In vitro Activity of Sparfloxacin and Its Combination with Efflux Pump Blockers Against Methicillin-Resistant Staphylococcus aureus and Escherichia coli

Authors

  • Rahima Tahir Shaheed Zulfikar Ali Bhutto Institute of Science and Technology, SZABIST University,Karachi,Pakistan. https://orcid.org/0009-0002-6777-3721
  • Neha Farid Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan. https://orcid.org/0000-0003-4051-4674
  • Khansa Syed Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.
  • Misbah Mohammad Hanif Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.
  • Asma Bashir Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan. https://orcid.org/0000-0002-0912-9199
  • Kashif Ali Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan. https://orcid.org/0000-0002-3913-9443

DOI:

https://doi.org/10.36283/ziun-pjmd14-3/006

Keywords:

Sparfloxacin, Multi-drug resistance, MRSA, Escherichia Coli, Minimum Inhibitory Concentration, Minimum Bactericidal Concentration

Abstract

Background: Multi-drug resistance has emerged as a significant global health challenge that has resulted in the occurrence of numerous diseases. This paper highlighted the potential of Sparfloxacin as a solution to antimicrobial resistance when used alone or in combination with efflux pump blockers. Sparfloxacin is a fluoroquinolone antibiotic that inhibits the bacterial DNA gyrase, thereby preventing DNA replication.  The purpose of this study was to determine the efficacy of Sparfloxacin against MRSA and E. coli, and whether it could be used either solely or in combination with the efflux pump blockers to overcome multidrug resistance.

Methods: The study targeted two pathogens, Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The research methods included the determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of Sparfloxacin solely, and in combination with Tamoxifen and Verapamil. The study was conducted over a time period of one year, and the study design was basic.

Result: The effective concentration of Sparfloxacin was found to be 0.001µg/ml for MRSA and 5µg/ml for E. coli. Whereas, when used in combination with the efflux pump blocker, the effective concentration was found to be 0.31µg/ml with 128µg/ml of Tamoxifen for both the microbes. Verapamil with Sparfloxacin (0.31µg/ml) was found to be effective with 24µg/ml as MBC, and 12µg/ml as MIC value against Methicillin-Resistant Staphylococcus aureus. For E. coli, the MBC value of Verapamil with Sparfloxacin (20µg/ml) was found to be 166.66µg/ml.

Conclusion: The study suggested that Sparfloxacin could be a potential solution to multidrug resistance, even when used solely, unlike other antibiotics, which show better efficacy at higher concentrations. Tamoxifen and Verapamil can be used with other antibiotics to enhance their efficacy against the multidrug-resistant strains.

Author Biographies

  • Rahima Tahir, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology, SZABIST University,Karachi,Pakistan.

    Graduate of BS Biosciences,

  • Neha Farid, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.

     Department of Biosciences and Senior Lecturer,

  • Khansa Syed, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.

    Graduate of BS Biosciences,

  • Misbah Mohammad Hanif, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.

    Graduate of BS Biosciences,

  • Asma Bashir, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.

     Department of Biosciences and Assistant Professor,

  • Kashif Ali, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology,SZABIST University,Karachi,Pakistan.

    Dean of Faculty of Life Sciences,

References

1. World Health Organization. WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance, to guide research, development, and strategies to prevent and control antimicrobial resistance. World Health Organization; 2024 May 17. ISBN-978-92-4-009346-1 (electronic version); https://www.who.int/publications/i/item/9789240093461

2. Mancuso G, Midiri A, Gerace E, Biondo C. Bacterial antibiotic resistance: the most critical pathogens. Pathogens. 2021 Oct 12;10(10):1310. https://doi.org/10.3390/pathogens10101310

3. Gaurav A, Bakht P, Saini M, Pandey S, Pathania R. Role of bacterial efflux pumps in antibiotic resistance, virulence, and strategies to discover novel efflux pump inhibitors. Microbiology. 2023 May 24;169(5):001333. https://doi.org/10.1099/mic.0.001333

4. Nikaido H, Pagès JM. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS microbiology reviews. 2012 Mar 1;36(2):340-63. https://doi.org/10.1111/j.1574-6976.2011.00290.x

5. Asrani P, Tiwari K, Eapen MS, McAlinden KD, Haug G, Johansen MD, Hansbro PM, Flanagan KL, Hassan MI, Sohal SS. Clinical features and mechanistic insights into drug repurposing for combating COVID-19. The International Journal of Biochemistry & Cell Biology. 2022 Jan 1;142: 106114. https://doi.org/10.1016/j.biocel.2021.106114 .

6. Laws M, Jin P, Rahman KM. Efflux pumps in Mycobacterium tuberculosis and their inhibition to tackle antimicrobial resistance. Trends in microbiology. 2022 Jan 1;30(1):57-68. https://doi.org/10.1016/j.tim.2021.05.001

7. Saabir F, Hussain A, Mulani M, Kulkarni S, Tambe S. Efflux pump and its inhibitors: cause and cure for multidrug resistance. 2022 Apr; 10(3): 177–194. https://doi.org/10.7324/JABB.2022.100322

8. Panadero IM, Torres JF, Hmadcha K, Princiotto S, Cutarella L, Mori M, Dallavalle S, Christodoulou MS, Smani Y. Antibacterial activity of tamoxifen derivatives against methicillin-resistant Staphylococcus aureus. bioRxiv. 2024 Jul 19:2024-07. https://doi.org/10.3389/fphar.2025.1549288

9. Pang H, Zhang G, Yan N, Lang J, Liang Y, Xu X, Cui Y, Wu X, Li X, Shan M, Wang X. Evaluating the Risk of Breast Cancer Recurrence and Metastasis After Adjuvant Tamoxifen Therapy by Integrating Polymorphisms in Cytochrome P450 Genes and Clinicopathological Characteristics. Frontiers in Oncology. 2021 Nov 19;11: 738222. https://doi.org/10.3389/fonc.2021.738222

10. Adams KN, Szumowski JD, Ramakrishnan L. Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs. The Journal of infectious diseases. 2014 Aug 1;210(3):456-66. https://doi.org/10.1093/infdis/jiu095 .

