Session 4

Question 1

How do we classify antimicrobials?

Answer 1

• Antibacterial, antifungal, antiviral & antiprotozoal agents
• Antibacterial agents can be classified: –Bactericidal (kill the bacteria) or bacteriostatic (stop it from dividing)
–Spectrum –‘broad’ v. ‘narrow’ –Target site (mechanism of action)
–Chemical structure (antibacterial class)

Question 2

How do we choose an antibiotic?

Answer 2

• Is it active against target organism?
• Does it reach the site of infection?
• Is it available in the right formulation(IV vs oral)?
• What is the half life (decides dosing frequency)?
• Does it interact with other drugs?
• Is there toxicity issues?
• Does it require therapeutic drug monitoring?

Question 3

How do we measure antibiotic activity?

Answer 3

Disc sensitivity testing - zone of inhibition.
Minimum inhibitory concentration (MIC) –broth microdilution - increasing concentration of antibiotic in test tubes. bacterial growth causes solution to become cloudy. first test tube that remains clear when left t incubate is the MIC.
E test - strip that is impregnated with antibiotic with varying concentration. Left in agar with bacteria to incubate. point at which there’s no bacterial growth is MIC (measurement seen on E strip.)

Question 4

What are the 4 mechanisms of antibacterials?

Answer 4

Target cell wall - Beta-lactams (penicillins, cephalosporin), glycopeptides.

Target protein synthesis - Tetracyclines, aminoglycosides, macrolides

Target cell membrane function - Polymixins (e.g. colistin)

Target nucleic acid synthesis - Quinolones, trimethoprim, rifampicin.

Question 5

How does penicillin work?

Answer 5

Penicillin binding protein forms cross linkage between peptidoglycan in the cell wall. Penicillin blocks the binding site of penicillin binding protein and so inhibits this process resulting in weaker cell walls by disrupting the cell wall synthesis

Question 6

How does Vancomycin work?

Answer 6

Vancomycin binds to the alanine residue on peptidoglycan so that penicillin binding protein cant which disrupts cell wall synthesis.

Question 7

What are the types of resistance?

Answer 7

• Intrinsic –No target or access for the drug –Usually permanent
• Acquired –acquires new genetic material or mutates –Usually permanent
• Adaptive –The organism responds to a stress (e.g. subinhibitory level of antibiotic)

Question 8

What are the mechanisms of resistance?

Answer 8

• Enzymatic modification or destruction of antibiotics
• Enzymatic alteration of antibiotic targets
• Mutations of bacterial target sites

Question 9

Explain how chromosomal mutation leads to resistance.

Answer 9

A gene within the chromosome of a bacterium mutates giving the bacteria resistance against an antibiotic. The antibiotic kills off the rest of the population leaving only the resistant bacterium. this goes onto replicate and each subsequent generation carries the resistance gene.

Question 10

Explain the process of horizontal gene transfer.

Answer 10

A resistance gene sits within a plasmid. A pilus on the cell surface of the resistant bacterium connects with the sensitive bacterium and in a process genetic information on the plasmid is shared. The recipient bacterium is now resistant. The bacteria do not need to be of the same species.

Question 11

What are the different classes of beta-lactams?

Answer 11

Penicillins
Cephalosporins
Carbapenems
Monobactams
All share a beta-lactam ring.

Question 12

What is co-amoxiclav?

Answer 12

Penicillin class beta-lactam. IT is amoxicillin combined with clavulanic acid which stabilises the antibiotic against beta lactamases so by preserving its antibiotic activity.

Question 13

Explain cephalosporin strength

Answer 13

With increasing generation comes more strength (although doesn’t render previous generation useless)

Question 14

What are carbapenems used for?

Answer 14

Used as very broad spectrum antibiotics.

Question 15

Give information on what each of the penicillins is used for.

Answer 15

• Penicillin
– Mainly active against streptococci
• Amoxicillin
– Also some activity against Gram-negatives
• Flucloxacillin
– Active against staphylococci & streptococci
• Β-lactamase inhibitor combinations
– Co-amoxiclav (all of above +anaerobes + ↑Gneg
– Piperacillin/tazobactam (as above + ↑↑ Gneg incl pseudomonas)

Question 16

What are cephalosporins used for?

