Antibiotics - Therapeutic Spectrum and Limitations

Dr. Amal Kumar Dhara (MPharm, PhD) has over 20 years of teaching and research experience in the fields of Pharmacology and Toxicology, especially in the areas of neuropharmacology and anti-inflammatory, antiulcer, and free radical scavenging activities of indigenous Indian plants. He earned his PhD in Pharmaceutical Sciences from Jadavpur University, Kolkata, West Bengal, India. Currently, Dr. Dhara works as a Lecturer in Pharmacy (Associate Professor) at Contai Polytechnic, Purba Medinipur, West Bengal, India. Dr. Amit Kumar Nayak (MPharm, PhD) is working as a professor, at the Department of Pharmaceutics, School of Pharmaceutical Sciences, Siksha ‘O' Anusandhan (Deemed to be University), Odisha, India. He has earned his PhD from IFTM University, Moradabad, Uttar Pradesh, India. He has over 14 years of research experiences in the field of pharmaceutics, especially in the development and characterization of novel biopolymeric and nanostructured drug delivery systems. Till date, he has authored more than 138 research and review publications in various high-impact peer-reviewed journals and 135 book chapters. He has edited/authored 23 international books to his credit. Dr. Nayak has presented his research work at several conferences. He has received University Foundation Day Research Award, 2019 and 2022 by Biju Patnaik University of Technology, Odisha. Dr. Nayak is a life member of the Association of Pharmaceutical Teachers of India (APTI) and a registered pharmacist. Dr. Debprasad Chattopadhyay (PhD) has over 38 years of research experience in the field of Microbiology, Virology, Traditional Medicine, Ethnomedicine, and Molecular Medicine in identifying nature-based leads against difficult-to-treat diseases through documentation and validation of purity, safety, and potency (PSP) of traditional practices of Indian tribes with mode or molecular mechanism of action. He is currently the editor of the prestigious journal Frontiers in Pharmacology, editorial board member of the Journal of Ethnopharmacology, and reviewer of more than 40 peer-reviewed journals. He is the recipient of several awards such as Outstanding Ethnopharmacologist (2016), Best Science Communicator (2009), Amiya Bose Oration (2008), R.V. Rajam Endowment of IMA 1998, and International Society of Chemotherapy Young Scientist 1991.

Contributors
Preface

I
Introduction

1. Introduction to antibiotic therapy
Amal Kumar Dhara and Amit Kumar Nayak

1 Introduction
2 Bacterial infection
3 Antibiotic era
4 Challenges in the development of antibiotics
5 Classes of antibiotics and their therapeutic spectrum
6 ß-Lactam antibiotics
7 Aminoglycoside antibiotics
8 Chloramphenicol and tetracyclines
9 Macrolide antibiotics
10 Lincosamide and glycopeptide antibiotics
11 Polypeptide antibiotics
12 Antifungal antibiotics
13 Antitubercular antibiotics
14 Toxicity of antibiotics
15 Antimicrobial resistance
16 Prospect of probiotics and natural products
17 Conclusion
References

II
Microbial infection and antibiotics development

2. Bacterial infections: Types and pathophysiology
V.T. Anju, Siddhardha Busi, Mahima S. Mohan, and Madhu Dyavaiah

1 Infection: An overview
2 Bacterial infections and mechanism of pathogenesis
3 Types of bacterial infections and pathophysiology
4 Conclusions
References

3. Antibiotics role in past and present: A challenge to find new possibilites in development
Kumar Bhavna, Deepika Raina, Shradha Singh Raghav, Manmohan Singhal, Neeraj Kumar Sethiya, Samir Bhargava, and Abhijeet Ojha

1 Introduction
2 Mechanisms of resistance to antibiotics
3 Antimicrobial chemotherapy
4 The golden era of antibiotics
5 Conclusion
References

4. Challenges in the development of novel antibiotics
David Elder

1 Introduction
2 Target product profiles for new antibacterials
3 Developing novel antibiotics
4 Case studies: Development of novel antibiotics
5 The role of public–private partnerships (PPPs) in developing new antibiotics
6 Conclusions
References

III
Antibiotics and therapeutics

5. Beta-lactam antibiotics
Carlos Barreiro, Sonia Marti´nez-Ca´mara, Carlos Garci´a-Estrada, Manuel de la Torre, and Jose L. Barredo

1 Introduction
2 Beta-lactam antibiotics: Types, structure, and mechanism of action
3 Penicillins and cephalosporins: Discovery and biosynthetic pathways
4 Resistances: Mechanism and clinical relevance
5 Omics in the development of beta-lactams
6 Future outlook
Acknowledgments
References

6. Aminoglycoside antibiotics
Julia Revuelta and Agatha Bastida

1 Introduction
2 Targeting RNA with AGAs
3 Aminoglycoside resistance
4 Toxicity
5 Pharmacokinetics and pharmacodynamics
6 Development of second-generation AGAs
7 Aminoglycoside-based biomaterials
8 Outlook and future perspectives
References

