Chapter 1:Introduction to the resistance problem

Pop quiz

1.) What is the difference between a protein and a gene

2.) What does MRSA stand for?

3.) List three different types of pathogens.

4.) In addition to antibiotics, what is another way to combat pathogen infections?

5.) What is the different between narrow- and broad-spectrum antibiotics?

Homework

ReadingsWednesday, 1/29/14: Chapter 2Monday, 2/3/14: Chapters 3-4

Wednesday, 2/5/14Topic summary #1 is due, which is on the Frontline documentaryRead A Brief History of the Antibiotic Era, which we will be discussing in class(Freely available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109405/)

Monday, 2/17/14Topic summary #2 is due, which is on A Brief History of the Antibiotic Era

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Syllabus updates:I haven’t been taking attendance (obviously)There will only be one oral presentationUpdated grade percentages: participation = 10%, written summaries = 25%, oral presentation = 10% (others are unchanged).

b-lactam antibiotics

penicillin methicillin

From Wikipedia: The β-lactam ring is part of the core structure of several antibiotic families, including penicillins, cephalosporins, carbapenems, and monobactams, which are, therefore, also called β-lactam antibiotics. Nearly all of these antibiotics work by inhibiting bacterial cell wall biosynthesis. This has a lethal effect on bacteria. Bacteria do, however, contain within their populations, in smaller quantities, bacteria that are resistant against β-lactam antibiotics. b-lactam ring

Methicillin-resistant Staphylococcus aureus (MRSA)

1959: Methicillin was introduced1960: Resistance was observed in the United States

Spread through hospitals, making surgical procedures and long-term catheter use more dangerous.

Can lead to pneumonia (infection of the lungs), commonly following the flu.

Very prevalent in skin infections introduced via abrasions.

CA-MRSA = Community-associated MRSA (vs. HA-, which stands for hospital-associated).

From 1999 to 2006, MRSA infections increased ~90%, nearly all from CA-MRSA.

MRSA infection

S. aureus bacteria

Hospital sanitation

MRSA in hospitals is largely an infection-control problem.

Netherlands have aggressive approach: screening, isolation of positive cases, cleaning of entire hospital wards, and paid leave for healthcare works that have become carriers.

Cost is expected to be half of what it cost to treat bloodstream infections.

In the US, however, just part of the cost of doing business (until recently).

Pittsburg hospital adopted Dutch model and saved an estimated $1M/yr.

Pathogens

From Wikipedia: A pathogen in the oldest and broadest sense is anything that can produce disease.

Typically the term is used to mean an infectious agent (colloquially known as a germ) - a microorganism, in the widest sense such as a virus, bacterium, prion, or fungus, that causes disease in its host.

The host may be an animal, a plant, a fungi or even another microorganism. Some of the diseases that a pathogen can cause are smallpox, influenza, mumps, measles, chickenpox, ebola and rubella.

Typically a distinction is made between pathogens and parasites (i.e., protozoa) due to their larger size, but no distinction is made here because antibiotics are used to treat both.

Protozoa

Bacteria vs. viruses vs. fungi

Prokaryotic Eukaryotic

Bacteria vs. viruses vs. fungi

Means of transmission

Antibiotics are ‘small molecules’ that disrupt specific lifecycles of the infection

Intravenous (IV) antibiotics are antibiotic medications designed to be delivered directly into the bloodstream.

Delivering antibiotics intravenously means that the drugs act quickly, which can be critical in an emergency situation.

When drugs are introduced directly into the bloodstream, they will travel rapidly to the site of an infection and immediately begin working.

By contrast, drugs taken by mouth must be absorbed through the gut before they can start attacking an infection.

For people with severe infections, intravenous antibiotics may be used because they will take effect quickly.

Semantics

Antibiotics = antibacterial vs. antifungal vs. antiviral

Each are distinct class with little cross-reactivity.

The viral lifecycle

Tamiflu works by disrupting the viral lifecycle

Broad vs. narrow spectrum antibiotics

From Wikipedia: The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-causing bacteria, which acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of bacteria.

Broad spectrum antibiotics can change the body's normal microbial content by attacking indiscriminately both the pathological and naturally occurring, beneficial or harmless bacteria found in the intestines, lungs and bladder.

Uses: • For drug resistant bacteria• Superinfections (multiple pathogens)• After operation to prevent infections

from occurring

Thoughts on antibiotic resistance

• Pathogens differ in their susceptibility to antibiotics, and thus each species must be considered individually.

• Resistance to one antibiotic may not affect susceptibility to another, meaning antibiotics should also be considered individually.

• Dose is a compromise between effectiveness and toxicity, so the definition of resistance should consider treatment regimen.

• Because pathogens are communicable, treatments just good enough to eliminate symptoms is inadequate because the small number of remaining pathogens are more likely to be antibiotic resistant (even though they aren’t a major concern to the host at that point in time due to low abundance).

Antibiotic resistance is widespread

Antibiotic resistance can increase rapidly

Antibiotic resistance is divided into three types

1.) Acquired resistance is based on selection of more resistant pathogens – either through mutation or horizontal gene transfer (via plasmids) – during the course of treatment.

2.) Disseminated resistance already exists before treatment starts.

3.) Intrinsically resistant bacteria are pathogen species that are unaffected by particular antibiotics. Typically require vaccines and good infection control practices to combat. Viruses typically fall into this category.

The importance of treatment regimens

Before selection 1

After selection 1

Final population 1

Final population 2

After selection 2

Before selection 2

Before selection 3

After selection 3

Final population 3

Acquired resistance

Acquired resistance

Vaccines block disease

The immune response is very complicated

Brief overview of the immune response Antibody protein

Vaccines are based on my different targets

Vaccines save lives!

Fears fueled the resurgence of preventable diseases

http://www.npr.org/blogs/health/2014/01/25/265750719/how-vaccine-fears-fueled-the-resurgence-of-preventable-diseases