Combination Therapy Against Multidrug Resistance

Mohmmad Younus Wani, Aijaz Ahmad

• Publisher: Academic Press
• Year: 2020
• Print ISBN: 9780128205761
• eBook ISBN: 9780128205785
• Topic: Medicine
• Subtopic: Pharmaceutical, Biotechnology & Healthcare Industry

Combination Therapy against Multidrug Resistance explores the potential of combination therapy as an efficient strategy to combat multi-drug resistance. Multidrug resistance (MDR) occurs when microorganisms such as bacteria, fungi, viruses, and parasites are excessively exposed to antimicrobial drugs such as antibiotics, antifungals, or antivirals, and in response the microorganism undergoes mutations or develops different resistance mechanisms to combat the drug for its survival. MDR is becoming an increasingly serious problem in both developed and developing nations. Bacterial resistance to antibiotics has developed faster than the production of new antibiotics, making bacterial infections increasingly difficult to treat, and the same is true for a variety of other diseases. Combination therapy proves to be a promising strategy as it offers potential benefits such as a broad spectrum of efficacy, greater potency than the drugs used in monotherapy, improved safety and tolerability, and reduction in the number of resistant organisms. This book considers how combination therapy can be applied in multiple situations, including cancer, HIV, tuberculosis, fungal infections, and more. Combination Therapy Against Multidrug Resistance gathers the most relevant information on the prospects of combination therapy as a strategy to combat multridrug resistance and helping to motivate the industrial sector and government agencies to invest more in research and development of this strategy as a weapon to tackle the multidrug resistance problem. It will be useful to academics and researchers involved in the development of new antimicrobial or antiinfective agents and treatment strtategies to combat multidrug resistance. Clinicians and medical nurses working in the field of infection prevention and control (IPC) will also find the book relevant- Explores strategic methods with investigation of both short- and long-term goals to combat multidrug resistance- Presents a broad scope to understand fully the ways to apply combined therapy to multidrug resistance- Provides an overview of combination therapy, but also includes specific cases such as cancer, tuberculosis, HIV and malaria

Chapter 1

Combination therapy: Current status and future perspectives

Manzoor Ahmad Malik^a; Mohmmad Younus Wani^b; Athar Adil Hashmi^{a a} Bioinorganic Lab., Department of Chemistry, Jamia Millia Islamia (Central University), New Delhi, India
^b Department of Chemistry, College of Science, University of Jeddah, Jeddah, Saudi Arabia

Abstract

A one-size-fits-all approach to treating diseases of current concern seems increasingly ineffective, more difficult, and unrealistic. Due largely to resistant strains of disease-causing pathogens and genetic differences in patients, modern medicine is beginning to change its approach. This shift is seen in the attention being paid toward personalized medicine, attempts at fewer side effects, broad spectrum activity, and ongoing research into gene therapy and immunotherapy. One method gaining attention is the use of combination drugs or combination therapy, sometimes referred to as polytherapy, which is a broad term for the use of multiple medications or therapies to fight the same condition. While it typically denotes the use of two or more drugs, it can also include immunotherapy, nonmedical therapies, including psychological therapy, and other means of therapy or treatment. The practice may not be new, but there has been a large increase in the number of approved and researched combination therapies over the past decade. The one drug-one target or magic bullet model has limited viability, and combination therapy is now the norm in the treatment of many cancers, viral infections such as HIV, and tuberculosis treatment. Overall, current data support that combination therapy with two or more drugs appears to be more effective than monotherapy to combat the multidrug resistance problem.

