Comparison of Minimum Inhibitory Concentration (MIC) value of statin drugs: A Systematic Review

Author(s): Meenakshi Gupta, Anoop Kumar*.

Journal Name: Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry

Volume 17 , Issue 1 , 2019

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Abstract:

Background: Microbial infection and its resistance to clinically approved drugs create a huge threat to human health. Emerging reports have indicated the potential of statin drugs in the treatment of various types of microbial infections. However, it is still unclear, how much concentration of statin is effective against microbial infections. In literature, Minimum Inhibitory Concentration (MIC) values of statin drugs vary according to strain, species, and the type of statins. Thus, the main aim of the current study is to compare the MIC values of various types of statins against various types of micro-organisms.

Methodology: The data related to statin and microbial infection has been extracted from Pub Med (from September 1987 to October 2017). A total of 662 studies have been published from 1987 -2017 regarding statin and microbial infections. After inclusion and exclusion criteria, finally, 28 studies have been selected for comparative analysis of MIC values.

Results: All the statin drugs have shown a significant effect on various types of microbial infections. Among all the tested statin drugs, Simvastatin has lower MIC value in almost all types of microorganisms as compared to other statin drugs. However, on S. pneumoniae and aspergillus, Fluvastatin has the lowest MIC values as compared to Simvastatin. Atorvastatin was found to be the most potent against almost all strains of gram-negative bacteria. However, Rosuvastatin and Pravastatin have high MIC value against all types of microorganisms. Further, FICI value indicated the synergetic effect of Simvastatin with Amphotericin B, Itraconazole, and Fluconazole against various strains of Cryptococcus.

Conclusion: In conclusion, Simvastatin, Atorvastatin, and Fluvastatin could be developed as potential antimicrobial agents. However, further studies are required to understand its complete safety and efficacy profile.

Keywords: Microbial infections, drug-resistance, statin drugs, MIC values, antimicrobial activity, HMG-CoA reductase.

