Preferences help
enabled [disable] Abstract
Number of results
2017 | 64 | 2 | 255-263
Article title

In vitro pharmacological interaction of caffeine and first-line antibiotics is antagonistic against clinically important bacterial pathogens

Title variants
Languages of publication
The in vitro antibacterial activity of pure caffeine powder and its interaction with first line antibiotic against bacterial isolates were investigated with the macrobroth dilution and the checkerboard assay methods. This study showed that caffeine and the antibiotics exhibited various degrees of antibacterial activities. While caffeine had MICs ranging between 67.19 and 268.75 µg/ml, chloramphenicol was characterized by MICs between 0.98 and 31.25 µg/ml, kanamycin - 15.63-62.5 µg/ml, nalidixic acid - 0.49-250 µg/ml, erythromycin - 0.49-62.5 µg/ml, tetracycline - 1.99-62.5 µg/ml and metronidazole - 15.63-31.25 µg/ml. Combining ½ MICs and MICs of caffeine with the antibiotics as well as direct combination of caffeine and the antibiotics resulted in significant reduction of antibiotics' effectiveness. The fractional inhibitory concentration index (FICI) for the combination of ½ MICs of caffeine with different antibiotics showed antagonistic interactions with the antibiotics except kanamycin which had additive and indifferent interactions with caffeine. The FICI of the MICs of caffeine combined with antibiotics showed a reduction in the number of antagonistic interactions as chloramphenicol, nalidixic acid and erythromycin showed some indifferent interactions while kanamycin was the only antibiotic that showed indifferent interaction against all the bacterial isolates. The direct combination of caffeine and the antibiotics resulted in significant antagonistic interactions higher than in the case when caffeine, at the ½ MICs and MICs, was combined with the antibiotics. Although caffeine demonstrated significant antibacterial activity against the selected bacterial isolates, its combination with the selected antibiotics resulted in significant antagonistic interactions. Caffeine should not be combined with antibiotics as this could result in serious therapeutic failure and, possibly, drug toxicity in vivo.
Physical description
  • Agyemang-Yeboah F, Oppong SY (2013) Caffeine: The wonder compound, chemistry and properties. Ghana: Kwame Nkrumah University, MSc thesis
  • Almeida AA, Farah A, Silva DA, Nunan EA, Gloria MB (2006) Antibacterial activity of coffee extracts and selected coffee chemical compounds against Enterobacteria. J Agric Food Chem 54: 8738-8743. doi: 10.1021/jf0617317.
  • Almeida AAP, Naghetini CC, Santos VR, Antonio AG, Farah A, Glória MBA (2012) Influence of natural coffee compounds, coffee extracts and increased levels of caffeine on the inhibition of Streptococcus mutans. Food Res Int 49: 459-461. doi: 10.1016/j.foodres.2012.07.026
  • Antonio AG, Moraes RS, Perrone D, Maria LC, Santos KRN, Iorio NLP, Farah A (2010) Species, roasting degree and decaffeination influence the antibacterial activity of coffee against Streptococcus mutans. Food Chem 118: 782-788. doi: 10.1016/j.foodchem.2009.05.063
  • Ashihara H (2006) Metabolism of alkaloids in coffee plants. Brazil J Plant Physiol 18: 1-8. doi: 10.1590/S1677-04202006000100001
  • Banerjee S, Verma PK, Mitra RK, Basu G, Pal SK (2012) Probing the interior of self-assembled caffeine dimer at various temperatures. J Fluoresc 22: 753-769. doi: 10.1007/s10895-011-1011-3.
  • Belitz HD, Grosch W, Schieberle P (2009) Food Chemistry: Coffee, Tea, Cocoa. Berlin Heidelberg: Springer-Verlag
  • Cano-Marquina A, Tarín JJ, Cano A (2013) The impact of coffee on health. Maturitas 75: 7-21. doi: 10.1016/j.maturitas.2013.02.002.
  • Cano-Marquina A, Tarin JJ, Cano A (2013) The impact of coffee on health. Maturitas 75: 7-21. doi: 10.1016/j.maturitas.2013.02.002.
  • Charles BG, Rawal BD (1979) The combined action of methylxanthines with erythromycin and tetracyclines on Staphylococcus aureus. Microbios Lett 10: 143-147.
  • Chen, J, Zhang S, Yang X (2013) Control of brown rot on nectarines by tea polyphenol combined with tea saponin. Crop Prot 45: 29-35. doi: 10.1016/j.cropro.2012.11.006
  • Chou T (1992) Wake up and smell the coffee: Caffeine, coffee and medical consequences. West J Med 157: 544-553.
