{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:59Z","timestamp":1791919079305,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of South Africa: Thuthuka","award":["TTK210401591599"],"award-info":[{"award-number":["TTK210401591599"]}]},{"name":"National Research Foundation of South Africa: Thuthuka","award":["USDP-JRF"],"award-info":[{"award-number":["USDP-JRF"]}]},{"name":"South African Department of Higher Education and Training: The University Capacity Development Programme","award":["TTK210401591599"],"award-info":[{"award-number":["TTK210401591599"]}]},{"name":"South African Department of Higher Education and Training: The University Capacity Development Programme","award":["USDP-JRF"],"award-info":[{"award-number":["USDP-JRF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The World Health Organization (WHO) has proposed the use of integrative medicine to achieve extended healthcare coverage in developing countries facing high morbidity. Traditional remedies are frequently employed to prevent and treat infections among South Africans; however, the ways in which they interact with conventional antimicrobials are largely unknown. Therefore, this study aimed to explore the interactions between commonly traded medicinal plants at a traditional medicine market in KwaZulu-Natal (KZN), South Africa, and conventional antibiotics and antifungals. Methods: To determine the interactive antimicrobial profiles for plant\/conventional antimicrobial combinations, minimum inhibitory concentration (MIC) assays were performed against ESKAPE pathogens and the yeasts Candida albicans and Candida glabrata. Calculated fractional inhibitory concentration (\u03a3FIC) values were used to identify synergism or antagonism, with synergistic interactions further tested in vitro for toxicity. Results: A total of 952 combinations were tested, of which 5.8% and 54.6% of the plant\/antibiotic combinations were synergistic and antagonistic, respectively; additionally, 1.7% and 58.6% of the plant\/antifungal combinations showed synergism or antagonism, respectively. The most toxic plant\/antibiotic combination was Artemisia afra with doxycycline (71.1% mortality). The most toxic plant\/antifungal combination was Acorus calamus with fluconazole (78.8% mortality). Conclusions: When medicinal plants acquired from a traditional medicine market in South Africa are used in combination with conventional antibiotics and antifungals, more than half of the combinations exhibit antagonism, which is concerning.<\/jats:p>","DOI":"10.3390\/antibiotics14050512","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T11:02:27Z","timestamp":1747306947000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Conventional Antimicrobial and Medicinal Plants from a Traditional Medicine Market in South Africa: An Interactive Antimicrobial and Toxicity Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-8666","authenticated-orcid":false,"given":"Zelna","family":"Booth","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3357-2761","authenticated-orcid":false,"given":"Sabiha","family":"Essack","sequence":"additional","affiliation":[{"name":"Antimicrobial Research Unit, University of KwaZulu-Natal, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-1845","authenticated-orcid":false,"given":"Sandy","family":"van Vuuren","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, Faculty of Health Sciences, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","first-page":"189","article-title":"Economics of the traditional medicine trade in South Africa","volume":"2007","author":"Mander","year":"2007","journal-title":"S. Afr. Health Rev."},{"key":"ref_2","unstructured":"World Health Organization (WHO) (2013). WHO Traditional Medicine Strategy (2013\u20132023), World Health Organization. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241506096."},{"key":"ref_3","first-page":"91","article-title":"South African women\u2019s use of African traditional medicine during pregnancy: A scoping review","volume":"27","author":"Dlamini","year":"2023","journal-title":"Afr. J. Reprod. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.sajb.2011.08.011","article-title":"The potential of South African plants in the development of new medicinal products","volume":"77","year":"2011","journal-title":"S. Afr. J. Bot."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.13005\/bpj\/2771","article-title":"South African medicinal plants used in the treatment of human bacterial infections: An updated review","volume":"16","author":"Bih","year":"2023","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.sajb.2024.10.048","article-title":"Toxicity and antimicrobial interactions with conventional antimicrobials of commonly traded medicinal plants from Faraday muthi market (Johannesburg, South Africa)","volume":"175","author":"Booth","year":"2024","journal-title":"S. Afr. J. Bot."},{"key":"ref_7","unstructured":"(2024, March 15). EUCAST (European Committee on Antimicrobial Susceptibility Testing), Clinical Breakpoints\u2014Breakpoints and Guidance. Available online: https:\/\/www.eucast.org\/eucast_news\/news_singleview."},{"key":"ref_8","unstructured":"Clinical Laboratory Standards Institute (CLSI) (2021). M100\u2014Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [31st ed.]. Available online: https:\/\/clsi.org\/about\/press-releases\/clsi-publishes-m100-performance-standards-for-antimicrobial-susceptibility-testing-31st-edition\/."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Abia, A.L.K., and Essack, S.Y. (2023). The combined use of African natural products and conventional antimicrobials: An alternative tool against antimicrobial resistance. Antimicrobial Research and One Health in Africa, Springer Nature.","DOI":"10.1007\/978-3-031-23796-6"},{"key":"ref_10","unstructured":"EMGuidance (2024, March 15). Medicines Online Guide. Available online: https:\/\/emguidance.com."},{"key":"ref_11","unstructured":"National Health Service (NHS) (2023, November 25). Medicines A to Z 2014. Available online: https:\/\/www.nhs.uk\/medicines\/."},{"key":"ref_12","unstructured":"National Department of Health, South Africa (2024, March 15). Essential Drugs Programme. Hospital Level (Adults) Standard Treatment Guidelines and Essential Medicines List. EML Clinical Guideline. 5th ed, Available online: https:\/\/www.health.gov.za\/wp-content\/uploads\/2024\/02\/Primary-Healthcare-STGs-and-EML-7th-edition-2020-v3.0.pdf."