Amphotericin B: The inhibitory concentration of amphotericin B on Cryptococcus neoformans is 0.0 1 ~ 1.56 μ g/ml, which is one of the first choice drugs to treat cryptoencephalopathy. The cure rate of cryptococcal meningitis is 56.6% ~ 865, 438+0%, but 65,438+0/3 cases may recur after stopping taking medicine, and need maintenance treatment.
The application method of (1) amphotericin B: intravenous drip, starting with the first small dose of 1 ~ 5mg, and then increasing by 5mg (children 1 ~ 2 mg) every day until 0.5 ~ 0.75 mg/kg body weight every day. The course of treatment is determined according to the time when cerebrospinal fluid turns negative and the general situation. Generally, it is used for 2 ~ 3 months, and it still needs to be maintained with fluconazole or itraconazole for 3 ~ 4 months after cerebrospinal fluid turns negative.
(2) Toxic and side effects: common chills, fever, damage to liver, kidney, myocardium and hematopoietic system, hypokalemia, atrial paroxysmal tachycardia and death from ventricular fibrillation have also been reported. Pay attention to the following points when intravenous infusion of amphotericin B:
① The infusion speed should be slow and controlled at 20 ~ 30dr/min；;
② The infusion bottle was wrapped with black cloth to prevent amphotericin B from being damaged by light;
③ Amphotericin B should be diluted to 5mg/mL with water for injection, and then diluted with 500 ml of 5% glucose solution. It is not advisable to dilute with normal saline to avoid precipitation.
④ Dexamethasone 2 ~ 5mg or hydrocortisone 50mg can be added to the liquid medicine for infusion.
⑤ intramuscular injection of promethazine 25mg before infusion.
⑥ In case of serious reaction during use, the drug can be temporarily stopped and the symptoms can be treated.
Intrathecal injection of amphotericin B can directly achieve a high inhibitory concentration in cerebrospinal fluid, especially for severe cases. Generally, 0. 1 ~ 1 mg is mixed with dexamethasone 1 ~ 2 mg and an appropriate amount of cerebrospinal fluid, and then injected slowly, 1 ~ 3 times a week. Intrathecal injection of amphotericin B can cause serious adverse reactions such as chemical meningitis, aggravated headache, leg pain, difficulty in defecation, arachnoid adhesion and shock.
2. Liposome-encapsulated liposome B: It is a new preparation containing amphotericin B in bilayer liposome. Amphotericin B liposome reduced the binding with cholesterol and enhanced the binding with ergot, thus reducing the toxic and side effects of amphotericin B. According to statistics, the toxicity of amphotericin B liposome is about 1/70 of amphotericin B. The main reason for the decrease of toxicity is that the coagulation state of amphotericin B changed after it was mixed into liposome and became a completely single monomer. In amphotericin B liposome, amphotericin B is slowly released into the body. A small amount of amphotericin B released is not enough to damage the cell membrane of the host, but focuses on the infected focus to kill fungi, thus achieving the effect of attenuation.
Precautions for application:
① Firstly, amphotericin B liposomes were diluted by shaking with water for injection, so that all amphotericin B liposomes became dispersed phase with a concentration of 4 mg/ml;
② The diluted amphotericin B liposome was further diluted to 0.2 ~ 2 mg/ml with 5% glucose solution, and then intravenously dripped in the dark with a blood transfusion filter within 6 hours. The dose can be gradually increased from 0.3mg/kg to1~ 2 mg kg-1d-1,and the total amount of cryptococcal meningitis can reach.
3.5- fluorocytosine (5-FC): The minimum inhibitory concentration of 5-FC on Cryptococcus is 0.09 ~ 7.8 mg/mL, but the drug resistance can be rapidly developed when 5-FC is used alone. Therefore, when combined with amphotericin B, amphotericin B acts on fungal cell membrane, changing its permeability, causing bacteria to be destroyed, and making 5-FC easily enter fungal cell membrane to play its role. Therefore, the usual dosage is 50 ~150mg kg-1d-1,taken orally for 3 ~ 4 times, or intravenously 1% 5-FC injection. Adverse reactions mainly include nausea, vomiting, rash, chills, liver, kidney and hematopoietic system damage, especially those with liver damage should be used with caution.
