Abstract
The therapeutic value of synergistic interactions has been known since antiquity,
and many different cultural healing systems still rely on this principle in the belief
that combination therapy may enhance efficacy. This paper intends to provide an overview,
from an antimicrobial perspective, on the research undertaken and interactive principles
involved in pharmacognosy studies. Methods used to determine antimicrobial interactions
include basic combination studies, the sum of the fractional inhibitory concentration
index (ΣFIC), isobole interpretations, and death kinetic (time-kill) assays. The various
interactions are discussed with reference to molecules, different plant parts or fractions,
different plant species, and combinations with nonbotanical antimicrobial agents.
It is recommended for future development in the field of phytosynergy that consideration
should be given to the selection criteria for the two inhibitors. A more conservative
approach should be adopted when classifying synergy. When examining interactions in
plant-based studies, antagonistic interactions should not be ignored. Combinations
involving more than two test samples should be examined where applicable, and very
importantly, the mechanism of action of synergistic interactions should be given precedence.
It is encouraging to observe the upsurge in papers exploring the complex interactions
of medicinal plants, and undoubtedly this will become increasingly important in our
continued quest to understand the mechanism of action of phytotherapy. The scientific
validation of efficacious antimicrobial combinations could lead to patentable entities
making research in the field of phytosynergy not only academically rewarding but also
commercially relevant.
Key words
additive - antagonistic - synergistic - interactions - antimicrobial - plant
References
- 1 Shealy C N. The illustrated encyclopaedia of healing remedies. Australia; Element
Books 1998
- 2
Li R C, Schentag J J, Nix D E.
The fractional maximal effect method: a new way to characterize the effect of antibiotic
combinations and other nonlinear pharmacodynamic interactions.
Antimicrob Agents Chemother.
1993;
37
523-531
- 3
Inui T, Wang Y, Deng S, Smith D C, Franzblau S G, Pauli G F.
Counter-current chromatography based analysis of synergy in an anti-tuberculosis ethnobotanical.
J Chromatogr A.
2007;
1151
211-215
- 4
Cottarel G, Wierzbowski J.
Combination drugs, an emerging option for antibacterial therapy.
Trends Biotechnol.
2007;
12
547-555
- 5
Chou T-C.
Theoretical basis, experimental design, and computerized simulation of synergism and
antagonism in drug combination studies.
Pharmacol Rev.
2006;
58
623-642
- 6
Wagner H.
Multitarget therapy-the future of treatment for more than just functional dyspepsia.
Phytomedicine.
2006;
13
SV122-SV129
- 7
Biavatti M W.
Synergy: an old wisdom, a new paradigm for pharmacotherapy.
Braz J Pharm Sci.
2009;
45
371-378
- 8
Ma X H, Zheng C J, Han L Y, Xie B, Jia J, Cao Z W, Li Y X, Chen Y Z.
Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular
interaction and network perspectives.
Drug Discov Today.
2009;
14
581-588
- 9
Berenbaum M C.
What is synergy?.
Pharmacol Rev.
1989;
41
93-141
- 10
Odds F C.
Synergy, antagonism, and what the chequerboard puts between them.
J Antimicrob Chemother.
2003;
52
1-3
- 11
Lambert R J W, Lambert R.
A model for the efficacy of combined inhibitors.
J Appl Microbiol.
2003;
95
734-743
- 12
Johnson M D, MacDougall C, Ostrosky-Zeichner L, Perfect J R, Rex J H.
Combination antifungal therapy.
Antimicrob Agents Chemother.
2004;
48
693-715
- 13
Bell A.
Antimalarial drug synergism and antagonism: mechanistic and clinical significance.
FEMS Microbiol Lett.
2005;
253
171-184
- 14
ESCMID .
Terminology relating to methods for the determination of susceptibility of bacteria
to antimicrobial agents. The European Society of Clinical Microbiology and Infectious
Diseases Eucast Definitive document E.Def 1.2.
CMI.
2000;
6
503-515
- 15
Williamson E M.
Synergy and other interactions in phytomedicines.
Phytomedicine.
2001;
8
401-409
- 16
White R L, Burgess D S, Manduru M, Bosso J A.
Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard and Etest.
Antimicrob Agents Chemother.
1996;
40
1914-1918
- 17
Wu M, Woolson R F.
A comparison of several tests for drug synergy.
Commun Statist Simula.
1998;
27
303-327
- 18
Bonapace C R, White R L, Friedrich L V, Basso J A.
Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill and checkerboard methods.
Diagn Micro Infect Dis.
2000;
38
43-50
- 19
Lewis R E, Diekema D J, Messer S A, Pfaller M A, Klepser M E.
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
345-351
- 20
Ryan R W, Kwasnik I, Tilton R C.
Methodological variation in antibiotic synergy test against enterococci.
J Clin Microbiol.
