دورية أكاديمية
Combination antifungal therapy for cryptococcal meningitis.
| العنوان: | Combination antifungal therapy for cryptococcal meningitis. |
|---|---|
| المؤلفون: | Day JN; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Chau TTH; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Wolbers M; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Mai PP; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Dung NT; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Mai NH; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Phu NH; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Nghia HD; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Phong ND; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Thai CQ; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Thai LH; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Chuong LV; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Sinh DX; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Duong VA; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Hoang TN; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Diep PT; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Campbell JI; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Sieu TPM; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Baker SG; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Chau NVV; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Hien TT; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Lalloo DG; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom., Farrar JJ; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme Vietnam (J.N.D., T.T.H.C., M.W., N.H.M., N.H.P., H.D.N., C.Q.T., L.H.T., V.A.D., T.N.H., P.T.D., S.G.B., T.T.H., J.J.F.), and the Hospital for Tropical Diseases (T.T.H.C., P.P.M., N.T.D., N.H.M., N.H.P., H.D.N., N.D.P., L.V.C., D.X.S., T.P.M.S., N.V.V.C.) - both in Ho Chi Minh City, Vietnam; and the Centre for Tropical Medicine, Oxford University, Oxford (J.N.D., M.W., J.I.C., S.G.B., T.T.H., J.J.F.), and the Liverpool School of Tropical Medicine, Liverpool (D.G.L.) - both in the United Kingdom. |
| المصدر: | The New England journal of medicine [N Engl J Med] 2013 Apr 04; Vol. 368 (14), pp. 1291-1302. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print Cited Medium: Internet ISSN: 1533-4406 (Electronic) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Boston, Massachusetts Medical Society. |
| مواضيع طبية MeSH: | Amphotericin B/*therapeutic use , Antifungal Agents/*therapeutic use , Flucytosine/*therapeutic use , Meningitis, Cryptococcal/*drug therapy, Adult ; Amphotericin B/adverse effects ; Antifungal Agents/adverse effects ; Drug Therapy, Combination ; Female ; Flucytosine/adverse effects ; Humans ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Male ; Meningitis, Cryptococcal/mortality |
| مستخلص: | Background: Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. Methods: We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. Results: A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units [CFU] per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. Conclusions: Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.). |
| التعليقات: | Comment in: N Engl J Med. 2013 Apr 4;368(14):1354-6. (PMID: 23550675) Comment in: N Engl J Med. 2013 Jun 27;368(26):2522-3. (PMID: 23802521) Comment in: N Engl J Med. 2013 Jun 27;368(26):2522. (PMID: 23802522) |
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| معلومات مُعتمدة: | 100087 United Kingdom WT_ Wellcome Trust; 089276/Z/09/Z United Kingdom WT_ Wellcome Trust; 089276 United Kingdom WT_ Wellcome Trust; 077078/Z/05/A United Kingdom WT_ Wellcome Trust; 077078 United Kingdom WT_ Wellcome Trust; G1100684 United Kingdom MRC_ Medical Research Council; 096466 United Kingdom WT_ Wellcome Trust; 097147 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust |
| فهرسة مساهمة: | Indexing Agency: NLM Local ID #: EMS57406. |
| سلسلة جزيئية: | ISRCTN ISRCTN95123928 |
| المشرفين على المادة: | 0 (Antifungal Agents) 7XU7A7DROE (Amphotericin B) D83282DT06 (Flucytosine) |
| تواريخ الأحداث: | Date Created: 20130405 Date Completed: 20130411 Latest Revision: 20230701 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3978204 |
| DOI: | 10.1056/NEJMoa1110404 |
| PMID: | 23550668 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1533-4406 |
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| DOI: | 10.1056/NEJMoa1110404 |