Antimicrobial Agents

Question 1

Define antibiotic

Answer 1

• An antibacterial drug is a chemical substance that kills or inhibits the growth of bacteria at a discrete target site
• Generally limited range of activity related to presence or absence of target site and ability of drug to reach target

Question 2

List the major sites of action of antibiotics

Answer 2

• DNA synthesis - quinolones inhibit folding/unfolding of bacteria
  
  • Folic acid antagonists - bacteria cannot produce folic acid itself, folic acid needed in synthesis and repair of DNA
• Protein synthesis - aminoglycosides, macrolides, tetracyclines
• Cell wall synthesis - beta-lactams, glycopeptides (vancomycin)

Question 3

State the primary therapeutic reasons for antibiotic use

Answer 3

• Prophylaxis

- Post infective treatment

Question 4

Describe the use of antibiotics as prophylaxis

Answer 4

• Prophylaxis given to people at increased risk of infection
• Peri-operative - prevention of surgical site infections
  
  • Doses repeated for prolonged surgery
• Short term - meningitis contacts
• Long term - asplenia, immunodeficiency

Question 5

Describe the use of antibiotics as post infective treatment

Answer 5

• Post infective treatment - given to clinically significant infections
• Clinically significant means an infection that left untreated will cause death, permanent harm or medium to long term disability
• Treatment of culture proven infection - takes time (2-3 days)
• Empirical treatment of suspected infection

Question 6

Understand the factors governing antibiotic choice

Answer 6

• Likely cause of infection?
  
  • Anatomical site, age, travel history, PMH, duration of illness
• Which antibiotics are likely to be effective?
  
  • Severity of infection, immune status of patient, baseline rate of resistance
• Which antibiotic is the best choice?
  
  • Age, toxicity, efficacy, cost, administration route, organ function, allergies, drug interactions, pregnancy, breast feeding

Question 7

List the common ADRS for antibiotics

Answer 7

• Toxicities
• Allergic reactions
• Idiosyncratic reactions - unexpected effects not related to dose
• Ecological effects - C. difficile
• Drug interactions

Question 8

Define minimum inhibitory concentration

Answer 8

Minimum concentration of antibiotic required to inhibit growth of a bacterium in vitro

Question 9

Explain the disk sensitivity test

Answer 9

• To measure susceptibility of bacteria to antibacterials - conduct disk sensitivity tests
• Incubate small antibacterial disk on agar plate with test bacterium and measure zone of inhibition of bacterial growth

Question 10

Describe the term breakpoint

Answer 10

• Breakpoint - chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic
• If MIC ≤ breakpoint, then bacteria susceptible to antibiotic
• If MIC ≥ breakpoint, then bacteria resistant to antibiotic

Question 11

Describe the terms time dependent and concentration dependent killing

Answer 11

• Time dependent killing - successful treatment requires prolonged antibiotic presence at site of infection
  
  • Percentage of time free drug concentration exceeds MIC (%ft > MIC)
• Concentration dependent killing - successful treatment requires high antibiotic concentration at site of infection
  - Ratio of maximum drug concentration to MIC (Cmax :MIC)

Question 12

Understand main genetic mechanism underlying microbial resistance

Answer 12

• Chromosomal mutations can result in change in the number or structure of chromosomes in cells
  
  • These are large changes that affect millions of genes, and thus have a great impact
• Horizontal gene transfer - genes responsible for antibiotic resistance in one bacteria is transferred to another bacteria and thus becomes resistant
• Both mechanisms lead to mutations which can spread through replication of affected cells

Question 13

Describe biochemical mechanisms of antibiotic resistance

Answer 13

• Reduced intracellular antibiotic accumulation
  
  • Decreased permeability, active efflux mechanisms
• Antibiotic inactivation - ß-lactamase
• Alteration of target site - penicillin binding protein
• Alteration of metabolic pathways - bacteria use other resources for metabolism

Question 14

Define MDR, XDR and PDR

Answer 14

• Multi-drug resistant (MDR) - non-susceptibility to at least one agent in three or more antimicrobial categories
• Extensively drug resistant (XDR) - non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
• Pan-drug resistant (PDR) - non-susceptibility to all agents in all antimicrobial categories

Question 15

Identify the main interventions for antimicrobial stewardship

Answer 15

• Persuasive - education, consensus, reminders
• Restrictive - restricted susceptibility reporting, formulary restriction
• Structural - computerized records, rapid lab test, quality monitoring