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In vitro susceptibility studies of Cryptococcus neoformans isolated from patients with no clinical response to

L Rodero1, S Córdoba, P Cahn

  • 1Departamento Micología, Instituto Nacional de Enfermedades Infecciosas, ANLIS 'Dr Carlos G. Malbrán', Av. Velez Sarsfield 563, 1281 Buenos Aires, Argentina. lrodero@mail.retina.ar

The Journal of Antimicrobial Chemotherapy
|February 8, 2000
PubMed

Insights

Antifungal drug combinations, particularly amphotericin B with flucytosine or rifampicin, showed synergistic activity against Cryptococcus neoformans isolates from treatment-failure AIDS patients. Fluconazole plus flucytosine was ineffective.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Cryptococcus neoformans is an opportunistic fungal pathogen causing life-threatening infections, particularly in immunocompromised individuals like AIDS patients.
  • Treatment failures and drug resistance are significant challenges in managing cryptococcal infections, necessitating evaluation of alternative therapeutic strategies.
  • Isolates studied were from patients with poor clinical outcomes despite amphotericin B therapy, highlighting the need for effective treatment options.

Purpose of the Study:

  • To evaluate the in vitro antifungal activity of amphotericin B (AMB), fluconazole (FCZ), and flucytosine (5FC) alone and in combination against Cryptococcus neoformans.
  • To assess the efficacy of drug combinations including AMB plus 5FC, AMB plus rifampicin (RIF), and FCZ plus 5FC.
  • To investigate the susceptibility patterns of C. neoformans isolates from AIDS patients with treatment failure.

Main Methods:

  • Time-kill curves (TKC) were employed to assess the fungicidal and fungistatic activities of individual drugs and their combinations.
  • Five clinical isolates of Cryptococcus neoformans obtained from AIDS patients with poor treatment responses were used.
  • Antifungal agents tested included AMB, FCZ, 5FC, and combinations of AMB/5FC, AMB/RIF, and FCZ/5FC.

Main Results:

  • Amphotericin B alone demonstrated no fungicidal activity, exhibiting a persistent or tolerant effect against all tested isolates.
  • Combinations of AMB plus 5FC and AMB plus RIF showed significant synergistic antifungal activity against most isolates.
  • The combination of fluconazole plus flucytosine failed to inhibit the growth of any of the C. neoformans isolates.

Conclusions:

  • Amphotericin B monotherapy may be insufficient for treating C. neoformans infections in certain patient populations.
  • Combinations of amphotericin B with flucytosine or rifampicin represent promising synergistic therapeutic strategies against resistant C. neoformans.
  • Fluconazole combined with flucytosine appears ineffective and should not be considered for treating these challenging C. neoformans infections.

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