While the roleof itraconazole in the treatment of invasivecandidiasis remains to be rationalized, it is beingused as an alternative to amphotericin B forempirical treatment in persistently neutro p e n i ccancer patients (excluding allogeneic transplantrecipients) and in allergic bro n c h o p u l m o n a r ya s p e rgillosis patients to prevent A s p e rg i l l u scolonization [6, 9] .Address correspondence to:Prof. Zia U. Khan, Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait. Tel: 498-6504, Fax: 5332719, E-mail:Ziauddin@hsc.edu.kw