In Vitro Interactions of Amphotericin B Combined with Non-antifungal Agents Against Rhodotorula mucilaginosa Strains
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Rhodotorula species are emerging as opportunistic pathogens, causing catheter-associated fungemia in patients with compromised immunity. R. mucilaginosa is considered the most common species involved in human infections. Correct identification and susceptibility testing of Rhodotorula isolates recovered from the blood stream or central nervous system are essential to determine the best management of this unusual infection. The antifungal susceptibility tests showed that Rhodotorula was susceptible to low concentrations of amphotericin B (AMB) but was less susceptible to voriconazole. Combinations of AMB plus several non-antifungal medications were evaluated against 35 susceptible (Rm AMB-S) and resistant (Rm AMB-R) clinical Rhodotorula isolates using the broth microdilution checkerboard technique. We showed that in vitro exposure to increasing concentrations of AMB changed the susceptibility profile to these strains, which were named the Rm AMB-R group. The most synergistic interactions were AMB + simvastatin, followed by AMB + amlodipine and AMB + warfarin. Synergism and antagonism were observed in both groups for the combination AMB + cyclosporine A. AMB combined with a fluoroquinolone (AMB + levofloxacin) also demonstrated antagonism for the Rm AMB-S strains, but a high percentage of synergistic interactions was observed for the Rm AMB-R group. A combination drug approach can provide a different strategy to treat infections caused by AMB-resistant R. mucilaginosa.
KeywordsRhodotorula mucilaginosa Combination test Synergism Resistance Amphotericin B
This study was supported by CNPq (the National Council for Scientific and Technological Development of Brazil), ID 026/15.
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Conflict of interest
The authors declare that they have no conflict of interest.
The authors declare that the data/results of the manuscript do not constitute plagiarism and have not been published elsewhere.
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This article does not contain any studies on human and animal performed by any of the authors.
- 6.Ahmed A, Aggarwal M, Chiu R, Ramratnam B, Rinaldi M, Flanigan TP. A fatal case of Rhodotorula meningitis in AIDS. Med Health R I. 1998;81(1):22–3.Google Scholar
- 8.White T, Bruns T, Lee S, et al. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. PCR Protoc: Guide Methods Appl. 1990;18:315–22.Google Scholar
- 10.Clinical Laboratory and Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts. CLSI document M27-A3. 3rd ed. Wayne: Clinical Laboratory and Standards Institute; 2008. p. 1–40.Google Scholar
- 31.Hong RH, Koch RJ. Possible role of anticoagulation in the treatment of rhinocerebral mucormycosis. Otolaryngol Head Neck Surg. 2000;122(4):577–8.Google Scholar
- 39.Petrou MA, Rogers TR. In-vitro activity of antifungal agents in combination with four quinolones. Drugs Exp Clin Res. 1988;14(1):9–18.Google Scholar