Two Cases of Cryptococcal Meningitis, one Treated with 5-Fluorocytosine

Watkins, Jackson; Campbell, M. J.; Gardner-Medwin, D.; Ingham, H. R.; Murray, I. G.

doi:10.1136/bmj.3.5661.29

Cited by 35 publications

(13 citation statements)

References 5 publications

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“…The fluorinated pyrimidine, 5-fluorocytosine (5-FC), has been found effective in the treatment of systemic candidiasis, cryptococcal meningitis, and certain other fungal infections (4,6,12,13,(15)(16)(17)(18)(19)(20). It has the advantage of oral administration and produces few toxic effects.…”

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confidence: 99%

Chemotherapeutic Activity of 5-Fluorocytosine and Amphotericin B Against Candida albicans in Mice

Titsworth

Grünberg

1973

Antimicrob Agents Chemother

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The effect of treatment with combinations of the two antifungal agents, 5-fluorocytosine (5-FC) and amphotericin B (AB), against systemic Candida albicans infections in mice was investigated. Graded doses of the single substances and of combinations of the drugs were administered daily for 21 days.The 50% curative dose (CDS,) values were calculated on the basis of the presence or absence of C. albicans in cultures prepared from the kidneys of animals that succumbed during the experimental period or were sacrificed at the termination of the experiments. Overall, when graded doses of AB were administered in the presence of a constant, inactive dose of 5-FC (approximately one-half to one-fourth the CD50 of 5-FC), the CD50 values for AB were lower than those for amphotericin B alone. Similarly, the CD50s for 6-FC were reduced when AB was administered at a constant dose equal to one-half to one-fourth the CD50 of AB alone. In no instance was there evidence of antagonism.

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confidence: 99%

Chemotherapeutic Activity of 5-Fluorocytosine and Amphotericin B Against Candida albicans in Mice

Titsworth

Grünberg

1973

Antimicrob Agents Chemother

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“…Use of 5-FC for the treatment of fungal infections in man first appeared in the literature in 1967 (5), since which time 10 articles in the English literature have reported experience with a total of 22 patients with cryptococcal disease, 19 with Candida infection, and 1 with Torulopsis glabrata septicemia (3,4,(8)(9)(10)(15)(16)(17)(18)(19). Although this agent is undergoing clinical investigation in a number of centers at the present time, relatively little is known about its pharmacological properties.…”

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confidence: 99%

Pharmacological Studies with 5-Fluorocytosine

Block

Bennett

1972

Antimicrob Agents Chemother

107

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A cylinder plate bioassay for 5-fluorocytosine (5-FC) is described which permits determination of 5-FC concentrations in biological fluids in the presence of amphotericin B. Using this assay, we determined serum concentrations in 12 patients after a single dose of drug and in 8 patients receiving daily 5-FC at 6-hr intervals (4 to 120 days). Drug was detectable in serum as early as 0.5 hr and concentrations were measurable as long as 24 hr after a dose, regardless of renal function. Peak concentrations occurred 6 hr after the initial drug dose, but were seen between 1 and 2 hr after a dose in all patients receiving a minimum of 4 days of therapy. Mild to moderate renal impairment produced marked increases in peak 5-FC concentrations in the serum of a group of eight patients on three different dosage schedules. Five patients were studied before and after amphotericin B-induced renal insufficiency. Peak concentrations increased from 14 to 142% concomitant with the change in renal function. Parallel studies in rabbits confirmed the results in our patients. 5-FC half-life in the serum of 10 rabbits increased from 3.35 0.27 to 24.63 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 ,ug/ml and were 74.4 + 5.6% of simultaneously determined serum concentrations. The effect of renal function on 5-FC concentrations in cerebrospinal fluid was similar to that seen with serum.

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“…(e) papiUoedema can be associated with an active choroiditis but is generally associated with raised intracranial pressure or direct spread via the leptomeninges secondary to a meningitis (Cohen, 1944;Heinsius, 1950;Friedenwald et al, 1952;Turner, 1959;Okun & Butler, 1964;Hiles & Font, 1968). (f) Neuro-ophthalmic involvement can manifest itself as III, IV or VI nerve palsies with diplopia, ptosis, pupillary abnormalities, and nystagmus (Okun & Butler, 1964) or as a internuclear or supranuclear ophthalmoplegia (Watkins et al, 1969;Goyea & Heilman, 1972). (g) Orbital involvement was reported by Gill, (1934) and Krainer et al, (1846).…”

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confidence: 99%