L2 - Part 1 - Treatment of Bacterial Infection

Question 1

What is empirical treatment, and what factors influence it?

Answer 1

Clinical symptoms
Site of infection
Patient history (age, medical history, immunocompromised status)
Acquisition source (travel history, hospital-acquired)

Question 2

What samples are taken before starting empirical treatment?

Answer 2

Urine
Blood
Cerebrospinal fluid (CSF)
Sputum
Biopsy from the site of infection

Question 3

How does targeting folic acid synthesis treat bacterial infections?

Answer 3

Folic acid is essential for nucleic acid synthesis in bacteria.
Antibiotics target enzymes in the folic acid synthesis pathway.
Humans obtain folic acid from the diet, making this pathway a selective target.

Question 4

How do ribosomes differ between bacteria and humans, and why is this significant?

Answer 4

Bacterial ribosomes have a slightly different active site than human ribosomes.
Antibiotics can selectively inhibit bacterial protein synthesis without affecting human cells.

Question 5

What is a blood agar plate, and how is it used?

Answer 5

Blood agar plates contain RBCs that change color upon lysis.
Detects bacterial toxins (haemolysins) based on the type of haemolysis.

Question 6

What are the types of haemolysis observed on blood agar plates?

Answer 6

Alpha haemolysis:
Partial lysis of RBCs.
Light greenish discoloration (caused by peroxide).
Beta haemolysis:
Complete lysis of RBCs.
Transparent zone (caused by streptolysin toxin).
Gamma haemolysis:
No lysis of RBCs.

Question 7

What methods are used to identify microorganisms in culture?

Answer 7

Culture:
Use of selective media and specific conditions (e.g., aerobic/anaerobic).
Chromogenic agar with selective agents enhances identification.
Some bacteria thrive only in specific conditions (e.g., aerobic, anaerobic).

Question 8

How is microscopy used to identify microorganisms?

Answer 8

Examines morphology (shape/structure).
Uses staining techniques to differentiate microorganisms (e.g., Gram staining).

Question 9

What is the role of PCR in microorganism identification?

Answer 9

PCR detects DNA/RNA from microorganisms.
Primarily used for viruses, but applicable to bacteria and fungi as well.

Question 10

How is a patient’s immune response used to identify microorganisms?

Answer 10

Detects markers like:
Antibodies against the microorganism.
C-reactive protein (inflammatory marker).
Mantoux test (for TB detection).

Question 11

What are common methods of antigen detection?

Answer 11

ELISA (Enzyme-Linked Immunosorbent Assay):
Uses immobilized antibodies to bind specific proteins.
Enzyme converts substrate to a colored product for detection.
Agglutination tests (e.g., Staphaureus test):
Detects antigen-antibody clumping.

Question 12

What biochemical tests are used to identify microorganisms?

Answer 12

Enzyme assays (e.g., catalase test).
Haemolysis assays (detect haemolysin activity).
Mass spectrometry for precise microbial identification.

Question 13

What is the role of urease in microorganism identification?

Answer 13

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Converts urea to ammonia (NH₃) and carbon dioxide (CO₂).
Increases pH, causing a color change in pH indicators.

Question 14

Which microorganisms produce urease, and how is it significant?

Answer 14

Proteus and Helicobacter are urease producers.
Urease production helps bacteria survive in acidic environments by neutralizing acidity.

Question 15

What is catalase, and why is it considered a virulence factor?

Answer 15

Catalase protects bacteria by breaking down hydrogen peroxide (H₂O₂) into:
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Protects bacteria from being killed by host immune cells.
Aids bacteria in establishing infection.

Question 16

How is the catalase test performed, and what does it indicate?

Answer 16

Test:
Place bacteria on a slide.
Add H₂O₂.
Bubbles (O₂ production) indicate the presence of catalase.
Identifies catalase activity in bacteria.

Question 17

How does the catalase test distinguish Staphylococci from Streptococci?

Answer 17

Staphylococci: Catalase positive (+ve) → bubbles observed.
Streptococci: Catalase negative (-ve) → no bubbles observed.

Question 18

What is the Staphaurex Test, and what does it detect?