  • Cogo K, Montan MF, Bergamaschi Cde C, D Andrade E, Rosalen PL, Groppo FC (2008) In vitro evaluation of the effect of nicotine, cotinine and caffeine on oral microorganisms. Can J Microbiol 54: 501- 508. doi: 0.1139/W08-032.
  • Conlay LA, Conant JA, DeBros F, Wurtman R (1997) Caffeine alters plasma adenosine levels. Nature 389: 136. doi: 10.1038/38160.
  • Coso JD, Munoz-Fernandez VE, Munoz G, Fernandez-Elıas VE, Ortega JF, Hamouti N, Barbero JC, Munoz-Guerra J (2012) Effects of a caffeine-containing energy drink on simulated soccer performance. PLoS ONE 7: e31380. doi: 10.1371/journal.pone.0031380.
  • Cortez D (2003) Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases. J Biol Chem 278: 37139-37145. doi: 10.1074/jbc.M307088200.
  • Daly JW (2007) Caffeine analogs: biomedical impact. Cell Mol Life Sci 64: 2153-2169.
  • Davies DB, Veselkov DA, Djimant LN, Veselkov AN (2001) Hetero-association of caffeine and aromatic drugs and their competitive binding with a DNA oligomer. Eur Biophys J 30: 354-366.
  • Desbrow B, Hughes R, Leveritt M, Scheelings P (2007) An examination of consumer exposure to caffeine from retail coffee outlets. Food Chem Toxicol 45: 1588-1592. doi: 10.1016/j.fct.2007.02.020.
  • DeVries JW, Johnson KD, Heroff JC (1981) HPLC determination of caffeine and theobromine content of various natural and red dutch cocoas. Hoppe Seyler's Z Physiol Chem 358: 807-817
  • Eliopoulos GM, Eliopoulos CT (1988) Antibiotic combinations: should they be tested? Clin Microbiol Rev 1: 139-156.
  • Esinome CO, Okoye FBC, Nworu CS, Agubata CO (2008) In vitro interaction between caffeine and come penicillin antibiotics against Staphylococcu aureus. Trop J Pharm Res 7: 969-974
  • Etherton GM, Kochar MS (1993) Coffee. Facts and controversies. Arch Fam Med 2: 317-322.
  • Florey K (1986) Analytical profiles of drug substances. In Analytical profiles of drug substances Al-Badr AA, Brewer AG, Brenner SG, Deangelis JN, Mollica AJ eds. p 71. London: Academic Press
  • Funk GD (2009) Losing sleep over the caffeination of prematurity. J Physiol 587: 5299-5300. doi: 10.1113/jphysiol.2009.182303.
  • Furuhata K, Dogazaki C, Hara M, Furuyama M (2002) Inactivation of Legionella pneumophila by phenol compounds contained in coffee. J Antibact Antifung Agents 30: 291-297
  • Greer F, Hudson R, Ross R, Graham T (2001) Caffeine ingestion decreases glucose disposal during a hyperinsulinemic - euglycemic clamp in sedentary humans. Diabetes 50: 2349–2354. doi: 10.2337/diabetes.50.10.2349.
  • Grigg GW, Hall RM, Hart NK, Kavulak DR, Lamberton JA, Lane A (1985) Amplification of the antibiotic effects of the bleomycins and tallysomycins: its dependence on the nature of the variable groups. J Antibiot (Tokyo) 38: 99-110.
  • Guo S, Zhu Q, Yang B, Wang J, Ye B (2011) Determination of caffeine content in tea based on poly(safranine T) electro active film modified electrode. Food Chem 129: 1311-1314. doi: 10.1016/j.foodchem.2011.05.095.
  • Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK, National Healthcare Safety Network Team & Participating National Healthcare Safety Network Facilities (2008) NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol 29: 996–1011. doi: 10.1086/591861.
  • Hill P (1991) It is not what you eat, but how you eat it digestion, life-style, nutrition. Nutrition 7: 385-395.
  • Hosseinzadeh H, Bazzaz BS, Sadat MM (2006) In vitro evaluation of methylxanthines and some antibiotics: interaction against Staphylococcus aureus and Pseudomonas aeruginosa. Iranian Biomed J 10: 163-167
  • Jacobson BH, Thurman-Lacey SR (1992) Effect of caffeine on motor performance by caffeine-naive and familiar subjects. Percept Mot Skills 74: 151-157.
  • James JE, Paull I (1985) Caffeine and human reproduction. Rev Environ Health 5: 151-167.
  • Kang TM, Yuan J, Nguyen A, Becket E, Yang H, Miller JH (2012) The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli: caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in escherichia coli and bacillus anthracis. Antimicrob Agents Chemother 56: 3216-3223. doi: 10.1128/AAC.00066-12.
  • Kapuscinski J, Kimmel M (1993) Thermodynamical model of mixed aggregation of intercalators with caffeine in aqueous solution. Biophys Chem 46: 153-163. doi: 10.1016/0301-4622(93)85022-A.
