Antimicrobial Resistance

define antimicrobial resistance:

occurs when microorganisms no longer respond to antimicrobial medicines

benefits of antibiotics:

kill harmful bacteria that make you sick, many infections that could not be treated before can now be treated, minimize the infection risk of modern medicine

risks of antibiotics

they kill good bacteria that keeps you healthy, side effects such as dysbiosis, giving antibiotics to infants and children can create a higher risk of chronic disease as an adult, antibiotics have an impact not just for the person taking them but also the broader community because of antibiotic resistance

define narrow-spectrum antibiotics

more targeted, can only kill a few types of bacteria, less likely to contribute to resistance and are preferred when the pathogen is identified

define broad-spectrum antibiotics:

can kill many different types of bacteria, useful when the causative agent is unknown but may promote resistance and disrupt normal flora

how do gram-positive bacteria differ from gram negative

they have a single membrane and thick cell wall, compared to double cell membrane and thin cell wall (-)

what are acid-fast positive bacteria?

have thick, waxy cell envelope, highly impermeable, intrinsic resistance to many antibiotics (mycobacterium spp.)

mechanisms of resistance:

modification of drug target, modification of drug, reduced influx of drug into the cell, increased efflux of drug out of the cell

how do bacteria become resistant?

natural or intrinsic resistance, random mutations, acquired resistance

define natural or intrinsic resistance:

innate ability of a bacterial species to resist activity of a particular antimicrobial agent through its inherent structural or functional characteristics

T/F: it has been estimated that one in every 10⁶ - 10⁹ bacteria will develop resistance under antibiotic pressure

true

define acquired resistance

bacteria can acquire resistance genes from other bacteria (most common in gram negative)

how does antimicrobial resistance spread

vertical gene transfer or horizontal gene transfer

what is vertical gene transfer

occurs during reproduction, between generations of cells

what is horizontal gene transfer

transfer of genes between cells of the same generation

define difficult-to-treat resistance (DTR) for gram negative pathogens

resistance to all first-line agents; that is, all beta lactams, including carbapenems and beta-lactamase inhibitor combinations, and fluoroquinolones

how can antimicrobial resistance be detected?

phenotypic detection (growth-based assays), hydrolysis method, genotypic testing (targeted, next generation sequencing, and lateral flow immunoassays).

examples of growth-based assays

Disk diffusion (Kirby-Bauer Test), broth or aga dilution, automated systems, E-test (gradient diffusion)

what are hydrolysis methods?

detect antibiotic degradation products

examples of targeted genotypic testing

PCR, microassay

examples of next generation sequencing

whole-genome sequencng, metagenomics

examples of lateral flow immunoassays

detect resistance enzymes through the use of specific antibodies

define resistance:

bacteria grown in the presence of antibiotics —→ increased MIC

define tolerance:

bacteria survive transient exposure to lethal concentrations of antibiotics but do not grow —→ MIC no change (prolonged minimum duration for killing, slow growth or dormancy)

define persistence:

a subpopulation of cells become tolerant —→ MIC no change

pros of phage therapy

phages are natural and easy to find, against both susceptible and antibiotic-resistant bacteria, used alone or with antibiotics and other drugs, only one dose may be enough, minimal disruption of normal flora, they are not (less) harmful to the body

cons of phage therapy:

formulation and stabilization of pharmaceutical preparations, different PKPD than antibiotics, personalize use, trigger the immune system to overreact or cause an imbalance, narrow spectrum of activity, possible emergence of phage resistance.