Answer 18

A commercial test to identify Staphylococcus aureus.
Uses latex beads coated with:
Antibody (IgG).
Fibrinogen.
Causes clumping of S. aureus due to interaction with virulence factors.

Question 19

What are the key virulence factors of Staphylococcus aureus?

Answer 19

Protein A:
Binds antibodies upside down (via Fc region).
Prevents antibody-mediated immunity (e.g., complement activation, phagocytosis).
Coagulase:
Converts fibrinogen to fibrin → induces blood clotting.
Clot may protect bacteria from host immune defences.

Question 20

How does the Staphaurex Test work?

Answer 20

Detects Protein A and Coagulase of S. aureus.
Mechanism:
Latex beads coated with IgG and fibrinogen.
Interaction with S. aureus causes visible clumping.

Question 21

What is MALDI-TOF mass spectrometry?

Answer 21

MALDI-TOF: Matrix-Assisted Laser Desorption Ionization–Time-of-Flight.
A mass spectrometry technique to identify microbes based on their unique mass spectra profiles.
Used to generate a “fingerprint” of cell surface molecules.

Question 22

How is CRP used to evaluate a patient’s immune response?

Answer 22

CRP (C-reactive protein): A biomarker to differentiate bacterial and viral infections.
Also monitors infection progression and treatment effectiveness.

Question 23

Can CRP levels vary by infection type?

Answer 23

Generally low or unchanged in viral infections.
Exceptions exist for some viral infections that slightly elevate CRP.

Question 24

What are narrow-spectrum antibiotics?

Answer 24

Target one specific type of bacteria.
Ideal when pathogen identity is known → fewer side effects.

Question 25

What is the role of commensal flora?

Answer 25

Protect against pathogens by:
Secreting substances (e.g., altering pH).
Competing for nutrients.
Can provide nutrients to the host.

Question 26

How can antibiotic use lead to superinfection?

Answer 26

Killing commensal flora allows pathogens to overgrow. Examples:
Tetracyclines → Candida (thrush).
Clindamycin → Clostridium difficile → pseudomembranous colitis (40% mortality rate).

Question 27

What is the Disk Diffusion (Kirby-Bauer) Test?

Answer 27

A method to test bacterial susceptibility to antibiotics.
Involves placing antibiotic-impregnated disks on an agar plate with bacteria.
Zones of inhibition around disks indicate effectiveness; larger zones = more effective antibiotic.

Question 28

What is the MIC Test Strip?

Answer 28

Used to determine the Minimum Inhibitory Concentration (MIC) of an antibiotic.
MIC strip contains a gradient of antibiotic concentrations.

Question 29

How is the MIC Test performed?

Answer 29

Bacteria are grown on a Petri dish.
An MIC strip is placed on the agar.
The zone of inhibition is measured around the strip to determine effectiveness.

Question 30

How is the MIC determined from the test?

Answer 30

The MIC value is identified by referring to a table that correlates the zone size to the concentration of the antibiotic.
The smallest concentration that inhibits bacterial growth is the MIC.

Question 31

What is the Broth Dilution Test?

Answer 31

A method to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of an antibiotic.
Involves growing bacteria in liquid media with different concentrations of an antibiotic.

Question 32

What does the Broth Dilution Test measure?

Answer 32

MIC: The lowest concentration of antibiotic that inhibits bacterial growth.
MBC: The lowest concentration that kills the bacteria (measured by sub-culturing on antibiotic-free agar).

Question 33

What is the difference between Bacteriostatic and Bactericidal antimicrobials?

Answer 33

Bacteriostatic: Inhibits bacterial growth but does not kill the bacteria.
Bactericidal: Kills the bacteria by reaching a concentration that is lethal.

Question 34

What is the relationship between MIC and MBC in Bacteriostatic and Bactericidal drugs?

Answer 34

Bacteriostatic: MBC is much higher than MIC.
Bactericidal: MBC is no more than 4x MIC, meaning it kills the bacteria at concentrations close to MIC.

Question 35

What age-related factors affect drug metabolism in neonates?