  • Kawamukai M, Murao K, Utsumi R, Himeno M, Komano T (1986) Cell filamentation in an Escherichia coli K-12 fic mutant caused by theophylline or an adenylate cyclase gene (cya)-containing plasmid. FEMS Microb Lett 34: 117-120. doi: 10.1111/j.1574-6968.1986.tb01360.x
  • Kruger A (1996) Chronic psychiatric patients' use of caffeine: pharmacological effects and mechanisms. Psychol Rep 78: 915-923. doi: 10.2466/pr0.1996.78.3.915.
  • Lachman LJ, Ravin L (1959) Complexation of benzocaine, procaine, and teracine with caffeine J Am Pharm Assoc Am Pharm Assoc 45: 120-123.
  • Larsen RW, Jasuja R, Hetzler RK, Muraoka PT, Andrada VG, Jameson M (1996) Spectroscopic and molecular modeling studies of caffeine complexes with DNA intercalators. Biophys J 70: 443-452. doi: 10.1016/S0006-3495(96)79587-5.
  • Lelo A, Birkett DJ, Robson RA, Miners JO (1986) Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man. Br J Clin Pharmacol 22: 177-182.
  • Li Y, Feng Y, Zhu S, Luo C, Ma J, Zhong F (2012) The effect of alkalization on the bioactive and flavor related components in commercial cocoa powder. J Food Comp Anal 25: 17-23
  • Leonard B (2000) Stress, depression and the activation of the immune system. World J Biol Psychiatry 1: 17-25.
  • Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156: 445-453.
  • Mandal S, Mandal MD, Pal NK (2004) Evaluation of combination effect of ciprofloxacin and cefazolin against Salmonella enteric serovar typhi isolates by in vitro methods. Calicut Med J 2: e2.
  • Matha A, Adbels OH (1982) Complex formation between antihistaminic drugs and caffeine. J Am Pharm Assoc Am Pharm Assoc 9: 208
  • Minamisawa M, Yoshida S, Takai N (2004) Determination of biologically active substances in roasted coffees using a diode-array HPLC system. Anal Sci 20: 325-328. doi: 10.2116/analsci.20.325.
  • Misumi M, Tanaka N (1980) Mechanism of inhibition of translocation by kanamycin and viomycin: a comparative study with fusidic acid. Biochem Biophys Res Commun 92: 647-654.
  • Mitchell DC, Knight CA, Hockenberry J, Teplansky R, Hartman TJ (2014) Beverage caffeine intakes in the US. Food Chem Toxicol 63: 136-142. doi: 10.1016/j.fct.2013.10.042.
  • Mohammed MJ, Al-Bayati FA (2009) Isolation, identification and purification of caffeine from Coffea arabica L. and Camellia sinensis L.: A combination antibacterial study. Int J Green Pharm 3: 52-57. doi: 10.4103/0973-8258.49375
  • Mohanpuria P, Kumar V, Yadav SK (2010) Tea caffeine: metabolism, functions and reduction strategies. J Food Sci Biotech 19: 275-287. doi: 10.1007/s10068-010-0041-y
  • Najafi NM, Hamid AS, Afshin RK (2003) Determination of caffeine in black tea leaves by fourier transform infrared spectrometry using multiple linear regression. Microchem J 75: 151-158
  • Namboodiripad PA, Kori S (2008) Can coffee prevent caries? J Conserv Dent 12: 17-21. doi: 10.4103/0972-0707.53336.
  • Nehlig A, Daval JL, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Rev 17: 139-170. doi: 10.1016/0165-0173(92)90012-B.
  • Nehlig A, Boyet S (2000) Dose-response study of caffeine effect of cerebral functional activity with a specific focus on dependence. Brain Res 858: 71-77. doi: 10.1016/S0006-8993(99)02480-4.
  • Olajuyigbe OO, Afolayan AJ (2012) In vitro antibacterial and time kill assessment of crude methanolic stem bark extract of Acacia mearnsi De Wild against bacteria in shigellosis. Molecules 17: 2103-2118. doi: 10.3390/molecules17022103.
  • Osman F, McCready S (1998) Differential effects of caffeine on DNA damage and replication cell cycle checkpoints in the fission yeast Schizosaccharomyces pombe. Mol Gen Genet 260: 319-334.
  • Poehlsgaard J, Douthwaite S (2005) The bacterial ribosome as a target for antibiotics. Nat Rev Microbiol 3: 870-881.
  • Petersen PJ, Labthavikul P, Jones CH, Bradford PA (2006) In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis. J Antimicrob Chemother 57: 573-576. doi: 10.1093/jac/dki477.
