5-Fluorocytosine and Urinary Candidiasis

Davies, R. R.; Reeves, D. S.

doi:10.1136/bmj.1.5749.577

Cited by 37 publications

(22 citation statements)

References 11 publications

(2 reference statements)

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“…Values determined for unknowns were reasonable and comparable to thoseT obtained in earlier Reading from left to right the other disks contain serum with the following drugs: (top row) 5FC, 20, 10, and 5 jig/ml; (middle row) amphotericin B (AMB), 10, 2.5, and 1.25 ug/ml; (bottom row) 5FC, 20 jig/ml and AMB, 10 Ag/ml; 5FC, 10 Mg/ml and AMB, 2.5 Mg/ml; 5FC, 5 ,ug/ml and AMB, 1.25 Mg/ml. The bright white band surrounding each disk represents diffusion of serum into the adjacent agar.…”

Section: Resultsmentioning

confidence: 99%

“…This resulted in a lx YNB agar seeded homogeneously with approximately 5 (ii) Cut well. Using a 5-mm diameter cylinder punch, wells were cut into the seeded YNB agar such that there were nine evenly distributed wells per plate.…”

Section: Methodsmentioning

confidence: 99%

“…The drug is usually well tolerated, producing few side effects. However, it has been suggested that the high serum levels which often accompany impaired renal function may be associated with bone marrow suppression and focal hepatic necrosis (5,14). Some investigators find it desirable to maintain serum levels of 5FC below 120 ,ug/ml for this reason (12).…”

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confidence: 99%

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Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B

Kaspar

Drutz

1975

Antimicrob Agents Chemother

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It is important that serum levels of 5-fluorocytosine (5FC) be measured to insure therapeutic levels while avoiding toxicity. This is particularly true in patients with renal insufficiency. The concurrent use of amphotericin B and 5FC complicates the measurement of 5FC in the serum, since fungi used in conventional bioassay systems are uniformly susceptible to amphotericin B. This paper describes the development of a simple, reliable, 6-h bioassay for 5FC in the presence of amphotericin B. The assay is based upon the fact that 5FC diffuses readily through yeast nitrogen base agar, whereas amphotericin B apparently does not. This assay allows rapid adjustments in therapy of patients receiving both 5FC and amphotericin B and has permitted us to maintain 5FC serum levels between limits of 25 and 120 ,g/ml in patients with altered renal function.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B

Kaspar

Drutz

1975

Antimicrob Agents Chemother

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“…There are, however, many reports of successful treatment with 5FC-some after the failure of amphotericin B-in cryptococcal meningitis and pulmonary infection (McGill et al, 1969; Utz et aZ., 1969), in candida and torulopsis septicaemia and endocarditis (Tassel and Madoff, 1968;Webb et al, 1970;Record et al, 1971;Steer et al), in urinary-tract infection (Davies and Reeves, 1971;Schonebeck, 1971) and in eye infection (Richards et al, 1969). Many of these authors also report treatment failures with 5FC, often but not always with the development of resistance to this agent.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of Yeasts to 5-Fluorocytosine

Speller

Davies

1973

Journal of Medical Microbiology

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“…In the face of decreasing renal function, excessively high levels of 5-FC may accumulate. To avoid the potentially toxic effects of 5-FC on the bone marrow and other organs (3,4,6,7,11), it is imperative that 5-FC levels be monitored closely in patients on combination therapy. Block and Bennett have described a method involving separation of 5-FC and AmB by ultrafiltration, allowing quantitation of serum 5-FC levels (3).…”

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Simple Assay for 5-Fluorocytosine in the Presence of Amphotericin B

Kauffman

Carleton²,

Frame³

1976

Antimicrob Agents Chemother

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A simple method for the measurement of 5-fluorocytosine in the presence of amphotericin B is described. The antifungal activity of amphotericin B is abolished by heating serum at 100 C for 45 min. 5-Fluorocytosine is unaffected by this treatment, and serum levels can be subsequently assayed by either tube dilution or disk diffusion methods.Combined drug therapy with amphotericin B (AmB) and 5-fluorocytosine (5-FC) has potential usefulness in the treatment of severe fungal infections caused by Cryptococcus neoformans, Torulopsis glabrata, and Candida species (1, 11). Because of its nephrotoxic effects, administration of AmB frequently leads to a diminished creatinine clearance (10). 5-FC is excreted almost entirely by the kidneys (12). In the face of decreasing renal function, excessively high levels of 5-FC may accumulate. To avoid the potentially toxic effects of 5-FC on the bone marrow and other organs (3,4,6,7,11), it is imperative that 5-FC levels be monitored closely in patients on combination therapy. Block and Bennett have described a method involving separation of 5-FC and AmB by ultrafiltration, allowing quantitation of serum 5-FC levels (3). Kaspar and Drutz have used differential diffusion rates of AmB and 5-FC as a means of assaying for 5-FC in the presence of AmB (5). Reported herein is a simple method of heat inactivation of AmB so that levels of 5-FC can be accurately assayed during combined therapy with both drugs.MATERIALS AND METHODS Preparation of standards. A stock solution of 1,000 ,ug of AmB (E. R. Squibb & Sons, Princeton, N.J.) per ml was prepared in sterile distilled water. The 5-FC (Hoffmann-La Roche, Inc., Nutley, N.J.) stock solution, 1,000 ug/ml, was prepared in 0.85% saline. Further dilutions of these standards were prepared with pooled human sera in saline so that a final concentration of 10% serum was achieved.Effect of heat on antifungal activity of AmB and 5-FC. Standard solutions, prepared as described above in 10% human serum, were heated at different temperatures for varying lengths of time. The temperatures employed were 37, 56, 100 (achieved by using flowing steam at 0 lb/in2 in a standard autoclave), and 121 C (21 lb/in2). The antifungal activity of each drug was then tested by the tube dilution method outlined below.

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5-Fluorocytosine and Urinary Candidiasis

Cited by 37 publications

References 11 publications

Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B

Rapid, Simple Bioassay for 5-Fluorocytosine in the Presence of Amphotericin B

Sensitivity of Yeasts to 5-Fluorocytosine

Simple Assay for 5-Fluorocytosine in the Presence of Amphotericin B

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