10.1 Antimicrobial Resistance

Antimicrobial resistance is the ability of a microorganism to survive and multiply in the presence of an antimicrobial agent (that would otherwise kill or inhibit the growth of this microorganism). This is a distinguishing trait that allows microbes to out-compete their competitors.

Many different types of antimicrobial resistances have also been reported.

10.1.1 Key antimicrobial resistance events

Figure 10.4: Key Events in the History of Antimicrobial Resistance

Prior to 1943, the antibiotic penicillin wasn’t used very much.

Note that the data in the above figure is based on early reports of antimicrobial resistance in scientific literature.

In the case of Pan Drug-Resistant (i.e., PDR) Acinetobacter and Pseudomonas, the year is based on reports of healthcare transmissions or outbreaks.

10.1.1.1 Intrinsic resistance

Intrinsic resistance is the innate ability of a microbe to resist an antimicrobial substance because of its functional or structural characteristics - for instance:

1. Its lack of affinity to a particular antimicrobial
2. Lack of accessibility for the antimicrobial
3. Expulsion of the antimicrobial via effective pump systems
4. Production of enzymes that inhibit the antimicrobial

Several examples of intrinsic resistance include:

1. Gram-positive bacterium lack Penicilin-Binding Proteins (i.e., PBPs) that aztreonam - a \(\beta\)-lactam antibiotic - requires to bind to a bacterium.
2. Gram-negative bacterium cannot uptake vancomycin because of its outer membrane.
3. Anaerobic bacteria cannot metabolize aminoglycosides and hence, are resistant to that particular class of antibiotics.
4. Aerobic bacteria cannot metabolize metronidazole to its active form.

10.1.2 Strategies in acquiring antimicrobial resistance

This section outlines several methods that bacteria can use to gain antibiotic resistance against one or more classes of antimicrobials:

1. Selection

   

   Figure 10.5: Strategies for Acquiring Antimicrobial Resistance

   This graphic effectively sums up this point. Due to selection pressure exerted upon the bacteria’s population via antibiotics, antibiotic-resistant bacteria are favored and hence, live to create the next generation (hence propagating the antibiotic resistance).

2. Horizontal gene transfer

   

   Figure 10.6: Modes of Horizontal Gene Transfer

   There are one of three ways that this can occur:

   1. Transformation

      Bacteria uptake DNA that code for antibiotic-resistance proteins.

   2. Transduction

      Bacteriophages transfer bacterial DNA from bacterium to bacterium.

   3. Conjugation

      Bacterial cells share DNA via pili

10.1.2.1 Mechanistic basic

Figure 10.7: Bacterial Methods of Countering the Effects of Antimicrobials

There are also one of several ways in which antimicrobials fail to exhibit their intended effect(s) on the bacterium:

1. Efflux pumps

   Efflux pumps can pump the antimicrobial substance out of the cell.

2. Modification of the antimicrobial

   Chemical alterations of an antimicrobial and destruction of the antimicrobial can prevent the drug from exhibiting its effects.

3. Modification of targets

   If an antimicrobial is intended to work on a specific protein or a process, then it is possible that the bacterium could be able to alter the target proteins of the drug.