},{"key":"ref_13","unstructured":"(2024, March 15). South African Medicines Formulary (SAMF), 14th ed 2023. University of Cape Town. Division of Clinical Pharmacology Eds. South African Medical Association. Available online: https:\/\/samf-app.com\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.5051\/jpis.2015.45.6.223","article-title":"Antimicrobial susceptibility and pathogenic genes of Staphylococcus aureus isolated from the oral cavity of patients with periodontitis","volume":"6","author":"Kim","year":"2015","journal-title":"J. Periodontal Implant. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13756-023-01243-x","article-title":"A meta-analysis on the prevalence of resistance of Staphylococcus aureus to different antibiotics in Nigeria","volume":"12","author":"Ezeh","year":"2023","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_16","unstructured":"Watt, J.M., and Breyer-Brandwijk, M.-G. (1962). The Medicinal and Poisonous Plants of Southern and Eastern Africa, Livingstone. [2nd ed.]."},{"key":"ref_17","unstructured":"Van Wyk, B.-E., and Wink, M. (2004). Medicinal Plants of the World, Briza Publications."},{"key":"ref_18","unstructured":"Van Wyk, B.-E., Oudthoorn, B., and Gericke, N. (2009). Medicinal Plants of South Africa, Briza Publications."},{"key":"ref_19","first-page":"651","article-title":"Antibacterial effects of Artemisia afra leaf crude extract against some selected multi-antibiotic resistant clinical pathogens","volume":"32","author":"Haile","year":"2022","journal-title":"Ethiop. J. Health Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Del Giudice, P. (2020). Skin infections caused by Staphylococcus aureus. Acta Derm. Venereol., 100.","DOI":"10.2340\/00015555-3466"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.phymed.2012.09.029","article-title":"\u03b2-asarone, an active principle of Acorus calamus rhizome, inhibit morphogenesis, biofilm formation and ergosterol biosynthesis in Candida albicans","volume":"20","author":"Rajput","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_22","first-page":"517","article-title":"Antimicrobial activities of the crude methanol extract of Acorus calamus Linn","volume":"27","author":"Phongpaichit","year":"2005","journal-title":"J. Sci Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1007\/s12010-015-1537-y","article-title":"Asarones from Acorus calamus in combination with azoles and Amphotericin B: A novel synergistic combination to compete against human pathogenic Candida species in vitro","volume":"175","author":"Kumar","year":"2015","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Priyadharsini, V.J., Girjia, A.S., and Paramasivan, A. (2018). An insight into the emergence of Acinetobacter baumannii as an oro-dental pathogen and its drug resistance gene profile\u2014An in-silico approach. Heliyon, 4.","DOI":"10.1016\/j.heliyon.2018.e01051"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s12223-020-00785-6","article-title":"Assessment of antifungal resistance and associated molecular mechanism in Candida albicans isolates from different cohorts of patients in North Indian state of Haryana","volume":"65","author":"Kumar","year":"2020","journal-title":"Folia Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1034\/j.1601-0825.2002.00017.x","article-title":"Oral fungal and bacterial infections in HIV-infected individuals: An overview in Africa","volume":"8","author":"Hodgson","year":"2002","journal-title":"Oral Dis."},{"key":"ref_27","unstructured":"United Nations AIDS (UNAIDS) (2024, August 17). UNAIDS Country Reports 2009. Available online: http:\/\/www.unaids.org\/en\/regionscountries\/countries\/chad\/."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kolisa, Y.M., Yengopal, V., Shumba, K., and Igumbor, J. (2019). The burden of oral conditions among adolescents living with HIV at a clinic in Johannesburg, South Africa. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222568"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mullick, J.B., Majumdar, T., Ray, J., and Sil, S.K. (2015). Changing trends of Candida isolates and their antifungal susceptibility pattern in vulvovaginal candidiasis cases of Tripura, Northeast India. J. Evol. Med. Dent. Sci., 4.","DOI":"10.14260\/jemds\/2015\/2317"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.apjtb.2015.12.019","article-title":"Emergence of non-albicans Candida species and antifungal resistance in intensive care unit patients","volume":"6","author":"Kaur","year":"2016","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sanches, M.D., Mimura, L.A.N., Oliveira, L.R.C., Ishikawa, L.L.W., Garces, H.G., Bagagli , E., Sartori , A., Kurokawa , C.S., and Fraga-Silva, T.F. (2018). Differential behaviour of non-albicans Candida species in the central nervous system of immunocompetent and immunosuppressed mice. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02968"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jmii.2010.08.010","article-title":"Candida albicans versus non-albicans bloodstream infections: The comparison of risk factors and outcome","volume":"44","author":"Chi","year":"2011","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_33","unstructured":"World Health Organization (WHO) (2024, August 15). Bacterial Pathogens of Public Health Importance to Guide Research, Development, and Strategies to Prevent, and Control Antimicrobial Resistance. The WHO Bacterial Priority Pathogens List., Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240093461."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1055\/s-0030-1250736","article-title":"Plant-based antimicrobial studies\u2014Methods and approaches to study the interactions between natural products","volume":"77","author":"Viljoen","year":"2011","journal-title":"Planta Medica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4103\/0973-1296.66929","article-title":"Toxicity evaluation of Xanthorrhoea johnsonii leaf methanolic extract using the Artemia franciscana bioassay","volume":"6","author":"Cock","year":"2010","journal-title":"Pharmacogn. Mag."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.jep.2011.04.071","article-title":"Toxicity of medicinal plants used in traditional medicine in Northern Peru","volume":"137","author":"Bussmann","year":"2011","journal-title":"J. Ethnopharmacol."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/512\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:33:28Z","timestamp":1760031208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,15]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["antibiotics14050512"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14050512","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,15]]}}}