4. Fluconazole: Fluconazole is a new broad-spectrum triazole antifungal drug with a relative molecular weight of 306.3. It is water-soluble and can be completely absorbed by oral administration. It can enter cerebrospinal fluid well through the blood-brain barrier. The concentration of fluconazole in cerebrospinal fluid can reach 90% ~ 100% of the blood concentration, and the half-life is 36 h. 80% of the original fluconazole is excreted by the kidney, which has toxic and side effects. Generally, 400mg is injected intravenously for the first time, then it can be changed to 200 ~ 400 mg/d, and after 3 ~ 4 months, Cryptococcus neoformans in cerebrospinal fluid turns negative, it can be changed to 50 ~ 150 mg/d orally. Combined application with amphotericin B in the early stage can make cerebrospinal fluid turn negative faster and reduce the dosage and side effects of amphotericin B. Side effects: Adverse reactions are mild, and a few patients may have nausea, rash, increased liver enzymes and decreased blood potassium. Stevens-Johson syndrome has also been reported.
5. Itraconazole: Itraconazole is a broad-spectrum triazole antifungal agent, which is greatly influenced by gastrointestinal factors. It is not easy to enter cerebrospinal fluid through the blood-brain barrier, but its concentration is high in brain tissue, and the minimum inhibitory concentration for Cryptococcus is 0.0 1 ~ 12.5 mg/ml. We advocate the combined application of amphotericin B or maintenance therapy after cerebrospinal fluid turns negative, with an oral dose of 200 ~ 400 mg/d ... Side effects: nausea, vomiting, rash and elevated liver enzymes occur in a few patients, but generally do not affect the treatment.
At present, anti-fungal treatment advocates staged combined treatment. That is, it is divided into two stages: initial treatment and maintenance treatment. The combined use of antifungal drugs is beneficial to the judgment of treatment outcome and the adjustment of the types and doses of antifungal drugs. The initial treatment usually lasts 8 ~ 12 weeks. Amphotericin B should be combined with 5-FC or triazole antifungal drugs to make Cryptococcus neoformans in cerebrospinal fluid turn negative as soon as possible. After cryptococcus neoformans in cerebrospinal fluid turns negative, triazole antifungal drugs should be taken orally for 3 ~ 4 months to prevent recurrence.
(2) reducing intracranial pressure
Symptoms of increased intracranial pressure must be treated in time, otherwise brain hernia may lead to death. Every 6 ~ 8 hours, 20% mannitol (250mL) can be used for rapid intravenous drip, and 25% albumin solution (20mL) and furosemide (20 ~ 40 mg) can be used for intravenous injection if necessary. Alternate application of the two can enhance the effect of reducing intracranial pressure. In addition, intravenous injection of 60mL of 50% hypertonic glucose and oral administration of 50% glycerol syrup can also reduce intracranial pressure to some extent. If the therapeutic effect of dehydrated diuretics is still not satisfactory, lumbar puncture can be used to slowly release cerebrospinal fluid to achieve the purpose of decompression. For patients with intractable intracranial hypertension who are ineffective in the above treatment, ventricular drainage can be used for decompression.
(3) correct electrolyte disorder
During the treatment of cryptococcosis in the central nervous system, due to the extensive use of dehydrating diuretics, amphotericin B and corticosteroids, hypokalemia and other water and electrolyte disorders are easily caused, which should be reviewed and corrected in time. For hypokalemia, 4 ~ 8g potassium is injected intravenously and 3 ~ 6g potassium is taken orally every day, and the specific dosage depends on the condition.
supportive treatment
Conscious patients should be encouraged to eat high-protein and nutritious food to enhance their resistance. At the same time, fresh human plasma or whole blood can be imported to supplement various vitamins. Patients with emaciation, anorexia, insomnia and other symptoms can also be treated with traditional Chinese medicine according to the treatment method of strengthening the body resistance and eliminating evil. In addition, psychological care should be strengthened to enhance patients' confidence in overcoming diseases.
(5) Surgical treatment
The localized cryptococcal granuloma in the brain can be surgically removed and treated with systemic antifungal drugs according to the situation after operation, so as to achieve the goal of radical cure.