• This record comes from PubMed

Evaluation of In Vitro Synergistic Effects of Tetracycline with Alkaloid-Related Compounds against Diarrhoeic Bacteria

. 2024 May 30 ; 25 (11) : . [epub] 20240530

Language English Country Switzerland Media electronic

Document type Journal Article

Grant support
IGA 20233109 the Internal Grant Agency of the Faculty of Tropical AgriSciences

Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine.

See more in PubMed

GBD 2016 Diarrhoeal Disease Collaborators Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: A systematic analysis for the global burden of disease study 2016. Lancet Infect. Dis. 2018;18:1211–1228. doi: 10.1016/S1473-3099(18)30362-1. PubMed DOI PMC

Kosek M., Bern C., Guerrant R.L. The magnitude of the global burden of diarrhea from studies published 1992–2000. Bull. World Health Organ. 2003;81:197–204. PubMed PMC

Diarrhoeal Disease. 2017. [(accessed on 29 July 2022)]. Available online: https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease.

Cooke M.L. Causes and management of diarrhoea in children in a clinical setting. South. Afr. J. Clin. Nutr. 2010;23:42–46. doi: 10.1080/16070658.2010.11734269. DOI

Sah R., Khadka S., Shah D., Adhikari M., Shrestha N., Kattel H.P., Sharma S., Mishra S., Parajuli K., Sherchand J., et al. Vancomycin resistant Enterococcus faecalis causing diarrhea in renal transplant patient. Int. Educ. Sci. Res. J. 2019;2:9.

Al-Dahmoshi H.O.M., Rabeea H.W.S., Aridhee A.S.A., Al-Khafaji N.S.K., Al-Allak M.H., Lazm A.M., Jebur M.S. Phenotypic investigation of vancomycin, teicoplanin and linezolid resistance among Enterococcus spp. isolated from children diarrhea. J. Pure Appl. Microbiol. 2019;13:531–536. doi: 10.22207/JPAM.13.1.59. DOI

Ünüvar S. Microbial Foodborne Diseases. In: Holban A.M., Grumezescu A.M., editors. Handbook of Food Bioengineering, Foodborne Diseases. Academic Press; New York NY, USA: 2018. pp. 1–31.

Quraishi F., Shaheen S., Memon Z., Fatima G. Culture and sensitivity patterns of various antibiotics used for the treatment of pediatric infectious diarrhea in children under 5 years of age: A tertiary care experience from Karachi. Int. J. Clin. Med. 2018;9:684–696. doi: 10.4236/ijcm.2018.99057. DOI

Santosham M., Reid R. Diarrhoea Management. [(accessed on 21 April 2024)]. Available online: https://iris.who.int/bitstream/handle/10665/53517/WH-1986-Apr-p8-9-eng.pdf?sequence=1.

Guidelines for the Control of Shigellosis, Including Epidemics due to Shigella dysenteriae Type 1. 2005. [(accessed on 4 April 2024)]. Available online: https://iris.who.int/bitstream/handle/10665/43252/924159330X.pdf?sequence=1.

Global Taskforce on Cholerae Control Recommendations for the Use of Antibiotics for the Treatment of Cholera. 2022. [(accessed on 4 April 2024)]. Available online: https://www.gtfcc.org/wp-content/uploads/2019/10/gtfcc-technical-note-on-use-of-antibiotics-for-the-treatment-of-cholera-1.pdf.

Jandhyala S.M., Talukdar R., Subramanyam C., Vuyyuru H., Sasikala M., Nageshwar R.D. Role of the normal gut microbiota. World J. Gastroenterol. 2015;21:8787–8803. doi: 10.3748/wjg.v21.i29.8787. PubMed DOI PMC

Rolhion N., Chassaing B. When pathogenic bacteria meet the intestinal microbiota. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2016;371:20150504. doi: 10.1098/rstb.2015.0504. PubMed DOI PMC

Vogt S.L., Finlay B.B. Gut microbiota-mediated protection against diarrheal infections. J. Travel. Med. 2017;24:S39–S43. doi: 10.1093/jtm/taw086. PubMed DOI PMC

Cunha B.A. Nosocomial diarrhea. Crit. Care Clin. 1998;14:329–338. doi: 10.1016/S0749-0704(05)70398-5. PubMed DOI

World Health Organization. 2020. [(accessed on 5 August 2022)]. Available online: https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance.