1981;
13
73-75
- 21
Paull A, Marks J.
A new method for the determination of bactericidal antibiotic synergy.
J Antimicrob Chemother.
1987;
20
831-838
- 22
Rand K H, Houck H J, Brown P, Bennett D.
Reproducibility of the microdilution checkerboard method for antibiotic synergy.
Antimicrob Agents Chemother.
1993;
37
613-615
- 23
Mackay M L, Milne K, Gould I M.
Comparison of methods for assessing synergistic antibiotic interactions.
Int J Antimicrob Agents.
2000;
15
125-129
- 24
White D B, Faessel H M, Slocum H K, Khinkis L, Greco W R.
Nonlinear response surface and mixture experiment methodologies applied to the study
of synergism.
Biom J.
2004;
46
56-71
- 25
Tallarida R J.
An overview of drug combination analysis with isobolograms.
J Pharmacol Exp Ther.
2006;
319
1-7
- 26
Boucher A N, Tam V H.
Mathematical formulation of additivity for antimicrobial agents.
Diagn Micro Infect Dis.
2006;
55
319-325
- 27
Tam V H, Schilling A N, Nikolaou M.
Modelling time-kill studies to discern the pharmacodynamics of meropenem.
J Antimicrob Chemother.
2005;
55
699-706
- 28
Jain S R, Kar A.
The antibacterial activity of some essential oils and their combinations.
Planta Med.
1971;
20
118-123
- 29
Geda A K.
Antibacterial activity of essential oils and their combinations.
Fat Sci Technol.
1995;
12
458-460
- 30
Sato M, Tanaka H, Yamaguchi R, Kato K, Etoh H.
Synergistic effects of mupirocin and an isoflavanone isolated from Erythrina variegata on growth and recovery of methicillin-resistant Staphylococcus aureus.
Int J Antimicrob Agents.
2004;
24
241-246
- 31
Braga L C, Leite A A M, Xavier K G S, Takahashi J A, Bemquerer M P, Chartone-Souza E,
Nascimento A M A.
Synergistic interaction between pomegranate extract and antibiotics against Staphylococcus aureus.
Can J Microbiol.
2005;
51
541-547
- 32
Lee Y S, Kang O H, Choi J G, Oh Y C, Chae H S, Kim J H, Park H, Sohn D H, Wang Z-T,
Kwon D Y.
Synergistic effects of the combination of galangin with gentamicin against methicillin-resistant
Staphylococcus aureus.
J Microbiol.
2008;
46
283-288
- 33
Van Vuuren S F, du Toit L C, Parry A, Pillay V, Choonara Y E.
Encapsulation of essential oils within a polymeric liposomal formulation for enhancement
of antimicrobial efficacy.
Nat Prod Commun.
2010;
5
1401-1408
- 34
Christoph F, Stahl-Biskup E.
Death kinetics of Staphylococcus aureus, exposed to commercial tea tree oils.
J Essent Oil Res.
2001;
13
98-102
- 35
Viljoen A M, van Vuuren S F, Ernst E, Klepser M, Demirci B, Başer K H C, van Wyk B E.
Osmitopsis asteriscoides (Asteraceae) – the antimicrobial activity and essential oil composition of a Cape-Dutch
remedy.
J Ethnopharmacol.
2003;
88
137-143
- 36
Lin Y T, Labbe R G, Shetty K.
Inhibition of Vibrio parahaemolyticus in seafood systems using oregano and cranberry phytochemical synergies and lactic
acid.
Innovat Food Sci Emerg Technol.
2005;
6
453-458
- 37
Viljoen A M, van Vuuren S F, Gwebu L, Demirci B, Başer K H C.
The geographical variation and antimicrobial activity of African Wormwood (Artemisia afra Jacq.) essential oil.
J Essent Oil Res.
2006;
18
19-25
- 38
Apostolidis E, Kwon Y I, Shetty K.
Inhibition of Listeria monocytogenes by oregano, cranberry and sodium lactate combination in broth and cooked ground beef
systems and likely mode of action through proline metabolism.
Int J Food Microbiol.
2008;
128
317-324
- 39
Kamatou G P P, Viljoen A M, van Vuuren S F.
In vitro evidence of antimicrobial synergy between Salvia chamelaeagnea and Leonotis leonurus.
S Afr J Bot.
2006;
72
634-636
- 40 Van Vuuren S F. The antimicrobial activity and essential oil composition of medicinal
aromatic plants used in African traditional healing [PhD thesis]. South Africa; University
of the Witwatersrand 2007
- 41
Van Vuuren S F, Viljoen A M.
In vitro evidence of phyto-synergy for plant part combinations of Croton gratissimus (Euphorbiaceae) used in African traditional healing.
J Ethnopharmacol.
2008;
119
700-704
- 42
Iten F, Saller R, Abel G, Reichling J.
