Synergistic Combinations of Antibiotics with Cumin, Oregano and Rosewood Oils as a Strategy to Preserve the Antibiotic Repertoire

Author(s): Lucy Owen, Katie Laird*

Journal Name: Current Traditional Medicine

Volume 5 , Issue 4 , 2019

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Abstract:

Background: Formulations employing synergistic combinations of antibiotics with Essential Oils (EOs) could help preserve the antibiotic repertoire by improving their activity against resistant bacteria.

Objective: This study was aimed to screen the antibiotics oxacillin and ciprofloxacin for synergistic interactions with cumin, oregano and rosewood EOs and the EO components cuminaldehyde, carvacrol and linalool against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus (antibiotic sensitive and resistant isolates). This will provide information on formulations with synergistic combinations of EOs and antibiotics that might resensitise antibiotic resistant bacteria.

Methods: Antimicrobial interactions between double and triple combinations of EOs, EO components and antibiotics were determined using the checkerboard method. The most active triple combinations were then assessed by a time-kill assay.

Results: Two synergistic EO-antibiotic combinations and eight additive EO-antibiotic combinations reduced the antibiotic minimum inhibitory concentration below clinical sensitivity breakpoints according to the checkerboard method. However, all the tested combinations were additive according to the time-kill assay; while the combinations completely killed S. aureus, E. coli and P. aeruginosa cells in 2 h. At least one EO compound from the combination alone completely killed the cells of test species.

Conclusion: Positive interactions support the use of EOs or EO components to enhance antibiotic efficacy against antibiotic resistant bacteria. The EO-antibiotic combinations tested by the time kill assay were indifferent; therefore, the observed antimicrobial activity did not arise from synergistic mechanisms as indicated by the checkerboard method. Investigation of other synergistic combinations identified by the checkerboard method could reveal more promising candidates.

Keywords: Essential oil, antibiotic, synergy, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli.

