Antimicrobial chemotherapy

Question 1

How do bactericidal antibiotics work?

Answer 1

They kill the bacteria E.g penicillin.

Question 2

How do bacteriostatic antibiotics work?

Answer 2

They inhibit the growth of the bacteria. E.g. erythromycin

Question 3

What is meant by saying an organism is sensitive?

Answer 3

Sensitive means the organism has been inhibited or killed by the drug available at the site of infection.

Question 4

What is meant by saying an organism is resistant?

Answer 4

The organism is not killed nor inhibited by the drug at the site of infection.

Question 5

What is MBC?

Answer 5

Minimum bacterial concentration - needed to kill the organism.

Question 6

What is MIC?

Answer 6

Minimum Inhibitory concentration - needed to inhibit growth.

Question 7

What are an antibiotics mechanism of action?

Answer 7

Inhibition of cell wall synthesis
Inhibition of nucleic acid synthesis
Inhibition of protein synthesis

Question 8

What is the role of Glycopeptides?

Answer 8

Used in the inhibition of cell wall synthesis
Only act on gram positive bacteria.
Inhibit assembly of a peptidoglycan precursor.
Only given parenterally.
E.g Vancomycin

Question 9

What is the role of Beta lactams?

Answer 9

Used in the inhibition of cell wall synthesis.
Inhibits the enzymes (penicillin-binding proteins, PBPs)
responsible for cross-linking the carbohydrate chains.
Works on all bacteria
E.g penicillin, cephalosporins

Question 10

What are the role of Aminoglycosides?

Answer 10

Used in the inhibition of protein synthesis
Enter ribosome and inhibit the translation of mRNA.
Gram negative bacteria
E.g Gentamicin

Question 11

What is the role of Macroslides?

Answer 11

Used in the inhibition of protein synthesis.
Enter ribosome and inhibit the translation of mRNA.
Gram positive bacteria
Alternatives to penicillin
E.g erythromycin

Question 12

What is the role of Tetracyclines?

Answer 12

Used in the inhibition of protein synthesis
Enter ribosome and inhibit the translation of mRNA.
Staph. aureus, Strep. pyogenes and Strep. pneumoniae
strains are resistant

Question 13

What is the role of Oxalzolidones?

Answer 13

Used in the inhibition of protein synthesis.
Enter ribosome and inhibit the translation of mRNA.
Given orally
E.g Linezolid - kept for serious infections only.

Question 14

What is the role of Cyclic Lipopeptide?

Answer 14

Used in the inhibition of protein synthesis.
Enter ribosome and inhibit the translation of mRNA.
Gram positive bacteria
E.g Daptomycin - especially MRSA.

Question 15

What is the role of Fluoroquinolones?

Answer 15

Used in the inhibition of nucleic acid synthesis
Inhibits DNA gyrase
Given orally or parentally
Particularly effective on gram negative bacteria
E.g ciprofloxacin

Question 16

What are streptococci always resistant to?

Answer 16

Aminoglycosides.

Question 17

What drug are gram negative bacteria always resistant to?

Answer 17

Vancomycin.

Question 18

How can resistance be acquired?

Answer 18

Spontaneous mutation - change in structure or function which no longer allows the antibiotic to act (target may have changed)

Spread of resistance - the gene/s that code for resistance can spread from organism to organism or from species to species. Genes can be carried on plasmids or on transposons (packets of DNA which insert themselves into the chromosome).

Question 19

What are beta-lactamases?

Answer 19

Bacterial enzymes which cleave the β–lactam ring of the antibiotic and thus render it inactive.

Question 20

In what organisms are beta-lactamases most common?

Answer 20

Gram negative bacilli

Staphh aureus

Question 21

What are the methods of combating beta-lactamases?

Answer 21

To introduce a second component to the antibiotic
(β-lactamase inhibitor) protecting the antibiotic
from enzymatic degradation E.g co-amoxiclav

To modify the antibiotic side chain producing new antibiotic resistant to the actions of β-lactamase. E.g flucloxacillin

Question 22

How do micro-organisms develop resistance to beta-lactams?