Additive antimicrobial effects of the active components of the essential oil of Thymus vulgaris-chemotype carvacrol.
Planta Med.
2009;
75
1-6
- 43
Romano C, Abadi K, Repetto V, Vojnov A A, Moreno S.
Synergistic antioxidant and antibacterial activity of rosemary plus butylated derivatives.
Food Chem.
2009;
115
456-461
- 44
Janssen A M, Scheffer J J C, Svendsen A B.
Antimicrobial activity of essential oils: a 1976–1986 literature review. Aspects of
the test methods.
Planta Med.
1987;
53
395-398
- 45 Hewitt W, Vincent S. Theory and application of microbiological assay. London; Academic
Press (Inc.) 2003
- 46
Eloff J N.
A sensitive and quick microplate method to determine the minimal inhibitory concentration
of plant extracts for bacteria.
Planta Med.
1998;
64
711-713
- 47 NCCLS .Methods for dilution antimicrobial susceptibility tests for bacteria, 6th
edition. Wayne; Clinical and Laboratory Standards Institute 2003
- 48 Beale A S, Sutherland R. Measurement of combined antibiotic action in antibiotics:
Assessment of antimicrobial activity and resistance. London, UK; Academic Press (Inc.)
1983
- 49
Dufour M, Simmonds R S, Bremer P J.
Development of a method to quantify in vitro the synergistic activity of “natural” antimicrobials.
Int J Food Microbiol.
2003;
85
249-258
- 50
Berenbaum M C.
A method for testing for synergy with any number of agents.
J Infect Dis.
1978;
137
122-130
- 51
Critchley I A, Sahm D F, Kelly L J, Karlowsky J A.
In vitro synergy studies using aztreonam and fluoroquinolone combinations against six species
of Gram-negative bacilli.
Chemotherapy.
2003;
49
44-48
- 52
Santiesteban-López A, Palou E, López-Malo A.
Susceptibility of food-borne bacteria to binary combinations of antimicrobials at
selected a(w) and pH.
J Appl Microbiol.
2007;
102
486-497
- 53
Schelz Z, Molnar J, Hohmann J.
Antimicrobial and antiplasmid activities of essential oils.
Fitoterapia.
2006;
77
279-285
- 54
Netikul T, Leelaporn A, Leelarasmee A, Kiratisin P.
In vitro activities of fosfomycin and carbapenem combinations against carbapenem non-susceptible
Escherichia coli and Klebsiella pneumoniae.
Int J Antimicrob Agents.
2010;
35
609-610
- 55
De Oliveira C E V, Stamford T L M, Neto N J G, de Souza E L.
Inhibition of Staphylococcus aureus in broth and meat broth using synergies of phenolics and organic acids.
Int J Food Microbiol.
2010;
137
312-316
- 56
Berenbaum M C.
Correlations between methods for measurements of synergy.
J Infect Dis.
1980;
142
476-478
- 57
Acar J F.
Antibiotic synergy and antagonism. Antibiotic therapy.
Med Clin N Am.
2000;
84
1391-1406
- 58
Harris R.
Synergism in the essential oil world.
Int J Aromather.
2002;
12
179-186
- 59
Pattnaik S, Subramanyam V R, Bapaji M, Kole C R.
Antibacterial and antifungal activity of aromatic constituents of essential oils.
Microbiology.
1997;
89
39-46
- 60
Lachowicz K J, Jones G P, Briggs D R, Bienvenu F E, Wan J, Wilcock A, Coventry M J.
The synergistic preservative effects of the essential oils of sweet basil (Ocimum basilicum L.) against acid-tolerant food microflora.
Lett Appl Microbiol.
1998;
26
209-214
- 61
Pina-Vaz C, Gonçalves Rodrigues A, Pinto E, Costa-de-Oliveira S, Tavares C, Salgueiro L,
Cavaleiro C, Gonçalves M J, Martinez-de-Oliveira J.
Antifungal activity of Thymus oils and their major compounds.
J Eur Acad Dermatol Venereol.
2004;
18
73-78
- 62
Michiels J, Missotten J, Fremaut D, De Smet S, Dierick N.
In vitro dose-response of carvacrol, thymol, eugenol and trans-cinnamaldehyde and interaction
of combinations for the antimicrobial activity against the pig gut flora.
Livest Sci.
2007;
109
157-160
- 63
Van Zyl R, Seatlholo S T, van Vuuren S F, Viljoen A M.
Pharmacological interactions of essential oil constituents on the viability of micro-organisms.
Nat Prod Commun.
2010;
5
1381-1386
- 64
Tzakou O, Pitarokili D, Chinou I O, Harvala C.
Composition and antimicrobial activity of the essential oil of Salvia ringens.
Planta Med.
2001;
67
81-83
- 65
Aggarwal K K, Khanuja S P S, Ahmad A, Kumar T R S, Gupta V K, Kumar S.