7. Chloramphenicol and tetracycline (broad spectrum antibiotics)
Manmohan Singhal, Mohit Agrawal, Kumar Bhavna, Neeraj Kumar Sethiya, Samir Bhargava, Komal Satish Gondkar, Kumud Joshi, Vijay Singh Rana, Jagannath Sahoo, and Mandeep Kumar Arora

1 Introduction
2 Tetracyclins
3 Mode of action of tetracyclines
4 Tetracycline resistance with mechanisms in biochemistry and genetics
5 Chloramphenicol
6 Structural-activity relationship
7 Chloramphenicol resistance
8 Combination effect of chloramphenicol with other antibiotics
9 Conclusion
Further reading

8. Macrolide antibiotics
Manmohan Singhal, Mohit Agrawal, Kumar Bhavna, Komal Satish Gondkar, Neeraj Kumar Sethiya, Kumud Joshi, Ritik Kumar, Uddipak Rai, Samir Bhargava, and Vijay Singh Rana

1 Introduction
2 The binding site of macrolide
3 Mode of action
4 Classification of macrolide antibiotics
5 Administration
6 Side effects
7 Contradictions
8 Monitoring
9 Toxicity
10 Resistance
11 Conclusion
Further reading

9. Lincosamide and glycopeptide antibiotics
Ijaz Hussain, Tania Jabbar, Asma Naureen, Sadaf-Ul-Hassan, Amjad Hussain, Muhammad Rehan Hasan Shah Gilani, Naseem Abbas, and Syed Ali Raza Naqvi

1 Introduction
2 Structures of lincosamides and glycopeptides antibiotics
3 Mechanism of action
4 Bacterial resistance
5 Semisynthetic glycopeptide antibiotics
6 Biological activity and medicinal importance
7 Conclusion
References

10. Antimicrobial lipopeptides: Multifaceted designs to curb antimicrobial resistance
Sudip Mukherjee, Rajib Dey, Yash Acharya, and Jayanta Haldar

1 Introduction
2 Naturally occurring lipopeptide antimicrobials
3 Semisynthetic glycolipopeptides
4 Synthetically designed lipopeptide antimicrobials
5 Conclusion and future outlook
References

11. Antifungal compounds: With special emphasis on echinocandins, polyenes, and heterocyclic benzofurans
D. Sampritha Devi, Megh Bose, and Regina Sharmila Dass

1 Introduction
2 Polyenes
3 Echinocandins
4 Heterocyclic benzofurans
5 Conclusion
References
Further reading

12. Antibiotics in the management of tuberculosis and cancer
Niranjan Koirala, Monica Butnariu, Mamata Panthi, Roshani Gurung, Sundar Adhikari, Romit Kumar Subba, Zenisha Acharya, and Jelena Popovic-Djordjevic

1 Introduction to antibiotics, tuberculosis, and cancer
2 Antibiotics in the management of tuberculosis
3 Antibiotics in the management of cancer
4 Recent advances in the antibiotics discovery for tuberculosis: Biotechnology perspectives
5 Recent advances in the antibiotics discovery for cancer: Biotechnology perspectives
6 Conclusion and future perspective
References
Further reading

IV
Toxicity and antibiotic resistance

13. Toxicity consideration of antibiotics
Sameh S. Ali, Asmaa Ali, Tamer Elsamahy, Kamal M. Okasha, and Jianzhong Sun

1 Introduction
2 Mechanism of antibiotic toxicity
3 Risk factors influencing antibiotic toxicity
4 Common features of antibiotic toxicity
5 Consideration to avoid antibiotic toxicity
6 Conclusion
References

14. Rational use of antibiotics—Save antibiotics for future generations
Indira P. Sarethy, Nidhi Srivastava, Swapnil Chaturvedi, Nidhi Chauhan, and Michael Danquah

1 Introduction
2 Antimicrobial drug resistance overview
3 Global burden of antibiotics in different sectors
4 Cause of spread of antimicrobial drug resistance
5 Global impact of unsustainable management
6 Steps required for saving antibiotics for future generations
7 Currently active National Action Plans on AMR
8 Future prospects and conclusions
Consent for publication
Conflict of interest
Acknowledgments
References

15. Combined use of antibiotics
Jinli Wang, Jinwu Meng, Jinyue Zhu, Siya Li, Tianxin Qiu, Wenjia Wang, Jinxue Ding, Kun Li, and Jiaguo Liu

1 Introduction
2 Combination antibiotics therapy for multidrug-resistant bacteria
3 Combinations of antibiotics with Class Ia antibiotic adjuvants
4 Combined use of antibiotics with Class Ib adjuvants
5 Combined use of antibiotics with Class II adjuvants
6 Future perspectives
References

16. Antibiotic resistance—A global crisis
Zeuko’o Menkem Elisabeth

1 Introduction
2 Antibiotic resistance
3 Causes of antibiotic resistance
4 Management of antibiotic resistance
5 Conclusion
References

17. Traditional medicine in the management of microbial infections as antimicrobials: Pros and cons
Joyeta Ghosh, Partha Palit, Subhasish Maity, Vedprakash Dwivedi, Jyoti Das, Chittaranjan Sinha, and Debprasad Chattopadhyay

