STUDY PURPOSE: To estimate the relative effectiveness of all anti-fungal agents for a number of outcomes (mixed treatment comparison)
TYPE OF STUDY: Systematic review (studies included were randomized, controlled trials)
DATABASES USED: MEDLINE, EMBASE, United States National Institutes of Health Clinical Trials Registry, and Google Scholar
KEYWORDS: (Invasive fungal infections, IFI, fungus, fungal, fungemia, mycosis, candidiasis, Candida, Aspergillus, invasive mold infections, IMI, aspergillosis) and (prophylaxis, prophylactic, prevention) and (antifungal, amphotericin, azoles, triazoles, fluconazole, itraconazole, isavuconazole, voriconazole, posaconazole, ravuconazole, echinocandin, micafungin, caspofungin, anidulafungin)
INCLUSION CRITERIA: All randomized, controlled trials on antifungal agents that were newly introduced or are currently being used as invasive fungal infection (IFI) prophylaxis among adult patients with hematological malignancies undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) were eligible.
EXCLUSION CRITERIA: Studies were limited to those written in English and published in international peer-reviewed journals. Because the focus was on IFI, studies that reported only noninvasive, single-site fungal infections were excluded. Studies that investigated antifungal agents that are not suggested for prophylactic use by current guidelines or agents of outdated formulations such as (non-liposomal) amphotericin B, ketoconazole, miconazole, and nystatin were also excluded. Studies that analyzed only graft-versus-host disease patients were excluded as this patient population is at a significantly higher risk of IFI.
TOTAL REFERENCES RETRIEVED: 2,154 abstracts identified; 2,079 excluded; 75 relevant abstracts identified; 33 excluded as nonrandomized controlled trial data, not a patient population of interest, or not a prophylactic strategy; 42 potentially relevant full-text articles; 17 excluded as no IFIs were observed, not current agents for prophylactic strategy, agent combinations, or not written in English
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two investigators independently scanned all title and abstracts. The same investigators independently conducted the data extraction.
Through the meta-analysis, it was observed that fluconazole and liposomal amphotericin B were significantly better than placebo/no prophylaxis in reducing what were proven to be or were likely IFIs. Posaconazole prophylaxis was found to be more effective in comparison with fluconazole prophylaxis. All antifungal agents, with the exception of caspofungin and itraconazole, were observed to have a significant prophylactic effect compared to a placebo or to no prophylaxis. Posaconazole was found to be significantly more effective than fluconazole and itraconazole. For proven or probable IC, all agents with the exception of micafungin were more effective than placebo/no prophylaxis. Itraconazole solution and caspofungin had a significant advantage against IC compared to fluconazole. For IA infection, posaconazole improved prophylaxis when compared to placebo/no prophylaxis, fluconazole, and itraconazole solution. Liposomal amphotericin B and micafungin were more effective against IA infections compared to placebo/no prophylaxis and fluconazole. Voriconazole was significantly more effective than fluconazole. Posaconazole was the only agent achieving a significant reduction in the risk of all-cause mortality. For reducing IFI related mortality, all agents except micafungin and caspofungin were found to be significantly superior to a placebo. Posaconazole was found to be superior to fluconazole and itraconazole. The relative effectiveness of voriconazole was not determined.