Clinical Neurology and Neurosurgery

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Clinical Neurology and Neurosurgery

  1. 1. Clinical Neurology and Neurosurgery 111 (2009) 565–567 Contents lists available at ScienceDirect Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro Preoperative antifungal therapy may improve survival in patients with Aspergillus brain abscess Mohammad Wasaya,∗ , Junaid Patela , Iqbal Azama , Muhammad Aslam Khana , Raymond A. Smego Jr.b a Department of Neurology, Medicine, Infectious Diseases and Community Health, Aga Khan University, Karachi 74800, Pakistan b The Commonwealth Medical College, Philadelphia, PA, USA a r t i c l e i n f o Article history: Received 21 August 2008 Received in revised form 24 February 2009 Accepted 26 February 2009 Available online 28 March 2009 Keywords: Aspergillus Abcess Fungus Amphotericin Itraconazole a b s t r a c t Objective: The objective of this study was to determine if the preoperative use of antifungal therapy positively influences clinical outcome in patients with Aspergillus brain abscess. Methods: We studied 25 patients with confirmed diagnosis of cerebral aspergillosis. We compared base- line characteristics and outcomes of patients treated with either amphotericin B or itraconazole either pre-operatively (n = 11) or post-operatively (n = 14) at a tertiary care hospital in Karachi. Results: Twenty-five patients were included in the study. Cerebral aspergillosis was largely a disease of immune competent people (80%). Baseline clinical characteristics between the two treatment groups were comparable i.e., age (P > 0.896), gender (P > 0.999), coma at presentation (P > 0.999), immunosuppression (P > 0.623), number of abscesses (P > 0.999) and interval between presentation and surgery (P > 0.447). Overall mortality was 40%. The overall outcome was significantly better (P < 0.001) in patients treated with antifungal therapy before surgery. All 11 patients who received antifungal therapy before surgery survived, but only preoperative itraconazole treatment was statistically associated with an improved survival compared to delayed treatment. Conclusion: Cerebral aspergillosis was largely a disease of immune competent people (80%). Overall mortality was 40%. The outcome was significantly better in patients treated with antifungal therapy (especially itraconazole) before surgery suggesting a possible beneficial effect of pre-surgical treatment with antifungal therapy. © 2009 Elsevier B.V. All rights reserved. Amphotericin B is considered the antifungal drug of choice for central nervous system (CNS) aspergillosis but its efficacy is poor, and reported mortality exceeds 90% in patients treated with amphotericin. Recent case reports or case series have demonstrated improved survival treating CNS aspergillosis with itraconazole [1–4] or voriconazole [5–7], but most of these studies have involved only one or two patients. We sought to determine if the preopera- tive use of antifungal therapy positively influences clinical outcome in these patients. There are no randomized controlled trials or non-randomized comparison of the role of empiric, preoperative antifungal therapy versus postoperative antifungal treatment for the treatment of cerebral aspergillosis. ∗ Corresponding author at: Department of Neurology, The Aga Khan University, Karachi 74800, Pakistan. Tel.: +92 21 4930051x4665/4681; fax: +92 21 4934294. E-mailaddresses:mohammad.wasay@aku.edu, mohammadwasay@hotmail.com (M. Wasay). 1. Methods We retrospectively reviewed the medical records of all patients with histopathologically or microbiologically confirmed brain abscess due to Aspergillus species admitted to the Aga Khan Univer- sity in Karachi, Pakistan, between 1996 and 2006, and compared the baseline characteristics and outcomes of patients treated with either amphotericin B or itraconazole either pre-operatively (n = 11) or post-operatively (n = 14). Patients were identified through ICD-9 coding system. We reviewed 32 charts and excluded 7 patients due to unconfirmed diagnosis. None of these patients was treated with voriconazole or liposomal amphotericin due to non-availability of these medications in Pakistan. Patients were not randomized to antifungal therapy; the selection of medication was based entirely on the attending physician’s preference. Patients with malignancy, diabetes, HIV infection, or receiving steroids or chemotherapy were labeled as immunosuppressed. Itraconazole (200–400 mg twice a day) was given orally to nine patients 2–7 days before the surgical procedure, and to four patients after the procedure. In the amphotericin B-treated group, the drug (1 mg/kg/day) was begun empirically 2 days prior to 0303-8467/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2009.02.007
  2. 2. 566 M. Wasay et al. / Clinical Neurology and Neurosurgery 111 (2009) 565–567 Table 1 Baseline characteristics of patients. Variable Preoperative (n = 11) Postoperative (n = 14) P Mean age ± S.D. 51 ± 17 52 ± 20 >0.896 Male/female 7/4 10/4 >0.999 Average course duration (S.D.) 3 weeks (±1.5) 4 weeks (±1.7) >0.136 Coma at presentation 2 (18%) 2 (14%) >0.999 Immune suppression 3 (27%) 2 (14%) >0.623 MRI Solitary abcess 9 (82%) 12 (86%) >0.999 Multiple abcessess 2 (18%) 2 (14%) Interval between presentation and surgery (days) (S.D.) 5 days (±3.6) 4 days (±2.9) >0.447 Table 2 Outcome of patients. Variable Preoperative (n = 11) Postoperative (n = 14) P Overall outcome <0.001 Death 0 10 Improved 7 1 No change 4 2 Worsening 0 1 Mean length of stay (days) (S.D.) 9 (±4.5) 14 (±6) <0.029 surgery in 2 patients and was administered after surgical proce- dure in 10 patients. Fisher Exact test was used for preoperative and postoperative