Antibacterial Classes

Question 1

What are the broad classes of antibacterials based on chemical structure?

Answer 1

1. DNA synthesis
2. Protein Synthesis
3. Cell wall synthesis

Question 2

What two types of antibacterial drugs affect DNA synthesis? Give examples

Answer 2

1. Quinolones - Ciprofloxacin

2. Folic acid antagonists - Trimethoprim, Co-trimethoxazole (trimethoprim and sulphonylmethaxazole)

Question 3

What three types of antibacterial drugs affect protein synthesis? Give examples

Answer 3

1. Macrolides - Erythromycin, Clarithromycin
2. Aminoglycosides - Gentamicin
3. Tetracyclines - Tetracycline and Doxycycline

Question 4

What 2 types of antibacterial drugs affect cell wall synthesis?

Answer 4

1. Beta lactams
   (a) Penicillins - 6 - Penicillin V, Piperacillin, Tazocin (Tazobactam and Piperacillin), Amoxicillin, Co-amoxiclav (amoxicillin and clavulanate), Benzylpenicillin, Flucoxacillin
   (b) Cephalosporins - Ceftriaxone (3rd gen)
   (c) Carbapenems - Meropenem
2. Glycopeptides - Vancomycin

Question 5

Quinolones

Example:
Mechanism of action:
Active against:

Answer 5

Ciprofloxacin

X DNA gyrase -> X DNA super-coiling -> X DNA synthesis

Active against gram negatives and some atypical pathogens

Question 6

Folic Acid Synthesis

Example:
Mechanism of action:
Used for:

Answer 6

Trimethoprim, Co-trimethoxazole (trimethoprim and sulphonylmethoxazole)

X Folic acid synthesis -> X DNA synthesis and DNA methylation

Trimethoprim - UTI
Co-trimethoxazole - MRSA, PCP pneumonia

Question 7

Macrolides

Example:
Active against:
Penicillin allergy safe?
ADRs:

Answer 7

Erythromycin, Clarithromycin

Active against mild gram positive infections and atypical pneumonia pathogens

Safe to use with penicillin allergy for mild gram positive infections

ADRs: nausea, vomiting, diarrhoea

Question 8

Tetracyclines

Example:
Route of administration:
Active against: 
Penicillin allergy safe? 
ADRs:

Answer 8

Tetracycline, Doxycycline

Oral administration

Active against gram positive, chlamydia, some protozoas and atypical pneumonia pathogens

Safe to use with penicillin allergy

ADRs: stain teeth yellow, renal/hepatic problems, nausea, D&V, C. diff

Question 9

Aminoglycosides

Example:
Active against:
ADRs:
TDM required?

Answer 9

Gentamicin

Active against: gram negative - usually reserved for gram negative sepsis

ADRs: ototoxic and hepatotoxic

TDM required

Question 10

Beta-lactams: Penicillins

Mechanism of action:
Examples and what each is active against:
ADRs:

Answer 10

Binds to pbp, preventing it from cross-linking bacterial cell walls

Penicillin - streptococci
Amoxicillin - streptococci and some gram negatives
Flucoxacillin - streps and staphs
Co-amoxiclav - streps, staphs, gram negs, anaerobes
Piperacillin/Tazocin - streps, staphs, anaerobes, gram negs, even pseudomonas!

ADRs: liver problems, high hypersensitivity, CNS toxicity, C. diff associate, electrolyte disturbances

Question 11

Beta-lactams: Cephalosporins

Example: 
Active against: 
Used in:
Penicillin allergy safe? 
ADRs:

Answer 11

Ceftriaxone (3rd gen) - each gen increasingly active against gram neg but less against gram postiive, staphs and streps

Used in meningitis - effective in CSF

Careful with penicillin allergies!!

ADRs: hypersensitivity, hepatotoxic, C. diff

Question 12

Beta-lactams: Carbapenems

Example:
Active against:
Penicillin allergy safe?
ADRs:

Answer 12

Meropenem

Active against streps, staphs, gram positive, most gram negs, and anaerobes

Careful in penicillin allergy!!!

ADRs: hypersensitivity, CNS toxicity, C. diff

Question 13

Glycopeptides

Example:
Mechanism of action:
Active against: 
Administration route:
Penicillin allergy safe? 
ADRs: 
TDM?

Answer 13

Vancomycin

Sits on amino acid on cell wall so that bpb can’t bind -> X DNA synthesis

Active against gram positives but some enterococci are resistant to vancomycin

IV apart from C. diff - oral

Penicillin allergy safe!

Ototoxic

TDM

Question 14

In what 2 ways can we measure antibacterial activity?

Answer 14

Disc sensitivity - size of inhibition zone corresponds with sensitivity of bacteria to the antibacterial

MIC (minimum inhibitory concentration) - minimum concentration of antibiotic that inhibits bacterial growth in vitro

Question 15

In Pharmacodynamics, what does a time dependent killing pattern elicit about a drug’s property. Give some examples. How does this differ from concentration dependent killing pattern? Give examples.

Answer 15

Time dependent killing - successful treatment requires prolonged treatment duration of antibiotic at infection site but not at a high concentration - penicillins, cephalosporins, glycopeptides

Concentration dependent killing - successful treatment requires high concentration of antibiotic at infection site but not for long duration - aminoglycosides and quinolones

Question 16

What is the point of TDM?

Answer 16

Therapeutic drug monitoring ensures adequate dose/non-toxic dose especially for a drug with a small therapuetic window e.g. vancomycin and gentamicin

Question 17

Markers of potential toxicity

Answer 17

CK and eosinophils - daptamicin
FBC - Inezolid, Chloramphenicol
Renal function - aminoglycosides, tetracyclines
Auditory function - aminoglycosides, glycopeptides
Stool charts - most antibacterials in hospital

Question 18

What are the 3 ways in which anti-bacterial resistance can occur?

Answer 18

1. Altered enzyme active site so that the enzyme has a lower affinity for the drug
2. Altered uptake of drug - decreased permeability with beta-lactams, increased with tetracyclines
3. Drug inactivating enzymes - aminoglycosides, Beta-lactamases (co-amoxiclav, tazocillin)

Question 19

Genetics of antibacterial resistance can occur in 2 ways. what are those two ways?

Answer 19

1. Chromosomal gene mutation - mutation for resistance gene comes about, antibacterial is introduced, but the bacteria carrying the mutated gene survives and the replicates
2. Horizontal gene trasnfer
   - conjugation: transfer of plasmid
   - transduction: via a vector (phages)
   - transformation: transfer of free DNA