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

June 2007KUWAIT MEDICAL JOURNAL 103I n d i c a t i o n s : C a n d i d a infections: intra-abdominalabscesses, peritonitis and pleural space infections,candidemia, esophageal candidiasis; invasiveaspergillosis in patients refractory or intolerant toother antifungal therapies; empiric therapy infebrile neutropenic patients.Dosage: Intravenous: adults: load 70 mg, then 50mg daily; children 50 mg/m2 daily; neonates: 1mg/kg daily X 2 doses then 2 mg/kg daily. (Note:more pediatric studies are required to determineoptimal doses).MICAFUNGINLike caspofungin, micafungin exhibits identicalspectrum of in vitro activity against C. albicans, nonal b i c a n s species and A s p e rg i l l u s species but notagainst zygomycetes and C. neoformans. It has fewerd ru g - d rug interactions and relatively lessexpensive than caspofungin [ 46 ] . It is eff i c a c i o u sagainst invasive candidiasis and asperg i l l o s i s .Although soluble in water, it has poor oralbioavailability. Its pharmacokinetics is similar inadults and children and metabolism is hepatic. Itreceived FDA a p p roval in March 2005 foresophageal candidiasis and for Candida infectionprophylaxis in hematopoietic stem cell transplantrecipients. Two clinical trials have been reported forthe treatment of invasive candidiasis withmicafungin (Table 3) [ 47 , 48 ] . In the first nonrandomized,non-comparative study, micafunginwas found safe and effective in the treatment ofrefractory and new cases of candidemia includingthose caused by C. glabrata with an overall successrate (complete and partial) of 83% [47] . In the secondmulticenter, open-label study, the clinical responsefor candidemia was 100% and for esophagealcandidiasis 71% [ 48 ] . Recently, de Wet et al [ 49 ]conducted a randomized, double blind studycomparing intravenous micafungin (150 mg/d)with intravenous fluconazole (200 mg/d) in thetreatment of esophageal candidiasis. Micafunginwas found to be as efficacious as intravenousfluconazole. In a randomized, double blind trialthat included adults and children with neutropenia,micafungin compared favorably with fluconazolein preventing invasive fungal infections afterhemopoietic stem cell transplantation (80% versus73.5% respectively; p = 0.03) [50] .Indications: Esophageal candidiasis, prophylaxisof Candida infections in patients undergoing stemcell transplantation.Dosage: Intravenous (Mycamine): Adults: Candidainfection prophylaxis in hematopoietic stem celltransplant patients: 50 mg/day over 1 h;esophageal candidiasis: 150 mg/day over 1 h.C h i l d ren: 3 mg/kg (more pediatric studies areneeded to determine optimal dose).ANIDULAFUNGINAnidulafungin (Eraxis) received FDA approvalfor treating candidemia in February 2006. The drugis active in vitro against most Candida spp withfungicidal activity, but like caspofungin, C .parapsilosis and C. guillermondii are more resistant tothis agent [51] . It is fungistatic against Aspergillus spp.and not active against C. neoformans or B .d e r m a t i t i d i s [ 52 ] . Although clinical experience islimited, anidulafungin is comparable tofluconazole in esophageal candidiasis [53] . At the endof randomized, double-blind study of 601 patientswith endoscopically and micro b i o l o g i c a l l ydocumented esophageal candidiasis, rate ofendoscopic success for anidulafungin was 97.2% ascompared to 98.8% in fluconazole group. This wasfound statistically non-inferior to that offluconazole [53] . In a phase 2, randomized, doserangingstudy evaluating the safety and efficacy ofanidulafungin in 123 invasive candidiasis andcandidemia patients, at the end of treatment, thesuccess rates were 84, 90, and 89% in the 50, 75 and100 mg groups, respectively (Table 3) [54] .Indications: Candidemia, esophageal candidiasis,abdominal abscesses, and peritonitis.Dosage: Intravenous: Candidemia: adult: load 200mg day 1, followed by a 100 mg daily dose, tocontinue for at least 14 days after last positiveculture; esophageal candidiasis: load 100 mg day 1,followed by a 50 mg daily dose, continue for at least14 days and for at least seven days followingresolution of symptoms. Doses in children are notyet established.COMBINATION THERAPYWith the availability of voriconazole, lipidformulations of amphotericin B, and echinocandins,the possibilities of using combination antifungalagents have greatly increased. The combination ofamphotericin B and 5-Flucytosine is wellestablished for the treatment of cryptococcalm e n i n g i t i s [ 12 ] . Initial combination studies usingazole antifungals and polyenes in animal modelsyielded synergistic, additive, indifferent or evenantagonistic re s u l t s [ 55 ] . A recently completedrandomized, blinded clinical trial in candidemiapatients suggested a trend towards impro v e doutcomes among non-neutropenic patientsreceiving amphotericin B (0.6-0.7 mg/kg) andfluconazole (800 mg/day) versus fluconazole (800mg/day) alone [ 56 , 57 ] . Results of this study