Zhang Z., Li J., Ma L., Yang X., Fei B., Leung P.H.M., Tao X. Mechanistic study of synergistic antimicrobial effects between poly (3-hydroxybutyrate) oligomer and polyethylene glycol. Polymers. 2020;12:2735. doi: 10.3390/polym12112735. PubMed DOI PMC

Peña-Miller R., Lähnemann D., Schulenburg H., Ackermann M., Beardmore R. The optimal deployment of synergistic antibiotics: A control-theoretic approach. J. R. Soc. Interface. 2012;9:2488–2502. doi: 10.1098/rsif.2012.0279. PubMed DOI PMC

Doldán-Martelli V., Míguez D.G. Synergistic interaction between selective drugs in cell populations models. PLoS ONE. 2015;10:e0117558. doi: 10.1371/journal.pone.0117558. PubMed DOI PMC

Windiasti G., Feng J., Ma L., Hu Y., Hakeem M.J., Amoako K., Delaquis P., Lu X. Investigating the synergistic antimicrobial effect of carvacrol and zinc oxide nanoparticles against Campylobacter jejuni. Food Control. 2019;96:39–46. doi: 10.1016/j.foodcont.2018.08.028. DOI

Olajuyigbe O.O. Synergistic influence of tetracycline on the antibacterial activities of amoxicillin against resistant bacteria. J. Pharm. Allied Health Sci. 2012;2:12–20. doi: 10.3923/jpahs.2012.12.20. DOI

UNASYN-Ampicillin Sodium and Sulbactam Sodium Injection, Powder, for Solution Roerig. [(accessed on 23 October 2023)]. Available online: https://labeling.pfizer.com/showlabeling.aspx?id=617.

Khin-Maung-U, Myo-Khin, Nyunt-Nyunt-Wai, Aye-Kyaw, Tin-U Clinical trial of berberine in acute watery diarrhoea. Br. Med. J. (Clin. Res. Ed.) 1985;291:1601–1605. doi: 10.1136/bmj.291.6509.1601. PubMed DOI PMC

Hamoud R., Reichling J., Wink M. Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant bacteria. J. Pharm. Pharmacol. 2015;67:264–273. doi: 10.1111/jphp.12326. PubMed DOI

Jean B., Hatton C.K. Pharmacognosy Phytochemistry Medicinal Plants. 2nd ed. Lavoisier Pub.; Paris, France: 1999.

Dey A., Mukherjee A., Chaudhury M. Alkaloids From Apocynaceae: Origin, pharmacotherapeutic properties, and structure-activity studies. Stud. Nat. Prod. Chem. 2017;52:373–488.

Awuchi C. The biochemistry, toxicology, and uses of the pharmacologically active phytochemicals: Alkaloids, terpenes, polyphenols, and glycosides. J. Food Pharm. Sci. 2019;7:131–150. doi: 10.22146/jfps.666. DOI

Croaker A., King G.J., Pyne J.H., Anoopkumar-Dukie S., Liu L. Sanguinaria canadensis: Traditional medicine, phytochemical composition, biological activities and current uses. Int. J. Mol. Sci. 2016;17:1414. doi: 10.3390/ijms17091414. PubMed DOI PMC

Tenenbaum H., Dahan M., Soell M. Effectiveness of a sanguinarine regimen after scaling and root planing. J. Periodontol. 1999;70:307–311. doi: 10.1902/jop.1999.70.3.307. PubMed DOI

Kuete V. Toxicological Survey of African Medicinal Plants. Elsevier; New York, NY, USA: 2014. Health Effects of Alkaloids from African Medicinal Plants; pp. 611–634.

