What Is Multidrug Resistance (MDR)?

Multidrug resistance is an increasingly common term you might hear and wonder what is behind it.

Multidrug resistance should be handled with utmost care and in a proper way. Multidrug resistance (MDR) is the process in which microorganisms become resistant to specific antibiotics.  The class of drugs included in this multiple drug resistance are: 

• Antibiotics
• Antifungals
• Antiparasitic
• Antivirals

What is the significance of investigating MDR in a variety of fields?

Multidrug resistance is of high consideration in public health as well as in the fields of 

• Microbiology
• Pharmacology
• Medicine

Multiple drug resistance that is linked with antimicrobial drugs is one of the supreme risks for universal public health. Furthermore, this threat has created complications in treating patients but can also result in fatalities. Nanoparticle delivery of drugs is encouraged to overcome this resistance to drugs.¹    

This multiple drug resistance is also seen in cancer patients due to their physiological functions, efflux pump drugs, gram-negative bacteria, and nanotechnology is gaining increased interest in cancer treatment.¹ 

Do you know the cause of multidrug resistance (MDR)?

Multidrug resistance is an extensively challenging healthcare risk that is being faced globally, and the disease that has been impacted most is tuberculosis. 

In order to control multidrug-resistant tuberculosis (MDR-TB), various perspectives and approaches are continuously conducted to eradicate this resistance. MDR-TR are resistant to

second-line drugs such as fluoroquinolones.²

The main reason for this resistance is:²

• Poor healthcare structure
• Design of resistance buildup due to wrong treatment
• Passing of resistance in public and establishments

Other causes of this MDR-TB are:³

• Earlier diagnosed cases of tuberculosis
• Already treated with Anti-Tb drugs

What mechanism is involved in MDR?

Every drug goes through some mechanism phase, and MDR is involved in the process of

Limiting antibiotic access

When there is gene mutation inside the cell, then that process also causes encryption of the outer protein membrane that leads to less penetration for antibiotics such as Klebsiella pneumoniae.

As the main protein is suppressed and the cell membrane is filled with another protein medium the membrane permeability for some antibiotics such as Escherichia coli and Acinetobacter are decreased.⁴

The addition of an efflux pump of several genes is related to plasmid and genomic 

When there is powerful pumping of efflux cells inside, the number of antimicrobials decreases. This upregulation creates resistance to previous antibiotics that are functional, such as Pseudomonas aeruginosa and Escherichia coli.⁴

Self-control and protection of objective antibiotics

If the positioning of the mark is altered, antibiotics' irrevocable affection can be decreased. Resistant to linezolid is found in staphylococcus aureus and Klebsiella pneumoniae.  Mutation of this kind can be found in recessive genes that are alleles.⁴

Hydrolytic enzymes in antibiotics antagonism

Antibiotics genetic enzymes degenerate as resistance attained by plasmid and chromosomal decoding e.g. beta-lactamase is an enzyme used to break down the entire beta-lactam, but this whole beta-lactamase is restricted by carbapenem and carbapenemase.⁴ 

Balanced antibiotic resistance

Antibiotics with other active groups inactive the gene enzyme detection such as resistance of aminoglycosides in Campylobacter coli. ⁴

What impact is generated in MDR?

Multidrug resistance (MDR) has greatly influenced the clinical results and economic pattern of health-related disease in adults. These outcomes yield to:⁵ 

• High costs of hospitals
• The period of stay is increased.
• Discharge mortality

The rate of transmission is impacted by the comparison of resistance and sensitivity in three forms:⁶

• Resistant strain transmission is enhanced in the host. 
• Either sensitivity strain is favoured or sensitivity-resistant strain is recommended.
• The three forms rely on the balance of the total frequency of transmission.

Moreover, MDR gives rise to hindrance in the control of infection by:⁷

• Aggravating resistant pathogens dissemination 
• Treatment efficacy reduced
• Prolonged infection in a patient

Public cleanliness is also another factor in the control of multiple drug resistance. Similarly, travel and commerce have elevated potential in the spread of resistance, thus affecting the economic condition of the country. 

What is the significance of MDR?

It is known that multidrug resistance disease causes remarkable hazards to healthcare as these pathogens result in increased morbidity, cost and mortality. The best possible passage way forward is to  manage the expansion of Multiple drug-resistant diseases by carrying out the evolution of novel techniques to refine the MDR.⁸

What kind of strategies can be adapted to improve MDR?

