Lecture 14 - Antimicrobial Resistance Overview

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Questions and Answers

What is the primary mechanism by which bacteria can resist antibiotics through altering their permeability?

Transport of antibiotics outside the cell

Modification or reduced production of porins (correct)

Enzymatic inactivation of antibiotics

Mutational alteration of antibiotic targets

Which criterion classifies antimicrobial classes that treat serious bacterial infections as critically important for human medicine?

The antimicrobial class can treat only nonhuman bacterial infections

The antimicrobial class is frequently used in veterinary medicine

The antimicrobial class is ineffective against resistant bacteria

The antimicrobial class is one of the few alternatives for serious infections in humans (correct)

What does the term 'antibiotic target modification' refer to?

Replacement of the antibiotic with another drug

Transport of the antibiotic outside the cell

Enzymatic inactivation of the antibiotic

Mutational alteration or enzymatic modification of the antibiotic target (correct)

What mechanism does antibiotic efflux represent in terms of antibiotic resistance?

Transport of antibiotics outside the bacterial cell Signup and view all the answers

Which of the following describes the mechanism of resistance termed 'resistance by absence'?

Deletion of a gene, such as for a porin Signup and view all the answers

What classification is given to antimicrobial classes which either meet criterion C1 or C2?

Highly important Signup and view all the answers

What implication does high frequency use of an antimicrobial class have in human medicine according to prioritization criteria?

It may lead to increased selection of antibiotic resistance Signup and view all the answers

In terms of antibiotic resistance, what does 'target protection' mean?

Shielding the antibiotic target from binding Signup and view all the answers

What does it indicate when a microbe has a minimum inhibitory concentration (MIC) that is toxic to humans?

The microbe is deemed resistant to the antibiotic. Signup and view all the answers

Which statement best describes intrinsic resistance in bacteria?

It is natural resistance to certain antibiotics due to inherent characteristics. Signup and view all the answers

What are anti-antibiotics commonly known as in microbial defense mechanisms?

Counter-attack mechanisms. Signup and view all the answers

What is a consequence of high selective pressure on bacteria concerning antibiotic resistance?

Bacteria can acquire resistance genes more rapidly. Signup and view all the answers

Why is it crucial to classify antibiotics?

To determine their effectiveness against resistant bacteria. Signup and view all the answers

What does the term 'clinical resistance' imply about the bacterial infection?

The bacteria remain unaffected by antibiotic treatment. Signup and view all the answers

What does the acronym MIC stand for in the context of antibiotics?

Minimum inhibitory concentration. Signup and view all the answers

What is a key factor influencing clinical outcomes in antibiotic treatment?

Type of bacteria and infection site. Signup and view all the answers

Which statement is true about the antibiotic resistome?

It predicts over 13,000 antibiotic-resistant genes. Signup and view all the answers

Which type of resistance poses the highest risk to public health?

Acquired resistance. Signup and view all the answers

What does the acronym WHO stand for in the context of antibiotic classification?

World Health Organization. Signup and view all the answers

How is antibiotic resistance acquired by bacteria?

Through genetic mutations and gaining resistant genes. Signup and view all the answers

What occurs when the MIC is within a dosage that is non-toxic to humans?

The bacteria are susceptible to the treatment. Signup and view all the answers

What major mechanisms help explain how bacteria resist antibiotics?

Genetic mutations and acquisition of resistant genes. Signup and view all the answers

Study Notes

Antimicrobrial Resistance Overview

Lecture covers different types of antibiotic resistance, origins, major mechanisms, and WHO antibiotic classification.
Students will be able to identify differences between antibiotic resistance types, explain how antibiotic resistance arises, be familiar with major resistance mechanisms, and explain why classifying antibiotics is important.
A microbe is resistant to antibiotics if an achievable concentration of the drug is insufficient to eliminate the bacteria. This is measured by the Minimum Inhibitory Concentration (MIC).

What does it mean for a microbe to be resistant to antibiotics?

MIC is the minimum concentration of an antibiotic required to completely inhibit bacterial growth in a Petri dish.
A microbe is considered resistant when the MIC is above the achievable concentration that's non-toxic to humans.

Clinical Resistance

Antibiotic resistance is relative to the antibiotic concentration that kills bacteria in a Petri dish.
The infection is considered susceptible if the antibiotic concentration sufficient to kill the bacteria is also non-toxic to humans.
The infection is resistant if the MIC of the antibiotic required to treat the bacteria is toxic to humans.

What doesn't kill you makes you stronger

Developing antibiotic resistance doesn't take long.

Selection for antibiotic resistance

Antibiotic resistance develops in several microbial ecosystems.
Clinical ecosystems have high selection pressure, while environmental ecosystems have low pressure.

Antibiotic Resistome exceeds 13,000 genes

ARDB (Antibiotic Resistance Genes Database) contains information on antibiotic resistance genes, including their mode of action, and more.
Bioinformatics analysis suggests over 13,000 antibiotic-resistant genes exist across various bacterial genomes.

Anti-antibiotics are natural defense mechanisms

Humans don't develop antibiotic resistance.
Bacteria naturally develop mechanisms to counteract other microbes, to defend themselves.
High selective pressure drives bacteria to develop resistance, leading to life-threatening infections.

Two major types of resistance

Intrinsic: natural-occurring resistance to antibiotics, like a thick outer membrane in Gram-negative bacteria.
- Bacteria that naturally produce antibiotics have an intrinsic ability to defend themselves.
Acquired: genetic mutations and acquisition of antibiotic resistant genes.

Major mechanism of antibiotic resistance

Directly targeting antibiotic:
Antibiotic inactivation: Enzymtically inactivate the antibiotic.
Targeting antibiotic availability:
Antibiotic efflux: transport antibiotic out of the cell.
Reduced permeability: Reduced production or modification of porins.
Resistance by absence: porin gene deletion.
Target modification: Modification of antibiotic target via mutations or enzymatic changes.
Antibiotic target replacement: Replacing the antibiotic action target.
Antibiotic target protection: Protecting the antibiotic action target from the antibiotic.

WHO antibiotic classification

Criterion 1 (C1): Antimicrobial class is the sole or one of limited therapies for serious bacterial infection.
Criterion 2 (C2): Used to treat infections in people with bacteria that can be transmitted from animals or have acquired resistance from other sources.
Critically important: Antimicrobial classes that meet both C1 and C2.
Highly important: Antimicrobial classes that meet either C1 or C2.
Important: Antimicrobial classes NOT meeting C1 or C2.

WHO antibiotic prioritization

Prioritization Criterion 1 (P1): High proportion of use in patients with serious infections in health settings.
Prioritization Criterion 2 (P2): High frequency of use and may favor selection of resistance.
Prioritization Criterion 3 (P3): Transmission or resistance genes from non-human sources.
Highest priority: Meets all criteria.
High priority: Meets two criteria.

Examples of highest priority, critically important antimicrobials

This slide shows examples of antimicrobial classes (Cephalosporins, Glycopeptides, Macrolides/ketolides, Polymyxins, Quinolones) and indicates whether they meet the criteria with "yes"/"no" for C1, C2, and the prioritization criteria (P1, P2, P3).

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Description

This quiz explores the different types of antibiotic resistance, their origins, and major mechanisms. Students will learn how resistance arises and why antibiotic classification is crucial. Understanding the concept of Minimum Inhibitory Concentration (MIC) is also a focus, detailing how it relates to microbial resistance.