Osei-Owusu H., Kudera T., Strakova M., Rondevaldova J., Skrivanova E., Novy P., Kokoska L. In vitro selective combinatory effect of ciprofloxacin with nitroxoline, sanguinarine, and zinc pyrithione against diarrhea-causing and gut beneficial bacteria. Microbiol. Spectr. 2022;10:e0106322. doi: 10.1128/spectrum.01063-22. PubMed DOI PMC

Kresken M., Körber-Irrgang B. In vitro activity of nitroxoline against Escherichia coli urine isolates from outpatient departments in Germany. Antimicrob. Agents Chemother. 2014;58:7019–7020. doi: 10.1128/AAC.03946-14. PubMed DOI PMC

Vivanco J.M., Bais H.P., Stermitz F.R., Thelen G.C., Callaway R.M. Biogeographical variation in community response to root allelochemistry: Novel weapons and exotic invasion. Ecol. Lett. 2004;7:285–292. doi: 10.1111/j.1461-0248.2004.00576.x. DOI

Han G., Bingxiang X., Xiaopeng W. Studies on active principles of Polyalthia nemoralis-I. The isolation and identification of natural zinc compound. Acta Chim. Sin. 1981;39:433–437.

Saunders C.W., Scheynius A., Heitman J. Malassezia fungi are specialized to live on skin and associated with dandruff, eczema, and other skin diseases. PLoS Pathog. 2012;8:100270. doi: 10.1371/journal.ppat.1002701. PubMed DOI PMC

Leong C., Wang J., Toi M.J., Lam Y.I., Goh J.P., Lee S.M., Dawson T.L. Effect of zinc pyrithione shampoo treatment on skin commensal Malassezia. Med. Mycol. 2021;59:210–213. doi: 10.1093/mmy/myaa068. PubMed DOI

Britannica, The Editors of Encyclopaedia . Encyclopedia Britannica; [(accessed on 7 April 2022)]. “Tetracycline”. Available online: https://www.britannica.com/science/tetracycline.

Dwivedi G.R., Maurya A., Yadav D.K., Singh V., Khan F., Gupta M.K., Singh M., Darokar M.P., Srivastava S.K. Synergy of clavine alkaloid ‘chanoclavine’ with tetracycline against multi-drug-resistant E. coli. J. Biomol. Struct. Dyn. 2019;37:1307–1325. doi: 10.1080/07391102.2018.1458654. PubMed DOI

Clinical and Laboratory Standards Institute . Performance Standards for Antimicrobial Susceptibility Testing. 30th ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2020. Approved Standard.

Sirichoat A., Flórez A.B., Vázquez L., Buppasiri P., Panya M., Lulitanond V., Mayo B. Antibiotic resistance-susceptibility profiles of Enterococcus faecalis and Streptococcus spp. from the human vagina, and genome analysis of the genetic basis of intrinsic and acquired resistances. Front. Microbiol. 2020;11:1438. doi: 10.3389/fmicb.2020.01438. PubMed DOI PMC

Pohl A., Lübke-Becker A., Heuwieser W. Minimum inhibitory concentrations of frequently used antibiotics against Escherichia coli and Trueperella pyogenes isolated from uteri of postpartum dairy cows. J. Dairy. Sci. 2018;101:1355–1364. doi: 10.3168/jds.2017-12694. PubMed DOI

Han F., Walker R.D., Janes M.E., Prinyawiwatkul W., Ge B. Antimicrobial susceptibilities of Vibrio parahaemolyticus and Vibrio vulnificus isolates from Louisiana Gulf and retail raw oysters. Appl. Environ. Microbiol. 2007;73:7096–7098. doi: 10.1128/AEM.01116-07. PubMed DOI PMC

Stock I., Wiedemann B. An in-vitro study of the antimicrobial susceptibilities of Yersinia enterocolitica and the definition of a database. J. Antimicrob. Chemother. 1999;43:37–45. doi: 10.1093/jac/43.1.37. PubMed DOI

Li Q., Sherwood J.S., Logue C.M. Antimicrobial resistance of Listeria spp. recovered from processed bison. Lett. Appl. Microbiol. 2007;44:86–91. doi: 10.1111/j.1472-765X.2006.02027.x. PubMed DOI

