In Vitro Activity of Amphotericin B in Combination with Statins against Clinical and Environmental Rhizopus oryzae Strains
-
Mahsa NAEIMI ESHKALETI
,
Parivash KORDBACHEH
,
Seyed Jamal HASHEMI
,
Mehraban FALAHATI
,
Farideh ZAINI
,
Hossein MIRHENDI
,
Mahin SAFARA
,
Leila HOSSEINPOOR
Abstract
Background: Mucormycosis is an acute and invasive fungal infection with a high mortality rate. Mucorales are less sensitive than other types of fungi to most antifungal agents. Amphotericin B (AMB) is one treatment option for this infection, but in recent studies, the antifungal activity of statins against Mucorales was shown. Therefore, therapy that combines AMB with these agents may have better effects in management of patients with mucormycosis. We evaluated the in vitro activity of AMB alone and in combination with statins, against Mucorales.
Methods: Susceptibility profiles of AMB alone and in combination with two statins, atorvastatin (ATO) and lovastatin (LOV) determined against clinical (n: 15) and environmental (n: 5) Rhizopus oryzae isolates, obtained between Jan 2009 and Oct 2016 from patients with uncontrolled diabetes mellitus and cancer referred to the Department of Parasitology and Medical Mycology of Tehran University of Medical Sciences, Tehran, Iran. It was performed by microdilution method, based on the Clinical and Laboratory Standard Institute (CLSI) M38-A2 guideline.
Results: All clinical and environmental isolates were susceptible to AMB (MIC≤1 µg/mL). The results of the interactions between AMB and the two statins were positive. The AMB-ATO (GM: 0.13 µg/Ml) combination produced greater activity than the AMB-LOV (GM: 0.26 µg/mL) combination. AMB, in combination with ATO and LOV, reacts positively against clinical and environmental R. oryzae isolates.
Conclusion: This combination strategy may lead to more effective treatment of mucormycosis and fewer side effects using low dose of AMB.
1. Ribes JA, Vanover-Sams CL, Baker DJ (2000). Zygomycetes in human disease. Clin Microbiol Rev, 13(2):236-301.
2. Kontoyiannis D, Lionakis M, Lewis R et al (2005). Zygomycosis in the era of Aspergillus-active antifungal therapy in a tertiary care cancer center: a case-control observational study of 27 recent cases. J Infect Dis, 191(8):1350-1360.
3. Greenberg RN, Scott LJ, Vaughn HH, Ribes JA (2004). Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis, 17(6):517-525.
4. Lewis RE, Kontoyiannis DP (2013). Epidemiology and treatment of mucormycosis. Future microbiology, 8(9):1163-1175.
5. Chayakulkeeree M, Ghannoum MA (2006). Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect Dis, 25(4):215-229.
6. Roden MM, Zaoutis TE, Buchanan WL et al (2005). Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis, 41(5):634-653.
7. Petrikkos G, Skiada A, Lortholary O et al (2012). Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis, 1:S23-34.
8. Kontoyiannis DP, Lewis RE (2006). Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am, 20(3):581-607.
9. Nosanchuk JD (2006). Current status and future of antifungal therapy for systemic mycoses. Recent patents on anti-infective drug discovery, 1(1):75-84.
10. Dannaoui E, Meletiadis J, Mouton JW et al (2003). In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother, 51(1):45-52.
11. Sun QN, Fothergill AW, McCarthy DI, Rinaldi MG, Graybill JR (2002). In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrobial Agents Chemotherapy, 46(5):1581-1582.
12. Alastruey-Izquierdo A, Castelli MV, Cuesta I et al (2009). Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers. Antimicrob Agents Chemother, 53(4):1686-1689.
13. Macreadie IG, Johnson G, Schlosser T, Macreadie PI (2006). Growth inhibition of Candida species and Aspergillus fumigatus by statins. FEMS Microbiol Lett, 262(1):9-13.
14. Nyilasi I, Kocsubé S, Krizsán K et al (2014). Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Med Mycol, 52(2):140-148.
15. Afeltra J, Verweij P (2003). Antifungal activity of nonantifungal drugs. Eur J Clin Microbiol Infect Dis, 22(7):397-407.
16. Kontoyiannis DP (2007). Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis, 44(8):1089-1090.
17. Bellanger A-P, Tatara AM, Shirazi F et al (2016). Statin concentrations below the minimum inhibitory concentration attenuate the virulence of Rhizopus oryzae. J Infect Dis, 214(1):114-121.