Keywords

Combination therapy; Drugs; Multidrug resistance; Synergy

Abbreviations

AIDS acquired immunodeficiency syndrome

AMP antimicrobial peptides

ART antiretroviral therapy

ARVs antiretroviral drugs

CDC Centers for Disease Control

DNA deoxyribose nucleic acid

FDA Food and Drug Administration

FDC fixed dose combination

HIV human immunodeficiency virus

MBL metallo-beta-lactamase

MDR multidrug resistance

MRSA methicillin-resistant Staphylococcus aureus

WHO World Health Organization

1.1 Introduction

Our bodies are equipped with natural (specific and nonspecific) defense mechanisms to fight off invading microbes or unwanted changes that may cause disease. An infection or a disease occurs when the body’s defense system gives up or loses the battle and that is when drugs come to our rescue. Possibly the earliest written accounts of medical therapeutics used by humans are found in the famous Ebers papyrus, which is an almost 20-m long, 110-page medical scroll named after the German Egyptologist Georg Ebers, who acquired it in 1872. Hundreds of treatment options are described in the Ebers papyrus for diseases afflicting ancient Egyptians in ∼ 1500 BC, and these treatments involved mixing various herbs, leaves, shrubs, minerals, and animal excreta—forming a combination (Jones, 2011).

The isolation and characterization of the active principles in medicinal plants signified a major challenge, which was later met by the development of synthetic drugs. Today we have 10,000 + ever-more targeted and increasingly powerful high-tech medicines that can treat and often cure conditions that have confounded healers for thousands of years. These drugs, particularly antibiotics, have moved us from being helpless victims of epidemics to being able to fight off potentially deadly diseases. However, sadly enough, with these new medicines has come an increase in the misuse, overuse, and abuse of some of them, which has led to the emergence of multidrug resistance (MDR), a global problem of great concern.

The upsurge in microbial resistance has become a significant threat worldwide. Development of resistance to the available drug candidates has resulted in considerable patient mortality and morbidity (Tamma, Cosgrove, & Maragakis, 2012). Although researchers are involved in the development of new drug candidates for combating the serious problems created by rising multidrug resistance (MDR), the situation appears to be far more complex. During the past two decades, only two new classes of antibiotics have been introduced into clinical use, but none of them is assuredly active against gram-negative bacteria. Daptomycin, which was offered clinically in 2003, lost ground a year later due to the development of resistance in patients with Enterococcus faecium and MRSA infections (Worthington & Melander, 2013). Multidrug resistance against other life-threatening diseases such as malaria, tuberculosis, cancer, and viral diseases such as HIV/AIDS is already ringing alarm bells; it is feared that we may lose the battle if new treatment modalities or strategies are not discovered. Among the various strategies that could augment the current treatment regimen and add to the armament against multidrug resistance is combination therapy. It is imperative to examine the influence of drugs beyond what they can accomplish alone. A combination of drug candidates can act as a multiplier and thereby increase the sum of their benefits.

Drug combinations have been discussed for the treatment of diagnosed conditions for some time, such as aspolol (a combination of atenolol and aspirin) for patients diagnosed with cardiovascular disease. For preventive use, Wald and Law proposed the use of a combination of well-known and inexpensive medications in one pill (called a polypill) for defense against cardiovascular disease (Wald & Law, 2003). Based on the emerging and ongoing clinical studies and research outcomes it is now clear that the use of drug combinations is an effective approach for the treatment of complicated and refractory diseases. The Drug Combination Database (DCDB) has a collection of 1363 drug combinations (330 approved and 1033 investigational, including 237 unsuccessful usag...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1: Combination therapy: Current status and future perspectives
• Chapter 2: Combination therapy against multidrug resistance
• Chapter 3: Multidrug resistance and the prospects of combination therapy
• Chapter 4: Combination therapy against human infections caused by Candida species
• Chapter 5: Metallodrug-driven combination chemotherapy in cancer treatment
• Chapter 6: Combination antituberculosis therapy: Opportunities and challenges to combat drug-resistant tuberculosis
• Chapter 7: Synergistic effect of drugs against multiple drug-resistant swine pathogen Streptococcus suis
• Chapter 8: Combination therapy and multidrug resistance in malaria parasite
• Chapter 9: Combination therapy as an effective tool for treatment of drug-resistant viral infections
• Chapter 10: Combination therapy against human infections caused by viruses
• Chapter 11: Phenotype screenings of drugs for combination therapy against multidrug resistance
• Chapter 12: New approaches for targeting drug resistance through drug combination
• Index