In vitro susceptibility of Paracoccidioides brasiliensis yeast form to antifungal agents

Restrepo, Angela; Tabares, Catalina de Bedoutand Angela M.

doi:10.1590/S0036-46651984000600006

Abstracts

A study was conducted to determine the susceptibility of P. brasiliensis yeast form to amphotericin B (A), ketoconazole (K), 5-fluorocytosine (5-FC) and rifampin (R). The three isolates tested produced minimal inhibitory concentrations (MICs) (mcg/ml) in the following range: A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 and R: 40-80. The minimal fungicidal concentrations (MFC) were several times higher than the corresponding MICs. Precise MFC for 5-FC were not obtained (> 500 mcg/ml). Combination of K plus A proved synergic, with the fractional inhibitory concentration (FIC) indices revealing synergy when the drugs were combined at the 1 to 1 and 1 to 5 MIC ratios. R (40 mcg/ml) appeared to antagonize K. These results indicate promise for the combined use of K plus A as a therapeutical regimen.

Se realizó un estudio con el objeto de determinar la susceptibilidad de la fase levaduri-forme del P. brasiliensis a la Anfotericina B (A), el Ketoconazol (K), la 5-fluorocitosina (5-FC) y la rifampicina. Las 3 cepas estudiadas tuvieron las siguientes concentraciones inhibitorias mínimas (MIC) (mcg/ml) A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 y R: 40-80. Las concentraciones fungicidas mínimas (MFC) resultaron más altas que las MICs correspondientes. En el caso de la 5-FC no se obtuvo una cifra MFC precisa (> 500 mcg/ml). La combinación de K más A mostró ser sinérgica al combinarse las drogas en relación 1:1 y 1:5 de los MICs respectivos. R (40 mcg/ml) se mostró antagonista del K. Los resultados indican que la combinación A + K pudiera constituir un adecuado régimen terapéutico en ciertos pacientes.

In vitro susceptibility of Paracoccidioides brasiliensis yeast form to antifungal agents

Susceptibilidad in vitro de la forma levaduriforme de Paracoccidioides brasiliensis a los agentes antifungicos

Angela Restrepo; Catalina de Bedoutand Angela M. Tabares

Corporación de Investigaciones Biológicas, Hospital Pablo Tobón Uribe, Medellín, Colombia

SUMMARY

A study was conducted to determine the susceptibility of P. brasiliensis yeast form to amphotericin B (A), ketoconazole (K), 5-fluorocytosine (5-FC) and rifampin (R). The three isolates tested produced minimal inhibitory concentrations (MICs) (mcg/ml) in the following range: A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 and R: 40-80. The minimal fungicidal concentrations (MFC) were several times higher than the corresponding MICs. Precise MFC for 5-FC were not obtained (> 500 mcg/ml). Combination of K plus A proved synergic, with the fractional inhibitory concentration (FIC) indices revealing synergy when the drugs were combined at the 1 to 1 and 1 to 5 MIC ratios. R (40 mcg/ml) appeared to antagonize K. These results indicate promise for the combined use of K plus A as a therapeutical regimen.

RESUMEN

Se realizó un estudio con el objeto de determinar la susceptibilidad de la fase levaduri-forme del P. brasiliensis a la Anfotericina B (A), el Ketoconazol (K), la 5-fluorocitosina (5-FC) y la rifampicina. Las 3 cepas estudiadas tuvieron las siguientes concentraciones inhibitorias mínimas (MIC) (mcg/ml) A: 0.09-0.18; K: 0.001-0.007; 5-FC: 62.5-250 y R: 40-80. Las concentraciones fungicidas mínimas (MFC) resultaron más altas que las MICs correspondientes. En el caso de la 5-FC no se obtuvo una cifra MFC precisa (> 500 mcg/ml). La combinación de K más A mostró ser sinérgica al combinarse las drogas en relación 1:1 y 1:5 de los MICs respectivos. R (40 mcg/ml) se mostró antagonista del K. Los resultados indican que la combinación A + K pudiera constituir un adecuado régimen terapéutico en ciertos pacientes.

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ACKNOWLEDGEMENTS

This work was supported by the Fondo Colombiano de Investigaciones Científicas (Col-ciencias), Bogotá, (Project Nr. 97145-3-04-80).

Recebido para publicação em 13/2/1984.