18. Nyilasi I, Kocsube S, Pesti M et al (2010). In vitro interactions between primycin and different statins in their effects against some clinically important fungi. J Med Microbiol, 59(Pt2):200-205.
19. Nash JD, Burgess DS, Talbert RL (2002). Effect of fluvastatin and pravastatin, HMG-CoA reductase inhibitors, on fluconazole activity against Candida albicans. J Med Microbiol, 51(2):105-109.
20. Gallagher JC, Ashley ESD, Drew RH, Perfect JR (2003). Antifungal pharmacotherapy for invasive mould infections. Expert Opin Pharmacother, 4(2):147-164.
21. Vazquez JA (2007). Combination antifungal therapy: the new frontier.
22. Pryce TM, Palladino S, Price DM et al (2006). Rapid identification of fungal pathogens in BacT/ALERT, BACTEC, and BBL MGIT media using polymerase chain reaction and DNA sequencing of the internal transcribed spacer regions. Diagn Microbiol Infect Dis, 54(4):289-297.
23. CLSI (2008). Reference method for broth dilution antifungal susceptibilitytesting of filamentous Fungi; Approved standard, 2nd edition. CLSI Document. M38-A2. Clinical and laboratory Standards Institute, Wan.
24. Chamilos G, Lewis RE, Kontoyiannis DP (2008). Delaying amphotericin B–based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis, 47(4):503-509.
25. Gyetvai Á, Emri T, Takács K et al (2006). Lovastatin possesses a fungistatic effect against Candida albicans, but does not trigger apoptosis in this opportunistic human pathogen. FEMS yeast research, 6(8):1140-1148.
26. Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C (2010). Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged, 54(1):33-36.
27. Chamilos G, Lewis RE, Kontoyiannis DP (2006). Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob Agents Chemother, 50(1):96-103.
28. Song JL, Lyons CN, Holleman S, Oliver BG, White TC (2003). Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans. Med Mycol, 41(5):417-425.
29. Nyilasi I, Kocsubé S, Krizsán K et al (2010). In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi. FEMS Microbiol Lett, 307(2):175-184.
30. Galgóczy L, Nyilasi I, Papp T, Vágvölgyi C (2009). Are statins applicable for the prevention and treatment of zygomycosis? Clinical infectious diseases, 49:483-484.
31. Barrios-González J, Miranda RU (2010). Biotechnological production and applications of statins. Appl Microbiol Biotechnol, 85(4):869-883.
32. Galgóczy L, Lukács G, Nyilasi I, Papp T, Vágvölgyi C (2010). Antifungal activity of statins and their interaction with amphotericin B against clinically important Zygomycetes. Acta Biol Hung, 61(3):356-365.
2. Kontoyiannis D, Lionakis M, Lewis R et al (2005). Zygomycosis in the era of Aspergillus-active antifungal therapy in a tertiary care cancer center: a case-control observational study of 27 recent cases. J Infect Dis, 191(8):1350-1360.
3. Greenberg RN, Scott LJ, Vaughn HH, Ribes JA (2004). Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis, 17(6):517-525.
4. Lewis RE, Kontoyiannis DP (2013). Epidemiology and treatment of mucormycosis. Future microbiology, 8(9):1163-1175.
5. Chayakulkeeree M, Ghannoum MA (2006). Zygomycosis: the re-emerging fungal infection. Eur J Clin Microbiol Infect Dis, 25(4):215-229.
6. Roden MM, Zaoutis TE, Buchanan WL et al (2005). Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis, 41(5):634-653.
7. Petrikkos G, Skiada A, Lortholary O et al (2012). Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis, 1:S23-34.
8. Kontoyiannis DP, Lewis RE (2006). Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am, 20(3):581-607.
9. Nosanchuk JD (2006). Current status and future of antifungal therapy for systemic mycoses. Recent patents on anti-infective drug discovery, 1(1):75-84.
10. Dannaoui E, Meletiadis J, Mouton JW et al (2003). In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother, 51(1):45-52.
11. Sun QN, Fothergill AW, McCarthy DI, Rinaldi MG, Graybill JR (2002). In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrobial Agents Chemotherapy, 46(5):1581-1582.
