Curcumin-meropenem synergy in carbapenem resistant Klebsiella pneumoniae curcumin-meropenem synergy
,
Abstract
Background and Objectives: The frequency of multiple resistant bacterial infections, including carbapenems, is increasing worldwide. As the decrease in treatment options causes difficulties in treatment, interest in new antimicrobials is increasing. One of the promising natural ingredients is curcumin. It is known to be effective in bacteria such as Pseudomonas aeruginosa, Escherichia coli, Burkholderia pseudomallei through efflux pump inhibition, toxin inhibition and enzymes. However, because its bioavailability is poor, it seffectiveness occurs in combination with antibiotics. In the study, the interaction of meropenem and curcumin in carbapenemase producing strains of Klebsiella pneumoniae was tested.
Materials and Methods: Thirty-nine Klebsiella pneumoniae isolates, resistant to meropenem, were used in this study. From those 15 MBL, 6 KPC, 17 OXA-48 and 1 AmpC resistance pattern were detected by combination disk method. Meropenem and Curcumin MIC values were determined by liquid microdilution. Checkerboard liquid microdilution was used to determine the synergy between meropenem and curcumin.
Results: Synergistic effects were observed in 4 isolates producing MBL, 3 isolates producing KPC, 4 isolates producing OXA-48, and 1 isolates producing AmpC (totally 12 isolates) according to the calculated FICI. No antagonistic effects were observed in any isolates.
Conclusion: Curcumin was thought to be an alternative antimicrobial in combination therapies that would positively contribute to the treatment of bacterial infection. The effectiveness of this combination should be confirmed by other in vitro and clinical studies.
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16. Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN. Curcumin for malaria therapy. Biochem Biophys Res Commun 2005;326:472-474.
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19. Eng SA, Nathan S. Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection. Front Microbiol 2015;6:290.
20. Rai D, Singh JK, Roy N, Panda D. Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. Biochem J 2008;410:147-155.
21. Negi N, Prakash P, Gupta ML, Mohapatra TM. Possible role of curcumin as an efflux pump inhibitor in multi drug resistant clinical isolates of Pseudomonas aeruginosa. J Clin Diagn Res 2014;8:DC04-7.
22. Rudrappa T, Bais HP. Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 2008;56:1955-1962.
23. Zacchino SA, Butassi E, Liberto MD, Raimondi M, Postigo A, Sortino M. Plant phenolics and terpenoids as adjuvants of antibacterial and antifungal drugs. Phytomedicine 2017;37:27-48.
24. Mun SH, Joung DK, Kim YS, Kang OH, Kim SB, Seo YS, et al. Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedicine 2013;20:714-718.
25. Marathe SA, Kumar R, Ajitkumar P, Nagaraja V, Chakravortty D. Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella typhimurium and Salmonella Typhi. J Antimicrob Chemother 2013;68:139-152.
26. Doern CD. When does 2 plus 2 equal 5? a review of antimicrobial synergy testing. J Clin Microbiol 2014;52:4124-4128.
27. Giske CG, Martinez L, Cantón R, Stefani S, Skov R, Glupczynski Y, et al. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance [Internet]. version 2, 2017. https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf
28. Hu W, Li M, Lu W, Guo S, Li J. Evaluation of MASTDISCS Combi Carba plus for the identification of metallo-β-lactamases, KPC and OXA-48 carbapenemase genes in Enterobacteriaceae clinical isolates. Lett Appl Microbiol 2020;70:42-47.
29. Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 2014;20:862-872.
30. Krishnappa LG, Marie MAM, Al Sheikh YA. Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and in vitro synergy of the colistin–meropenem combination. J Chemother 2015;27:277-282.
31. Laishram S, Anandan S, Devi BY, Elakkiya M, Priyanka B, Bhuvaneshwari T, et al. Determination of synergy between sulbactam, meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance. J Chemother 2016;28:297-303.
32. Tseng SP, Wang SF, Ma L, Wang TY, Yang TY, Siu LK, et al. The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan. J Microbiol Immunol Infect 2017;50:653-661.
33. Hemaiswarya S, Kruthiventi AK, Doble M. Synergism between natural products and antibiotics against infectious diseases. Phytomedicine 2008;15:639-652.
34. Kali A, Bhuvaneshwar D, Charles PM, Seetha KS. Antibacterial synergy of curcumin with antibiotics against biofilm producing clinical bacterial isolates. J Basic Clin Pharm 2016;7:93-96.
2. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791-1798.
3. World Health Organization. Central Asian and Eastern European surveillance of antimicrobial resistance annual report 2016 [Internet]. 2016. available from: https://www.euro.who.int/__data/assets/pdf_file/0009/323568/CAESAR-annual-report-2016.pdf
4. Çakar A, Akyön Y, Gür D, Karatuna O, Öǧünç D, Baysan BO, et al. Investigation of carbapenemases in carbapenem-resistant Escherichia coli and Klebsiella pneumoniae strains isolated in 2014 in Turkey. Mikrobiyol Bul 2016;50:21-33.
5. Cui X, Zhang H, Du H. Carbapenemases in Enterobacteriaceae: detection and antimicrobial therapy. Front Microbiol 2019;10:1823.
6. Suay-Gracia B, Pérez-Gracia MT. Present and future of Carbapenem-Resistant Enterobacteriaceae (CRE) infections. Antibiotics (Basel) 2019;8:122.
7. Schwartz KL, Morris SK. Travel and the spread of drug-resistant bacteria. Curr Infect Dis Rep 2018;20:29.
8. World Health Organization. Central Asian and Eastern European surveillance of antimicrobial resistance annual report 2017 [Internet]. 2017. available from: https://www.euro.who.int/__data/assets/pdf_file/0005/354434/WHO_CAESAR_annualreport_2017.pdf
9. Yoo JH. The infinity war: How to cope with carbapenem-resistant Enterobacteriaceae. J Korean Med Sci 2018;33(40):e255.
