Module 16: Antibiotics

Question 1

T/F

Bacteria are single celled organisms that can be shaped as rods, spheres, or spirals.

Answer 1

True

Question 2

Are most bacteria rendered harmless? If so, how?

Answer 2

Most bacteria are rendered harmless by our immune system and some even play beneficial roles

Question 3

What bacteria cause disease?

Answer 3

Pathogenic

Question 4

What are the 4 virulence factors of bacterial pathogenicity?

Answer 4

o Fimbriae and pilli
o Flagella
o Secretion of toxins and enzymes
o Invasion

Question 5

What are fimbriae and pili?

• What do they allow?
• Example

Answer 5

Fimbriae and pilli are hair like structures that project from the surface of bacterial cells.
- They allow bacteria to attach to certain sites in our body so they are not washed away.

For example, the bacteria E. coli are known to cause bladder infections
- E. coli produce fimbriae that attach to the urogenital tract.

Question 6

Describe bacterial flagella:

Answer 6

The flagellum that bacteria possess allows them to “swim” through the watery environment of our body to the site where they may survive

Question 7

What is the function of bacteria secreting toxins or enzymes?

Answer 7

Secreted toxins can have a wide array of effects including nausea, vomiting, diarrhea, cramps, pain, fever, or even paralysis

In addition to toxins, bacteria also release enzymes. Some of these enzymes can degrade tissue or breakdown antibodies, our defense against infection

Question 8

What is bacterial invasion?

- Example

Answer 8

When bacteria enters the cell

For example, the bacteria that cause Salmonella invade cells of the intestine and cause severe diarrhea.
- Bacteria that cause tuberculosis usually enter our body in the lungs and can “hide” inside cells making it impossible for our immune system to act on them

Question 9

What is gram staining?

- Why is it important?

Answer 9

Gram staining is a technique that is used to classify bacteria as either gram positive or gram negative.
- The gram stain tells us about the cell wall structure of bacteria, in particular the amount of peptidoglycan; This can be important in the determination of which antibiotic we use

Question 10

Describe the difference btw gram-positive vs. gram-negative:

Answer 10

Gram positive cells have a thick peptidoglycan wall that stains purple during gram staining

• no outer membrane
• techoic acids
• no LPSs
• No porins

Gram negative cells have a thin peptidoglycan layer and stain pink during gram staining

• outer membrane
• no techoic acids
• LPSs
• Porins

Question 11

What are typical signs of infection (4)?

- Other signs?

Answer 11

Fever, overall malaise, local redness, and swelling

- Increased respiratory rate and tachycardia

Question 12

Infection:

- Why may Its show no sign of fever?

Answer 12

In some cases patients may not have a fever despite having an infection

• For example, newborn babies may have an immature hypothalamus or the elderly may have decreased hypothalamic function
• The hypothalamus is important in regulating body temperature.

Question 13

What is selective toxicity and why is it important?

Answer 13

Selective toxicity means the therapy is able to destroy the bacteria without harming the host (i.e. human cells
- The treatment of a bacterial infection is critically dependent on the ability to produce selective toxicity

Question 14

How is selective toxicity produced?

Answer 14

Selective toxicity is produced by targeting differences between the cellular chemistry of bacteria and humans

Question 15

Antibiotic therapy produces selective toxicity by (3):

Answer 15

1) Disrupting the bacterial cell wall (human cells do not have a cell wall).
2) Targeting enzymes that are unique to bacteria.
3) Disrupting bacterial protein synthesis (bacterial and human ribosomes are different).

Question 16

Several questions must be considered when selecting an antibiotic including (4):

Answer 16

1. Has the infectious bacteria been identified?
2. Bacterial sensitivity to the antibiotic?
3. Can the antibiotic access the site of infection?
4. Is the patient able to battle the infection?

Question 17

Selecting antibiotic: Identification of the Bacteria

• When is it identified?
• What tests provides info on structural features?
• What properly identifies it?

Answer 17

• Ideally, bacteria are identified prior to selection of the treatment.
• The gram stain is a rapid test that provides information on the structural features of the bacteria.
• In general, culturing the bacteria to properly identify it will provide the best basis for selection of the therapy

Question 18

Selecting antibiotic: Bacterial Sensitivity to Antibiotic

• Bacteriostatic
• Bactericidal

Answer 18

Bacteriostatic: Stops the growth and replication of bacteria and in doing so, stops the spread of infection.
- The body’s immune system can then attack and remove the bacteria.

Bactericidal: Drugs kill the bacteria
- Microbiologists can culture bacteria and determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of antibiotic drugs.

Question 19

Selecting antibiotic: Penetration to the Site of Action

• What do they require?
• Examples (5)

Answer 19

Some infections are difficult for antibiotics to penetrate.
- These infections require careful selection of antibiotics that are able to penetrate to the site of action

Examples:
o Meningitis
o Urinary Tract Infections
o Osteomyelitis
o Abscesses 
o Otitis Media

Question 20

Infections difficult for antibiotics to penetrate: Meningitis

• What is it?
• What type of antibiotic needed?

