The growth rate of S. aureus when treated with Azithromycin alone and combined with Syzygium cumini decoctation

Rio Risandiansyah, Yoni Rina Bintari



Introductiom: Resistance to antibiotics is the result of adaptive and spontaneous mutations, which can be suppressed by use of combinatory antibiotics. Synergistic effects between certain plants in combination with antibiotics is known, yet the mutation frequency of such combinations is still unexplored. Therefore, this study aims to measure the spontaneous mutational frequency of S. aureus for Azithromycin (AZM) resistance alone and in combination with Syzygium cumini decocta (SCD), known for its antimutagenic effect.

Method: This study uses fluctuation analysis with 39 replicate cultures in selective media using AZM alone, SCD alone, and AZM combined with SCD at 1x MIC and analysing resistant strains based on its log phase delay in liquid media in a 24-hour period. AZM and SCD showed antibiotic activity against S. aureus.

Results: Time-point growth comparison showed two cultures in AZM selective medium with no delayed log phase between S. aureus in non-selective medium and absorbance >1.0 after 24 hours, indicating resistance to AZM.

Conclusion: Increased growth suppression was observed in combination between AZM combined with SCD, compared to AZM and SCD alone. The spontaneous mutation frequency of S. aureus against AZM was 0.182, while both SCD and AZM combined with SCD had zero mutational events for antibiotic resistance.

Keywords:Antibiotic Resistance, Combinatorial Antibiotic Therapy (CAT), Mutation frequency, Syzygium cumini.

Full Text:



Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, et al. Antibiotic resistance-the need for global solutions. Vol. 13, The Lancet Infectious Diseases. 2013. p. 105798.

Alanis AJ. Resistance to antibiotics: are we in the post-antibiotic era?. Arch Med Res. 2005;36(6):697705.

Fair RJ, Tor Y. Antibiotics and Bacterial Resistance in the 21st Century. Perspect Medicin Chem. Libertas Academica; 2014 Aug 28;6:2564.

Kemenkes. Profil Kesehatan Indonesia Tahun 2014. Yudianto, Budijanto D, Hardhana B, Soenardi TA, editors. Jakarta: Kementerian Kesehatan Republik Indonesia; 2015.

Chen CJ, Huang YC. New epidemiology of Staphylococcus aureus infection in Asia. Clin Microbiol Infect. European Society of Clinical Infectious Diseases; 2014;20(7):60523.

Chan YH, Fan MM, Fok CM, Lok ZL, Ni M, Sin CF, et al. Antibiotics nonadherence and knowledge in a community with the worlds leading prevalence of antibiotics resistance: Implications for public health intervention. Am J Infect Control. Elsevier Inc; 2012;40(2):1137.

Alvan G, Edlund C, Heddini A. The global need for effective antibiotics - A summary of plenary presentations. Drug Resist Updat. Elsevier Ltd; 2011;14(2):706.

Paulson JA, Zaoutis TE. Nontherapeutic Use of Antimicrobial Agents in Animal Agriculture: Implications for Pediatrics. Pediatrics. 2015;136(6):e1670-7.

World Health Organization (2015). Global Action Plan on Antimicrobial Resistance. Geneva, Switzerland: WHO Document Production Services, p.10.

Mahomoodally MF, Dilmohamed S. Antibacterial and antibiotic potentiating activity of Vangueria madagascariensis leaves and ripe fruit pericarp against human pathogenic clinical bacterial isolates. J Tradit Complement Med. Elsevier Ltd; 2015;59.

Martins M, Dastidar SG, Fanning S, Kristiansen JE, Molnar J, Pags JM, et al. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Agents. 2008;31(3):198208.

Yadav, S.S., Meshram G., Shinde D., Patil R.C, Manohar, S.M., Upadhye M.V. Antibacterial and Anticancer Activity of Bioactive Fraction of Syzygium cumini L. Seeds. HAYATI J Biosci. Bogor Agricultural University, Indonesia; 2011;(Vol 18, No 3 (2011): September 2011):118.

Hfling JF, Anibal PC, Obando-Pereda GA, Peixoto IAT, Furletti VF, Foglio MA, et al. Antimicrobial potential of some plant extracts against Candida species. Braz J Biol. 2010;70(4):10658.

Khan S, Imran M, Imran M, Pindari N. Antimicrobial activity of various ethanolic plant extracts against pathogenic multi drug resistant Candida spp. Bioinformation. Biomedical Informatics; 2017 Mar 31;13(3):6772.

Ayyanar M, Subash-Babu P. Syzygium cumini (L.) Skeels: A review of its phytochemical constituents and traditional uses. Asian Pac J Trop Biomed. Asian Pacific Tropical Medicine Press; 2012 Mar 7;2(3):2406.

Mohamed AA, Ali SI, El-Baz FK. Antioxidant and Antibacterial Activities of Crude Extracts and Essential Oils of Syzygium cumini Leaves. Carter DA, editor. PLoS One. San Francisco, USA: Public Library of Science; 2013 Apr 12;8(4):e60269.

Kaneria M, Baravalia Y, Vaghasiya Y, Chanda S. Determination of Antibacterial and Antioxidant Potential of Some Medicinal Plants from Saurashtra Region, India. Indian J Pharm Sci. India: Medknow Publications; 2009 Nov 11;71(4):40612.

Dorfman MS, Wagner RS, Jamison T, Bell B, Stroman DW. The pharmacodynamic properties of azithromycin in a kinetics-of-kill model and implications for bacterial conjunctivitis treatment. Adv Ther. 2008;25(3):20817.

Sandberg A, Hessler JHR, Skov RL, Blom J, Frimodt-Mller N. Intracellular Activity of Antibiotics against Staphylococcus aureus in a Mouse Peritonitis Model. Antimicrob Agents Chemother. 2009 May 1;53(5):187483.

Parnham MJ, Haber VE, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: Mechanisms of action and their relevance for clinical applications. Pharmacol Ther. 2014;143(2):22545.

LaPlante KL, Rybak MJ, Leuthner KD, Chin JN. Impact of Enterococcus faecalis on the Bactericidal Activities of Arbekacin, Daptomycin, Linezolid, and Tigecycline against Methicillin-Resistant Staphylococcus aureus in a Mixed-Pathogen Pharmacodynamic Model. Antimicrob Agents Chemother. American Society for Microbiology; 2006 Apr 27;50(4):1298303.

Sander P, Springer B, Prammananan T, Sturmfels A, Kappler M, Pletschette M, et al. Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations. Antimicrob Agents Chemother. American Society for Microbiology; 2002 May 21;46(5):120411.

Yurtsev EA, Chao HX, Datta MS, Artemova T, Gore J. Bacterial cheating drives the population dynamics of cooperative antibiotic resistance plasmids. Mol Syst Biol. Nature Publishing Group; 2013 Aug 6;9:683.

Theophel K, Schacht VJ, Schlter M, Schnell S, Stingu CS, Schaumann R, et al. The importance of growth kinetic analysis in determining bacterial susceptibility against antibiotics and silver nanoparticles. Front Microbiol. 2014;5(NOV):110.

Li B, Qiu Y, Shi H, Yin H. The importance of lag time extension in determining bacterial resistance to antibiotics. Analyst. Royal Society of Chemistry; 2016;141(10):305967.

Chou, T-C. Drug combination studies and their synergy quantification using the Chou-Talalay Method. Cancer Res. 2010;Jan 15;70(2):440-6.


  • There are currently no refbacks.


JIMR - Journal of Islamic Medicine Research is licensed under a Creative Commons Attribution 4.0 International License