[1]
Tacconelli E, Carrara E, Savoldi A, et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18(3): 318-27.
[http://dx.doi.org/10.1016/S1473-3099(17)30753-3] [PMID: 29276051]
[2]
Butler MS, Blaskovich MA, Cooper MA. Antibiotics in the clinical pipeline at the end of 2015. J Antibiot (Tokyo) 2017; 70(1): 3-24.
[http://dx.doi.org/10.1038/ja.2016.72] [PMID: 27353164]
[3]
Luepke KH, Suda KJ, Boucher H, et al. Past, present, and future of antibacterial economics: Increasing bacterial resistance, limited antibiotic pipeline, and societal implications. Pharmacotherapy 2017; 37(1): 71-84.
[http://dx.doi.org/10.1002/phar.1868] [PMID: 27859453]
[4]
Pantel L, Florin T, Dobosz-Bartoszek M, et al. Odilorhabdins, antibacterial agents that cause miscoding by binding at a new ribosomal site Mol Cell 2018; 70(1): 83-94. e7.
[http://dx.doi.org/10.1016/j.molcel.2018.03.001] [PMID: 29625040]
[5]
Orchard A, Sandasi M, Kamatou G, Viljoen A, van Vuuren S. The in vitro antimicrobial activity and chemometric modelling of 59 commercial essential oils against pathogens of dermatological relevance. Chem Biodivers 2017; 14(1)e1600218 [Accessed 20 Dec. 2018
[http://dx.doi.org/10.1002/cbdv.201600218] [PMID: 27546349]
[6]
Alanís-Garza BA, Bocanegra-Ibarias P, Waksman de Torres N, et al. Antimicrobial activity of essential oils-derived volatile compounds against several nosocomial pathogens including representative multidrug-resistant A. Baumannii clinical isolates. J Essent Oil Res 2018; 30: 341-6.
[http://dx.doi.org/10.1080/10412905.2018.1483269]
[7]
Owen L, White AW, Laird K. Characterisation and screening of antimicrobial essential oil components against clinically important antibiotic-resistant bacteria using thin layer chromatography-direct bioautography hyphenated with GC-MS, LC-MS and NMR. Phytochem Anal 2019; 30(2): 121-31.
[http://dx.doi.org/10.1002/pca.2797] [PMID: 30280447]
[8]
Owen L, Laird K. Synchronous application of antibiotics and essential oils: Dual mechanisms of action as a potential solution to antibiotic resistance. Crit Rev Microbiol 2018; 44(4): 414-35.
[http://dx.doi.org/10.1080/1040841X.2018.1423616] [PMID: 29319372]
[9]
Wang YM, Kong LC, Liu J, Ma HX. Synergistic effect of eugenol with colistin against clinical isolated colistin-resistant Escherichia coli strains. Antimicrob Resist Infect Control 2018; 7: 17. [Accessed 20 Dec. 2018
[http://dx.doi.org/10.1186/s13756-018-0303-7] [PMID: 29423192]
[10]
Benameur Q, Gervasi T, Pellizzeri V, et al. Antibacterial activity of Thymus vulgaris essential oil alone and in combination with cefotaxime against blaESBL producing multidrug resistant Enterobacteriaceae isolates. Nat Prod Res 2018; 2: 1-8.
[http://dx.doi.org/10.1080/14786419.2018.1466124] [PMID: 29726697]
[11]
Allen HK, Trachsel J, Looft T, Casey TA. Finding alternatives to antibiotics. Ann N Y Acad Sci 2014; 1323: 91-100.
[http://dx.doi.org/10.1111/nyas.12468] [PMID: 24953233]
[12]
ISO 20776-1: Clinical laboratory testing and in vitro diagnostic test systems - Susceptibility testing of infectious agents and evaluation of performance of antimicrobial susceptibility test devices - Part 1: Reference method for testing the in vitro activity of antimicrobial agents against rapidly growing aerobic bacteria involved in infectious diseases. In: ISO. Geneva, Switzerland 2006.
[13]
European Committee of Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters 2018. Accessed on: http://www.eucast.org
[14]
Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 2003; 52(1): 1.
[http://dx.doi.org/10.1093/jac/dkg301] [PMID: 12805255]
[15]
BS EN 1040:2005 Chemical disinfectants and antiseptics - Quantitative suspension test for the evaluation of basic bactericidal activity of chemical disinfectants and antiseptics - Test method and requirements (phase 1). London, UK: BSI 2005.
[16]
Valcourt C, Saulnier P, Umerska A, et al. Synergistic interactions between doxycycline and terpenic components of essential oils encapsulated within lipid nanocapsules against gram negative bacteria. Int J Pharm 2016; 498(1-2): 23-31.
[http://dx.doi.org/10.1016/j.ijpharm.2015.11.042] [PMID: 26631640]
[17]
Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J Pharm Pharmacol 2015; 67(4): 473-85.
[http://dx.doi.org/10.1111/jphp.12334] [PMID: 25557808]
[18]
Llana-Ruiz-Cabello M, Gutiérrez-Praena D, Pichardo S, et al. Cytotoxicity and morphological effects induced by carvacrol and thymol on the human cell line Caco-2. Food Chem Toxicol 2014; 64: 281-90.
[http://dx.doi.org/10.1016/j.fct.2013.12.005] [PMID: 24326232]
[19]
Luz Ida S, de Melo AN, Bezerra TK, Madruga MS, Magnani M, de Souza EL. Sublethal amounts of Origanum vulgare L. essential oil and carvacrol cause injury and changes in membrane fatty acid of Salmonella Typhimurium cultivated in a meat broth. Foodborne Pathog Dis 2014; 11(5): 357-61.