Answer 20

Is an infection of the meninges, which are the membranes that cover the brain and spinal cord
- Effective treatment requires an antibiotic that penetrates the meninges and effectively eradicates the bacteria

Question 21

Infections difficult for antibiotics to penetrate: UTIs

• What is it?
• Common type?
• What type of antibiotic treatment is needed?

Answer 21

Urinary tract infections occur when bacteria enter any part of the urinary system.

• The most common type is an infection of the bladder, which may be caused during catheterization.
• Effective treatment of UTIs requires an antibiotic that enters the urinary system

Question 22

Infections difficult for antibiotics to penetrate: Osteomyelitis

• What is it?
• Why are treatments limited?
• Duration of treatment?

Answer 22

Osteomyelitis is an infection of the bone.

• Very few antibiotics are able to enter the bone, making treatment options limited.
• Treatment of osteomyelitis usually requires antibiotics for 4 – 6 weeks

Question 23

Infections difficult for antibiotics to penetrate: Abscesses

• Why do they occur?
• Why are they difficult to treat?

Answer 23

Skin abscesses occur when pus or other infected material collect under the skin.
- Abscesses are difficult to treat with antibiotics because they are poorly perfused with blood

Question 24

Infections difficult for antibiotics to penetrate: Otitis Media

• What is it?
• More common in?
• Why is treatment difficult?

Answer 24

Otitis media is an infection of the middle ear and more commonly referred to as an ear infection.

• Anybody can get an ear infection, but they are much more common in children.
• Many antibiotics do not penetrate the inner ear and are therefore not effective in the treatment of otitis media

Question 25

Selecting antibiotic: Ability of the PT to Battle Infection - Why is it a critical determinant of a PT to fight infection? - Examples (3)

Answer 25

The immunological state of the patient can be a critical determinant in the selection of an antibiotic. - Bactericidal antibiotics kill bacteria and can therefore be used effectively in patients with compromised immune function. - Bacteriostatic antibiotics only decrease the ability of bacteria to multiply, and therefore require the actions of the immune system to kill the bacteria. - Patients with compromised immune function may not respond to bacteriostatic antibiotics ``` Examples: o AIDS o Organ transplantation o Cancer chemotherapy and also elderly patients ```

Question 26

What are the (6) complications of antibiotic therapy?