Answer 35

Size: Neonates are smaller, affecting drug distribution.
Hepatic elimination: The liver is not fully developed, limiting the ability to metabolize certain drugs.

Question 36

What are some drugs contraindicated in neonates and why?

Answer 36

Chloramphenicol: Can cause grey baby syndrome (40% mortality rate).
Tetracyclines: Affect bone growth.
Fluoroquinolones: Affect cartilage growth.
Aminoglycosides: Risk of ototoxicity (damage to the ears).
Sulfonamides: Risk of kernicterus (brain damage due to jaundice).

Question 37

How does renal function affect drug metabolism in the elderly?

Answer 37

Renal function declines with age, leading to reduced drug elimination.
Poor kidney function can result in drug accumulation, increasing the risk of toxicity.

Question 38

What is a significant concern with Aminoglycosides in the elderly?

Answer 38

Aminoglycosides (e.g., Gentamicin) can cause nephrotoxicity (kidney damage) in elderly patients due to reduced renal function.

Question 39

How can drugs be adjusted for elderly patients with reduced renal function?

Answer 39

Adjust the dose or dosage schedule based on renal function.
Alternatively, use drugs excreted via the liver/biliary route instead of the kidneys.

Question 40

How can genetic polymorphisms affect drug metabolism?

Answer 40

Genetic polymorphisms can cause deficiencies in liver enzymes, affecting the metabolism of drugs.
For example, Glucose-6-phosphate dehydrogenase (G6PD) deficiency leads to haemolysis when treated with sulfonamides.

Question 41

What are the implications of genetic deficiencies on drug metabolism in patients with impaired hepatic function?

Answer 41

Genetic deficiencies (e.g., G6PD deficiency) can cause adverse reactions to certain drugs, especially in those with impaired liver function.
Liver disease can reduce the liver’s ability to metabolize drugs, leading to toxicity.

Question 42

How does impaired immune function affect infection control?

Answer 42

Increased risk of developing infections due to reduced immune response.
Impaired clearance of infection once established, as the immune system is less efficient at eliminating pathogens.

Question 43

What are some causes of impaired immune function in neonates?

Answer 43

Immune system underdeveloped
No prior exposure to infections, making them more vulnerable to pathogens

Question 44

How does age affect immune function?

Answer 44

Elderly individuals experience a decline in immune function, leading to a weaker defense against infections.

Question 45

What are some immune deficiencies that impair immune function?

Answer 45

Inherited deficiencies (e.g., Complement deficiencies)
Acquired Immune Deficiency Syndrome (AIDS) – HIV targets and eliminates T-cells, weakening the immune response.

Question 46

How does poor perfusion affect drug treatment in patients?

Answer 46

Diabetes can cause decreased circulation, particularly in the lower extremities.
This can affect the distribution of drugs.
Topical application may be preferred, or higher doses may be required for adequate therapeutic effects.

Question 47

How does poor compliance contribute to antibiotic resistance?

Answer 47

Patients often stop taking antibiotics once symptoms alleviate, but this can allow antibiotic-resistant bacteria to persist and multiply.
Incomplete courses of antibiotics encourage the growth of resistant strains.

Question 48

How does polypharmacy affect elderly patients’ compliance with antibiotic treatment?

Answer 48

Elderly patients often take multiple medications (polypharmacy), leading to confusion and difficulty adhering to antibiotic regimens.
This can result in missed doses and inconsistent drug levels, potentially worsening treatment outcomes.

Question 49

How can inducers of CYP enzymes affect drug metabolism?

Answer 49

Inducers increase CYP enzyme activity, leading to faster metabolism of drugs.
Example: Rifampicin and St. John’s Wort.
If a patient is on a combined contraceptive pill, these inducers can increase metabolism, potentially reducing the efficacy of the contraceptive.

Question 50

What is the effect of CYP inhibitors on drug metabolism?

Answer 50

CYP inhibitors decrease CYP enzyme activity, slowing down the metabolism of drugs.
Examples include Chloramphenicol, Ciprofloxacin (fluoroquinolones), Clarithromycin (macrolides), and Grapefruit juice.
If a patient on warfarin uses any of these inhibitors, metabolism of warfarin decreases, making it active for longer, which can increase the risk of bleeding.

