789. Sertraline Demonstrates Fungicidal Activity Against Coccidioides immitis In Vitro
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Background:

Coccidioidomycosis causes substantial morbidity in endemic areas, and treatment of disseminated infections may require lifelong antifungal therapy. The anti-depressant serotonin-reuptake inhibitor sertraline has been reported to have activity against other fungi in vitro, possibly via toxicity to yeast vesicular transport systems.  As improved treatment options are needed for coccidioidomycosis, the fungicidal activity of sertraline against C. immitis was investigated in vitro

Methods:

C. immitis was identified in fungal cultures from clinical specimens using the Hologic Gen-Probe nucleic acid based assay. C. immitiscolonies were isolated from cultures on Sabouraud-dextrose agar slants in the biosafety level 3 laboratory of Community Regional Medical Center. Stock solutions of sertraline and fluconazole were made at 5 mg/mL in DMSO. Following reference protocol Clinical and Laboratory Standards Institute M27-S4 and M38-A2, Minimum Inhibitory Concentration (MIC) was determined after a 5 day incubation in RPMI culture medium. The Minimum Fungicidal Concentration (MFC) was determined after this incubation by plating 0.25 ml of each culture on Saboraud-dextrose agar plates.

Results:

For four clinical isolates of C. immitisthe MIC and MFC were determined for fluconazole, sertraline and for the two drugs combined at equal concentration:

MIC and MFC results for four clinical isolates of C. immitis

Drug

MIC (mcg/mL)

fluconazole

4

8

16

32

sertraline

4

4

8

8

fluc + sert

4

2

4

4

 

MFC (mcg/mL)

fluconazole

4

16

16

32

sertraline

4

8

8

8

fluc + sert

2

4

4

4

Conclusion:

For four clinical isolates of C immitis, sertraline had an equal or lower MIC than the standard of care treatment fluconazole. The sertraline MFC was also equal or lower than that of fluconazole. In combination the two drugs had at least additive effectiveness.  The MIC of sertraline for C. immitis is higher than sertraline therapeutic blood concentrations, however, sertraline concentrations in the central nervous system (CNS) can approach these levels. These results indicate that sertraline may have potential as an additional agent for the treatment of C. immitis infection.

Simon Paul, M.D., Infectious Diseases, UCSF - Fresno, Fresno, CA, Roger Mortimer, MD, Family Medicine, UCSF - Fresno, Fresno, CA and Marilyn Mitchell, MT(ASCP)MS, Community Regional Medical Center, Fresno, CA

Disclosures:

S. Paul, None

R. Mortimer, None

M. Mitchell, None

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