Antimicrobial Chemotherapy

Question 1

MIC

Answer 1

Minimal Inhibitory Concentration - the minimum concentration of antimicrobial needed to inhibit visible growth of a given organism.

Question 2

MBC

Answer 2

Minimal bactericidal concentration - the minimum concentration of the antimicrobial needed to kill a given organism.

Question 3

Sensitive

Answer 3

An organism is considered sensitive if it is inhibited or killed by levels of the antimicrobial that are available at the site of infection.

Question 4

Resistant

Answer 4

An organism that is not killed or inhibited by levels of the antimicrobial that are available at the site of the infection. When it is unlikely to respond to attainable levels of drug in tissue.

Question 5

Bacteriocidal

Answer 5

An antimicrobial that kills bacteria e.g. penicillin

Question 6

Bacteriostatic

Answer 6

An antimicrobial that inhibits growth of bacteria e.g. erythromycin

Question 7

Synergy

Answer 7

coordinated/correlated action of 2+ substances so that the combined action is greater than the sum of each acting separately.

Question 8

Antagonism

Answer 8

opposing actions of drugs

Question 9

Antibiotics

Answer 9

May inhibit or kill bacteria by acting at one of three different areas of metabolic activity.

1) Inhibition of cell wall synthesis; B-lactams (penicillins and cephalosporins) and glycopeptides (vancomycin and teicophlanin)
2) Inhibition of protein synthesis, work in ribsomes; aminoglycosides (gentamicin), macrolids (erythromycin, clarithromycin and tetracyclines), oxazolidinones (linezolid), cyclic lipopeptides (daptomycin).
3) Inhibitors of nucleic acid synthesis; trimethoprim and sulphamethoxazole (co-trimoxazole), fluoroquinolones (ciprofloxacin)

Question 10

Antifungal drugs

Answer 10

1) Polyenes (amphotericin B, nystatin) which bind to ergosterol increasing permeability of the cell wall.
2) Azoles (miconazole, ketoconazole, fluconazole, itraconozole and voriconozole) inhibit ergosterol synthesis.
3) Allylamines (terbinafine) suppress ergosterol synthesis at a different stage.
4) Echinocandins (caspofungin, mycafungin, anidulafungin) inhibit synthesis of glucan polysaccharide in several types of fungi.

Question 11

Antiviral drugs

Answer 11

1) Virustatic - inhibit growth and/or respiration

2) Nucleoside analogues - interfere with nucleic acid synthesis.

Question 12

Inherent/intrinsic resistance

Answer 12

sometimes all strains of a spp. are naturally resistant to an abx. Usually due to inability of the drug to penetrate the cell wall.

Question 13

Acquired resistance

Answer 13

This can be due to a spontaneous mutation during multiplication of bacterial DNA resulting in a structural/functional change. Or the gene(s) that code for resistance can spread between organisms or species.

Question 14

Clinically important resistance mechanisms to B-lactams

Answer 14

1. B-lactamse production cleaves the abxs B-lactam ring
2. Alteration of of penicillin binding protein (PBP) target site.
3. Extended spectrum B-lactamases (ESBL)

Question 15

Other resistance mechanisms to abx

Answer 15

1. Glycopeptide resistance; vancomycin resistance is unusual in Gram positive organisms however VRE have recently appeared as the peptidoglycan precursor has altered structure.
2. Blocking transport of drug into cell
3. Actively transports drug out of the cell
4. Carbapenemase-producing Enterobacteriaceae

Question 16

Antiviral resistance

Answer 16

Testing is at its infancy and not commonly available. Genotypic analysis (sequencing a part of viral genome) helps in choosing treatment.

Question 17

Factors to be considered when choosing drug treatment

Answer 17

Patient charactersitics; age, renal function, liver function, pregnancy.
Drug related considerations; spectrum (narrow), monotherapy vs combination, penetration to site of infection, monitoring, dose and duration.
Indication; prophylaxis, therapy

Question 18

Common side effects with major drug groups

Answer 18

Allergic reactions, GI (nausea, vomiting, diarrhoea), thrush/vaginal candidiasis, liver toxicity, renal toxicity, neurological toxicity, ototoxicity, optic neuropathy, encephalopothy, convulsions, peripheral neuropathy, haematological toxicity (neutropenia, pancytopenia, folic acid deficiency, bone marrow suppression).

Question 19

Role of laboratory and clinical microbiologists in influencing antimicrobial use in practice

Answer 19

Advice, monitoring of efficacy and toxicity, susceptibility testing (automated methods, E-test)