Novel planning in controlling the MDR should be emphasised and new antimicrobial drugs should be introduced against the resistant bacteria. An analytical approach is required to make use of:

• Antiinfective peptides
• Compounds with anti-virulent activities
• Bacteriophage therapy
• New types of drugs

The class of drugs like: 

• Anti-psychotics
• Anti-parasitic
• Anti-neoplastic
• Anti-inflammatory 
• Statins

should be reprocessed to control the MDR. 

The World Health Organization has declared MDR a public global health threat. The bacteria can avoid the antiinfective action of the antimicrobials by following three ways:

• Resistance
• Persistence 
• Tolerance

In all these circumstances and mechanisms, bacterial persistence, resistance and tolerance are seen to combat the infection pathogens residing in the host.⁹

MDR in cancer also plays a significant part in minimising the resistance against chemotherapy drugs. It is best to stop the MDR in cancer at its onset, whether it has fully developed or in its latent phase because MDR in its mature period will be difficult to control and prevent. Hence, novel inhibitors of small molecules are used to prevent this MDR. This treatment helps in prolonging the efficacy and efficiency of the anti-cancer treatment, and more healthy and productive results will come by using these new treatment plans.¹⁰

How to overcome MDR with different approaches? 

Many new approaches are being designed to fight against the disease and other infections. Substitute methods intended to defeat MDR are listed below. 

Different target concentrations

This involves the elimination of productive biofilms of bacteria, which help them or act as a shield to decrease antiproliferative action. Drug discovery or novel techniques and applications of current therapeutic drugs should be natural. 

Active reflux in reducing the entry of target structure

Plasmids help in the chromosomal coding in the transmission from one bacteria to another.¹¹  Furthermore, increased pressure, more antibiotic use, and a growing population are also crucial objectives for the healthcare industry. Unusual and insufficient antibiotics are major factors in drug resistance. To manufacture new antibiotics to overcome the resistance factor, there are other approaches that can help to restrict the danger of MDR:¹²

• Immunomodulation
• Phage therapy
• Host associated therapy 
• Antibodies 

Nanomedicine also gives a structured objective for drug delivery to defeat the control of standard chemotherapy and its effectiveness. This can be achieved by refining the pharmacokinetics and bioavailability of drug delivery, enhancing the multifunctional nanoparticles. The core purpose of this technique is to fight against:¹³

• Cancer diversity
• Mechanism of drug efflux
• Restore DNA 
• Deal with multidrug resistance

How can research and future directions help in controlling MDR?

MDR is a global public health threat that has to be controlled and prevented in the near future.  It has already caused harm, and it will continue to do so if not handled and stopped.  Some possible methods to achieve this are listed below.

Knowing the MDR evolutionary dynamics

Linkage disequilibrium can help us out in solving the calculations by giving a framework for the importance of population formation. An epidemiological template to generate the dynamics of the population levels to see

MDR symmetry model

• Analytical structure for evolution dynamics
• Outcomes of the prescription of drugs for MDR¹⁴

Personalised drug attitude to evade MDR

One of the most common link to avoid MDR is phage therapy, as it shows great adaptability towards the disease of specific groups. They kill the bacteria and isolate themselves. In fact, they do not completely eliminate their host species, which is therapeutically beneficial in treating infections.¹⁵

As in the case of tuberculosis, the occurrence of Mycobacterium tuberculosis drug resistance is expanding tuberculosis all around the globe. Due to prolonged diagnosis, large span of treatment and many adverse events all yield to poor prediction of its cure.¹⁶ Thus, countries face a high burden on MDR-TB due to less resource allocation and bad budgeting in their healthcare. 

Summary

Multidrug resistance (MDR) is a pivotal threat in the pharmacology, medicine and microbiology fields.  Multiple drug resistance starts from efflux pumps, genetic factors, modification of drug targets and inactivation mechanisms of drugs.  Its effects constitute mortality, morbidity, drug manufacturing obstacles and elevated healthcare prices.  Multidrug resistance (MDR) is found in cancer patients and bacterial infections (MSRA).  MDR can be controlled by drug alterations, targeting efflux pumps and mixed therapies.  Its future aspect must rely on personalised medicine, novel technologies and evolution.  Partnership programs must be carried out globally to fight against this Multiple drug resistance effectively and positively.  The teamwork of doctors, researchers and pharmaceutical industries is necessary for the successful management of MDR.  Eventually, the combat against MDR is a joint duty that acts as good health for the people and the public as a whole.