Answer 16

• As ‘Generations’ increase there’s ↑Gneg effectivity and ↓Gpos effectivity
• ↑broad-spectrum but no anaerobe activity so agent needed for abdominal bacteria.
• Ceftriaxone has good activity in the CSF
• Concern over association with C. difficile diarrhoea due to over proliferation s other bacteria are killed.

Question 17

What are carbapenems used for?

Answer 17

• Carbapenems: meropenem, ertapenem, imipenem
–Very broad spectrum (incl anaerobes)
–Active against most (not all) Gram negs
–Generally safe in penicillin allergy
–Often considered the ‘reserve’ antibiotic for Gram-negative infections.

Question 18

What are the glycopeptide antibiotics that you need to know and what do they do?

Answer 18

• Vancomycin
– Active against most Gram pos (not Gnegs)
– Some enterococci resistant (VRE)
– Resistance in staphs rare
– Not absorbed so used intravenously (oral for C. difficile only)
– Therapeutic drug monitoring (TDM) required (narrow therapeutic window)
• Teicoplanin
– Similar activity to vancomycin
– Easier to administer as it doesn’t need to be monitored as closely.

Question 19

Give information on tetracyclines.

Answer 19

Tetracycline (both name of class and actual antibiotic. )& doxycycline
• Similar spectrum, both oral only
• Broad-spectrum but specific use in penicillin allergy, usually for Gram pos
• Active in atypical pathogens in pneumonia
• Active against chlamydia & some protozoa
• Shouldn’t be given to children <12 years, pregnant and breastfeeding women (causes staining of developing teeth).

Question 20

Give information on Aminoglyosides

Answer 20

Aminoglycosides
• Most common agent is gentamicin 
• Profound activity against Gram negs 
• Good activity in the blood/urine 
• Potentially nephrotoxic/ototoxic 
• Therapeutic drug monitoring (TDM) required 
• Generally reserved for severe Gram neg sepsis
*Prevents protein synthesis

Question 21

Give information on Macrolides

Answer 21

Macrolides
• e.g. erythromycin (& clarithromycin)
• Well distributed including intracellular penetration
• Alternative to penicillin for mild Gram pos infections
• Also active against atypical respiratory pathogens
* Prevent protein synthesis
*Given instead of doxycycline to children, pregnant and breast feeding women.

Question 22

Give information on Quinolones

Answer 22

Quinolones
• Commonest example ciprofloxacin
• Inhibit DNA gyrase
• Very active against Gram negs
• Also active against atypical pathogens
• Increasing resistance and risk of C. difficile
• Association with tendinitis and rupture, aortic dissection and central nervous system effects. As a result used as last resort.

Question 23

Give information on Trimethoprim & sulphonamides

Answer 23

• Inhibitors of folic acid synthesis 
• Trimethoprim used alone in the UK for 
• UTI 
• When combined with sulphamethoxazole 
–Co-trimoxazole 
–Used to treat Pneumocystis jirovecii –Has activity against MRSA

Question 24

Give some information on antifungals

Answer 24

Azoles (active against yeasts +/-molds
• Inhibit cell-membrane synthesis
• Fluconazoleused to treat Candida
• Itra/vori/posaconazole also active against Aspergillus

Polyenes (nystatin and amphotericin)
• Inhibit cell membrane function
• Nystatin for topical treatment of candida
• Amphotericin for IV treatment of systemic fungal infections (e.g. aspergillus)

Question 25

Give some information on Antivirals

Answer 25

Aciclovir • When phosphorylated inhibits viral DNA polymerase • Herpes simplex –genital herpes, encephalitis • Varicella zoster –chicken pox & shingles Oseltamivir(‘Tamiflu’) • Inhibits viral neuraminidase • Influenza A & B Specialist agents for HIV, HBV, HCV, CMV

Question 26

What is Metronidazole

Answer 26

Metronidazole is an antibacterial and Antiprotozoal agent • Active against anaerobic bacteria e.g. so given with cephalosporins • Also active against protozoa: –Amoebae (dysentery & systemic) –Giardia (diarrhoea) –Trichomonas(vaginitis)