Madiyarov R.S., Bektemirov A.M., Ibadova G.A., Abdukhalilova G.K., Khodiev A.V., Bodhidatta L., Sethabutr O., Mason C.J. Antimicrobial resistance patterns and prevalence of class 1 and 2 integrons in Shigella flexneri and Shigella sonnei isolated in Uzbekistan. Gut Pathog. 2010;2:18. doi: 10.1186/1757-4749-2-18. PubMed DOI PMC

Kudera T., Doskocil I., Salmonova H., Petrtyl M., Skrivanova E., Kokoska L. In vitro selective growth-inhibitory activities of phytochemicals, synthetic phytochemical analogs, and antibiotics against diarrheagenic/probiotic bacteria and cancer/normal intestinal cells. Pharmaceuticals. 2020;13:233. doi: 10.3390/ph13090233. PubMed DOI PMC

Omoya F.O., Ajayi K.O. Synergistic effect of combined antibiotics against some selected multidrug resistant human pathogenic bacteria isolated from poultry droppings in Akure, Nigeria. Adv. Microbiol. 2016;6:1075–1090. doi: 10.4236/aim.2016.614100. DOI

Chopra I., Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 2001;65:232–260. doi: 10.1128/MMBR.65.2.232-260.2001. PubMed DOI PMC

Grossman T.H. Tetracycline antibiotics and resistance. Cold Spring Harb. Perspect. Med. 2016;6:025387. doi: 10.1101/cshperspect.a025387. PubMed DOI PMC

White J.P., Cantor C.R. Role of magnesium in the binding of tetracycline to Escherichia coli ribosomes. J. Mol. Biol. 1971;58:397–400. doi: 10.1016/0022-2836(71)90255-5. PubMed DOI

Repac A.D., Parčina M., Gobin I., Petković D.M. Chelation in antibacterial drugs: From nitroxoline to cefiderocol and beyond. Antibiotics. 2022;11:1105. doi: 10.3390/antibiotics11081105. PubMed DOI PMC

Wang T., Flint S., Palmer J. Magnesium and calcium ions: Roles in bacterial cell attachment and biofilm structure maturation. Biofouling. 2019;35:959–974. doi: 10.1080/08927014.2019.1674811. PubMed DOI

Dinning A.J., Al-Adham I.S., Austin P., Charlton M., Collier P.J. Pyrithione biocide interactions with bacterial phospholipid, head groups. J. Appl. Microbiol. 1998;85:132–140. doi: 10.1046/j.1365-2672.1998.00477.x. PubMed DOI

Obiang-Obounou B.W., Kang O.H., Choi J.G., Keum J.H., Kim S.B., Mun S.H., Shin D.W., Kim K.W., Park C.B., Kim Y.G., et al. The mechanism of action of sanguinarine against methicillin-resistant Staphylococcus aureus. J. Toxicol. Sci. 2011;36:277–283. doi: 10.2131/jts.36.277. PubMed DOI

Shutter M.C., Akhondi H. StatPearls. StatPearls Publishing; Treasure Island, FL, USA: 2022. [(accessed on 10 April 2023)]. Tetracycline. Available online: https://www.ncbi.nlm.nih.gov/books/NBK549905/

Poiger H., Schlatter C. Interaction of cations and chelators with the intestinal absorption of tetracycline. Naunyn Schmiedebergs Arch. Pharmacol. 1979;306:89–92. doi: 10.1007/BF00515599. PubMed DOI

Rosenstock J., Smith L.P., Gurney M., Lee K., Weinberg W.G., Longfield J.N., Tauber W.B., Karney W.W. Comparison of single-dose tetracycline hydrochloride to conventional therapy of urinary tract infections. Antimicrob. Agents Chemother. 1985;27:652–654. doi: 10.1128/AAC.27.4.652. PubMed DOI PMC

Naber K.G., Niggemann H., Stein G. Review of the literature and individual patients’ data meta-analysis on efficacy and tolerance of nitroxoline in the treatment of uncomplicated urinary tract infections. BMC Infect. Dis. 2014;14:628. doi: 10.1186/s12879-014-0628-7. PubMed DOI PMC