1. BENNET, J. E.; DISMUKES, W. E.; DUMA, R. J.; MEDOFF, G. et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. New England J. Med. 301: 126-131, 1979.
2. BORELLI, D.; BRAN, J. L.; FUENTES, J.; LEGENDRE, R.; LEIDERMAN, E.; LEVINE, H. B.; RESTREPO, A. & STEVENS, D. A. Laboratory and clinical assessment of imidazole drugs. Post-grad. Med. J. 55: 657-661, 1979.
3. DEL NEGRO, G. Tratamento, controle de cura, profilaxia, pp. 271-281 in Paracoccidioidomicose DEL NEGRO, G.; LACAZ, C. S. & FIORILLO, A. M. (Editors). São Paulo, Sarvier, 1982.
4. DOUGHERTY, P. F.; YOTTER, D. W. & MATTHEWS, T. R. Chemically defined medium for susceptibility testing of antimicrobial agents. Antimicrob. Agents Chemother. 10: 923-925, 1976.
5. DROUHET, E. & DUPONT, B. Laboratory and clinical assessment of ketoconazole in deep-seated mycoses. Am. J. Med. 74 (Suppl.): 30-47, 1983.
6. ELION, G. B.; SINGERAND, S. & HITCHINGS, G. H. Antagonism of nucleic acid derivatives. J. Biol. Chem. 208: 477-488, 1954.
7. GALGIANI, J. N. & STEVENS, D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob. Agents Chemother. 10: 721-726, 1976.
8. LACAZ, C. S.; ULSON, C. M. & SAMPAIO, S. A. P. Ação in vitro da anfotericina B sobre o P. brasiliensis. Rev. Paul. Med. 54: 357-360, 1959.
9. LACAZ, C. S.; MINAMI, P. S. & FERNÁNDEZ, W. Ação in vitro de sulfametoxipiridazina sobre fungos patogênicos. Hospital (Rio) 73: 15-22, 1968.
10. MOODY, M. R.; YOUNG, W. M.; MORRIS, M_. J. & SCHIMPFF, S. C. In vitro activities of micona- zole, miconazole nitrate, and ketoconazole alone and combined with rifampin Candida spp and T. glabrata recovered from cancer patients. Antimicrob. Agents Chemother. 17: 871-875, 1980.
11. ODDS, P. C. Interactions among amphotericin B, 5-fluorocytosine, ketoconazole and miconazole against pathogenic fungi in vitro. Anthnicrob. Agents Chemother. 22: 763-770, 1982.
12. RESTREPO, A. & ARAN GO, M. D. In vitro susceptibility testing of P. brasiliensis to sulfonamides. Anthnicrob. Agents Chemother. 18: 190-194, 1980.
13. RESTREPO, A. & JIMÉNEZ, B. E. Growth of P. brasiliensis yeast phase in a chemically defined culture medium. J. Clin. Microbiol. 12: 279-281, 1980.
14. RESTREPO, A.; STEVENS, D. A.; GOMEZ, I.; LEI-DERMAN, E.; ANGEL, R.; FUENTES, J.; ARANA, A.; MEJÍA, G.; VANEGAS, A. C. & ROBLEDO, M. A. Ketoconazole: a new drug for the treatment of paracoccidioidomycosis. Rev. Infect. Dis. 2: 633-«42, 1980.
15. RESTREPO, A. & CANO, L. E. Recovery of fungi from seeded sputum samples. Effect of culture media and digestion procedures. Rev. Inst. Med. trop. São Paulo 23: 139-184, 1981.
16. SHADOMY, S. & ESPINEL-INGROFF, A. Susceptibility testing with antifugal drugs, pp. 647-653. In LENNETTE, E. H.; BALOWS, A.; HAUSLER, W. J. & TRUANT, J. P. (Ed.). Manual of Clinical Microbiology. 3rd. Washington, ASM, 1980.
17. STEVENS, D. A. & VO, P. T. Synergic interaction of trimethoprim sulfamethoxazole on P. brasiliensis. Anthnicrob. Agents Chemother. 21: 852-854, 1982.

Publication Dates

Publication in this collection
04 Apr 2013
Date of issue
Dec 1984

History

Received
13 Feb 1984

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BENNET, J. E.; DISMUKES, W. E.; DUMA, R. J.; MEDOFF, G. et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. New England J. Med. 301: 126-131, 1979.

