Microbiology 2

Question 1

Ecological plaque hypothesis

Answer 1

Prolonged acidification of the biofilm selects for acidogenic and acidoduric bacteria in the host microbiome

(disease is the result of an imbalance in the microflora by ecological stress resulting in an enrichment of certain disease-related micro-organisms)

Pathobiont emergence: phenomenon where commensal bacteria inhabiting specific ecological niche transition from harmless RS to pathogenic → infection
- Bacteria can obtain new genes to survive out of optimal environment by horizontal gene transfer

Question 2

Chlorhexidine and fluoride in caries control

Answer 2

CHx:
Able to suppress MS level with regular use: blocks MS binding to sugar-coated HA; inhibits PEP-PTS
Does not upset normal microbial ecology
Substantive - prolonged bactericidal effect
Synergistic effect w F- - increased bactericidal effect

F- :
Antibacterial at high conc : inhibits PEP-PTS, affects membrane integrity
Remineralisation - FAP.

Question 3

4 key pathogenic determinants of cariogenic bacteria

Answer 3

Having both high and low affinity systems
Acidogenic and acidoduric
EPS - attachment
IPS - glucose storage in bacteria, contributes to bacterial persistence during famine conditions

Question 4

Explain periapical lesions and Spread of periapical lesions

Answer 4

Md molar teeth → infection spreads along roots inferior to mylohyoid line → submandibular space

When tooth is infected → PAMPs trigger activation of immune cells resulting in release of cytokines, chemokines (type of cytokine that triggers WBC migration), prostaglandins → inflammation triggered
Can cause swelling and pain, fever and elevated heart rate: from release of pro-inflammatory cytokines by immune cells

Question 5

Antibiotic mechanisms

Answer 5

1) Cell wall synthesis inhibitors
Beta-lactam antibiotics
Penicillin:
Binds to transpeptidase, inhibiting it from catalysing cross-links between peptide side-chains of NAM and NAG sugars to form the peptidoglycan wall → bacteria lyses (suicide inhibitor)
Do not target eukaryotic cells since no peptidoglycan cell wall.
Bactercidal, but req cells to be actively growing
Can be degraded by bacterial Beta-lactamase (S. aureus)
Cephalosporins, carbapenems, monobactams - resistant

2) Protein synthesis inhibitor
Macrolides - bacteriostatic against 50S ribosomal units
Clindamycin, lincomycin - activity against G+ve, some G-ve eg Bacteroides - cindamycin more effective.
Tetracycline - broad-spectrum (but these days every bacteria is resistant)

3) Nucleic acid inhibitor
NOT selectively toxic - some useful in cancer chemo
Rifampicin - inhibit RNA polymerase
Metronidazole - 5-nitromidazole- breaks DNA strands
Quinolone - disrupt DNA gyrase for bacterial DNA synthesis.

4) Cell membrane distruption
Rarely used systematically as can affect eukaryotic cells’ membranes
Lysozyme, antifungals
Nystatin & Amphotericin B- form pores in the membrane, causing K+ leakage and acidification → death of fungus

Question 6

B-lactam antibiotics

Answer 6

Penicillin
Natural penicillin - narrow spectrum to G+ve
Semi-synthetic penicillin
Amoxicillin, ampicillin increased spectrum, improved oral administration
Augmentin - Amox + Clavulanic acid - inhibit B-lactamase
Methicillin - B lactamase resistance
Cephalosporins
Cefuroxine, Ceftriaxone, Ceftzidime
Carbapanem, Monobactams

Question 7

Antibiotic resistance

Answer 7

Altered target site for drug binding
- Altered penicillin-binding site → pen R
- Altered DNA gyrase → quinolone R
- Methylation of 50S → protein synthesis inhibitor (macrolide/lincosamide/streptogramine) R

Drug inactivation
B-lactamases
Aminoglycoside-modifying enzymes - -mycin R
Altered Permeation/Efflux
Quinolone efflux pumps
Mutation of porins for aminoglycoside uptake

Bacterial persisters - L-forms - bacteria that shed cell wall, resistant to cell wall inhibitors

Question 8

Reasons for inappropriate use of antibiotics

Answer 8

Patient-based
Desire for Tx, direct advertising

Physician-based
Desire for optimal therapy, avoid malpractice claims

Cost containment - AB course cheaper than further investigation

Lack of training - Inadequate understanding of immunodeficiency management

Inappropriate ordering/interpretation of lab testing

Industry-based: advertising

Question 9

How to minimise antibiotic resistance in the medical industry

Answer 9

Education programs
Microbiology reports
Hospital formulary
Minimum no. of agents, substitution for more effective, cheaper agents
Control of agents - automatic stop orders, drugs requiring specialist approval
Antibiotic audit

Limit access of pharmaceutical representatives

Question 10

10 principles of antibiotic prescribing

Answer 10

IIOAC
HRDDM

1. Are antibiotics indicated on clinical grounds
2. Have appropriate investigations been performed
3. Which organisms most likely to cause this infection
4. Which agent is best
5. Is an antibiotic combination appropriate
6. Any host factors relevant
7. Best route of administration
8. Appropriate dose
9. Optimal duration of therapy
10. Can therapy be modified when lab results are obtained