Antimicrobials and Chemotherapy in Clinical Practice

Question 1

Management of infection

e.g dental abscess

Answer 1

Antibiotic was previously the predominant choice

Amoxicillin/Penicillin

Question 2

Are antibiotics necessary

Answer 2

• is there non antibiotic option

- evidence of infection/bacterial colonisation

Question 3

What is the site of infection

Answer 3

Which organisms should be covered

Which antibiotics will penetrate that site e.g oral or genitalia, optimum pH

Question 4

What is organism sensitivity ?

Two types

Acquired two mechanisms

Answer 4

Primary resistance
- innate property e.g pseudomonas and penicillin

Acquired resistance
- genetic determinant of resistance acquired by bacteria due to mutation or gene transfer
Chromosomal e.g M. TB
Plasmid mediated e.g MRSA

Question 5

What is the appropriate or available route of administration?

AND?

Strep pharyngitis

Odontogenic neck space

• severe
• mild

MRSA bacteraemia

Answer 5

DOSAge interval/duration

Penicillin, oral, 6hrly, 10 days

IV cefuroxime - bypasses liver
Oral metronidazole - don’t get metabolised by liver –> improved bioavailability

Oral amoxycillin
oral metronidazole

Vancomycin, IV, bd, 2 weeks
NEPHROTOXIC

Question 6

Which antibiotics are safe for the patient

Factors to consider

Answer 6

• intolerance and anaphylaxis
• side effects
• age
• renal function
• liver function
• pregnancy and breast feeding
• drug interactions - either perpetrator or victim
• risk of C. difficile

Question 7

Pharyngitis vs Dental abscess

Centor criteria

Answer 7

Streptococcus pyogenes
EBV

Viridian’s group streptococci
Anaerobes
Gram -ve rods

Absence of cough
Fever
Swollen tender anterior cervical nodes
Tonsillar exudate

Question 8

How do bacteria resist antibiotics

Answer 8

Change antibiotic target e.g protein channel
Destroy antibiotic via enzyme
Prevent antibiotic access
Remove antibiotic from bacteria

Question 9

How does resistance develop?

Answer 9

Acquired
1. Spontaneous gene mutation
Mutation may provide advantage –> e.g antibiotic resistance being survival advantage

2. horizontal gene transfer
   - conjugation
   - transduction
   - transformation

Question 10

Conjugation

Answer 10

Transfer between bacteria

Question 11

Transduction

Answer 11

Virus infects bacteria and passes between bacteria

Question 12

Transformation

Answer 12

Naked DNA from dead bacterium gets absorbed by live bacterium

Question 13

How do we detect resistance/sensitivity?

MIC and MBC

Answer 13

1. Antibiotic sensitivity testing
   - liquid culture with diluted AB - observe conc needed
   - antibiotic discs
   - e-tests

Inhibitory concentration and bactericidal concentration

2. Breakpoint plates
   - plates with specific breakpoint concentration of antibiotic in and see if sample grows or not

Lowest MIC does not indicate best antibiotic due to pharmacodynamics of body and pharmacokinetics of blood

Question 14

Lowest MIC

Also consider

Answer 14

does not indicate best antibiotic due to pharmacodynamics of body and pharmacokinetics of blood

protein binding
Distribution in site of infection
Exposure of organism to an antibiotic needed for its eradication

Question 15

what are antimicrobials

What is a target site

How do antimicrobials work

They must

Answer 15

Molecules which work by binding a target site on a bacteria

Points of biochemical reaction crucial to survival
varies with antibiotic class

Wall of bacteria (PBPs) 
Cell membrane 
DNA 
Ribosomes 
DNA gyrase

Bind to target site
Penetrate membrane
Occupy adequate number of binding sites and remain for sufficient amount of time
Avoid being effluxed
Binding site may change molecular configuration
Must remain intact and resist enzyme destruction

Question 16

E.g 1 Penicillin resistance

Answer 16

B lactamase breaks down Beta lactam ring in penicillin

Prevents function

Question 17

Two major determinants of bacteria killing include

Answer 17

Concentration and time that the antibiotic remains on these binding sites
Time dependent Antibiotics will fail if not taken when necessary

Question 18

Concentration dependent killing - key parameter

Time dependent killing - key parameter

Answer 18

How high conc is above MIC
Peak concentration/MIC ratio

Time that serum concentrations remain above the MIC during the dosing interval

T > MIC

• beta lactase
• clindamycin
• macrocodes
• oxazolidinones

Question 19

Risk of C. difficile - 5cs

Answer 19

CIPROFLOXACIN
CLINDAMYCIN 
CEPHALOSPORINS
CO-AMOXICLAV
CARBAPENEMS