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

104Advances in Therapy of Invasive Mycoses June 2007demonstrated a 69% success in favor ofcombination therapy (p = 0.043) over monotherapy(56%). However, success rates utilizing a Kaplan-Meier time -to- failure analysis was notsignificantly different (p = 0.08). The usefulness ofcombination of fluconazole with an echinocandinin Candida infections remains unclear.Currently, invasive aspergillosis is the focus ofcombination therapy in experimental and clinicals t u d i e s [ 58 , 59 ] . In a prospective, multicenter studycomprising patients of proven and pro b a b l einvasive aspergillosis, voriconazole andcaspogungin combination therapy was consideredpreferable to lipid formulation of amphotericin B ina subset of organ transplant recipients, such asthose with renal failure or A. fumigatus infection [60] .Adjunctive immunotherapies and immunereconstitutionwith a view to restoring orenhancing host defenses are other importantstrategies for the successful management of fungalinfection. Reduction of immunosuppression level,w h e re feasible, administration of re c o m b i n a n tcytokines and donor elicited granulocytetransfusion for neutropenic patients have beenused with encouraging results in experimental andclinical studies [61] . Recently, there have been studiesof adjunctive interferon and antibody therapy forcryptococcal meningitis [62] . More recently, Pachl etal [63] reported that an antibody fragment of heatshock protein 90 (Mycograb; manufactured byNeuTec Pharma, Manchester, UK) is effective in thetreatment of human candidiasis. In a double-blind,randomized study involving 117 culture confirmedpatients, a complete overall response was obtainedin 48% patients in the amphotericin B group ascompared to 84% in amphotericin B and Mycograbcombination group, reducing Candida attributablemortality to > four-fold. This molecule has directantifungal activity in vitro against C. albicans and C.neoformans through an unknown mechanism. Thisis a notable advance, giving a new direction to thefield of antimicrobial therapy.CONCLUSIONClinical mycology has entered into an era ofunprecedented therapeutic development. Optionsfor treatment of invasive fungal infections haveincreased with new agents that exhibit improvedtolerability and increased range of activity. Nowattention is being focused on examining the efficacyof these agents in combination with older or neweragents in randomized, controlled clinical studies. Itis hoped that with the availability of newtherapeutic alternatives, it will be possible todevelop effective strategies to prevent and treatthese life-threatening infections in the near future.REFERENCES1. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasiveaspergillosis in allogeneic stem cell transplant recipients:changes in epidemiology and risk factors. Blood 2002;100:4358-4366.2. C h a y a k u l k e e ree M, Ghannoum MA, Perfect JR.Zygomycosis: the re-emerging fungal infection. 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