  • Pons FW, Muller P (1990) Induction of frameshift mutations by caffeine in Escherichia coli K12. Mutagenesis 5: 173-178. doi: 10.1093/mutage/5.2.173.
  • Prescription drugs/caffeine interactions (2016). Accessed 01-05-2016
  • Pruthviraj P, Suchita B, Shital K, Shilpa K (2011) Evaluation of antibacterial activity of caffeine. Int J Res in Ayuveda Pharm 2: 1354-1357
  • Raber J (1998) Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation. from obesity to memory deficits. Mol Neurobiol 18: 1-22. doi: 10.1007/BF02741457.
  • Ramanaviciene A, Zukiene V, Acaite J, Ramanavicius A (2002) Influence of caffeine on lysozyme activity in the blood serum of mice. Acta Med Litu 4: 241-244
  • Ramanaviciene A, Mostovojus V, Bachmatova I, Ramanavicius A (2003a) Anti-bacterial effect of caffeine on Escherichia coli and Pseudomonas fluorescens. Acta Med Litu 10: 185-188
  • Ramanaviciene A, Acaite J, Dringeliene A, Markevicius A, Ramanavicius A (2003b) Effect of caffeine on mice immunocompetent cells. Acta Med Litu 2: 86-89
  • Ribeiro JA, Sebastiao AM (2010) Caffeine and adenosine. J Alzheimers Dis 20 (Suppl 1): S3-S15. doi: 10.3233/JAD-2010-1379.
  • Rodrigues CI, Marta L, Maia R, Miranda M, Ribeirinho M, Máguas C (2007) Application of solid-phase extraction to brewed coffee caffeine and organic acid determination by UV/HPLC. J Food Comp Anal 20: 440-448. doi: 10.1016/j.jfca.2006.08.005
  • Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283: 2674-2679. doi: 10.1001/jama.283.20.2674.
  • Sacks LE, Thompson PA (1977) Increased spore yields of Clostridium perfringens in the presence of methylxanthines. Appl Environ Microbiol 34: 189-93.
  • Sakurai H, Mitsuhashi N, Tamaki Y, Akimoto T, Murata O, Kitamoto Y, Maebayashi K, Ishikawa H, Hayakawa K, Niibe H (1999) Interaction between low dose-rate irradiation, mild hyperthermia and low-dose caffeine in a human lung cancer cell line. Int J Radiat Biol 75: 739-745. doi: 10.1080/095530099140087.
  • Sandlie I, Lossius I, Sjåstad K, Kleppe K (1983) Mechanism of caffeine-induced inhibition of DNA synthesis in Escherichia coli. FEBS Lett 151: 237-242.
  • Sawynok J (1995) Pharmacological rationale for the clinical use of caffeine. Drugs 49: 37-50.
  • Selby CP, Sancar A (1990) Molecular mechanisms of DNA repair inhibition by caffeine. Proc Natl Acad Sci USA 87: 3522-3525.
  • Suárez-Quiroz ML, González-Rios O, Barel M, Guyot B, Schorr-Galindo S, Guiraud JP (2004) Effect of chemical and environmental factors on Aspergillus ochraceus growth and toxigenesis in green coffee. Food Microbiol 21: 629-634
  • Tornaletti S, Russo P, Parodi S, Pedrini AM (1989) Studies on DNA binding of caffeine and derivatives: evidence of intercalation by DNA unwinding experiments. Biochim Biophys Acta 1007: 112-115.
  • Traganos F, Kaminska-Eddy B, Darzynkiewicz Z (1991) Caffeine reverses the cytotoxic and cell kinetic effects of Novantrone (mitoxantrone). Cell Prolif 24: 305-319. doi: 10.1111/j.1365-2184.1991.tb01159.x.
  • Veselkov DA, Kodintsev VV, Pakhomov VI, Dymant LN, Davies DB, Veselkov AN (2002) 1H-NMR analysis of heteroassociation of caffeine with antibiotic actinomycin D in aqueous solutions. Biofizika 45: 197-206.
  • Vinod DR (2004) Pharmacognosy and Phytochemistry. Carrier Publication, 1st edn, vol II, pp 311
  • Wilmot M (2006) In vitro inhibition of phytopathogenic fungi by caffeine, tea catechins theanine, polyphenon g, black-, green- and rooibos tea extracts. Pretoria, South Africa: Pretoria University, MSc thesis
  • Yen WJ, Wang BS, Chang LW, Duh PD (2005) Antioxidant properties of roasted coffee residues. J Agric Food Chem 53: 2658-2663. doi: 10.1021/jf0402429.
  • Youn JH, Gulve EA, Holloszy JO (1991) Calcium stimulates glucose transport in skeletal muscles by a partway independent of contraction. Am J Physiol 260: C555-C561.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.