[http://dx.doi.org/10.1089/fpd.2013.1695] [PMID: 24588810]
[20]
La Storia A, Ercolini D, Marinello F, Di Pasqua R, Villani F, Mauriello G. Atomic force microscopy analysis shows surface structure changes in carvacrol-treated bacterial cells. Res Microbiol 2011; 162(2): 164-72.
[http://dx.doi.org/10.1016/j.resmic.2010.11.006] [PMID: 21168481]
[21]
Pei RS, Zhou F, Ji BP, Xu J. Evaluation of combined antibacterial effects of eugenol, cinnamaldehyde, thymol, and carvacrol against E. coli with an improved method. J Food Sci 2009; 74(7): M379-83.
[http://dx.doi.org/10.1111/j.1750-3841.2009.01287.x] [PMID: 19895484]
[22]
Knezevic P, Aleksic V, Simin N, Svircev E, Petrovic A, Mimica-Dukic N. Antimicrobial activity of Eucalyptus camaldulensis essential oils and their interactions with conventional antimicrobial agents against multi-drug resistant Acinetobacter baumannii. J Ethnopharmacol 2016; 178: 125-36.
[http://dx.doi.org/10.1016/j.jep.2015.12.008] [PMID: 26671210]
[23]
Monogue ML, Kuti JL, Nicolau DP. Optimizing antibiotic dosing strategies for the treatment of gram-negative infections in the era of resistance. Expert Rev Clin Pharmacol 2016; 9(3): 459-76.
[http://dx.doi.org/10.1586/17512433.2016.1133286] [PMID: 26678036]
[24]
Kovač J, Šimunović K, Wu Z, et al. Antibiotic resistance modulation and modes of action of (-)-α-pinene in Campylobacter jejuni. PLoS One 2015; 10(4)e0122871 [Accessed 20 Dec. 2018
[http://dx.doi.org/10.1371/journal.pone.0122871] [PMID: 25830640]
[25]
Ruppé É, Woerther PL, Barbier F. Mechanisms of antimicrobial resistance in gram-negative bacilli. Ann Intensive Care 2015; 5(1): 61.
[http://dx.doi.org/10.1186/s13613-015-0061-0] [PMID: 26261001]
[26]
Redgrave LS, Sutton SB, Webber MA, Piddock LJ. Fluoroquinolone resistance: Mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol 2014; 22(8): 438-45.
[http://dx.doi.org/10.1016/j.tim.2014.04.007] [PMID: 24842194]
[27]
Radulović N, Misić M, Aleksić J, Doković D, Palić R, Stojanović G. Antimicrobial synergism and antagonism of salicylaldehyde in Filipendula vulgaris essential oil. Fitoterapia 2007; 78(7-8): 565-70.
[http://dx.doi.org/10.1016/j.fitote.2007.03.022] [PMID: 17590530]
[28]
Gonzales PR, Pesesky MW, Bouley R, et al. Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA. Nat Chem Biol 2015; 11(11): 855-61.
[http://dx.doi.org/10.1038/nchembio.1911] [PMID: 26368589]
[29]
Tangjitjaroenkun J, Chavasiri W, Thunyaharn S, Yompakdee C. Bactericidal effects and time-kill studies of the essential oil from the fruits of Zanthoxylum limonella on multi-drug resistant bacteria. J Essent Oil Res 2012; 24: 363-70.
[http://dx.doi.org/10.1080/10412905.2012.692907]
[30]
Pankey G, Ashcraft D, Patel N. In vitro synergy of daptomycin plus rifampin against Enterococcus faecium resistant to both linezolid and vancomycin. Antimicrob Agents Chemother 2005; 49(12): 5166-8.
[http://dx.doi.org/10.1128/AAC.49.12.5166-5168.2005] [PMID: 16304195]
[31]
Grégoire N, Raherison S, Grignon C, et al. Semimechanistic pharmacokinetic-pharmacodynamic model with adaptation development for time-kill experiments of ciprofloxacin against Pseudomonas aeruginosa. Antimicrob Agents Chemother 2010; 54(6): 2379-84.
[http://dx.doi.org/10.1128/AAC.01478-08] [PMID: 20368392]
[32]
Kalita S, Kandimalla R, Devi B, et al. Dual delivery of chloramphenicol and essential oil by poly-ε-caprolactone-Pluronic nanocapsules to treat MRSA-Candida co-infected chronic burn wounds. RSC Advances 2017; 7: 1749-58.
[http://dx.doi.org/10.1039/C6RA26561H]
[33]
Foweraker JE, Laughton CR, Brown DF, Bilton D. Comparison of methods to test antibiotic combinations against heterogeneous populations of multiresistant Pseudomonas aeruginosa from patients with acute infective exacerbations in cystic fibrosis. Antimicrob Agents Chemother 2009; 53(11): 4809-15.
[http://dx.doi.org/10.1128/AAC.00269-09] [PMID: 19704123]
[34]
Sopirala MM, Mangino JE, Gebreyes WA, et al. Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2010; 54(11): 4678-83.
[http://dx.doi.org/10.1128/AAC.00497-10] [PMID: 20713678]
[35]
Rand KH, Houck HJ, Brown P, Bennett D. Reproducibility of the microdilution checkerboard method for antibiotic synergy. Antimicrob Agents Chemother 1993; 37(3): 613-5.
[http://dx.doi.org/10.1128/AAC.37.3.613] [PMID: 8460929]
[36]
Lewis RE, Diekema DJ, Messer SA, Pfaller MA, Klepser ME. Comparison of Etest, chequerboard dilution and time-kill studies for the detection of synergy or antagonism between antifungal agents tested against Candida species. J Antimicrob Chemother 2002; 49(2): 345-51.
[http://dx.doi.org/10.1093/jac/49.2.345] [PMID: 11815578]


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Article Details

VOLUME: 5
ISSUE: 4
Year: 2019
Page: [337 - 353]
Pages: 17
DOI: 10.2174/2215083805666190521102152
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