groups for treatment used and different outcomes. Independent samples t-test was used to compare the two treat- ments for mean age, course duration, interval between presentation and surgery, and length of hospital stay. 2. Results Twenty-five patients were included in the study. Cerebral aspergillosis was largely a disease of immune competent people (80%). Baseline clinical characteristics between the two treat- ment groups (Table 1) were comparable i.e., age (P > 0.896), gender (P > 0.999), coma at presentation (P > 0.999), immunosup- pression (P > 0.623), number of abscesses (P > 0.999) and interval between presentation and surgery (P > 0.447). Overall mortality was 40% (n = 10 patients; 3 = itraconazole-treated patients and 7 = amphotericin-treated patients). The overall outcome was signif- icantly better (P < 0.001) in patients treated with antifungal therapy before surgery (Table 2). All nine patients who received itracona- zole before their surgical procedure survived, while three out of four subjects whose treatment was begun only after surgery died; both patients who received preoperative amphotericin B survived compared to only 3 of 10 whose treatment was delayed until after surgery. All 11 patients who received antifungal therapy before surgery survived, but only preoperative itraconazole treatment was statistically associated with an improved survival compared to delayed treatment. Mean length of stay in pre-treatment group was shorter than post-treatment group (9 days versus 14 days, P < 0.02). 3. Discussion To our knowledge this is the first study comparing utility of pre-treatment antifungal therapy before surgical biopsy in patients with cerebral aspergillosis. Amphotericin B-based therapy has poor clinical efficacy in cerebral aspergillosis [8]. The administration of antifungal therapy before surgery for CNS aspergillosis may have a containment affect on brain lesions, and surgical exploration of brain lesions without antifungal drugs on board may be harmful. Overall outcome of these patients was better than most of the published reports. One possible reason for this difference could be the immune competent status of most of our patients. It is rare to see cerebral aspergillosis in immune competent people in western literature. The retrospective design, non-randomization of patients, and small sample size are limitations of our study. It is possible that longer duration of disease course in post-treatment group may have affected the outcome because patients in pre-treatment group sought medical attention a whole week earlier than post-treatment group. The time interval between presentation and surgery was not much difference in two groups. The empiric use of itracona- zole was more common than empiric amphotericin. It could be due to the fact that physician felt more comfortable in starting empiric itraconazole as compared to empiric amphotericin while waiting for the biopsy. Mean length of stay in pre-treatment group was shorter than post-treatment group. This difference may have important cost implications. The ratio of itraconazole/amphotericin was 9/2 and 4/10 in preoperative and postoperative group respec- tively. This difference was significant (Fisher’s Exact test: P < 0.015). This difference could be a potential source of bias. Other treat- ment options for cerebral aspergillosis include voriconazole and liposomal amphotericin but unfortunately these medications are not available in Pakistan. Nonetheless, our findings suggest that patients with suspected Apergillus brain abscess may benefit from pre-treatment with itraconazole before surgical biopsy of cerebral or sinonasal lesions. A larger, randomized, controlled trial is needed to confirm our findings. Acknowledgements These findings were presented in preliminary form at the 59th Annual meeting of American Academy of Neurology, Boston, USA (April 2007). Authors are thankful to Prof. Steve Roach, Ohio State University, Columbus, Ohio, USA, for review and valuable suggestions. References [1] Imai T, Yamamoto T, Tanaka S, Kashiwagi M, Chiba S, Matsumoto H, et al. Suc- cessful treatment of cerebral aspergillosis with a high oral dose of itraconazole after excisional surgery. Intern Med 1999;38:829–32. [2] Mikolich DJ, Kinsella LJ, Skowron G, Friedman J, Sugar AM. Aspergillus meningitis in an immunocompetent adult successfully treated with itraconazole. Clin Infect Dis 1996;23:1318–9. [3] Sánchez C, Mauri E, Dalmau D, Quintana S, Aparicio A, Garau J. Treatment of cerebral aspergillosis with itraconazole: do high doses improve the prognosis? Clin Infect Dis 1995;21:1485–7. [4] Kreisel W, Köchling G, von Schilling C, Azemar M, Kurzweil B, Bölken G, et al. Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis. Mycoses 1991;34:385–94.
  3. 3. M. Wasay et al. / Clinical Neurology and Neurosurgery 111 (2009) 565–567 567 [5] de Lastours V, Lefort A, Zappa M, Dufour V, Belmatoug N, Fantin B. Two cases of cerebral aspergillosis successfully treated with voriconazole. Eur J Clin Microbiol Infect Dis 2003;22:297–9. [6] Nataloni S, Gabbanelli V, Rossi R, Donati A, Pantanetti S, Pelaia P. Successful early voriconazole treatment of Aspergillus infection in two non- immunocompromised patients in the intensive care unit. Minerva Anestesiol 2007;73:371–5. [7] Stiefel M, Reiss T, Staege MS, Rengelshausen J, Burhenne J, Wawer A, et al. Suc- cessful treatment with voriconazole of Aspergillus brain abscess in a boy with medulloblastoma. Pediatr Blood Cancer 2007;49:203–7. [8] Schwartz S, Ruhnke M, Ribaud P, Reed E, Troke P, Thiel E. Poor efficacy of amphotericin B-based therapy in CNS aspergillosis. Mycoses 2007;50(3 (May)):196–200.

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