Reply To: Ibuprofen reverts resistance to azoles

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dvjorge
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rockemgirl;46981 wrote: Jorge,

Based on the study, what dose ibuprofen would you recommend to accompany azole treatment?
Today I started a combination rx antifungal azole treatment for a systemic, long-time, mycelial infection.
I’m grateful I happened to see this thread on the same day.
I have been reading your work for about 17 months. It’s outstanding. Thank you for
the education and your diligence in presenting as much research and myth busting as possible. It has been invaluable.

Probably 400 or 600 mg a day is enough. I think you will feel the die-off reaction. For instance, someone with a chronic vaginal candidiasis that has acquired resistance to the azoles will feel burning in the vagina if the drug is working. It is hard to say a proper dose since there isn’t medical information using it “in vivo” to treat resistant cases.

The resistance candida develops to the azoles is mostly caused by incorrect therapies using low dosages and short time of treatment.

Good luck and keep monitoring your liver enzymes.

Jorge.

[h][/h]Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry[h][/h]
Cidália Pina-Vaz1,2,*, Acácio Gonçalves Rodrigues1,2, Sofia Costa-de-Oliveira1, Elisabete Ricardo1 and Per-Anders Mårdh3
+ Author Affiliations

1Department of Microbiology, Porto Faculty of Medicine, Alameda Prof. Hernani Monteiro, 4200 Porto, Portugal; 2IPATIMUP—Institute of Pathology and Molecular Immunology of Porto University, Porto, Portugal; 3Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden
*Corresponding author. Tel: +351-91-9358514; Fax: +351-229962096; E-mail: [email protected]
Received April 29, 2005.
Revision received May 24, 2005.
Revision received June 15, 2005.
Accepted June 23, 2005.

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Abstract

Objectives: Resistance to antifungals often relates to efflux pumps exporting drugs; several modulators may block them, reverting resistance. Verapamil, β-oestradiol and progesterone, known efflux pump inhibitors of human neoplastic cells, and ibuprofen were tested as potential modulators of resistance of Candida spp.

Methods: Forty-two clinical isolates of Candida (38 fluconazole-resistant), two ATCC type strains and two C. albicans strains with known mechanisms of fluconazole resistance were incubated with subinhibitory concentrations of the modulators. After exposure, MICs of fluconazole, itraconazole and voriconazole were re-determined. Simultaneously, yeasts exposed to modulators were stained with FUN-1 and analysed by flow cytometry. 3H-labelled itraconazole was also used to study efflux in the presence and absence of modulators.

Results: Fluconazole MICs decreased in most strains after exposure to modulators, including control strains with documented efflux overexpression. No significant MIC variation was noticed for: all C. krusei strains tested, for the resistant strain by target change, for susceptible strains, and for a very few other clinical isolates. Reverted resistant phenotypes showed cross-resistance to itraconazole and to voriconazole, which was also reverted by the modulators. For these strains, an increase in FUN-1 staining and increased accumulation of 3H-labelled itraconazole were noticed after incubation with modulators.

Conclusions: Resistance related to overexpression of efflux pumps was common among clinical isolates and could be reverted by the assayed modulators, particularly ibuprofen. The mechanism of resistance in all tested C. krusei and in a few other strains seems, however, to be of a different nature. Ibuprofen is a promising compound in association with azoles, deserving future clinical trials. FUN-1 proved to be a good marker of efflux in Candida.