Question 51

How does higher affinity for albumin of one drug affect the distribution of another drug?

Answer 51

Scenario: Drug X has a higher affinity for albumin than an antibiotic.
Effect: The antibiotic is not bound to albumin, so it has more free drug available.
This leads to:
Increased tissue distribution and effective dose of the antibiotic.
Potentially increased toxicity of the antibiotic due to higher active concentration.
Shorter half-life of the antibiotic because it is cleared faster.

Question 52

What happens if an antibiotic has a higher affinity for albumin than another molecule (drug or endogenous)?

Answer 52

Scenario: The antibiotic has a higher affinity for albumin than another molecule X (could be a drug or an endogenous molecule like bilirubin).
Effect:
Reduced distribution/activity of the antibiotic because it is more tightly bound to albumin.
X (the displaced molecule) is released and can have harmful effects.
Example:
Sulfonamides displace bilirubin from fetal albumin.
This leads to increased bilirubin plasma concentration, causing kernicterus (a type of brain damage in neonates).

Question 53

What is the effect on distribution if an antibiotic has a higher affinity for albumin than X (where X could be another drug or endogenous molecule)?

Answer 53

Reduced distribution/activity of the antibiotic, as it is more bound to albumin.
X (the displaced molecule) is released, potentially causing harmful effects.
Example:
Sulfonamides displace bilirubin from fetal albumin.
This leads to increased bilirubin plasma concentration, which can cause kernicterus, a type of brain damage in neonates.

Question 54

What are the reasons for combining antibiotics?

Answer 54

Serious infection
Unknown microorganism
Multiple microorganisms involved
Prevent resistance (e.g., TB)
Enhance efficacy

Question 55

What is antagonism in polypharmacy/ drug interactions?

Answer 55

Antagonism occurs when one drug reduces the effectiveness of another. E.g., tetracycline (bacteriostatic) inhibits penicillin (bactericidal) action.

Question 56

What are the pros and cons of the oral route of administration?

Answer 56

Pros:

Convenient for patients to self-administer at home.
Effective for gastrointestinal infections.
Cons:

Uptake may be impaired with vomiting, diarrhea, or constipation.
Drug-food interactions (e.g., tetracycline binds to Ca²⁺, Al³⁺, Fe³⁺, reducing absorption).
Drugs must be resistant to digestive acids/enzymes (e.g., amoxicillin 90% absorption vs. benzyl penicillin 30%, destroyed by stomach acid).

Question 57

What are the pros and cons of the topical route of administration?

Answer 57

Pros:

Convenient for self-administration.
Local application minimizes systemic side effects.
Q: What are the pros and cons of the intravenous/intramuscular route of administration?

A:
Pros:

Rapid distribution into the bloodstream, ideal for critically ill patients.
Bypasses stomach acid.
Cons:
Can cause vein/site damage or irritation.
Can be painful.

Question 58

How do chemical properties of a drug affect its distribution?

Answer 58

Lipid soluble drugs are well-absorbed and widely distributed, including in body fat, cells, and the CSF.
Charged drugs (not lipid-soluble) stay mostly in the extracellular space, with a low volume of distribution.
Protein binding limits distribution, and can cause displacement of other drugs or affect carrier mechanisms.

Question 59

Which areas are easy and difficult targets for drug distribution?

Answer 59

Easy targets:
Neonates: Drugs are easily distributed via placenta or breastmilk.
Difficult targets:
Brain, Prostate, Eye, Intracellular bacteria: Very few drugs can effectively target these areas.

Question 60

Why is the brain a difficult target for drug distribution?

Answer 60

The blood-brain barrier (BBB) limits drug access to the brain.
Endothelial cells in the BBB are tightly joined by gap junctions, preventing diffusion between cells.

Question 61

Why is the prostate a difficult target for drug distribution?

Answer 61

The prostate has a low blood flow and restricted permeability, making it harder for many drugs to reach therapeutic levels.
Drugs must be lipophilic or have specific transport mechanisms to penetrate the prostate tissue effectively.