[1]
Tabish, S.A.; Syed, N. The future of humanity and microbes: Impact of emerging infectious diseases on global health and economies. Int. J. Sci. Res., 2015, 4(4), 2427-2442.
[2]
WHO; G.WHO methods and data sources for global burden of disease estimates. Geneva: Department of Health Statistics and Information Systems, 2000-2011.
[3]
Bannister, R.M.; Wanderlay, W.C.; Brew, J. Biocopea Limited Treatment of Microbial Infections, U.S. Patent Application 13/509. 2010, 534.
[4]
Caldwell, J.R.; Cluff, L.E. Adverse reactions to antimicrobial agents. JAMA, 1974, 230(1), 77-80.
[5]
Taylor, F.; Ward, K.; Moore, T.H.; Burke, M.; Davey Smith, G.; Casas, J.P.; Ebrahim, S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev., 2011, 1(1)
[http://dx.doi.org/10.1002/14651858.CD004816.pub5]
[6]
Stancu, C.; Sima, A. Statins: Mechanism of action and effects. J. Cell. Mol. Med., 2001, 5(4), 378-387.
[7]
Lefer, D.J. Statins as potent antiinflammatory drugs. Circulation, 2002, 106(16), 2041-2042.
[8]
Mach, F. Toward a role for statins in immunomodulation. Mol. Interv., 2002, 2(8), 478.
[9]
Davignon, J.; Jacob, R.F.; Mason, R.P. The antioxidant effects of statins. Coron. Artery Dis., 2004, 15(5), 251-258.
[10]
Kamińska, M.; Aliko, A.; Hellvard, A.; Marczyk, A.; Mydel, P. Effects of statins on multispecies oral biofilm. J. Oral Microbiol., 2017, 9(Suppl. 1), 1325249.
[11]
Graziano, T.S.; Cuzzullin, M.C.; Franco, G.C.; Schwartz-Filho, H.O.; de Andrade, E.D.; Groppo, F.C.; Cogo-Müller, K. Statins and antimicrobial effects: Simvastatin as a potential drug against Staphylococcus aureus biofilm. PLoS One, 2015, 10(5), 0128098.
[12]
Thangamani, S.; Mohammad, H.; Abushahba, M.F.; Hamed, M.I.; Sobreira, T.J.; Hedrick, V.E.; Paul, L.N.; Seleem, M.N. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci. Rep., 2015, 5, 16407.
[13]
Masadeh, M.; Mhaidat, N.; Alzoubi, K.; Al-azzam, S.; Alnasser, Z. Antibacterial activity of statins: A comparative study of atorvastatin, simvastatin, and rosuvastatin. Ann. Clin. Microbiol. Antimicrob., 2012, 11(1), 13-18.
[14]
Bergman, P.; Linde, C.; Pütsep, K.; Pohanka, A.; Normark, S.; Henriques-Normark, B.; Andersson, J.; Björkhem-Bergman, L. Studies on the antibacterial effects of statins-in vitro and in vivo. PLoS One, 2011, 6(8), 24394.
[15]
Delsesto, D.; Opal, S.M. Future perspectives on regulating pro-and anti-inflammatory responses in sepsis.In Sepsis-Pro-Inflammatory and Anti-Inflammatory Responses; Karger Publishers, 2011, Vol. 17, pp. 137-156.
[16]
Andrews, J.M. Determination of minimum inhibitory concentrations. J. Antimicrob. Chemother., 2001, 48(1), 5-16.
[17]
Nyilasi, I.; Kocsubé, S.; Krizsán, K.; Galgóczy, L.; Papp, T.; Pesti, M.; Nagy, K.; Vágvölgyi, C. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Sabouraudia, 2013, 52(2), 140-148.
[18]
Hennessy, E.; Adams, C.; Reen, F.J.; O’Gara, F. Statins as next generation anti-microbials: Is there potential for repurposing? Antimicrob. Agents Chemother., 2016, AAC-00192.
[19]
Bellanger, A.P.; Tatara, A.M.; Shirazi, F.; Gebremariam, T.; Albert, N.D.; Lewis, R.E.; Ibrahim, A.S.; Kontoyiannis, D.P. Statin concentrations below the minimum inhibitory concentration attenuate the virulence of Rhizopus oryzae. J. Infect. Dis., 2016, 214(1), 114-121.
[20]
Graziano, T.S.; Cuzzullin, M.C.; Franco, G.C.; Schwartz-Filho, H.O.; de Andrade, E.D.; Groppo, F.C.; Cogo-Müller, K. Statins and antimicrobial effects: Simvastatin as a potential drug against Staphylococcus aureus biofilm. PLoS One, 2015, 10(5), 0128098.
[21]
Natesan, S.K.; Chandrasekar, P.H.; Alangaden, G.J.; Manavathu, E.K. Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus in vitro. Diagn. Microbiol. Infect. Dis., 2008, 60(4), 369-373.
[22]
Brilhante, R.S.N.; Caetano, E.P.; Oliveira, J.S.D.; Castelo-Branco, D.D.S.C.; Souza, E.R.Y.; Alencar, L.P.D.; Cordeiro, R.D.A.; Bandeira, T.D.J.P.G.; Sidrim, J.J.C.; Rocha, M.F.G. Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species. Braz. J. Infect. Dis., 2015, 19(5), 459-465.
[23]
Qiao, J.; Kontoyiannis, D.P.; Wan, Z.; Li, R.; Liu, W. Antifungal activity of statins against Aspergillus species. Med. Mycol., 2007, 45(7), 589-593.
[24]
Welch, M.L.; Liappis, A.P.; Kan, V.L. Candidemia outcomes not improved with statin use. Med. Mycol., 2013, 51(2), 219-222.
[25]
Forrest, G.N.; Kopack, A.M.; Perencevich, E.N. Statins in candidemia: clinical outcomes from a matched cohort study. BMC Infect. Dis., 2010, 10(1), 152.
[26]
Jerwood, S.; Cohen, J. Unexpected antimicrobial effect of statins. J. Antimicrob. Chemother., 2007, 61(2), 362-364.
[27]
Van Laar, T.A.; Hole, C.; Karna, S.R.; Miller, C.L.; Reddick, R.; Wormley, F.L.; Seshu, J. Statins reduce spirochetal burden and modulate immune responses in the C3H/HeN mouse model of Lyme disease. Microbes Infect., 2016, 18(6), 430-435.
[28]
Brilhante, R.S.N.; Caetano, E.P.; Oliveira, J.S.D.; Castelo-Branco, D.D.S.C.; Souza, E.R.Y.; Alencar, L.P.D.; Cordeiro, R.D.A.; Bandeira, T.D.J.P.G.; Sidrim, J.J.C.; Rocha, M.F.G. Simvastatin inhibits planktonic cells and biofilms ofCandida and Cryptococcusspecies. Braz. J. Infect. Dis., 2015, 19(5), 459-465.
[29]
Klein-Marcuschamer, D.; Ajikumar, P.K.; Stephanopoulos, G. Engineering microbial cell factories for biosynthesis of isoprenoid molecules: beyond lycopene. Trends Biotechnol., 2007, 25(9), 417-424.
[30]
Chow, O.A.; von Köckritz-Blickwede, M.; Bright, A.T.; Hensler, M.E.; Zinkernagel, A.S.; Cogen, A.L.; Gallo, R.L.; Monestier, M.; Wang, Y.; Glass, C.K.; Nizet, V. Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe, 2010, 8(5), 445-454.
[31]
Radigan, K.A.; Urich, D.; Misharin, A.V.; Chiarella, S.E.; Soberanes, S.; Gonzalez, A.; Perlman, H.; Wunderink, R.G.; Budinger, G.S.; Mutlu, G.M. The effect of rosuvastatin in a murine model of influenza A infection. PLoS One, 2012, 7(4), 35788.
[32]
Graziano, T.S.; Cuzzullin, M.C.; Franco, G.C.; Schwartz-Filho, H.O.; de Andrade, E.D.; Groppo, F.C.; Cogo-Müller, K. Statins and antimicrobial effects: Simvastatin as a potential drug against Staphylococcus aureus biofilm. 2015, PLoS One, 10(5), 0128098.


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Article Details

VOLUME: 17
ISSUE: 1
Year: 2019
Page: [4 - 19]
Pages: 16
DOI: 10.2174/2211352516666180629124433

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