Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

Jayaseelan Murugaiyan¹, P Anand Kumar², G Srinivasa Rao³, Katia Iskandar^{4

5

6}, Stephen Hawser⁷, John P Hays⁸, Yara Mohsen^{9

10}, Saranya Adukkadukkam¹, Wireko Andrew Awuah¹¹, Ruiz Alvarez Maria Jose¹², Nanono Sylvia¹³, Esther Patience Nansubuga¹⁴, Bruno Tilocca¹⁵, Paola Roncada¹⁵, Natalia Roson-Calero¹⁶, Javier Moreno-Morales¹⁶, Rohul Amin¹⁷, Ballamoole Krishna Kumar¹⁸, Abishek Kumar¹⁹, Abdul-Rahman Toufik¹¹, Thaint Nadi Zaw²⁰, Oluwatosin O Akinwotu^{21

22}, Maneesh Paul Satyaseela²³, Maarten B M van Dongen²⁴

Affiliations

¹ Department of Biological Sciences, SRM University-AP, Guntur District, Amaravati 522240, India.
² Department of Veterinary Microbiology, NTR College of Veterinary Science, Sri Venkateswara Veterinary University, Gannavaram 521102, India.
³ Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, Sri Venkateswara Veterinary University, Tirupati 517502, India.
⁴ Department of Mathématiques Informatique et Télécommunications, Université Toulouse III, Paul Sabatier, INSERM, UMR 1295, 31000 Toulouse, France.
⁵ INSPECT-LB: Institut National de Santé Publique, d'Épidémiologie Clinique et de Toxicologie-Liban, Beirut 6573, Lebanon.
⁶ Faculty of Pharmacy, Lebanese University, Beirut 6573, Lebanon.
⁷ IHMA Europe Sàrl, 1870 Monthey, Switzerland.
⁸ Department of Medical Microbiology, Infectious Diseases, Erasmus University Medical Centre (Erasmus MC), 3015 GD Rotterdam, The Netherlands.
⁹ Department of Epidemiology, High Institute of Public Health, Alexandria University, Alexandria 21544, Egypt.
¹⁰ Infectious Disease Clinical Pharmacist, Antimicrobial Stewardship Department, International Medical Center Hospital, Cairo 11511, Egypt.
¹¹ Faculty of Medicine, Sumy State University, 40007 Sumy, Ukraine.
¹² Research Coordination and Support Service, National Institute of Health (ISS) Viale Regina -Elena, 299, 00161 Rome, Italy.
¹³ Infectious Diseases Institute (IDI), College of Health Sciences, Makerere University, Kampala 7072, Uganda.
¹⁴ School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
¹⁵ Department of Health Science, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
¹⁶ ISGlobal, Hospital Clínic-Universitat de Barcelona, 08036 Barcelona, Spain.
¹⁷ James P Grant School of Public Health, BRAC University, Dhaka 1212, Bangladesh.
¹⁸ Nitte (Deemed to be University), Division of Infectious Diseases, Nitte University Centre for Science Education and Research, Deralakatte, Mangalore 575018, India.
¹⁹ Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.
²⁰ Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK.
²¹ Department of Microbiology and Biotechnology Centre, Maharaja Sayajirao University of Baroda, Vadodara 390002, India.
²² Environmental and Biotechnology Unit, Department of Microbiology, University of Ibadan, 200132 Ibadan, Nigeria.
²³ Acharya Institute of Technology, Soladevanahalli, Bengaluru 560107, India.
²⁴ AMR Insights, 1017 EG Amsterdam, The Netherlands.

PMID: 35203804
PMCID: PMC8868457
DOI: 10.3390/antibiotics11020200

Review

Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

Jayaseelan Murugaiyan et al. Antibiotics (Basel). 2022.

. 2022 Feb 4;11(2):200.

doi: 10.3390/antibiotics11020200.