Wijma R.A., Huttner A., Koch B.C.P., Mouton J.W., Muller A.E. Review of the pharmacokinetic properties of nitrofurantoin and nitroxoline. J. Antimicrob. Chemother. 2018;73:2916–2926. doi: 10.1093/jac/dky255. PubMed DOI

Becci P.J., Schwartz H., Barnes H.H., Southard G.L. Short-term toxicity studies of sanguinarine and of two alkaloid extracts of Sanguinaria canadensis L. J. Toxicol. Environ. Health. 1987;20:199–208. doi: 10.1080/15287398709530972. PubMed DOI

Scientific Committee on Consumer Safety (SCCS) Opinion on Zinc Pyrithione. [(accessed on 12 April 2023)]. Available online: https://health.ec.europa.eu/system/files/2021-11/sccs_o_236.pdf.

Schwartz J.R., Shah R., Krigbaum H., Sacha J., Vogt A., Blume-Peytavi U. New insights on dandruff/seborrhoeic dermatitis: The role of the scalp follicular infundibulum in effective treatment strategies. Br. J. Dermatol. 2011;165((Suppl. 2)):18–23. doi: 10.1111/j.1365-2133.2011.10573.x. PubMed DOI

Clinical and Laboratory Standards Institute . Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 10th ed. Clinical and Laboratory Standards Institute; Wayne, PA, USA: 2015. Approved Standard.

Leber A. Clinical Microbiology Procedures Handbook. 4th ed. Volume 1–3. ASM Press; Washington, DC, USA: 2016. Synergism testing: Broth microdilution checkerboard and broth microdilution methods; pp. 1–23.

Cos P., Vlietinck A.J., Vanden Berghe D., Maes L. Anti-infective potential of natural products: How to develop a stronger in vitro ‘proof-of-concept’. J. Ethnopharmacol. 2006;106:290–302. doi: 10.1016/j.jep.2006.04.003. PubMed DOI

Jorgensen J.H., Turnidge J.D., Washington J.A. Antibacterial susceptibility tests: Dilution and disk diffusion methods. In: Murray P.R., Baron E.J., Pfaller M.A., Tenover F.C., Yolken R.H., editors. Manual of Clinical Microbiology. 7th ed. ASM Press; Washington, DC, USA: 1999. pp. 1526–1543.

Okoliegbe I.N., Hijazi K., Cooper K., Ironside C., Gould I.M. Antimicrobial synergy testing: Comparing the tobramycin and ceftazidime gradient diffusion methodology used in assessing synergy in cystic fibrosis-derived multidrug-resistant Pseudomonas aeruginosa. Antibiotics. 2021;10:967. doi: 10.3390/antibiotics10080967. PubMed DOI PMC

Frankova A., Vistejnova L., Merinas-Amo T., Leheckova Z., Doskocil I., Wong Soon J., Kudera T., Laupua F., Alonso-Moraga A., Kokoska L. In vitro antibacterial activity of extracts from Samoan medicinal plants and their effect on proliferation and migration of human fibroblasts. J. Ethnopharmacol. 2021;264:113220. doi: 10.1016/j.jep.2020.113220. PubMed DOI

European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) EUCAST Definitive Document E. Def 1.2. Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents. Clin. Microbiol. Infect. 2000;6:503–508. doi: 10.1046/j.1469-0691.2000.00149.x. PubMed DOI

Rakholiya K.D., Kaneria M.J., Chanda S.V. Medicinal plants as alternative sources of therapeutics against multidrug-resistant pathogenic microorganisms based on their antimicrobial potential and synergistic properties. In: Rai M.K., Kon K.V., editors. Fighting Multidrug Resistance with Herbal Extracts, Essential Oils and Their Components. Academic Press; New York, NY, USA: 2013. pp. 165–179.

Odds F.C. Synergy, antagonism, and what the chequerboard puts between them. J. Antimicrob. Chemother. 2003;52:1. doi: 10.1093/jac/dkg301. PubMed DOI

Williamson E.M. Synergy and other interactions in phytomedicines. Phytomedicine. 2001;8:401–409. doi: 10.1078/0944-7113-00060. PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...