Multiple Drug Resistance (MDR) Microorganisms: Introduction, Definition, Types, Resistance Mechanism and Prevention
Multiple Drug Resistance (MDR) Introduction
Multiple drug resistance (MDR) bacteria as shown above picture. MDR or multi-resistance is antimicrobial resistance shown by a species of microorganism as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms ( e.g. ). The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; besides bacteria, other organisms include MDR viruses, fungi, and parasites (resistant to multiple antiviral, antifungal, and antiparasitic drugs of a wide chemical variety).
Lomentospora prolificans infections are almost uniformly fatal because of their resistance to multiple antifungal agents.
Drug Resistance Types
There are three types of drug resistance in bacteria and they are-
XDR (extensively drug-resistant) and
PDR (pan drug-resistant)
MDR (multidrug-resistant): MDR is defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories as shown in the video.
XDR (extensively drug-resistant): XDR is defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories)
PDR (pan drug-resistant): PDR is defined as non-susceptibility to all agents in all antimicrobial categories as shown in this video.
Note: There are so many different definitions for multidrug-resistant (MDR) even though this definition is based on the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC). Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from their collaborative partners, Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the United States Food and Drug Administration (FDA).
Biochemical Mechanisms of Drug Resistance
Multidrug resistance in bacteria occurs by the accumulation, on-resistance (R) plasmids or transposons, of genes, with each coding for resistance to a specific agent, and/or by the action of multidrug efflux pumps, each of which can pump out more than one drug type and described as follows-
Mutational Alteration of the Target Protein
Enzymatic Inactivation of the Drug
Acquisition of Genes for Less Susceptible Target Proteins from Other Species
Bypassing of the Target
Preventing Drug Access to Targets
Source of the Resistance Genes
Microorganisms in the environment, especially Soil
Assembly, Maintenance, and Transfer of Resistance Genes
Assembly of Resistance Genes in R Plasmids
Maintenance of R Plasmids in the Host Cells
Cell-to-Cell Transfer of R Plasmids
Multidrug Efflux Pumps
Multidrug Efflux Pumps Belonging to the Major Facilitator Superfamily
Multidrug Efflux Pumps of the Small Multidrug Resistance Family
Multidrug Efflux Pumps of Resistance-Nodulation-Division Family
Multidrug Efflux Pumps of the ATP-Binding Cassette Superfamily
Multidrug Resistance caused by the Altered Physiological States
Prevention of antimicrobial resistance emergence
The following steps are crucial to limit the development of antimicrobial resistance and they are-
Use of the appropriate antimicrobial drug for the treatment of an infection. E.g. antibiotics for viral infections
Identify the causative agent of an infectious disease whenever it is possible.
Ignore the habit of relying on broad-spectrum antimicrobial agents and thus use a selective antimicrobial that targets the specific organism.
Complete an appropriate duration of antimicrobial treatment i.e. not too short and not too long.
Use the correct dose for eradication; subtherapeutic dosing is associated with resistance.
Clinicians/ prescribers should follow Antimicrobial stewardship.
Involve the public in World Antimicrobial Awareness Week (WAAW) conducted by WHO.
Multidrug resistance in bacteria may be generated by one of two mechanisms. First, these bacteria may accumulate multiple genes, each coding for resistance to a single drug, within a single cell. This accumulation occurs typically on-resistance (R) plasmids. Second, multidrug resistance may also occur by the increased expression of genes that code for multidrug efflux pumps, extruding a wide range of drugs.
Antibiotics are manufactured at an estimated scale of about 100,000 tons annually worldwide, and their use had a profound impact on the life of bacteria on earth. More strains of pathogens have become antibiotic-resistant, and some have become resistant to many antibiotics and chemotherapeutic agents, the phenomenon of multidrug resistance.
A notorious case is the methicillin-resistant Staphylococcus aureus (MRSA), which is resistant not only to methicillin (which was developed to fight against penicillinase-producing S. aureus) but usually also to aminoglycosides, macrolides, tetracycline, chloramphenicol, and lincosamides. Such strains are also resistant to disinfectants, and MRSA can act as a major source of hospital-acquired infections. An old antibiotic, vancomycin, was resurrected for the treatment of MRSA infections. However, transferable resistance to vancomycin is now quite common in Enterococcus and found its way finally to MRSA in 2002, although such strains are still rare
Research had time to react against the threat of MRSA. Thus, there are newly developed agents that are active against vancomycin-resistant MRSA, such as linezolid and quinupristin/dalfopristin. However, the emergence of “pan-resistant” gram-negative strains, notably those belonging to Pseudomonas aeruginosa and Acinetobacter baumanii, occurred more recently, after most major pharmaceutical companies stopped the development of new antibacterial agents. Hence, there are almost no agents that could be used against these strains, in which an outer membrane barrier of low permeability and an array of efficient multidrug efflux pumps are combined with multitudes of specific resistance mechanisms.
The estimate is that by 2050, there will be no effective antibiotic available if no new drug is developed or discovered.
Phage therapy will be the alternative choice to address the shortcomings of antibiotics in the future and research is still going. It is also called bacteriophage therapy. In this therapy, viruses are used to treat bacterial infections. As you know, bacterial viruses are called phages or bacteriophages. They only attack bacteria; phages are harmless to us.