CNS-aspergillosis: are there new treatment options?
Invasive aspergillosis is an increasing cause of morbidity and mortality in immunocompromised patients. Extension of invasive aspergillosis to the central nervous system (CNS) is associated with an exceeding high mortality which approaches 100%. One major factor contributing to this devastating outcome is a poor penetration into the CNS of frequently used antifungal drugs, such as amphotericin B or itraconazole. Voriconazole, a new triazole with broad activity against various fungi, including Aspergillus species, shows superior activity in invasive aspergillosis compared to treatment with conventional amphotericin B. Voriconazole readily penetrates the blood-brain barrier yielding fungicidal drug concentrations within the CNS. A growing number of patients with CNS aspergillosis has been successfully treated with voriconazole in recent years. The pharmacological properties, the broad antifungal activity and the promising clinical data suggest that the use of voriconazole in CNS aspergillosis might improve the outcome in this otherwise devastating clinical condition. However, additional clinical data are needed to determine more precisely the role of voriconazole in CNS aspergillosis. In this review, we have compiled the available pharmacological and clinical data on CNS aspergillosis.
Schwartz
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Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Freie Universität, Hindenburgdamm 30, D-12200 Berlin, Germany. stefan.schwartz@ukbf.fu-berlin.de
Thiel
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D000666:Amphotericin B / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001812:Blood-Brain Barrier; D000077336:Caspofungin; D020314:Central Nervous System Fungal Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D054714:Echinocandins; D005260:Female; D005437:Flucytosine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D017964:Itraconazole / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D055666:Lipopeptides; D008297:Male; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic; D011743:Pyrimidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010455:Peptides; D010456:Peptides, Cyclic; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D005437:Flucytosine; D000077336:Caspofungin; D065819:Voriconazole