Fluconazole and intrathecal injection of amphotericin B for treating cryptococcal meningitis

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BACKGROUND: At present, fluconazole and intrathecal injection of amphotericin B has been widely used to treat cryptococcal meningitis. However, the application of amphotericin B can shorten course and has good effects on the treatment of cryptococcal meningitis. OBJECTIVE: To observe the effects and poor response of the intrathecal injection of amphotericin B on the treatment of cryptococcal meningitis. DESIGN: Retrospective-case analysis. SETTING: Department of Neurology, Beijing Hospital of Ministry of Public Health. PARTICIPANTS: Eight patients with cryptococcal meningitis were selected from Department of Neurology, Beijing Hospital of Ministry of Public Health from January 1995 to January 2006. Among them, there were 3 males and 5 females aged from 17 to 41 years and the course ranged from 21 days to 3 months. Patients who had symptoms of febrile and headache, positive meninges excitation, positive latex agglutination of cryptococcus of cerebrospinal fluid and positive ink smear were selected in this study. All patients provided informed consent. METHODS: Eight patients were treated with the fluconazole and intrathecal injection of amphotericin B. ① Intracranial hypertension of patients was controlled with flowing cerebrospinal fluid by repeatedly piercing waist; meanwhile, patients were taken the intrathecal injection of amphotericin B combining with flucytosine or fluconazole treatment. The dosage of amphotericin B was 1-5 mg/d at the beginning of administration, and then, the samples were added with 2 mg dexasine and 500 mL 5% glucose solution. The dosage was increased 5.0 mg per day till 50 mg per day, and the total dosage was 3.0-4.0 g. In addition, 2 mg dexasine was mixed with 4.0-5.0 mL cerebrospinal fluid, and then the solution was gradually injected into sheath for once a week. Fluconazole was dripped into vein with the volume of 400 mg per day, and then, 14 days later, fluconazole was orally taken by patients. ② Other therapies, such as decreasing intracranial hypertension, were used at the same time of administration. When cryptococcus of cerebrospinal fluid was negative, patients received the secondary therapy at anaphase. The drug withdrawal was not performed untill ink smear of cerebrospinal fluid was negative for 3 successive cultures. ③ Evaluative criteria: Evaluative criteria were classified into 4 styles: Cure: Clinical symptoms and physical signs disappeared and ink smear of cerebrospinal fluid was negative for 3 successful cultures; Improvement: Clinical symptoms and physical signs were improved remarkably, amount of cerebrospinal fluid was decreased, and ink smear was not negative; inefficiency and death. MAIN OUTCOME MEASURE: Clinical effects and poor responses of intrathecal injection of amphotericin B and fluconazole treatment. RESULTS: Among 8 patients with cryptococcal meningitis, one died due to intracranial hypertension combining with cerebral hernia, and others were returned visit at 1 year after drug withdrawal. ① Clinical effects: Among 8 patients with cryptococcal meningitis, 4 were cured, 3 were improved, and one died. There was no relapse case. ② Results of mycological examination: After first intrathecal injection of 4 improved patients, the amount of cryptococcus of cerebrospinal fluid was decreased 20%-30%; in addition, after intrathecal injection for twice or three times, the amount was decreased 33%-50%. ③ Improvement of intracranial hypertension: Seven patients had the intracranial hypertension. After intrathecal injection for twice or three times, pressure of cerebrospinal fluid was decreased below 2 451.75 Pa, and the clinical symptoms were relieved remarkably. ④ Poor responses: After intrathecal injection, patients had headache, nausea, emesis and pain of lower limb. Especially, 2 cases had transient paraplegia of both lower limbs, one had retention of urine, and two had conscious disturbance. CONCLUSION: Controlling intracranial hypertension with repeatedly piercing waist and intrathecal injection of amphotericin B combining with fluconazole treatment are well therapeutic effects on the fluconazole treatment of cryptococcal meningitis. Healing rate is 50%; however, there are a lot of poor responses at various degrees. BACKGROUND: At present, fluconazole and intrathecal injection of amphotericin B has been widely used to treat cryptococcal meningitis. However, the application of amphotericin B can shorten course and has good effects on the treatment of cryptococcal meningitis. OBJECTIVE: To observe the effects and poor response of the intrathecal injection of amphotericin B on the treatment of cryptococcal meningitis. DESIGN: Retrospective-case analysis. SETTING: Department of Neurology, Beijing Hospital of Ministry of Public Health. PARTICIPANTS: Eight patients with cryptococcal meningitis were selected from Department of Neurology, Beijing Hospital of Ministry of Public Health from January 1995 to January 2006. Among them, there were 3 males and 5 females aged from 17 to 41 years and the course ranged from 21 days to 3 months. Patients who had symptoms of febrile and headache, positive meninges excitation, positive latex agglutination of cryptococcus of cerebrospinal fluid and positive ink smear we METHODS: Eight patients were treated with the fluconazole and intrathecal injection of amphotericin B. ① Intracranial hypertension of patients was controlled with flowing cerebrospinal fluid by repeatedly piercing waist; meanwhile, patients were taken the Intrathecal injection of amphotericin B combining with flucytosine or fluconazole treatment. The dosage of amphotericin B was 1-5 mg / d at the beginning of administration, and then, the samples were added with 2 mg dexasine and 500 mL of 5% glucose solution. The dosage was increased 5.0 mg per day till 50 mg per day, and the total dosage was 3.0-4.0 g. In addition, 2 mg dexasine was mixed with 4.0-5.0 mL cerebrospinal fluid, and then the solution was gradually injected into sheath for once a week. Fluconazole was dripped into vein with the volume of 400 mg per day, and then, 14 days later, fluconazole was orally taken by patients. intrThe cryptococcus of cerebrospinal fluid was negative for 3 successive cultures. ③ Evaluative criteria Improvement: Clinical symptoms and physical signs were improved remarkably, amount of cerebrospinal fluid was decreased, and ink smear was not negative; inefficiency and death. MAIN OUTCOME MEASURE: Clinical effects and poor responses of intrathecal injection of amphotericin B and fluconazole treatment. RESULTS: Among 8 patients with cryptococcal meningitis, one died due to intracranial hypertension combining with cerebral hernia, and others were returned visit at 1 year after drug withdrawal . ① Results of mycological examination: After first intrathecal injection of 4 improved patients, the amount of cryptococcal meningitis, 4 were cured, 3 were improved, and one died. There was no relapse case. In addition, after intrathecal injection for twice or three times, the amount was decreased 33% -50%. ③ Improvement of intracranial hypertension: Seven patients had the intracranial hypertension. After intrathecal injection for twice or three times, in amount, after intrathecal injection for twice or three times, the amount was decreased 33-50%. or three times, pressure of cerebrospinal fluid was decreased below 451.75 Pa, and the clinical symptoms were relieved remarkably. ④ Poor responses: After intrathecal injection, patients had headache, nausea, emesis and pain of lower limb. paraplegia of both lower limbs, one had retention of urine, and two had conscious disturbance. CONCLUSION: Controlling intracranial hypertension with repeated piercing wai st and intrathecal injection of amphotericin B combining with fluconazole treatment are well therapeutic effects on the fluconazole treatment of cryptococcal meningitis. Healing rate is 50%; however, there are a lot of poor responses at various degrees.
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