Antimicrobial activity profiles of the two enantiomers of limonene and carvone isolated
from the oils of Mentha spicata and Anethus sowa.
Flavour Fragr J.
2002;
17
59-63
- 66
Setzer W, Vogler B, Schmidt J, Leahy J, Rives R.
Antimicrobial activity of Artemisia douglasiana leaf essential oil.
Fitoterapia.
2004;
75
192-200
- 67
Jirovetz L, Buchbauer G, Denkova Z, Stoyanova A, Murgov I, Schmidt E, Geissler M.
Antimicrobial testings and gas chromatographic analysis of pure oxygenated monoterpenes
1,8-cineole, α-terpineol, terpinin-4-ol and camphor as well as target compounds in essential oils
of pine (Pinus pinaster), rosemary (Rosmarinus officinalis), tea tree (Melaleuca alternifolia).
Sci Pharm.
2005;
73
27-39
- 68
Bakkali F, Averbeck S, Averbeck D, Idaomar M.
Biological effects of essential oils – A review.
Food Chem Toxicol.
2008;
46
446-475
- 69
Radulović N, Mišić M, Aleksić J, Doković D, Palić R, Stojanović G.
Antimicrobial synergism and antagonism of salicylaldehyde in Filipendula vulgaris essential oil.
Fitoterapia.
2007;
78
565-570
- 70
Chalchat J C, Garry R.
Correlation between chemical composition and antimicrobial activity. VI. Activity
of some African essential oils.
J Essent Oil Res.
1997;
9
67-75
- 71
Yen T-B, Chang S-T.
Synergistic effects of cinnamaldehyde in combination with eugenol against wood decay
fungi.
Bioresour Technol.
2008;
99
232-236
- 72
Dilika F, Bremner P D, Meyer J J M.
Antibacterial activity of linoleic- and oleic acid isolated from Helichrysum pedunculatum, a plant used during circumcision rites.
Fitoterapia.
2000;
71
450-452
- 73
Galindo L A, Pultrini Ad M, Costa M.
Biological effects of Ocimum gratissimum L. are due to synergic action among multiple compounds present in essential oil.
J Nat Med.
2010;
64
436-441
- 74
Tyler V E.
Phytomedicines: back to the future.
J Nat Prod.
1999;
62
1589-1592
- 75 Watt J M, Breyer-Brandwijk M G. The medicinal and poisonous plants of southern
and eastern Africa, 2nd edition. London, UK; Livingstone 1962
- 76 Hutchings A, Scott A H, Lewis G, Cunningham A B. Zulu medicinal plants – an inventory. Pietermaritzburg,
South Africa; University of Natal Press 1996
- 77 Van Wyk B E, van Oudtshoorn B, Gericke N. Medicinal plants of South Africa. Pretoria,
South Africa; Briza 1997
- 78 Von Koenen E. Medicinal poisonous and edible plants in Namibia. Windhoek, Namibia;
Klaus Hess 2001
- 79 Ngwenya M A, Koopman A, Williams R. Zulu botanical knowledge: An introduction. Durban,
South Africa; National Botanical Institute 2003
- 80
Caceres A, Alvarez A V, Ovando A E, Samayoa B E.
Plants used in Guatemala for the treatment of respiratory diseases. Screening of 68
plants against gram-positive bacteria.
J Ethnopharmacol.
1991;
31
193-208
- 81
Vlietinck A J, van Hoof L, Totté J, Lasure A, van den Berghe D, Rwangabo P C, Mvukiyumwami J.
Screening of hundred Rwandese medicinal plants for antimicrobial and antiviral properties.
J Ethnopharmacol.
1995;
46
31-47
- 82
Rabe T, van Staden J.
Antibacterial activity of South African plants used for medicinal purposes.
J Ethnopharmacol.
1997;
56
81-87
- 83
Lin J, Opoku A R, Geheeb-Keller M, Hutchings A D, Terblanche S E, Jäger A K, van Staden J.
Preliminary screening of some traditional Zulu medicinal plants for anti-inflammatory
and anti-microbial activities.
J Ethnopharmacol.
1999;
68
267-274
- 84
Drewes S E, Khan F, van Vuuren S F, Viljoen A M.
Simple 1, 4-benzoquinones with antibacterial activity from stems and leaves of Gunnera perpensa.
Phytochemistry.
2005;
66
1812-1816
- 85
Eldeen I M S, Elgorashi E E, van Staden J.
Antibacterial, anti-inflammatory, anti-cholinesterase and mutagenic effects of extracts
obtained from some trees used in South African traditional medicine.
J Ethnopharmacol.
2005;
102
457-464
- 86
Kamatou G P P, van Zyl R L, Davids H, van Vuuren S F, Viljoen A M.
Synergistic and antagonistic interactions of essential oils on the biological activities
of the solvent extracts from three Salvia species.