[2] 2. BORELLI, D.; BRAN, J. L.; FUENTES, J.; LEGENDRE, R.; LEIDERMAN, E.; LEVINE, H. B.; RESTREPO, A. & STEVENS, D. A. Laboratory and clinical assessment of imidazole drugs. Post-grad. Med. J. 55: 657-661, 1979.

[3] 3. DEL NEGRO, G. Tratamento, controle de cura, profilaxia, pp. 271-281 in Paracoccidioidomicose DEL NEGRO, G.; LACAZ, C. S. & FIORILLO, A. M. (Editors). São Paulo, Sarvier, 1982.

[4] 4. DOUGHERTY, P. F.; YOTTER, D. W. & MATTHEWS, T. R. Chemically defined medium for susceptibility testing of antimicrobial agents. Antimicrob. Agents Chemother. 10: 923-925, 1976.

[5] 5. DROUHET, E. & DUPONT, B. Laboratory and clinical assessment of ketoconazole in deep-seated mycoses. Am. J. Med. 74 (Suppl.): 30-47, 1983.

[6] 6. ELION, G. B.; SINGERAND, S. & HITCHINGS, G. H. Antagonism of nucleic acid derivatives. J. Biol. Chem. 208: 477-488, 1954.

[7] 7. GALGIANI, J. N. & STEVENS, D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob. Agents Chemother. 10: 721-726, 1976.

[8] 8. LACAZ, C. S.; ULSON, C. M. & SAMPAIO, S. A. P. Ação in vitro da anfotericina B sobre o P. brasiliensis. Rev. Paul. Med. 54: 357-360, 1959.

[9] 9. LACAZ, C. S.; MINAMI, P. S. & FERNÁNDEZ, W. Ação in vitro de sulfametoxipiridazina sobre fungos patogênicos. Hospital (Rio) 73: 15-22, 1968.

[10] 10. MOODY, M. R.; YOUNG, W. M.; MORRIS, M_. J. & SCHIMPFF, S. C. In vitro activities of micona- zole, miconazole nitrate, and ketoconazole alone and combined with rifampin Candida spp and T. glabrata recovered from cancer patients. Antimicrob. Agents Chemother. 17: 871-875, 1980.

[11] 11. ODDS, P. C. Interactions among amphotericin B, 5-fluorocytosine, ketoconazole and miconazole against pathogenic fungi in vitro. Anthnicrob. Agents Chemother. 22: 763-770, 1982.

[12] 12. RESTREPO, A. & ARAN GO, M. D. In vitro susceptibility testing of P. brasiliensis to sulfonamides. Anthnicrob. Agents Chemother. 18: 190-194, 1980.

[13] 13. RESTREPO, A. & JIMÉNEZ, B. E. Growth of P. brasiliensis yeast phase in a chemically defined culture medium. J. Clin. Microbiol. 12: 279-281, 1980.

[14] 14. RESTREPO, A.; STEVENS, D. A.; GOMEZ, I.; LEI-DERMAN, E.; ANGEL, R.; FUENTES, J.; ARANA, A.; MEJÍA, G.; VANEGAS, A. C. & ROBLEDO, M. A. Ketoconazole: a new drug for the treatment of paracoccidioidomycosis. Rev. Infect. Dis. 2: 633-«42, 1980.

[15] 15. RESTREPO, A. & CANO, L. E. Recovery of fungi from seeded sputum samples. Effect of culture media and digestion procedures. Rev. Inst. Med. trop. São Paulo 23: 139-184, 1981.

[16] 16. SHADOMY, S. & ESPINEL-INGROFF, A. Susceptibility testing with antifugal drugs, pp. 647-653. In LENNETTE, E. H.; BALOWS, A.; HAUSLER, W. J. & TRUANT, J. P. (Ed.). Manual of Clinical Microbiology. 3rd. Washington, ASM, 1980.

[17] 17. STEVENS, D. A. & VO, P. T. Synergic interaction of trimethoprim sulfamethoxazole on P. brasiliensis. Anthnicrob. Agents Chemother. 21: 852-854, 1982.

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In vitro susceptibility of Paracoccidioides brasiliensis yeast form to antifungal agents

Susceptibilidad in vitro de la forma levaduriforme de Paracoccidioides brasiliensis a los agentes antifungicos

Abstracts

Publication Dates

History