In Vitro Interactions Between Antifungals and Immunosuppressants Against Aspergillus Fumigatus Isolates from Transplant and Nontransplant Patients

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2004 Nov 25

PMID 15561883

Citations 28

Authors

William J Steinbach

Nina Singh

Jackie L Miller

Daniel K Benjamin Jr

Wiley A Schell

Joseph Heitman

John R Perfect

Affiliations

Soon will be listed here.

Abstract

We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin B, voriconazole, and caspofungin) and three immunosuppressants (FK506, cyclosporine, and rapamycin). We were not able to detect a difference in calcineurin inhibitor antifungal activity against isolates from transplant recipients and nontransplant patients.

Citing Articles

Isavuconazole and Amphotericin B Synergic Antifungal Activity: In Vitro Evaluation on Pulmonary Aspergillosis Molds Isolates.

Calvo M, Lauricella F, Mellini A, Scalia G, Trovato L Antibiotics (Basel). 2024; 13(11).

PMID: 39596700 PMC: 11591417. DOI: 10.3390/antibiotics13111005.

Calcineurin activity in Fonsecaea pedrosoi: tacrolimus and cyclosporine A inhibited conidia growth, filamentation and showed synergism with itraconazole.

Sousa I, Tavares L, Silva B, Moreno D, Alviano C, Santos A Braz J Microbiol. 2024; 55(4):3643-3654.

PMID: 39044105 PMC: 11711851. DOI: 10.1007/s42770-024-01463-2.

Potential Antifungal Targets for sp. from the Calcineurin and Heat Shock Protein Pathways.

Ancuceanu R, Hovanet M, Cojocaru-Toma M, Anghel A, Dinu M Int J Mol Sci. 2022; 23(20).

PMID: 36293395 PMC: 9603945. DOI: 10.3390/ijms232012543.

Structure-guided approaches to targeting stress responses in human fungal pathogens.

LeBlanc E, Polvi E, Veri A, Prive G, Cowen L J Biol Chem. 2020; 295(42):14458-14472.

PMID: 32796038 PMC: 7573264. DOI: 10.1074/jbc.REV120.013731.

In Vitro Interaction between Isavuconazole and Tacrolimus, Cyclosporin A, or Sirolimus against Species.

Schwarz P, Dannaoui E J Fungi (Basel). 2020; 6(3).

PMID: 32650564 PMC: 7560155. DOI: 10.3390/jof6030103.

References

Denning D . Invasive aspergillosis. Clin Infect Dis. 1998; 26(4):781-803; quiz 804-5. DOI: 10.1086/513943. View

Odom A, Muir S, Lim E, Toffaletti D, Perfect J, Heitman J . Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J. 1997; 16(10):2576-89. PMC: 1169869. DOI: 10.1093/emboj/16.10.2576. View

Bell N, Karp C, Alfonso E, Schiffman J, Miller D . Effects of methylprednisolone and cyclosporine A on fungal growth in vitro. Cornea. 1999; 18(3):306-13. DOI: 10.1097/00003226-199905000-00012. View

Cardenas M, Cruz M, Del Poeta M, Chung N, Perfect J, Heitman J . Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action. Clin Microbiol Rev. 1999; 12(4):583-611. PMC: 88926. DOI: 10.1128/CMR.12.4.583. View

Cruz M, Del Poeta M, Wang P, Wenger R, Zenke G, Quesniaux V . Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin. Antimicrob Agents Chemother. 1999; 44(1):143-9. PMC: 89641. DOI: 10.1128/AAC.44.1.143-149.2000. View

Cruz M, Sia R, Olson M, Cox G, Heitman J . Comparison of the roles of calcineurin in physiology and virulence in serotype D and serotype A strains of Cryptococcus neoformans. Infect Immun. 2000; 68(2):982-5. PMC: 97236. DOI: 10.1128/IAI.68.2.982-985.2000. View

Del Poeta M, Cruz M, Cardenas M, Perfect J, Heitman J . Synergistic antifungal activities of bafilomycin A(1), fluconazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother. 2000; 44(3):739-46. PMC: 89756. DOI: 10.1128/AAC.44.3.739-746.2000. View

Marchetti O, Moreillon P, Glauser M, Bille J, Sanglard D . Potent synergism of the combination of fluconazole and cyclosporine in Candida albicans. Antimicrob Agents Chemother. 2000; 44(9):2373-81. PMC: 90072. DOI: 10.1128/AAC.44.9.2373-2381.2000. View

Marchetti O, Entenza J, Sanglard D, Bille J, Glauser M, Moreillon P . Fluconazole plus cyclosporine: a fungicidal combination effective against experimental endocarditis due to Candida albicans. Antimicrob Agents Chemother. 2000; 44(11):2932-8. PMC: 101583. DOI: 10.1128/AAC.44.11.2932-2938.2000. View

10.

Arikan S, Paetznick V, Rex J . In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother. 2000; 45(1):327-30. PMC: 90285. DOI: 10.1128/AAC.45.1.327-330.2001. View

11.

Rohde J, Heitman J, Cardenas M . The TOR kinases link nutrient sensing to cell growth. J Biol Chem. 2001; 276(13):9583-6. DOI: 10.1074/jbc.R000034200. View

12.

Lugardon K, Chasserot-Golaz S, Kieffer A, Nullans G, Kieffer B, Aunis D . Structural and biological characterization of chromofungin, the antifungal chromogranin A-(47-66)-derived peptide. J Biol Chem. 2001; 276(38):35875-82. DOI: 10.1074/jbc.M104670200. View

13.

Cruz M, Goldstein A, Blankenship J, Del Poeta M, Perfect J, McCusker J . Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR. Antimicrob Agents Chemother. 2001; 45(11):3162-70. PMC: 90798. DOI: 10.1128/AAC.45.11.3162-3170.2001. View

14.

Cruz M, Goldstein A, Blankenship J, Del Poeta M, Davis D, Cardenas M . Calcineurin is essential for survival during membrane stress in Candida albicans. EMBO J. 2002; 21(4):546-59. PMC: 125859. DOI: 10.1093/emboj/21.4.546. View

15.

Marr K, Carter R, Crippa F, Wald A, Corey L . Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002; 34(7):909-17. DOI: 10.1086/339202. View

16.

Fox D, Heitman J . Good fungi gone bad: the corruption of calcineurin. Bioessays. 2002; 24(10):894-903. DOI: 10.1002/bies.10157. View

17.

Singh N, Avery R, Munoz P, Pruett T, Alexander B, Jacobs R . Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clin Infect Dis. 2002; 36(1):46-52. DOI: 10.1086/345441. View

18.

Kontoyiannis D, Lewis R, Osherov N, Albert N, May G . Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J Antimicrob Chemother. 2003; 51(2):313-6. DOI: 10.1093/jac/dkg090. View

19.

Onyewu C, Blankenship J, Del Poeta M, Heitman J . Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei. Antimicrob Agents Chemother. 2003; 47(3):956-64. PMC: 149324. DOI: 10.1128/AAC.47.3.956-964.2003. View

20.

Blankenship J, Steinbach W, Perfect J, Heitman J . Teaching old drugs new tricks: reincarnating immunosuppressants as antifungal drugs. Curr Opin Investig Drugs. 2003; 4(2):192-9. View