Amphotericin intrathecal

The use of intrathecal amphotericin B is not recommended for the treatment of cryptococcal meningitis except in very ill patients or in those with recurrent or progressive disease despite aggressive IV amphotericin B therapy. The dosage of amphotericin B employed is usually 0.5 mg administered via the lumbar, cisternal, or intraventricular (via an Ommaya reservoir) route two or three times weekly. 

Cryptococcemia wilh positive serum antigen titer (>1 8), cutaneous infection, a positive urine culture, or prostatic disease Recurrent or progressive disease not responsive to amphotericin B Isolated pulmonary disease (without evidence of CNS infection) Clinician must decide whether to follow the pulmonary therapeutic regimen or the CNS (disseminated) regimen Amphotericin Brf IV 0.5-0.75 mj kj day intrathecal amphotericin B 0.5 mg 2-3 times weekly Mild to moderate symptoms or asymptomatic with a positive pulmonary specimen Fluconazole 200-400 mg orally daily x lifelong or Itraconazole 200-400 mg orally daily x lifelong or... 

CNS disease Lipid formulation of amphotericin BIV 3-6 mg/kg/day x 6-10 weeks (Note Induction therapy with azoles alone is discouraged.) Amphotericin Brf IV 0.7-1 mg/kg/day + flucytosine 100 mg/kg/ day orally x 2 wk, followed by fluconazole 400 mg orally daily for a minimum of 10 weeks (in patients intolerant to fluconazole, substitute itraconazole 200-400 mg orally daily) or Amphotericin B IV 0.7-1 mg/kg/day + 5-flucytosine 100 mg/kj day orally x 6-10 weeks or Amphotericin Brf IV 0.7-1 mg/kg/day x 10 weeks Refractory disease Intrathecal or intraventricular amphotericin B (continued)... 

Meningitis, cocc/d/o/c/a/orcAypfococca/-Administer amphotericin B deoxycholate intrathecally at initial doses of 0.025 mg, gradually increased to the maximum tolerable dose. The usual dose is 0.25 to 1 mg every 48 to 72 hours. A maximum total dose of 15 mg has been suggested. 

Combinations of amphotericin-B with flucytosine are sometimes used to reduce the occurrence of resistance. Amphotericin-B is not absorbed from the gastrointestinal tract which necessitates intravenous administration. It is 90% protein bound and widely distributed, except for the CNS. For the treatment of fungal meningitis therefore only intrathecal drug administrations can be effective. Amphotericin-B is eliminated very slowly in urine, mainly in an inactive form, with an elimination half-life of about 24 hours which can increase to up to 15 days with repeated doses. 

Abnormalities of liver function tests are occasionally seen, as is a varying degree of anemia due to reduced erythropoietin production by damaged renal tubular cells. After intrathecal therapy with amphotericin, seizures and a chemical arachnoiditis may develop, often with serious neurologic sequelae. 

Amphotericin B has been used intrathecally in patients with coccidioidal or cryptococcal meningitis. The side effects associated with this route of administration are headache, paraesthesia, nerve palsy, and visual impairment. To treat coccidioidal arthritis, amphotericin B may be injected intraarticularly (Figure 45.2). 

Amphotericin B" IV 0.5-0.75 mj kj day intrathecal amphotericin B 0.5 mg 2-3 times weekly Miid to moderate symptoms or asymptomatic with a positive pulmonary specimen Fluconazole 200-400 mg orally daily x lifelong or... 

Amphotericin IV 0.7-1 mg/k day x 10 weeks Refractory disease Intrathecal or intraventricular amphotericin B... 

Winn RE, Bower JH, Richards JF. Acute toxic delirium. Neurotoxicity of intrathecal administration of amphotericin B. Arch Intern Med 1979 139(6) 706-7. 

A marked improvement is generally noted after 4—8 weeks of treatment. Treatment is often continued until a total dose of 3 g is reached. In the case of coccidioidomycosis, for example, treatment with 0.4—0.8 mg,/kg/d may last months. The polyene is administered intrathecally to treat Coccidioides meningitis. However, the results are only moderate. It is very important to check renal and hepatic function during treatment with amphotericin B. 

Fluconazole is the drug of choice for treatment of coccidioidal meningitis because of much less morbidity than with intrathecal amphotericin B. In other forms of coccidioidomycosis, fluconazole is comparable to itraconazole. Fluconazole has activity against histoplasmosis, blastomycosis, sporotrichosis, and ringworm, but response is less than with equivalent doses of itraconazole. Fluconazole is not effective in the prevention or treatment of aspergillosis. As with other azoles, with the possible exception of posa-conazole, there is no activity in mucormycosis. 

Itraconazole, ketoconazole, fluconazole Ruconazole, intrathecal amphotericin B... 

Intrathecal infusion of amphotericin B (C-AMB) is used in patients with meningitis caused by Coccidioides. Treatment is initiated with 0.05-0.1 mg and increased on a three-times-weekly schedule to 0.5 mg, as tolerated. Therapy is then continued on a twice-weekly schedule. 

Arachnoiditis, manifested by fever and headache, can occur with intrathecal injection of C-AMB it may be decreased by intrathecal administration of 10-15 mg of hydrocortisone. Other serious problems that attend the use of intrathecal injections depend on the injection site. Local injections of amphotericin B into a joint or peritoneal dialysate fluid commonly produce irritation and pain. 

Amphotericin B given by slow IV infusion—poor penetration into the CNS (intrathecal possible)... 

VERY expensive. No effects on testosterone synthesis. Can initiate treatment intravenously, then switch to orals. Circumvents need to use intrathecal amphotericin for Coccidiomycosis meningitis. 

Amphotericin B (Figure 11.2) is not well absorbed from the gastrointestinal tract and it is only used orally for local treatment for oral infections. It is used in veterinary medicine for systemic fungal infections and is usually given intravenously or by intrathecal administration. It is poorly soluble in water and so most formulations make use of sodium deoxycholate, which then permits the formation of a suspension. In human and veterinary medicine, the limiting factor to systemic treatment with amphotericin B is nephrotoxicity. ... 

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