11. Tambat R, Mahey N, Chandal N, Verma DK, Jangra M, Thakur KG, Nandanwar H. A microbe-derived efflux pump inhibitor of the resistance-nodulation-cell division protein restores antibiotic susceptibility in Escherichia coli and Pseudomonas aeruginosa. ACS infectious diseases. 2022 Jan 19;8(2):255-70. https://doi.org/10.1021/acsinfecdis.1c00281

12. Douafer H, Andrieu V, Phanstiel IV O, Brunel JM. Antibiotic adjuvants: make antibiotics great again!. Journal of medicinal chemistry. 2019 May 7;62(19):8665-81. https://doi.org/10.1021/acs.jmedchem.8b01781

13. Kowalska-Krochmal B, Dudek-Wicher R. The minimum inhibitory concentration of antibiotics: methods, interpretation, clinical relevance. Pathogens. 2021 Feb 4;10(2):165. https://doi.org/10.3390/pathogens10020165

14. Bharadwaj A, Rastogi A, Pandey S, Gupta S, Sohal JS. Multidrug‐resistant bacteria: their mechanism of action and prophylaxis. BioMed research international. 2022;2022(1):5419874. https://doi.org/10.1155/2022/5419874

15. Weinstein MP, Lewis JS. The clinical and laboratory standards institute subcommittee on antimicrobial susceptibility testing: background, organization, functions, and processes. Journal of clinical microbiology. 2020 Feb 24;58(3):10-128. https://doi.org/10.1128/jcm.01864-19

16. Prasch S, Bucar F. Plant derived inhibitors of bacterial efflux pumps: an update. Phytochemistry Reviews. 2015 Dec; 14:961-74. https://doi.org/10.1007/s11101-015-9436-y

17. Zack KM, Sorenson T, Joshi SG. Types and mechanisms of Efflux Pump Systems and the potential of Efflux Pump Inhibitors in the restoration of Antimicrobial susceptibility, with a special reference to Acinetobacter baumannii. Pathogens. 2024 Feb 23;13(3):197. https://doi.org/10.3390/pathogens13030197

18. Vivas R, Barbosa AA, Dolabela SS, Jain S. Multidrug-resistant bacteria and alternative methods to control them: an overview. Microbial Drug Resistance. 2019 Jul 1;25(6):890-908. https://doi.org/10.1089/mdr.2018.0319

19. Seukep AJ, Kuete V, Nahar L, Sarker SD, Guo M. Plant-derived secondary metabolites as the main source of efflux pump inhibitors and methods for identification. Journal of pharmaceutical analysis. 2020 Aug 1;10(4):277-90. https://doi.org/10.1016/j.jpha.2019.11.002

20. Miró-Canturri A, Ayerbe-Algaba R, Vila-Domínguez A, Jiménez-Mejías ME, Pachón J, Smani Y. Repurposing of the tamoxifen metabolites to combat infections by multidrug-resistant Gram-negative bacilli. Antibiotics. 2021 Mar 22;10(3):336. https://doi.org/10.3390/antibiotics10030336

21. Yu F, Bender W. The mechanism of tamoxifen in breast cancer prevention. Breast cancer research. 2001 May 31;3(Suppl 1): A74. https://doi.org/10.1186/bcr404

22. Nishino K, Yamasaki S, Nakashima R, Zwama M, Hayashi-Nishino M. Function and inhibitory mechanisms of multidrug efflux pumps. Frontiers in Microbiology. 2021 Dec 3;12: 737288. https://doi.org/10.3389/fmicb.2021.737288

23. Huang L, Wu C, Gao H, Xu C, Dai M, Huang L, Hao H, Wang X, Cheng G. Bacterial multidrug efflux pumps at the frontline of antimicrobial resistance: an overview. Antibiotics. 2022 Apr 13;11(4):520. https://doi.org/10.3390/antibiotics11040520

24. Parumasivam T, Chan JG, Pang A, Quan DH, Triccas JA, Britton WJ, Chan HK. In vitro evaluation of inhalable verapamil-rifapentine particles for tuberculosis therapy. Molecular Pharmaceutics. 2016 Mar 7;13(3):979-89. https://doi.org/10.1021/acs.molpharmaceut.5b00833

25. Valıyeva G, Durupınar B, Coban AY. Efflux pump effects on Mycobacterium tuberculosis drug resistance. Journal of Chemotherapy. 2023 Oct 3;35(7):601-9. https://doi.org/10.1080/1120009X.2023.2173857

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Published

2025-07-21

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How to Cite

1.
Tahir R, Farid N, Syed K, Mohammad Hanif M, Bashir A, Ali K. In vitro Activity of Sparfloxacin and Its Combination with Efflux Pump Blockers Against Methicillin-Resistant Staphylococcus aureus and Escherichia coli. PJMD [Internet]. 2025 Jul. 21 [cited 2026 Jun. 4];14(3):31-8. Available from: https://ojs.zu.edu.pk/pjmd/article/view/3570

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