Module 16

Question 1

What are bacteria?

Answer 1

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

• Bacteria occupy almost every habitat on Earth, including humans!
• Most bacteria are rendered harmless by our immune system and some even play beneficial roles.
• However, some bacteria are pathogenic and cause diseases such as cholera, syphilis and tuberculosis.
• Before the discovery of antibiotics, bacterial infection was a major cause of morbidity and death.

Question 2

Bacteria have a number of virulence factors that they use to cause infection. Virulence factors include what?

Answer 2

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

Question 3

Describe Fimbriae and Pilli (bacterial virulence factors)

Answer 3

• 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 4

Describe Flagella (bacterial virulence factors)

Answer 4

• Bacteria typically live in aqueous environments and need to move to sites where they can survive.
• The flagellum that bacteria possess allows them to “swim” through the watery environment of our body to the site where they may survive.

Question 5

Describe Toxins and Enzymes (bacterial virulence factors)

Answer 5

• Some bacteria secrete toxins and/or enzymes.
• Secreted toxins can have a wide array of effects including nausea, vomiting, diarrhea, cramps, pain, fever, or even paralysis.
• In some cases, bacterial toxins produced outside of our body can mediate toxic reactions if they gain entry to our body. A good example is what occurs in some cases of poisoning.
• In addition to toxins, bacteria also release enzymes. Some of these enzymes can degrade tissue or breakdown antibodies, our defense against infection.

Question 6

Describe Invasion (bacterial virulence factors)

Answer 6

• Some bacteria can actually invade (enter) our cells.
• 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 7

What is gram staining?

Answer 7

Gram staining is a technique that is used to classify bacteria as either gram positive or gram negative.

Question 8

Why is it important to classify bacteria as either gram negative or gram positive?

Answer 8

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 9

What colour does gram positive bacteria stain during gram staining?

Answer 9

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

Question 10

What colour does gram negative bacteria stain during gram staining?

Answer 10

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

Question 11

Describe gram positive bacteria

Answer 11

• thick peptidoglycan layer (cell wall)
• techoic acids - provide rigidity to the cell wall. The major surface antigen in gram positive bacteria
• Do NOT have LPSs
• Do NOT have an outer membrane
• Do NOT have porins (a few exceptions)

Question 12

Describe gram negative bacteria

Answer 12

• Thin peptidoglycan layer (cell wall)
• Do NOT have techoic acids
• Lipopolysaccharides (LPSs) - Are a structural component of the outer membrane and the major surface antigen in gram negative bacteria
• Outer membrane - protects gram negative bacteria from bile salts and detergents
• Porins - on the outer membrane. Allow certain sugars, ions, and amino acids to enter the bacteria

Question 13

What are the typical signs of infection?

Answer 13

• The typical signs of infections include fever, overall malaise, local redness, and swelling.
• Other signs of infection include increased respiratory rate and tachycardia.
• 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.
• There may be other signs of infection depending on the location of the infection. For example, patients with a urinary tract infection feel the frequent need to urinate.

Question 14

What are several questions to consider when selecting an antibiotic?

Answer 14

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 15

What is selective toxicity?

Answer 15

• The treatment of a bacterial infection is critically dependent on the ability to produce selective toxicity.
• Selective toxicity means the therapy is able to destroy the bacteria without harming the host (i.e. human cells).
• Selective toxicity is produced by targeting differences between the cellular chemistry of bacteria and humans.

Question 16

Antibiotic therapy produce selective toxicity by doing what?

Answer 16

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

Question 17

Ideally, when are bacteria identified?

Answer 17

prior to selection of the treatment

Question 18

The _____ is a rapid test that provides information on the structural features of the bacteria.

Answer 18

gram stain

Question 19

In general, _____ the bacteria to properly identify it will provide the best basis for selection of the therapy.

Answer 19

culturing

o In some cases, cultures are not possible or reliable for identifying the bacteria. For example, cultures are rarely taken from children who have an ear infection because they are difficult to obtain. In addition, samples from patients with lower respiratory infections may contain several species of bacteria.

Question 20

Antibiotics can be _____ or _____.

Answer 20

bacteriostatic, bactericidal

• Microbiologists can culture bacteria and determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of antibiotic drugs.

Question 21

Describe bacteriostatic

Answer 21

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

Question 22

Describe bactericidal

Answer 22

o Drugs kill the bacteria.

Question 23

Define minimum inhibitory concentration (MIC)

Answer 23

In microbiology, the minimum inhibitory concentration is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria.

Question 24

Define minimum bactericidal concentration (MBC)

Answer 24

The minimum bactericidal concentration is the lowest concentration of an antibacterial agent required to kill a particular bacterium.

Question 25

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

Answer 25

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

Question 26

Describe Meningitis

Answer 26

• Is an infection of the meninges, which are the membranes that cover the brain and spinal cord.
• Bacterial meningitis is rare but is much more serious than viral meningitis (i.e. life threatening).
• Many antibiotics are unable to penetrate the meninges.
• Therefore, effective treatment requires an antibiotic that penetrates the meninges and effectively eradicates the bacteria.

Question 27

Describe Urinary Tract Infections (UTIs)

Answer 27

• 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 28

Describe Osteomyelitis

Answer 28

• 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 29

Describe Abscesses

Answer 29

• 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 30

Describe Otitis Media

Answer 30

• 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 31

Patients with compromised immune function may not respond to bacteriostatic antibiotics. Some examples of these patients include those having what?

Answer 31

o AIDS
o Organ transplantation
o Cancer chemotherapy
and also elderly patients

• 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.

Question 32

Antibiotics have a number of common complications which include what?

Answer 32

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

Question 33

How long is osteomyelitis typically treated with antibiotics for?

Answer 33

Treatment of osteomyelitis usually requires antibiotics for 4 – 6 weeks.

Question 34

Define penicillinase

Answer 34

An enzyme which can inactivate penicillin (and cephalosporin), produced by certain bacteria.

Question 35

Describe the mechanism of bacterial antibiotic resistance “Increased drug inactivation”

Answer 35

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

Question 36

Describe the mechanism of bacterial antibiotic resistance “Reduction of the drug at the site of the target”

Answer 36

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

Question 37

Describe the mechanism of bacterial antibiotic resistance “Alteration of the bacterial target”

Answer 37

• 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 38

List several strategies used to prevent bacterial antibiotic resistance

Answer 38

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 39

The most common antibiotic allergy is to what?

Answer 39

Penicillin

Question 40

List the signs of allergy

Answer 40

o Urticaria (hives)
o Anxiety
o Swelling of hands, feet, throat
o Difficulty breathing
o Hypotension

• Most allergic reactions experienced by patients are not true immune mediated allergies. These patients experience symptoms such as vomiting, diarrhea and non-specific rash.

Question 41

Most fatal antibiotic allergic reactions occur within _____ of dosing.

Answer 41

20 minutes

Question 42

What should you do if your patient is having an allergic reaction?

Answer 42

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 43

What is serum sickness?

Answer 43

• 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.

Question 44

What is the treatment for serum sickness?

Answer 44

Treatment of serum sickness includes antihistamine (for itching), analgesics (for pain), and corticosteroids (for inflammation).

Question 45

What is superinfection?

Answer 45

• 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 46

In addition to superinfection, destruction of normal bacterial flora can have what consequences?

Answer 46

o 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.
o 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.
o 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 47

Describe bone marrow toxicity

Answer 47

• Bone marrow toxicity is a very rare but serious complication of antibiotic therapy.
• 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.