10. Araújo CC, Leon LL. Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 2001;96:723-728.
11. Berry A, Collacchi B, Masella R, Varì R, Cirulli F. Curcuma Longa, the "Golden Spice" to counteract neuroinflammaging and cognitive decline-what have we learned and what needs to be done. Nutrients 2021;13:1519.
12. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol 2008;75:787-809.
13. Gunes H, Gulen D, Mutlu R, Gumus A, Tas T, Topkaya AE. Antibacterial effects of curcumin: an in vitro minimum inhibitory concentration study. Toxicol Ind Health 2016;32:246-250.
14. Martins CVB, da Silva DL, Neres ATM, Magalhães TFF, Watanabe GA, Modolo LV, et al. Curcumin as a promising antifungal of clinical interest. J Antimicrob Chemother 2009;63:337-339.
15. Nandakumar DN, Nagaraj VA, Vathsala PG, Rangarajan P, Padmanaban G. Curcumin-artemisinin combination therapy for malaria. Antimicrob Agents Chemother 2006;50:1859-1860.
16. Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN. Curcumin for malaria therapy. Biochem Biophys Res Commun 2005;326:472-474.
17. Moghadamtousi SZ, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014;2014:186864.
18. Sanchez-Villamil JI, Navarro-Garcia F, Castillo-Romero A, Gutierrez-Gutierrez F, Tapia D, Tapia-Pastrana G. Curcumin blocks cytotoxicity of Enteroaggregative and Enteropathogenic Escherichia coli by blocking Pet and EspC proteolytic release from bacterial outer membrane. Front Cell Infect Microbiol 2019;9:334.
19. Eng SA, Nathan S. Curcumin rescues Caenorhabditis elegans from a Burkholderia pseudomallei infection. Front Microbiol 2015;6:290.
20. Rai D, Singh JK, Roy N, Panda D. Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. Biochem J 2008;410:147-155.
21. Negi N, Prakash P, Gupta ML, Mohapatra TM. Possible role of curcumin as an efflux pump inhibitor in multi drug resistant clinical isolates of Pseudomonas aeruginosa. J Clin Diagn Res 2014;8:DC04-7.
22. Rudrappa T, Bais HP. Curcumin, a known phenolic from Curcuma longa, attenuates the virulence of Pseudomonas aeruginosa PAO1 in whole plant and animal pathogenicity models. J Agric Food Chem 2008;56:1955-1962.
23. Zacchino SA, Butassi E, Liberto MD, Raimondi M, Postigo A, Sortino M. Plant phenolics and terpenoids as adjuvants of antibacterial and antifungal drugs. Phytomedicine 2017;37:27-48.
24. Mun SH, Joung DK, Kim YS, Kang OH, Kim SB, Seo YS, et al. Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedicine 2013;20:714-718.
25. Marathe SA, Kumar R, Ajitkumar P, Nagaraja V, Chakravortty D. Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella typhimurium and Salmonella Typhi. J Antimicrob Chemother 2013;68:139-152.
26. Doern CD. When does 2 plus 2 equal 5? a review of antimicrobial synergy testing. J Clin Microbiol 2014;52:4124-4128.
27. Giske CG, Martinez L, Cantón R, Stefani S, Skov R, Glupczynski Y, et al. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance [Internet]. version 2, 2017. https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf
28. Hu W, Li M, Lu W, Guo S, Li J. Evaluation of MASTDISCS Combi Carba plus for the identification of metallo-β-lactamases, KPC and OXA-48 carbapenemase genes in Enterobacteriaceae clinical isolates. Lett Appl Microbiol 2020;70:42-47.
29. Tzouvelekis LS, Markogiannakis A, Piperaki E, Souli M, Daikos GL. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 2014;20:862-872.
30. Krishnappa LG, Marie MAM, Al Sheikh YA. Characterization of carbapenem resistance mechanisms in Klebsiella pneumoniae and in vitro synergy of the colistin–meropenem combination. J Chemother 2015;27:277-282.
31. Laishram S, Anandan S, Devi BY, Elakkiya M, Priyanka B, Bhuvaneshwari T, et al. Determination of synergy between sulbactam, meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance. J Chemother 2016;28:297-303.
32. Tseng SP, Wang SF, Ma L, Wang TY, Yang TY, Siu LK, et al. The plasmid-mediated fosfomycin resistance determinants and synergy of fosfomycin and meropenem in carbapenem-resistant Klebsiella pneumoniae isolates in Taiwan. J Microbiol Immunol Infect 2017;50:653-661.
33. Hemaiswarya S, Kruthiventi AK, Doble M. Synergism between natural products and antibiotics against infectious diseases. Phytomedicine 2008;15:639-652.
34. Kali A, Bhuvaneshwar D, Charles PM, Seetha KS. Antibacterial synergy of curcumin with antibiotics against biofilm producing clinical bacterial isolates. J Basic Clin Pharm 2016;7:93-96.
| Files | ||
| Issue | Vol 13 No 3 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v13i3.6397 | |
| Keywords | ||
| Curcumin; Klebsiella pneumoniae; Carbapenemase; Drug synergism; Anti-bacterial agents | ||
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How to Cite
1.
Gülen D, Şafak B, Erdal B, Günaydın B. Curcumin-meropenem synergy in carbapenem resistant Klebsiella pneumoniae curcumin-meropenem synergy. Iran J Microbiol. 2021;13(3):345-351.
