Antibiotics Part 2

Question 1

Describe features of Vancomycin

Answer 1

• It is a glycopeptide antibiotic which is ultrabroad spectrum for gram positive bacteria.
• Delivered IV but has difficult pharmacodynamics
• Less effective than fluclox for MSSA but used in patients who have MRSA or can’t take fluclox.
• Active against MRSA, streptococci, MSSA,
• Main issue in clinical use is underdosing

Not active against coliforms, difficult gram negatives or anaerobes

Question 2

What are the diffierent toxic effects seen with vancomycin

Answer 2

• Nephrotoxicity (with high doses)
• Red-man syndrome if injected rapidly (anaphylactoid syndrome)
• Ototoxicity
• Therefore theraputic drug monitoring is undertaken due to its narrow theraputic range

Question 3

What gene gave rise to S.aurus resistance and what drug can be used in MRSA

Answer 3

• MecA gene inherited from S. fleurettii
• Vancomycin is used

Question 4

Describe features of Gentamicin

Answer 4

• It is an aminoglycoside antibiotic with very broad spectrum which can only be delivered IV
• Principally useful against gram negatives so useful with intra-abdominal infections and UTI
• Low rates of resistance in community but not uncommon

Active against most gram negatives

Question 5

Explain the mechanism of action of aminoglycosides

Answer 5

• Reversibly binds to the 30S ribosome which causes a bacteriostatic action, prolonging the post-antibiotic effect.
• It has a bactericidal action by acting on the cell membrane. Results in rapid lysis early in dosing intervals with high doses

Question 6

What are the toxic side effects of aminoglycosides

Answer 6

• Nephrotoxicity
• Ototoxicity (hearing loss, loss of balance, oscillopsia)
• Neuromuscular blockage (usually only significant in patients with myasthenia gravis - AVOID in these patients)

Question 7

What is the dosing regimen for aminoglycosides

Answer 7

• Once daily dosing. High initial dose to take advantage of rapid killing.
• Leave long dosing interval (24-48hrs) to minimuse toxicity
• Make sure to measure trough level between doses to ensure drug is not accumulating
• Give for 3 days only

Question 8

What are personal risk factors for resistance?

Answer 8

• Antibiotic consumption within the last 6 months
• Overnight stays in hospitals
• Visiting countries with high incidence of drug resistance
• This resistence may occur for many months after acquired

Question 9

Describe features of Macrolides

Answer 9

• Class of antibiotics with a good spectrum of activity against gram positives and respiratory gram negatives
• Active against atypicals such as legionella, mycoplasm or chlamydia
• Ecellent oral absorption
• Examples include erythromycin, azithromycin and clarithromycin

Question 10

What are the main targets of antibiotics

Answer 10

• Cell wall biosynthesis (targeted by betalactams and vancomycin)
• Protein biosynthesis (argeted by macrolides, aminoglycosides and tetracyclines)
• DNA and RNS synthesis (Rifampin and quinolones)
• Folate metabolism (trimethoprim)

Question 11

What are the main side effects and drug interactions of macrolides

Answer 11

• Side effects are diarrhoea and vomiting, QT prolongations and hearing loss with long term use.
• Resistance among typical pathogens is common but in atypical pathogens is rare.
• Interacts with simvastatin so avoid co-prescription, atorvastatin and warfarin.

Question 12

Describe features of clindamycin

Answer 12

• Similar to macrolides as it has same mechanism, good oral absorptions and principally active against gram positives
• However no action against aerobic gram negatives or atypicals but does have excellent activity against anerobes so often used in abscesses
• It is highly effectice at stopping exotoxin production so added alongside other antibiotics in toxic shock syndrome and necrotising fasciitis

Question 13

Name and describe the C.differgic antibiotics

Answer 13

• These are antibiotics that dramatically disturb the colonic flora. C.diff forms spores which are difficult to erradicate from hospitals
• 4Cs are the common causes but all antibiotics can cause C.diff:
• Clindamycin
• Co-amoxiclav
• Cephalosporins
• Ciprofloxacin

Question 14

Describe features of tetracyclines

Answer 14

• Active against MSSA, streptococci and atypical organisms
• Relatively non doxic but avoid in children and pregnant women as it can cause bone abnormalities and tooth discolouration

Question 15

Describe features of Quinolones

Answer 15

• Broad spectrum, bactericidal antibiotics which targert Dna/RNS synthesis
• Excellent oral bioavailability
• Agtive gainst many atypical pathogens

Question 16

Explain side effects of quinolones

Answer 16

• Toxic side effects include: GI toxicity, QT prolongation and tendonitis which can cause tendon rupture.
• Resistance is emerging and is prone to causing C.diff esp. in N.America

Question 17

Name examples of quinolones and their uses

Answer 17

• Ciprofloxacin. Mainly used against gram negative pathogens, can be used against pseudomonas.
• Levofloxacin. It is an extended spectrum quinolone with increased activity against gram positive (MRSA). Used for LRTI/pneumonia

Question 18

What are the indications and interactions of rifampicin

Answer 18

• Used for tuberculosis (combination therapy) or in addition to another antibiotic in serious gram positive infections.
• Rifampicin is a potent CYP450 enzyme inducer so affect most drugs that undergo hepatic metabolism

NEVER prescribe rifampicin as a monotherapy.

Question 19

Explain the methanism of action of trimethorprim and other folate metabolism antibiotics

Answer 19

• Inhibition of folate metabolism pathway leads to impaired nucleotide synthesis and therefore impaired DNA replication

Question 20

Describe the uses and side effects of trimethoprim

Answer 20

• Good range against gram positive and negative but due to resistance is limited to uncompensated UTIs
• Toxic effects: Cause elevation of serum creatinine, elevation of serum potassium, Rash and Gi distrubances (uncommone)

Question 21

What is co-trimoxazole and its side effects

Answer 21

• Combination of trimethoprim and sulphamethoxazole
• Can cause bone marrow suppression and steven johnson syndrome
• Tends to only be used by specalists

Question 22

Describe features of metronidazole

Answer 22

• Enters the cell by passive diffusion and produces free redicles.
• More effective against anaerobic bacteria
• Often added to therapy for intra-abdominal infections
• Causes unpleasant reaction with alcohol and peripheral neuropathy