Antimicrobial Chemotherapy

Question 1

• Explain MIC and MBC

Answer 1

Minimal bactericidal concentration: minimum concentration of antimicrobial needed to kill a given organism

Minimal inhibitory concentration: minimum concentration of antimicrobial needed to inhibit growth of a given organism

Question 2

Sensitive / resistant

Answer 2

Sensitive: organism is sensitive if it is inhibited or killed by the antimicrobial available at site of infection

Resistant: organism is resistant if it is not killed or inhibited by the antimicrobial available at site of infection

Question 3

Bactericidial/bacteriostatic

Answer 3

• Bactericidal: antimicrobial that kills bacteria
• bacteriostatic: antimicrobial that inhibits growth of bacteria

Question 4

Synergy/antagonism

Answer 4

Synergistic: combination of two cidal drugs or two static drugs

Antagonism: one static and one cidal drug

Question 5

Factors to be considered in choosing suitable antimicrobial agents to prevent or treat infection

Answer 5

• Allergies

Question 6

• Role of laboratory and clinical microbiologists in influencing antimicrobial usage in clinical practice

Answer 6

Medical microbiologists: give advice on urgent treatment of infection before organism is isolated, identified and its antibiotic sensitivity tested

Question 7

Routes of administration of antibiotics

Answer 7

Topical: applied to a surface

Systematic: taken internally

Parental: intra-venously or intra-musularly

Question 8

Shapes of bacteria

Answer 8

• Spheres: (cocci)
• rods: (bacilli)
• spirals

Question 9

Mechanisms of action of antibiotics

Answer 9

Inhibit or kill bacteria by acting at 3 different areas of metabolic activity

• inhibition of cell wall synthesis (humans don’t have cell walls)
• inhibition of protein synthesis
• inhibition of nuclei acid synthesis

Question 10

Inhibition of cell wall synthesis

Answer 10

• Penicillins and cephalosporins
  (Most effective against gram positive bacteria)
• glycopeptides (only act on gram-positive organisms)
• vancomycin (no b-lactam ring) - toxicity is common

Question 11

Inhibition of protein synthesis

Answer 11

• Aminoglycosides: concentration-dependent bacterial antibiotics, useful in treatment of serious gram-negative infection
• macrolides: bactericidal or bacteriostatic antibiotics (gram-positive infections)
• tetracyclines: bacteriostatic antibiotics (gram-positive infections)

Question 12

Inhibition of nucleic acid synthesis

Answer 12

• G genetic material cannot be transferred, stops purine synthesis -
• Trimethoprim + sulphamethoxazole = co-trioxmazole ( inhibition of purine synthesis) bacteriostatic when combined with bactericidal antibiotics
• No formation of chromosome
• fluoroquinolones: bactericidal antibiotics (gram negative organisms)

Question 13

Types of resistance

Answer 13

-Inherent/intrinsic: (streptococci always resistant to aminoglycosides and gram negative organisms always resistant to vancomycin),

• acquired: spontaneous mutation or spread of resistance (conjugation, transduction or transformation)

Question 14

Current issues in antibiotic resistance: B-Lactamase production

Answer 14

~ (common in gram-negative bacilli) render b-Lactamase ring inactive by cleaving to it

~ combat: co-amoxiclav modifies antibiotic side chain producing new antibiotic resistant to b- Lactamase
Flucloxacillin protects antibiotic from enzymatic degradation

Question 15

Current issues in antibiotic resistance - glycopeptide resistance

Answer 15

• Resistance to vancomycin among gram-positive organisms was virtually unknown

Question 16

B-lactams: penicillins

Answer 16

Benzyl penicillin: gram positive organisms

Amoxicillin, ampicillin: gram-negative activity

Co-amoxiclav: b-lactamase producing coliforms

Flucloxacillin: staphylococcal infections

Piperacillin: extended gram-negative cover

Imipenem-meropenem: active against most bacteria, including anaerobes

Question 17

B-lactams: cephalosporins

Answer 17

Cephradine → cefuroxine → ceftriaxone + ceftazidime
( increasing in generation)

Gram-negative activity: increases through generations

Gram-positive activity: decreases proportionately through generations

Question 18

Commonly used agents (parenteral use only)

Answer 18

• Aminoglycosides
• glycopepticles

Question 19

Urinary tract agents

Answer 19

• Naliclixic acid
• nitrofurantion

Question 20

Side effects and toxicity

Answer 20

• Allergic reactions
• immediate hypersensitivity
• delayed hypersensitivity
• gastrointestinal effects
• thrush (overgrowth of yeast resulting in oral/vaginal candiasis)
• liver toxicity
• renal toxicity
• ototoxicity
• optic neuropathy
• peripheral neuropathy
• encephalopathy and convulsions
• haematological toxicity

Question 21

Advice on choice of Antimicrobial

Answer 21

1. Ensure that therapeutic levels have been achieved
2. To ensure that levels are not so high as to be toxic