Answer 26

``` o Resistance o Allergy o Serum sickness o Superinfection o Destruction of normal bacterial flora o Bone marrow toxicity ```

Question 27

Antibiotic Complications: Resistance - What is it? - Why is it a concern? - What are the (3) mechanisms?

Answer 27

- Antibiotic resistance refers to bacteria that did respond to an antibiotic and have lost sensitivity over time. - Antibiotic resistance is an enormous concern in medicine as over 70% of bacteria associated with hospital infections show some resistance to at least one antibiotic that was once effective in treating them Antibiotic resistance can be acquired by one of three major mechanisms: 1. Reduction of the drug at the site of the target. 2. Increased drug inactivation. 3. Alteration of the bacterial target

Question 28

Resistance Mechanisms: Reduction of the Drug at the Site of the Target

Answer 28

1. Over time, some bacteria will decrease the uptake of some antibiotics. 2. Similarly, some bacteria increase the expression of efflux pumps and therefore bacteria more effectively extrude antibiotics. 3. The combination of decreased uptake and increased efflux results in decreased drug that is able to access its bacterial target

Question 29

Resistance Mechanisms: Increase Drug Inactivation

Answer 29

Some bacteria have evolved to produce increased amounts of enzymes that inactivate antibiotics. - For example, some bacteria produce an enzyme called beta lactamase, which degrades all antibiotics that have a beta lactam ring in their structure (i.e. penicillins and cephalosporins).

Question 30

Resistance Mechanisms: Alteration of the Bacterial Target

Answer 30

- Like most drugs, antibiotics act on targets to produce their effect. - Over time, bacteria may evolve mutations in the target that make the antibiotic ineffective. - In the example, a mutation in bacterial ribosomes renders some antibiotics ineffective, as the antibiotics are not able to bind to the target

Question 31

What are the (4) strategies to prevent resistance?

Answer 31

1. Prevent infection - Vaccinate where appropriate, get catheters out if possible. 2. Diagnose and treat infection effectively - Many patients who have the common cold (a virus) expect their doctor to give antibiotics, despite the fact that they are not effective against viruses! 3. Use antibiotics wisely - Only use antibiotics when necessary. 4. Prevent transmission - Isolate the pathogen and prevent its spread - This can be as simple as washing your hands; As a rule you should wash your hands before and after you touch any patient.

Question 32

Antibiotic Complications: Allergy - Common allergy? - Signs of allergy? - When does most fatal reaction occur? Symptoms? - What to do?

Answer 32

Allergy is a significant concern for some patients. - The most common antibiotic allergy is penicillin. ``` Signs of allergy include: o Urticaria (hives) o Anxiety o Swelling of hands, feet, throat o Difficulty breathing o Hypotension ``` - Most fatal antibiotic allergic reactions occur within 20 minutes of dosing. - Most allergic reactions experienced by patients are not true immune mediated allergies; These patients experience symptoms such as vomiting, diarrhea and non-specific rash. If your patient is having an allergic reaction you should stop the antibiotic immediately and monitor vital signs - Patients may require treatment with diphenhydramine (an antihistamine) and an epipen (epinephrine, a vasoconstrictor).

Question 33

Antibiotic Complications: Serum Sickness - What is it? - What occurs during? - What does the body produce? Resulting in? - Treatment?

Answer 33

- Serum sickness is similar to an allergy but it typically develops 7-21 days after antibiotic exposure. - During serum sickness, the body’s immune system improperly identifies a drug or drug-protein complex as harmful. - The body then produces an immune reaction, which produces inflammation and other symptoms such as fever, hives, rash, joint pain, itching, angioedema and enlarged lymph nodes. - Treatment of serum sickness includes antihistamine (for itching), analgesics (for pain), and corticosteroids (for inflammation).

Question 34

Antibiotic Complications: Superinfection - What is is? - What kills pathogenic and normal bacteria flora? - What does this cause? - Why is it difficult to treat?

Answer 34

- Superinfection is an example of a special type of resistance. - Superinfection is a new type of infection that develops during the course of antibiotic therapy. - Broad spectrum antibiotics kill both pathogenic bacteria and normal bacterial flora; Destruction of normal bacterial flora can allow new bacteria to flourish. - Since superinfections are caused by drug-resistant bacteria, they are difficult to treat.

Question 35

Antibiotic complications: Destruction of normal bacteria flora - Consequences

Answer 35

In addition to superinfection, destruction of normal bacterial flora can have the following consequences: - Intestinal bacteria synthesize vitamin K. Patients taking the anticoagulant warfarin require vitamin K and are at increased risk of bleeding side effects when vitamin K is low. - Intestinal bacteria metabolize some drugs and contribute to the first pass effect. (Remember Module 4); Destruction of normal intestinal flora can lead to increased blood drug levels and therefore toxicity. - Intestinal bacteria are involved in enterohepatic recycling of drugs (Remember Module 5); Destruction of intestinal bacteria can decrease enterohepatic recycling and have devastating consequences to drug therapy (i.e. contraceptive failure with oral contraceptive drugs).

Question 36

Antibiotic complications: bone marrow toxicity - Symptoms? - Educate patients for?

Answer 36

- Symptoms of bone marrow toxicity include aplastic anemia, thrombocytopenia, agranulocytosis and leukopenia. - Patients should be educated to look out for symptoms such as sore throat, bruising, and fatigue as they are signs of bone marrow toxicity.

Question 37

Who discovered penicillin?

Answer 37

Alexander Flemming

Question 38

How does penicillin degrade bacterial cell walls?

Answer 38

The bacterial cell wall is composed of a peptidoglycan layer. - Transpeptidases are enzymes that function to form cross bridges between the peptidoglycan strands, therefore making the cell wall strong. Autolysins are bacterial enzymes that degrade the peptidoglycan cell wall. - Together transpeptidases and autolysins are called penicillin binding proteins (PBPs) and are the primary target of penicillin antibiotics.

Question 39

What is the mechanism of action of penicillin? - What does it inhibit vs activate? - What does it disrupt? - Net result? - What is penicillin considered? Effective against? - Gram positive or gram negative? Why?

Answer 39

- Penicillins inhibit transpeptidases and activate autolysins. - Therefore, penicillins disrupt synthesis of the cell wall and promote cell wall destruction. - The net result is bacteria take up excess water and die (lyse). - Thus, penicillins are considered bactericidal and are only effective against bacteria that are actively growing and dividing. - Penicillins are much more effective against gram positive bacteria because they do not have an outer membrane.

Question 40

What is penicillin resistance caused by? (3)

Answer 40

Penicillin resistance may be caused by: 1. Inability to reach its target 2. Inactivation 3. Mutation in PBPs that make them have low affinity for penicillins (i.e. methicillin resistant Staphylococcus aureus, MRSA)

Question 41

T/F The predominant mechanism of resistance is inactivation by enzymes called beta lactamases

Answer 41

True - These enzymes target the beta lactam ring of penicillins rendering the drug inactive - We now have beta lactamase inhibitors, which block this enzyme and help avoid resistance

Question 42

What are the classes of penicillins? (4)

Answer 42

- Narrow spectrum penicillins - Narrow spectrum penicillinase resistant penicillins - Broad spectrum penicillins - Extended spectrum penicillins