Nat Prod Commun.
2008;
3
1111-1115
- 87
Van Vuuren S F, Viljoen A M.
Interaction between the non-volatile and volatile fractions on the antimicrobial activity
of Tarchonanthus camphoratus.
S Afr J Bot.
2009;
75
505-509
- 88
Lee O H, Lee B Y.
Antioxidant and antimicrobial activities of individual and combined phenolics in Olea europaea leaf extract.
Bioresour Technol.
2010;
101
3751-3754
- 89
Chung I, Kwon S H, Shim S T, Kyung K H.
Synergistic anti-yeast activity of garlic oil and allyl alcohol derived from alliin
in garlic.
J Food Sci.
2007;
72
437-440
- 90
Van Vuuren S F, Viljoen A M, van Zyl R L, van Heerden F R, Başer K H C.
The antimicrobial, antimalarial and toxicity profiles of helihumulone, leaf essential
oil and extracts of Helichrysum cymosum (L.) D. Don subsp. cymosum.
S Afr J Bot.
2006;
72
287-290
- 91
Van Vuuren S F.
Antimicrobial activity of South African medicinal plants.
J Ethnopharmacol.
2008;
119
462-472
- 92
Lalli J Y, Viljoen A M, van Vuuren S F.
Potential interaction between the volatile and non-volatile fractions on the in vitro antimicrobial activity of three South African Pelargonium (Geraniaceae) species.
Nat Prod Commun.
2010;
5
1401-1408
- 93
Cano J H, Volpato G.
Herbal mixtures in the traditional medicine of eastern Cuba.
J Ethnopharmacol.
2004;
90
293-316
- 94
Al-Bayati F A.
Synergistic antibacterial activity between Thymus vulgaris and Pimpinella anisum essential oils and methanol extracts.
J Ethnopharmacol.
2008;
116
403-406
- 95
Cassella S, Cassella J P, Smith I.
Synergistic antifungal activity of tea tree (Melaleuca alternifolia) and lavender (Lavandula angustifolia) essential oils against dermatophyte infection.
Int J Aromather.
2002;
12
2-14
- 96
Thring T S A, Weitz F M.
Medicinal plant use in the Bredasdorp/Elim region of the southern Overberg in the
Western Cape Province of South Africa.
J Ethnopharmacol.
2006;
103
261-275
- 97
Van Wyk B E.
A broad review of commercially important southern African medicinal plants.
J Ethnopharmacol.
2008;
119
342-355
- 98 Van Wyk B E, Gericke N. People's plants. A guide to useful plants of southern Africa,
1st edition. Pretoria, South Africa; Briza 2000
- 99
Suliman S, van Vuuren S F, Viljoen A M.
Validating antimicrobial combination therapy in African traditional medicines-a case
for Artemisia afra.
S Afr J Bot.
2010;
76
655-661
- 100
Hsieh P C, Mau J L, Huang S H.
Antimicrobial effect of various combinations of plant extracts.
Food Microbiol.
2001;
18
35-43
- 101
Delaquis P J, Stanich K, Girard B, Mazza G.
Antimicrobial activity of individual and mixed fractions of dill, cilantro, coriander
and eucalyptus essential oils.
Int J Food Microbiol.
2002;
74
101-109
- 102
Gutierrez J, Barry-Ryan C, Bourke P.
Antimicrobial activity of plant essential oils using food model media: efficacy, synergistic
potential and interactions with food components.
Food Microbiol.
2009;
26
142-150
- 103
Vattem D A, Lin Y T, Ghaedian R, Shetty K.
Cranberry synergies for dietary management of Helicobacter pylori infections.
Process Biochem.
2005;
40
1583-1592
- 104
Fu Y J, Zu Y G, Chen L Y, Shi X G, Wang Z, Sun S, Efferth T.
Antimicrobial activity of clove and rosemary essential oils alone and in combination.
Phytother Res.
2007;
21
989-994
- 105
Ubalua A O, Oti E.
Evaluation of antimicrobial properties of some medicinal plants for fresh cassava
roots preservation.
Pakistan J Nutr.
2008;
7
679-681
- 106
Gutierrez J, Barry-Ryan C, Bourke P.
The antimicrobial efficacy of plant essential oil combinations and interactions with
food ingredients.
Int J Food Microbiol.
2008;
124
91-97
- 107
Kang R, Helms R, Stout M J, Jaber H, Chen Z, Nakatzu T.
Antimicrobial activity of the volatile constituents of Perilla frutescens and its synergistic effects with polygodial.
J Agric Food Chem.
1992;
40
2328-2330
- 108
Himejima M, Kubo I.
Antimicrobial agents from Licaria puchuri-major and their synergistic effect with polygodial.
J Nat Prod.
1992;
55
620-625
- 109
Stermitz F R, Lorenz P, Tawara J N, Zenewicz L A, Lewis K.
Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin,
a multidrug pump inhibitor.
Appl Biol Sci.
2000;
97
1433-1437
- 110
Zhao F R, Maoa H P, Zhang H, Hua L M, Wanga H, Wang Y F, Yanagihara N, Gao X M.
Antagonistic effects of two herbs in Zuojin Wan, a traditional Chinese medicine formula,
oncatecholamine secretion in bovine adrenal medullary cells.
Phytomedicine.
2010;
17
659-668
- 111
Van Vuuren S F, Suliman S, Viljoen A M.
The antimicrobial activity of four commercial essential oils in combination with conventional
antimicrobials.
Lett Appl Microbiol.
2009;
48
440-446
- 112
Cuzzolin L, Zaffani S, Benoni G.
Safety implications regarding use of phytomedicines.
Eur J Clin Pharmacol.
2006;
62
37-42
- 113
Lee Y S, Han C H, Kang S H, Lee S-J, Kim S W, Shin O R, Sim Y C, Lee S J, Cho Y H.
Synergistic effect between catechin and ciprofloxacin on chronic bacterial prostatis
rat model.
Int J Urol.
2005;
12
383-389
- 114
Kurita N, Koike S.
Synergistic antimicrobial effect of ethanol, sodium chloride, acetic acid and essential
oil components.
Agric Biol Chem.
1983;
47
67-75
- 115
Tunc S, Chollet E, Chalier P, Preziosi-Belloy L, Gontard N.
Combined effect of volatile antimicrobial agents on the growth of Penicillium notatum.
Int J Food Microbiol.
2007;
113
263-270
- 116
Nostro A, Cannatelli M A, Morelli I, Cioni P L, Bader A, Marino A, Alonzo V.
Preservative properties of Calamintha officinalis essential oil with and without EDTA.
Lett Appl Microbiol.
2002;
35
385-389
- 117
Gibbons S.
Plants as a source of bacterial resistance modulators.
Phytochem Rev.
2005;
4
63-78
- 118
Fujimura S, Takane H, Nakano Y, Watanabe A.
In vitro synergy studies based on tazobactam/piperacillin against clinical isolates of metallo-beta-lactamase-producing
Pseudomonas aeruginosa.
J Antimicrob Chemother.
2009;
64
1115-1116
- 119
Ednie L M, Credito K L, Khantipong M, Jacobs M R, Appelbaum P C.
Synergic activity, for anaerobes, of trovafloxacin with clindamycin or metronidazole:
chequerboard and time-kill methods.
J Antimicrob Chemother.
2000;
45
633-638
- 120
Gilbert B, Alves L F.
Synergy in plant medicines.
Curr Med Chem.
2003;
10
13-20
- 121
Wagner H, Ulrich-Merzenich G.
Synergy research: approaching a new generation of phytopharmaceuticals.
Phytomedicine.
2009;
16
97-110
- 122
Hemaiswarya S, Kruthiventi A K, Doble M.
Synergism between natural products and antibiotics against infectious diseases.
Phytomedicine.
2008;
15
639-652
- 123
Yamazaki K, Yamamoto T, Kawai Y, Inoue N.
Enhancement of antilisterial activity of essential oils constituents by nisin and
diglycerol fatty acid ester.
Food Microbiol.
2004;
21
283-289
- 124
Rios J L, Recio M.
Medicinal plants and antimicrobial activity.
J Ethnopharmacol.
2005;
100
80-84
- 125
Hendry E R, Worthington T, Conway B R, Lambert P A.
Antimicrobial efficacy of eucalyptus oil and 1,8-cineole alone and in combination
with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm
cultures.
J Ethnopharmacol.
2009;
64
1219-1225
- 126
Filoche S K, Soma K, Sissons C H.
Antimicrobial effects of essential oils in combination with chlorhexidine digluconate.
Oral Microbiol Immun.
2005;
20
221-225
- 127
Karpanen T J, Worthington T, Hendry E R, Conway B R, Lambert P A.
Antimicrobial efficacy of chlorhexidine digluconate alone and in combination with
eucalyptus oil, tea tree oil and thymol against planktonic and biofilm cultures of
Staphylococcus epidermidis.
J Ethnopharmacol.
2008;
62
1031-1036
- 128
Walencka E, Rozalska S, Wysokinska H, Rozalski M, Kuzma L, Rozalska B.
Salvipisone and aethiopinone from Salvia sclarea hairy roots modulate staphylococcal antibiotic resistance and express anti-biofilm
activity.
Planta Med.
2007;
73
545-551
- 129
Berenbaum M C.
The expected effect of a combination of agents: the general solution.
J Theor Biol.
1985;
114
413-431
- 130
Greco W R, Bravo G, Parsons J C.
The search for synergy: A critical review from a response surface perspective.
Pharmacol Rev.
1995;
47
332-382
- 131
Burfield T, Reekie S-L.