1 Introduction
2 Data synthesis
3 Mother nature: The pharmacopeia of the living kingdom
4 Role of TM in infection management
5 Traditional medicine on fungal infection
6 TM against viruses
7 TM in protozoal infections
8 Potential of TM-based future antimicrobials
9 Conclusion and future direction
Acknowledgment
References

V
Others

18. Quinolones as antimicrobial and antiresistance agents
Kadja Luana Chagas Monteiro, Marcone Gomes dos Santos Alc^antara, Nathalia Monteiro Lins Freire, Thiago Mendonc¸a de Aquino, and Edeildo Ferreira da Silva-Ju´nior

1 An overview of quinolones and their structureactivity relationship
2 Pharmacology and clinical uses
3 Mode of action
4 Mode of resistance
5 Quinolone-topoisomerase interactions
6 The state of the art in the basic research for new quinolones
7 Modulation of resistance: NorA efflux pump and MRSA
8 Conclusion
References

19. Herbal drugs as antibiotics
Shabihul Fatma Sayed

1 Introduction
2 What is the need for herbal antibiotics?
3 Therapeutic effects of herbs
4 Herbs for their Antibiotic actions
5 Herbal drugs as antibiotics in respiratory ailments
6 Conclusion
Acknowledgments
References

20. Challenges for use of antibiotics in pediatric and geriatric population
Kumar Bhavna, Komal Satish Gondkar, Priyanshu Kumar, Uddipak Rai, Manmohan Singhal, Vijay Singh Rana, Neeraj Kumar Sethiya, Samir Bhargava, Mandeep Kumar Arora, Abhijeet Ojha, and Anuj Nautiyal

1 Introduction
2 Considerations
3 Absorption
4 Distribution
5 Metabolism
6 Elimination
7 Pharmacodynamics properties of antibiotics used in both pediatric and geriatric patients
8 Adverse drug reaction and adverse drug events
9 Antibiotic allergy
10 Medication errors
11 Off-label antibiotic usage
12 Parents’ role
13 Prescriber role
14 Discussion
15 Conclusion
References

21. Role of antibiotics in hospital-acquired infections and community-acquired infections
Tuhina Banerjee, Swati Sharma, and Pue Rakshit

1 Introduction
2 Antibiotics: The magic bullets
3 Which came first? Antibiotics or AMR?
4 Antimicrobial resistance: A global challenge
5 Colonization to infection: Understanding the basics
6 Hospital and community: Two different ecosystems
7 Hospital-acquired infections: An introduction
8 Community-acquired infections (CAI): An introduction
9 When not to use antibiotics?
10 Challenges in implementation of rational antibiotic use policies and practices in LMIC
11 Preventive strategies against antibiotic misuse
12 Conclusions
References

22. Adult sepsis as an emerging hospitalacquired infection: Challenges and solutions
Puneet Gandhi and Parkhi Shrivastava

1 Introduction
2 Why is sepsis the most precarious HAI
3 Challenges in the diagnosis of sepsis
4 Treatment challenges
5 Clinical conditions compromising sepsis outcome
6 Tackling the challenges
7 Conclusion
References

23. Probiotics: A solution to the prevention of antimicrobial resistance
Chit Laa Poh, Kanwal Khalid, and Hui Xuan Lim

1 Introduction
2 Mechanisms of probiotic action
3 Antimicrobial activity of probiotics
4 Modulation of immune responses
5 Conclusion
References

24. Role of modern drug delivery in antibiotic therapy
Bulu Mohanta, Amit Kumar Nayak, and Amal Kumar Dhara

1 Introduction
2 Nanotechnological approaches for antibiotic delivery
3 Stimuli-responsive antibiotic drug delivery
4 Localized implantable antibiotic drug-delivery
5 Conclusion
References

25. Antibiotic residues in food
Zeuko’o Menkem Elisabeth

1 Introduction
2 Classes of antibiotics used in aquaculture (fish), agriculture (plant), poultry, and livestock (animal)
3 Laboratory testing of antibiotic residues
4 Antibiotic residues in food: Fish, plant, and animal foods
5 Health consequences of antibiotic residues
6 Management of antibiotic residues
7 Conclusion
References

26. Clinical trials, regulatory considerations, and market overview of antibiotics
Samir Bhargava, N.V. Satheesh Madhav, Amal Kumar Dhara, Ashish R. Dwivedi, Neeraj Kumar Sethiya, Devendra Kumar, Manmohan Singhal, Shyamali Thakur, Shraddha Manish Gupta, Kumar Bhavna, Anuj Nautiyal, Abhijeet Ojha, and Vijay Singh Rana

1 Introduction
2 Classification of antibiotics
3 The US regulator (Food and Drug Administration)
4 Different applications submitted at US-FDA
5 Antibacterial susceptibility test interpretive criteria of FDA
6 Role of clinical trials and FDA in antibiotic development
7 Natural product-based antibiotic discovery
8 Market overview of antibiotics
9 Conclusion
References

Index