Answer 22

Changing the structure of their PBPs
Mutations in PBP genes result in a modified target site to which β–lactams will no longer bind.
E.g Staph. aureus, known as Meticillin Resistant Staph. aureus or MRSA.

Question 23

What are some adverse reactions to antibiotics?

Answer 23

Allergic reactions- commonly associated with the β-lactam (penicillins and cephalosporins).

Immediate hypersensitivity- Anaphylactic shock This is IgE mediated occurs within minutes of administration.
Characterised by itching, urticaria, nausea, vomiting, wheezing and shock. Laryngeal oedema may prove fatal unless the airway is cleared.

Delayed hypersensitivity- Takes hours/days to develop.
Rashes, fever, serum sickness and erythema nodosum may also occur.

Question 24

Which group of antibiotics is most likely to cause nephrotoxicity?

Answer 24

Aminoglycosides

Question 25

How are adverse reactions prevented?

Answer 25

Antimicrobials only used when necessary and for the smallest dosage and duration as possible.
Antimicrobials with a low therapeutic margin should be monitored to ensure maximal efficacy and minimal toxicity
Extra monitoring and care taken when administering to susceptible patients.

Question 26

What are the possible outcomes when antimicrobials are used in combination?

Answer 26

1- Effects are additive. 1+1=2
2- Antagonistic- combined effect is less than the
sum of their individual contributions. 1+1=1
3- Synergistic- combined effect is greater than
the sum of their individual contributions. 1+1=3

Question 27

What affect will the combination of 2 cidal or 2 static drugs have?

Answer 27

Additive or Synergistic

Question 28

What affect will the combination 1 cidal and 1 static drug have?

Answer 28

Antagonistic

Question 29

How long is the standard course of therapy?

Answer 29

7 days

Question 30

How long is the course of therapy for a staph aureus infection?

Answer 30

At least 14 days of IV

Question 31

How long is the course of therapy for a simple UTI?

Answer 31

Short course of 3 days.

Question 32

What is the simplest way to measure MIC?

Answer 32

E-test.

Question 33

What is the role of Polyenes?

Answer 33

Bind to ergosterol, present in the fungal cell wall, increases permeability.
Active against both yeasts and moulds.
E.g Amphotericin B, Nystatin

Question 34

What is the role of Azoles?

Answer 34

Inhibition of ergosterol synthesis.
Oral and parental treatment of Yeast infections
E.g Fluconazole

Question 35

What is the role of Allylamines?

Answer 35

Suppress ergosterol synthesis, but act at a different stage of the synthetic pathway from azoles.
E.g terbinafine

Question 36

What is the role of Echinocandins?

Answer 36

Inhibit the synthesis of glucan polysaccharide in several types of fungi
Only used for serious candida infections.
E.g Caspofungin

Question 37

What is the difference between anti-viral drugs compared to antibiotics and anti-fungal drugs?

Answer 37

There are no virucidal agents, no drugs that kill viruses only static ones.

Question 38

What is the most common mechanism of action of antiviral drugs?

Answer 38

Many anti-viral drugs are nucleoside analogues which

interfere with nucleic acid synthesis.

Question 39

Describe some anti-herpes drugs?

Answer 39

Aciclovir- nucleoside analogue.
It is specific for virus-infected cells and
has very low toxicity for uninfected host cells.
Valganciclovir, Ganciclovir are other examples.

Question 40

Describe some anti-HIV drugs?

Answer 40

Zidovudine - first HIV drug.
Nucleoside analogue interfering with the action of reverse transcriptase.It slows the replication of the virus but does not kill it.
Nevirapine and Saquinavir are also used in combination with zidovudine to treat HIV.

Question 41

What is an interferon-a

Answer 41

Protein that, forms part of the host immune response. Used to treat chronic hepatitis B and C.
Given orally.

Question 42

What drugs ca be used in the treatment of viral respiratory infections?

Answer 42

Zanamivir and Oseltamivir treatment of influenza A or B within 48 hours of the onset of symptoms and for post-exposure prophylaxis. Ribavirin is also used and is inhaled as a fine spray.