Mosquitoes, malaria and essential oils.
Int J Aromather.
2005;
15
30-41
- 132
Lambert R J W, Johnston M D, Hanlon G W, Denyer S P.
Theory of antimicrobial combinations: biocide mixtures – synergy or addition?.
J Appl Microbiol.
2003;
94
747-759
- 133
Kerry D W, Hamilton-Miller J M T, Brumfitt W.
Trimethoprim and rifampicin: in vitro activities separately and in combination.
J Antimicrob Chemother.
1975;
1
417-427
- 134
Norden C W, Wentzel H, Keleti E.
Comparison of techniques for measurements of in vitro antibiotic synergism.
J Infect Dis.
1979;
140
629-633
- 135 Eliopoulos G M, Moellering Jr R C. Antimicrobial combinations. Antibiotics in
laboratory medicine, 3rd edition. Baltimore; Williams and Wilkins 1991
- 136
Moody J A.
Synergism testing: Broth microdilution checkerboard and broth microdilution. In: Isenberg
HD, editor. Clinical microbiology procedures handbook, 1st edition. Washington, DC.
American Society for Microbiology.
2003;
18
1-28
- 137
Krishnan-Natesan S, Chandrasekar P H, Manavathu E K, Revankar S G.
Successful treatment of primary cutaneous Aspergillus ustus infection with surgical debridement and a combination of voriconazole and terbinafine.
Diagn Microbiol Infect Dis.
2008;
62
443-446
- 138
Goñi P, López P, Sánchez C, Gómez-Lus R, Becerril R, Nerín C.
Antimicrobial activity in the vapour phase of a combination of cinnamon and clove
essential oils.
Food Chem.
2009;
116
982-989
- 139
Suresh B, Sriram S, Dhanaraj S A, Elango K, Chinnaswamy K.
Anticandidal activity of Santolina chamaecyparissus volatile oil.
J Ethnopharmacol.
1997;
55
151-159
- 140
Shin S, Kang C A.
Antifungal activity of the essential oil of Agastache rugosa Kuntze and its synergism with ketoconazole.
Lett Appl Microbiol.
2003;
36
111-115
- 141
Ibezim E C, Esimone C O, Nnamani P O, Onyishi I V, Brown S A, Obodo C E.
In vitro study of the interaction between some fluoroquinolones and extracts of kola nitida seed.
Afr J Biotechnol.
2006;
5
1781-1784
- 142
Ali N H, Kazmi S U, Faizi S.
Activity of synergistic combination Amoxy-cassia against Salmonella.
Pakistan J Pharm Sci.
2007;
20
140-145
- 143
Shin S.
Anti-Aspergillus activities of plant essential oils and their combination effects with ketoconazole
or amphotericin B.
Arch Pharm Res.
2003;
26
389-393
- 144
Rosato A, Vitali C, De Laurentis N, Armenise D, Milillo M A.
Antibacterial effect of some essential oils administered alone or in combination with
norfloxacin.
Phytomedicine.
2007;
14
727-732
- 145
Pyun M S, Shin S.
Antifungal effects of the volatile oils from Allium plants against Trichophyton species and synergism of the oils with ketoconazole.
Phytomedicine.
2006;
13
394-400
- 146
Sakagami Y, Iinuma M, Piyasena K G, Dharmaratne H R.
Antibacterial activity of α-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics.
Phytomedicine.
2005;
12
203-208
- 147
Al-hebshi N, Al-haroni M, Skaug N.
In vitro antimicrobial and resistance-modifying activities of aqueous crude khat extracts
against oral microorganisms.
Arch Oral Biol.
2006;
51
183-188
- 148
Yang Z C, Wang B C, Yang X S, Wang Q, Ran L.
The synergistic activity of antibiotics combined with eight traditional Chinese medicines
against two different strains of Staphylococcus aureus.
Colloids Surf B Biointerfaces.
2005;
41
79-81
- 149
Cha J D, Jeong M R, Jeong S I, Lee K Y.
Antibacterial activity of sophoraflavanone G isolated from the roots of Sophora flavescens.
J Microbiol Biotechnol.
2007;
17
858-864
- 150
Ahmed I, Aqil F.
In vitro efficacy of bioactive extracts of 15 medicinal plants against ESβL-producing multidrug-resistant enteric bacteria.
Microbial Res.
2007;
162
264-275
- 151
Rosato A, Vitali C, Gallo D, Balenzano L, Mallamaci R.
The inhibition of Candida species by selected essential oils and their synergism with amphotericin B.
Phytomedicine.
2008;
15
635-638
- 152
Toroglu S.
In vitro antimicrobial activity and antagonistic effect of essential oils from plant species.
J Environ Biol.
2007;
28
551-559
- 153
Adwan G M, Abu-shanab B A, Adwan K M.
In vitro activity of certain drugs in combination with plant extracts against Staphylococcus aureus infections.
Pakistan J Med Sci.
2008;
24
541-544
- 154
Rodrigues F F, Costa J G, Coutinho H D.
Synergy effects of the antibiotics gentamicin and the essential oil of Croton zehntneri.
Phytomedicine.
2009;
16
1052-1055
- 155
Kumar A S, Venkateshwaran K, Vanitha J, Saravanan V S, Ganesh M, Vasudevan M, Sivakumar
Bangladesh T.
Synergistic activity of methanolic extract of Thespesia populnea. (Malvaceae) flowers with oxytetracycline.
J Pharmacol.
2009;
4
13-16
- 156
Rosato A, Vitali C, Piarulli M, Mazzotta M, Argentieri M P, Mallamaci R.
In vitro synergic efficacy of the combination of nystatin with the essential oils of Origanum vulgare and Pelargonium graveolens against some Candida species.
Phytomedicine.
2009;
16
972-975
- 157
Adwan G, Abu-Shanab B, Adwan K.
Antibacterial activities of some plant extracts alone and in combination with different
antimicrobials against multidrug-resistant Pseudomonas aeruginosa strains.
Asian Pacific J Trop Med.
2010;
24
266-269
- 158
Amber K, Aijaz A, Immaculata X, Luqman K A, Nikhat M.
Anticandidal effect of Ocimum sanctum essential oil and its synergy with fluconazole and ketoconazole.
Phytomedicine.
2010;
17
921-925
- 159
D'Arrigo M D, Ginestra G, Mandalari G, Furneri P M, Bisignano G.
Synergism and postantibiotic effect of tobramycin and Melaleuca alternifolia (tea tree) oil against Staphylococcus aureus and Escherichia coli.
Phytomedicine.
2009;
17
317-322
- 160
Endo E H, Cortez D A C, Ueda-Nakamura T, Nakamura C V, Filho B P D.
Potent antifungal activity of extracts and pure compound isolated from pomegranate
peels and synergism with fluconazole against Candida albicans.
Res Microbiol.
DOI: 10.1016/j.resmic.2010.05.002
, advance online publication 21 June 2010
- 161
Palaniappan K, Holley R A.
Use of natural antimicrobials to increase antibiotic susceptibility of drug resistant
bacteria.
Int J Food Microbiol.
2010;
140
164-168
- 162
Mahboubi I M, Bidgoli F G.
In vitro synergistic efficacy of combination of amphotericin B with Myrtus communis essential oil against clinical isolates of Candida albicans.
Phytomedicine.
2010;
17
771-774
- 163
Saad A, Fadli M, Bouaziz M, Benharref A, Mezrioui N-E, Hassani L.
Anticandidal activity of the essential oils of Thymus maroccanus and Thymus broussonetii and their synergism with amphotericin B and fluconazol.
Phytomedicine.
DOI: 10.1016/j.phymed.2010.03.020
, advance online publication 18 June 2010
- 164
Nazer A I, Kobilinsky A, Tholozan J L, Dubois-Brissonnet F.
Combinations of food antimicrobials at low levels to inhibit the growth of Salmonella sv. typhimurium: a synergistic effect?.
Food Microbiol.
2005;
22
391-398
- 165
Fyfe L, Armstrong F, Stewart J.
Inhibition of Listeria monocytogenes and Salmonella enteriditis by combinations of plant oils and derivatives of benzoic acid: the development of
synergistic antimicrobial combinations.
Int J Antimicrob Agents.
1998;
9
195-199
- 166
Dimitrijević S I, Mihajlovski K R, Antonović D G, Milanović-Stevanović M R, Mijin D Z.
A study of the synergistic antilisterial effects of a sub-lethal dose of lactic acid
and essential oils from Thymus vulgaris L., Rosmarinus officinalis L. and Origanum vulgare L.
Food Chem.
2007;
104
774-782
- 167
Molinos A C, Abriouel H, López R L, Omar N B, Valdivia E, Gálvez A.
Enhanced bactericidal activity of enterocin AS-48 in combination with essential oils,
natural bioactive compounds and chemical preservatives against Listeria monocytogenes in ready-to-eat salad.
Food Chem Toxicol.
2009;
47
2216-2223
- 168
Govaris A, Solomakos N, Pexara A, Chatzopoulou P S.
The antimicrobial effect of oregano essential oil, nisin and their combination against
Salmonella enteritidis in minced sheep meat during refrigerated storage.
Int J Food Microbiol.
2010;
137
175-180
Prof. Sandy van Vuuren
Department of Pharmacy and Pharmacology
Faculty of Health Sciences
University of the Witwatersrand
7 York Road
Parktown 2193
South Africa
Telefon: + 27 01 17 17 21 57
Fax: + 27 01 16 42 43 55
eMail: Sandy.vanvuuren@wits.ac.za