Authors

Affiliations

¹ Department of Biological Sciences, SRM University-AP, Guntur District, Amaravati 522240, India.
² Department of Veterinary Microbiology, NTR College of Veterinary Science, Sri Venkateswara Veterinary University, Gannavaram 521102, India.
³ Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, Sri Venkateswara Veterinary University, Tirupati 517502, India.
⁴ Department of Mathématiques Informatique et Télécommunications, Université Toulouse III, Paul Sabatier, INSERM, UMR 1295, 31000 Toulouse, France.
⁵ INSPECT-LB: Institut National de Santé Publique, d'Épidémiologie Clinique et de Toxicologie-Liban, Beirut 6573, Lebanon.
⁶ Faculty of Pharmacy, Lebanese University, Beirut 6573, Lebanon.
⁷ IHMA Europe Sàrl, 1870 Monthey, Switzerland.
⁸ Department of Medical Microbiology, Infectious Diseases, Erasmus University Medical Centre (Erasmus MC), 3015 GD Rotterdam, The Netherlands.
⁹ Department of Epidemiology, High Institute of Public Health, Alexandria University, Alexandria 21544, Egypt.
¹⁰ Infectious Disease Clinical Pharmacist, Antimicrobial Stewardship Department, International Medical Center Hospital, Cairo 11511, Egypt.
¹¹ Faculty of Medicine, Sumy State University, 40007 Sumy, Ukraine.
¹² Research Coordination and Support Service, National Institute of Health (ISS) Viale Regina -Elena, 299, 00161 Rome, Italy.
¹³ Infectious Diseases Institute (IDI), College of Health Sciences, Makerere University, Kampala 7072, Uganda.
¹⁴ School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
¹⁵ Department of Health Science, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
¹⁶ ISGlobal, Hospital Clínic-Universitat de Barcelona, 08036 Barcelona, Spain.
¹⁷ James P Grant School of Public Health, BRAC University, Dhaka 1212, Bangladesh.
¹⁸ Nitte (Deemed to be University), Division of Infectious Diseases, Nitte University Centre for Science Education and Research, Deralakatte, Mangalore 575018, India.
¹⁹ Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, India.
²⁰ Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK.
²¹ Department of Microbiology and Biotechnology Centre, Maharaja Sayajirao University of Baroda, Vadodara 390002, India.
²² Environmental and Biotechnology Unit, Department of Microbiology, University of Ibadan, 200132 Ibadan, Nigeria.
²³ Acharya Institute of Technology, Soladevanahalli, Bengaluru 560107, India.
²⁴ AMR Insights, 1017 EG Amsterdam, The Netherlands.

PMID: 35203804
PMCID: PMC8868457
DOI: 10.3390/antibiotics11020200

Abstract

Antibiotic resistance, and, in a broader perspective, antimicrobial resistance (AMR), continues to evolve and spread beyond all boundaries. As a result, infectious diseases have become more challenging or even impossible to treat, leading to an increase in morbidity and mortality. Despite the failure of conventional, traditional antimicrobial therapy, in the past two decades, no novel class of antibiotics has been introduced. Consequently, several novel alternative strategies to combat these (multi-) drug-resistant infectious microorganisms have been identified. The purpose of this review is to gather and consider the strategies that are being applied or proposed as potential alternatives to traditional antibiotics. These strategies include combination therapy, techniques that target the enzymes or proteins responsible for antimicrobial resistance, resistant bacteria, drug delivery systems, physicochemical methods, and unconventional techniques, including the CRISPR-Cas system. These alternative strategies may have the potential to change the treatment of multi-drug-resistant pathogens in human clinical settings.

Keywords: anti-plasmids; anti-virulence; antibiotic alternatives; antibiotic resistance; antimicrobial peptides; antimicrobial resistance; antimicrobial-resistant enzymes; bacteriophages; biofilms; enzyme inhibitors.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Categories of alternative strategies to combat antimicrobial resistance.

**Figure 2**
Timeline of eight decades of antimicrobials discovery alongside AMR emergence. MDR: multi-drug-resistant, XDR: extensively-drug-resistant, and PDR: pan-drug-resistant.

**Figure 3**
Classes of antibiotics, mode of action, and inhibitors.

See this image and copyright information in PMC

References

1. World Health Organization Antimicrobial Resistance. [(accessed on 31 October 2021)]. Available online: https://www.who.int/news-room/fact-sheets/detail/Antimicrob.ial-resistance.
1. World Organization for Animal Health OIE List of Antimicrobial Agents of Veterinary Importance. Jun, 2019. [(accessed on 11 December 2021)]. Available online: https://www.oie.int/en/document/a_oie_list_Antimicrob.ials_june2019/
1. Nelson R.E., Hyun D., Jezek A., Samore M.H. Mortality, Length of Stay, and Healthcare Costs Associated With Multidrug-Resistant Bacterial Infections Among Elderly Hospitalized Patients in the United States. Clin. Infect. Dis. 2021:ciab696. doi: 10.1093/cid/ciab696. - DOI - PMC - PubMed
1. O’Neil J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. Government of the United Kingdom; London, UK: 2016.
1. Murray C.J., Ikuta K.S., Sharara F., Swetschinski L., Aguilar G.R., Gray A., Han C., Bisignano C., Rao P., Wool E., et al. Global burden of bacterial Antimicrobial resistance in 2019: A systematic analysis. Lancet. 2022 doi: 10.1016/S0140-6736(21)02724-0. - DOI - PMC - PubMed

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Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

Affiliations

Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous