COMPARISON OF AMPHOTERICIN-B WITH FLUCONAZOLE IN THE TREATMENT OF ACUTE AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS

被引:506
作者
SAAG, MS
POWDERLY, WG
CLOUD, GA
ROBINSON, P
GRIECO, MH
SHARKEY, PK
THOMPSON, SE
SUGAR, AM
TUAZON, CU
FISHER, JF
HYSLOP, N
JACOBSON, JM
HAFNER, R
DISMUKES, WE
机构
[1] UNIV ALABAMA, SCH MED, DEPT MED, DIV INFECT DIS, BIRMINGHAM, AL 35233 USA
[2] UNIV ALABAMA, SCH MED, CTR COMPREHENS CANC, DIV BIOSTAT, BIRMINGHAM, AL 35233 USA
[3] WASHINGTON UNIV, SCH MED, DIV INFECT DIS, ST LOUIS, MO 63110 USA
[4] ST LOUIS VET AFFAIRS MED CTR, ST LOUIS, MO USA
[5] COLUMBIA UNIV, ST LUKES ROOSEVELT HOSP, SCH MED, NEW YORK, NY 10027 USA
[6] UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA
[7] AUDIE L MURPHY VET AFFAIRS HOSP, SAN ANTONIO, TX USA
[8] EMORY UNIV, GRADY MEM HOSP, ATLANTA, GA 30322 USA
[9] BOSTON CITY HOSP, DEPT MED, BOSTON, MA 02118 USA
[10] BOSTON UNIV, UNIV HOSP, DEPT MED, BOSTON, MA 02215 USA
[11] GEORGE WASHINGTON UNIV, DEPT MED, WASHINGTON, DC 20052 USA
[12] MED COLL GEORGIA, DEPT MED, AUGUSTA, GA 30912 USA
[13] TULANE UNIV, DEPT MED, NEW ORLEANS, LA 70118 USA
[14] MT SINAI MED CTR, DEPT MED, DIV INFECT DIS, NEW YORK, NY 10029 USA
[15] BRONX VET AFFAIRS MED CTR, BRONX, NY USA
[16] NIAID, DIV AIDS, BETHESDA, MD 20892 USA
[17] NIAID, DIV MICROBIOL & INFECT DIS, BETHESDA, MD 20892 USA
[18] PFIZER INC, CENT RES, GROTON, CT 06340 USA
关键词
D O I
10.1056/NEJM199201093260202
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS): Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. Methods. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patents, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. Results. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P < 0.0001). Conclusions. Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.
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页码:83 / 89
页数:7
相关论文
共 25 条
  • [1] COMPARISON OF AMPHOTERICIN-B ALONE AND COMBINED WITH FLUCYTOSINE IN THE TREATMENT OF CRYPTOCCAL MENINGITIS
    BENNETT, JE
    DISMUKES, WE
    DUMA, RJ
    MEDOFF, G
    SANDE, MA
    GALLIS, H
    LEONARD, J
    FIELDS, BT
    BRADSHAW, M
    HAYWOOD, H
    MCGEE, ZA
    CATE, TR
    COBBS, CG
    WARNER, JF
    ALLING, DW
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1979, 301 (03) : 126 - 131
  • [2] PROVING THE NULL HYPOTHESIS IN CLINICAL-TRIALS
    BLACKWELDER, WC
    [J]. CONTROLLED CLINICAL TRIALS, 1982, 3 (04): : 345 - 353
  • [3] A PLACEBO-CONTROLLED TRIAL OF MAINTENANCE THERAPY WITH FLUCONAZOLE AFTER TREATMENT OF CRYPTOCOCCAL MENINGITIS IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME
    BOZZETTE, SA
    LARSEN, RA
    CHIU, J
    LEAL, MAE
    JACOBSEN, J
    ROTHMAN, P
    ROBINSON, P
    GILBERT, G
    MCCUTCHAN, JA
    TILLES, J
    LEEDOM, JM
    RICHMAN, DD
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (09) : 580 - 584
  • [4] INFECTIONS WITH CRYPTOCOCCUS-NEOFORMANS IN THE ACQUIRED IMMUNODEFICIENCY SYNDROME
    CHUCK, SL
    SANDE, MA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (12) : 794 - 799
  • [5] CLARK RA, 1990, REV INFECT DIS, V12, P768
  • [6] COX DR, 1972, J R STAT SOC B, V34, P187
  • [7] TREATMENT OF CRYPTOCOCCAL MENINGITIS IN MICE WITH FLUCONAZOLE
    DEFERNANDEZ, EP
    PATINO, MM
    GRAYBILL, JR
    TARBIT, MH
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1986, 18 (02) : 261 - 270
  • [8] DENNING DW, 1989, ARCH INTERN MED, V111, P125
  • [9] TREATMENT OF CRYPTOCOCCAL MENINGITIS WITH COMBINATION AMPHOTERICIN-B AND FLUCYTOSINE FOR 4 AS COMPARED WITH 6 WEEKS
    DISMUKES, WE
    CLOUD, G
    GALLIS, HA
    KERKERING, TM
    MEDOFF, G
    CRAVEN, PC
    KAPLOWITZ, LG
    FISHER, JF
    GREGG, CR
    BOWLES, CA
    SHADOMY, S
    STAMM, AM
    DIASIO, RB
    KAUFMAN, L
    SOONG, SJ
    BLACKWELDER, WC
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (06) : 334 - 341
  • [10] CRYPTOCOCCAL MENINGITIS IN PATIENTS WITH AIDS
    DISMUKES, WE
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1988, 157 (04) : 624 - 628