12. Alastruey-Izquierdo A, Castelli MV, Cuesta I et al (2009). Activity of posaconazole and other antifungal agents against Mucorales strains identified by sequencing of internal transcribed spacers. Antimicrob Agents Chemother, 53(4):1686-1689.
13. Macreadie IG, Johnson G, Schlosser T, Macreadie PI (2006). Growth inhibition of Candida species and Aspergillus fumigatus by statins. FEMS Microbiol Lett, 262(1):9-13.
14. Nyilasi I, Kocsubé S, Krizsán K et al (2014). Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Med Mycol, 52(2):140-148.
15. Afeltra J, Verweij P (2003). Antifungal activity of nonantifungal drugs. Eur J Clin Microbiol Infect Dis, 22(7):397-407.
16. Kontoyiannis DP (2007). Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis, 44(8):1089-1090.
17. Bellanger A-P, Tatara AM, Shirazi F et al (2016). Statin concentrations below the minimum inhibitory concentration attenuate the virulence of Rhizopus oryzae. J Infect Dis, 214(1):114-121.
18. Nyilasi I, Kocsube S, Pesti M et al (2010). In vitro interactions between primycin and different statins in their effects against some clinically important fungi. J Med Microbiol, 59(Pt2):200-205.
19. Nash JD, Burgess DS, Talbert RL (2002). Effect of fluvastatin and pravastatin, HMG-CoA reductase inhibitors, on fluconazole activity against Candida albicans. J Med Microbiol, 51(2):105-109.
20. Gallagher JC, Ashley ESD, Drew RH, Perfect JR (2003). Antifungal pharmacotherapy for invasive mould infections. Expert Opin Pharmacother, 4(2):147-164.
21. Vazquez JA (2007). Combination antifungal therapy: the new frontier.
22. Pryce TM, Palladino S, Price DM et al (2006). Rapid identification of fungal pathogens in BacT/ALERT, BACTEC, and BBL MGIT media using polymerase chain reaction and DNA sequencing of the internal transcribed spacer regions. Diagn Microbiol Infect Dis, 54(4):289-297.
23. CLSI (2008). Reference method for broth dilution antifungal susceptibilitytesting of filamentous Fungi; Approved standard, 2nd edition. CLSI Document. M38-A2. Clinical and laboratory Standards Institute, Wan.
24. Chamilos G, Lewis RE, Kontoyiannis DP (2008). Delaying amphotericin B–based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis, 47(4):503-509.
25. Gyetvai Á, Emri T, Takács K et al (2006). Lovastatin possesses a fungistatic effect against Candida albicans, but does not trigger apoptosis in this opportunistic human pathogen. FEMS yeast research, 6(8):1140-1148.
26. Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C (2010). Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged, 54(1):33-36.
27. Chamilos G, Lewis RE, Kontoyiannis DP (2006). Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob Agents Chemother, 50(1):96-103.
28. Song JL, Lyons CN, Holleman S, Oliver BG, White TC (2003). Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans. Med Mycol, 41(5):417-425.
29. Nyilasi I, Kocsubé S, Krizsán K et al (2010). In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi. FEMS Microbiol Lett, 307(2):175-184.
30. Galgóczy L, Nyilasi I, Papp T, Vágvölgyi C (2009). Are statins applicable for the prevention and treatment of zygomycosis? Clinical infectious diseases, 49:483-484.
31. Barrios-González J, Miranda RU (2010). Biotechnological production and applications of statins. Appl Microbiol Biotechnol, 85(4):869-883.
32. Galgóczy L, Lukács G, Nyilasi I, Papp T, Vágvölgyi C (2010). Antifungal activity of statins and their interaction with amphotericin B against clinically important Zygomycetes. Acta Biol Hung, 61(3):356-365.
| Files | ||
| Issue | Vol 48 No 5 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i5.1812 | |
| Keywords | ||
| Mucormycosis Mucorales Amphotericin B Atorvastatin Lovastatin Rhizopus oryzae | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
NAEIMI ESHKALETI M, KORDBACHEH P, HASHEMI SJ, FALAHATI M, ZAINI F, MIRHENDI H, SAFARA M, HOSSEINPOOR L. In Vitro Activity of Amphotericin B in Combination with Statins against Clinical and Environmental Rhizopus oryzae Strains. Iran J Public Health. 2019;48(5):943-948.
