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DGDispatch
Central Nervous System Fungal Infections Respond to Real-World Voriconazole Therapy: Presented at ICAAC
By Ed Susman
SAN FRANCISCO -- September 17, 2009 -- In a real-world setting, patients with fungal infections of the central nervous system (CNS) respond to treatment with voriconazole, although not as well as patients in clinical trials or in the published literature, researchers stated here at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
"Many of these patients were very ill when they were treated with voriconazole and their response rate was not a good as was observed in publications," said Stefan Schwartz, MD, Charite Campus Benjamin Franklin, Berlin, Germany, on September 16.
Dr. Schwartz and colleagues reviewed chart records of 192 patients who were treated with voriconazole -- often in salvage settings -- to combat infections in the CNS. The study included 114 patients from a clinical dataset and 78 patients from scientific publications since January 2002 -- the year voriconazole was marketed.
He said that 76% of the patients in the study received voriconazole as salvage therapy. Their prior antifungal therapy consisted predominantly of amphotericin B or azoles, but treatment with 5-fluorocytosine, echinocandins, and a few other treatments had also been tried. About 61% of the patients had received multiple courses of prior therapies either sequentially or as combinations.
A complete or partial response was recorded in 93 of 192 patients or 48% of the entire cohort, Dr. Schwartz said. He noted that 72% of the patients in the published series of studies achieved a complete or partial response while 32% of the patients in the real-world database had complete or partial responses (P < .001).
"This does not diminish the utility of voriconazole," he said. "We have nothing better. But it may indicate publication bias."
He noted that invasive fungal infections of the CNS are notoriously difficult to treat. "Published case series show that central nervous system aspergillosis, in particular, responds poorly to amphotericin B or itraconazole-based therapies resulting in a greater than 90% mortality rate," Dr. Schwartz said. Unlike other treatments, he said voriconazole displays broad antifungal activity and enhanced penetration into the CNS, including cerebrospinal fluid, brain tissue, and brain abscess material.
In their study, the researchers also noted that patients who underwent neurological surgical interventions in treating the infections appeared to do better than those only treated medically. About 62% of the 72 who underwent neurosurgery responded compared with 42% of the 120 patients with no known surgical intervention (P = .017).
"Only patients with a high diagnostic certainty were included, with proven infections present in 71% of these patients," he said. The patients' ages varied widely from less than 1 year to 81 years. Dr. Schwartz said 41 of the cases involved children aged younger than 18 years.
He said that 120 patients had identified infection with Aspergillus species; 34 patients were diagnosed with infections caused by Scedosporium species; the remaining 38 patients were infected with 12 different genera.
Most patients suffered from profound immunosuppression, including 35 with haematopoietic stem-cell transplantation, 35 with haematologic malignancies, and 25 solid organ transplant recipients. Another 40 patients had a variety of diseases and/or drug-induced conditions resulting in chronic immunosuppression while the remaining 57 suffered little or no underlying immunosuppression.
[Presentation title: Voriconazole Efficacy in 192 Fungal Central Nervous System (CNS) Infections. Abstract M-1056]
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