Management of intracranial fungal infections in patients with haematological malignancies

Abstract

SummaryThe incidence of, and mortality associated with, invasive fungal infections remains far higher than hoped. As a consequence of the overall increase in the incidence of such infections over time, the incidence of central nervous system (CNS) fungal infections is also increasing and, despite improvements in diagnostic techniques and the introduction of novel antifungal agents, therapy for CNS infections is still associated with discouragingly poor results. In patients with haematological malignancies, opportunistic infections with Candida or Aspergillus remain the most common infections affecting the CNS; however, opportunistic infections with less well-known fungi are becoming more common and must be considered in the differential diagnosis. New techniques for the early diagnosis of invasive fungal infections are emerging. Pharmacologic options for treating invasive fungal infections have also improved during the past few years, with new drugs becoming available that have broader antifungal spectra and better safety profiles. Other novel treatment approaches, such as combination therapy, are also being explored. Early investigations have produced encouraging results; however, large, prospective studies involving many patients are necessary to validate the widespread use of these approaches. This review analyses the existing guidelines for treatment of CNS fungal infections and the literature available on the use of new drugs to generate sets of recommendations for treatment of these life-threatening infections in patients with haematological malignancies.

Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

“…Given the increase in fungal infections, two triazoles (voriconazole and posaconazole) and three echinocandins (anidulafungin, caspofungin and micafungin) have been approved to treat and prevent these infections (Mattiuzzi & Giles, 2005) (Table 1). Of the three classes of antifungal agents currently in clinical use, only amphotericin B and the echinocandins, e.g.…”

Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014

“…• Continue therapy until at least 4 weeks after resolution of radiological signs and neurological symptoms 72,73 • Remove intraventricular devices 71,72 • There are limited data on posaconazole, voriconazole or echinocandins for CNS candidiasis [74][75][76][77] Ocular candidiasis AmB-D 0.7-1 mg/kg, daily plus 5-fluorouracil 25 mg/kg, 6-hourly 62,72 or fluconazole 400-800 mg, daily (6-12 mg/kg) L-AMB 3-5 mg/kg, daily or voriconazole 6 mg/kg, 12-hourly for two doses then 3-4 mg/kg, 12-hourly [78][79][80] • Treat for 4-6 weeks and until ocular lesions have resolved 72,81 • Consider intravitreal antifungal therapy or surgical vitrectomy in the presence of vitritis • Echinocandins are not recommended due to concerns regarding their ocular penetration 81 Candida osteomyelitis…”

Central nervous system immune reconstitution inflammatory syndrome (IRIS) after hematopoietic SCT

“…4 Hence, they are high-risk patients, susceptible to opportunistic infections, despite the use of prophylactic or pre-emptive medications against viruses, parasites and fungae. 5 CNS Candida infections are rare. 6,7 On MRI, they may manifest as small enhancing ring lesions (cerebral microabscesses), leptomeningeal enhancement (meningitis) or cerebral macroabscesses with surrounding edema.…”