Antibiotics

Question 1

Penicillins MOA

Answer 1

Binds to penicillin binding proteins on bacterial cell walls, inhibiting cell wall biosynthesis (disrupt the synthesis of the peptidoglycan layer). Bactericidal. Demonstrates time-dependent killing.

Question 2

Amoxicillin Coverage

Answer 2

Streptococci; Enterococcus faecalis; Listeria; N. meningitidis
Some Staph coverage
Excellent bioavailability.

Question 3

Ampicillin Coverage

Answer 3

Streptococci; Enterococcus faecalis; Listeria; N. meningitidis. [Same spectrum as amoxicillin.]
Good CSF penetration. Useful in severe listeria infections due to availability of an IV formulation

Question 4

Flucloxacillin Coverage

Answer 4

MSSA (and sometimes some MRSAs) some Streptococci (other penicillins covers more Streptococci species)

Question 5

Pencillin V

Answer 5

Streptococci; oral anaerobes (e.g. Actinomyces, Clostridium perfringens, Peptostreptococci,
Propionibacterium). Still no resistance with Group A Streptococcus (aka Streptococcus pyogenes)
Rheumatic fever prophylaxis

Question 6

Cephalosporins MOA

Answer 6

Binds to penicillin binding proteins on bacterial cell walls, inhibiting cell wall biosynthesis (disrupt the synthesis of the peptidoglycan layer). Bactericidal. Demonstrates time-dependent killing. Gram-negative coverage increases as generation increases.
All cephalosporins lack coverage of Listeria, atypicals, MRSA, & Enterococci (LAME).

Question 7

Cephalexin coverage

Answer 7

Streptococci; MSSA; ?Proteus; E. coli; Klebsiella Ceftriaxone

Question 8

Cefuroxime (2nd gen cephalosporin) coverage

Answer 8

Streptococci; MSSA; Moraxella; Haemophilus influenzae; Proteus; E. coli; Klebsiella.
Oral bioavailability greatly increased with food

Question 9

Ceftriaxone (3rd gen cephalosporin) coverage

Answer 9

excellent gram-negative coverage (e.g. Citrobacter, E. coli, Klebsiella,
Morganella, Proteus, Serratia)
1 off IM for Gonorrhoea

Question 10

Macrolides MOA

Answer 10

Macrolides are protein synthesis inhibitors.
This is by preventing peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid and inhibiting ribosomal translocation.
Macrolide antibiotics do so by binding reversibly to the P site on the 50S subunit of the bacterial ribosome.
Bacteriostatic.
Macrolides are actively concentrated within leukocytes, and thus are transported into the site of infection.

Question 11

Which Macrolide doesn’t interact with CYP3A4 ?

Answer 11

Azithromycin

Question 12

Benefit of Macrolides prophylaxis - specifically in chronic bronchiectasis?

Answer 12

Macrolides inhibit biofilm formation, inhibits production of immunostimulatory cytokines (from neutorphils) in response to pseudomonas and other chronic colonised infections.
Azithromycin also increases gut motility

Question 13

Azithromycin coverage

Answer 13

Streptococci; N. gonorrhoeae; Moraxella; Haemophilus influenzae; Legionella; many atypicals.
When using in pneumonia - the additional coverage compared with doxy is predominantly legionella cover (an Aaron ward question)

Question 14

Clarithromycin coverage

Erythromycin Coverage

Answer 14

CLINDA:
Streptococci; Moraxella; Haemophilus influenzae; Legionella; many atypicals.
(SAME AS AZITHRO BUT NO N.GONORRHOEA COVER)

ERYTHRO
As above but NO H. INFLUENZAE COVER - so only of use in young patients (<12) for pneumonia empirical therapy

Question 15

Key Drug interactions of Macrolides

Answer 15

Clarithromycin and erythromycin CYP3A4 & p-glycoprotein inhibitors (clarithromycin > erythromycin)

Question 16

Tetracycline Antibiotics MOA

Answer 16

Protein synthesis inhibitors. Bacteriostatic. They inhibit the initiation of translation in variety of ways by binding to the 30S ribosomal subunit, which is made up of 16S rRNA and 21 proteins.

Question 17

Condition to be wary of in Macrolide and Aminoglycoside antibiotics

Answer 17

Caution in myasthenia gravis

Question 18

Doxycycline coverage

Answer 18

Staphylococci (& often MRSA); Strep pneumoniae; Moraxella;
Haemophilus influenzae; many atypicals; many anaerobes including spirochetes

Aaron ward question: Why do we give doxy with amoxy in CAP? H.Influenzae coverage but as we can see above - also atypical and anaerobes

Take on empty stomach

Question 19

Fluroquinolones MOA

Answer 19

Inhibits DNA-gyrase, causing breakdown of bacterial DNA. Bactericidal. Concentration dependent killing (aim for high peak concentrations)

Question 20

Classical Adverse events on fluroquinolones

Answer 20

QT prolongation; confusion/psychosis, seizure, tendinopathy/tendon rupture, retinal detachment

Question 21

Drug interactions of fluroquinolones

Answer 21

CYP1A2 inhibition ↑levels of clozapine, duloxetine, methotrexate
increased INR with warfarin.
QT prolongation (watch for other QT-prolonging agents)

Question 22

Ciprofloxacin coverage

Answer 22

Primarily gram-negative coverage: Pseudomonas; Enterobacteriaceae; ?Neisseria; Haemophilus;
Moraxella; Pasteurella; many atypicals. Essentially no anaerobic coverage.

Question 23

Moxifloxacin

Answer 23

Strep pneumoniae; MSSA; Enterobacteriaceae; Neisseria; Haemophilus; Moraxella; Pasteurella;
many atypicals; some anaerobes

Does not penetrate urine

Question 24

Norfloxacin

Answer 24

Strep pneumoniae; MSSA; Enterobacteriaceae

Question 25

Antifolates MOA

Answer 25

Prevent bacterial folate synthesis. Sulfamethoxazole & trimethoprim inhibit successive steps in folic acid pathway, & thus are synergistic in combination. Combination bactericidal; concentration-dependent killing.

Question 26

Antifolates: contraindicated cohorts

Answer 26

History of drug induced-immune thrombocytopenia from sulfonamides or trimethoprim; megaloblastic anemia from folate deficiency; severe liver disease; previous SJS from sulfonamides.

Caution: patients with G6PD deficiency (risk of hemolysis)
And caution with those on K+ sparing diuretics: impairs urinary K excretion

Question 27

Sulfamethuxozole / Trimethoprim

Answer 27

Staphylococci (& often MRSA); Streptococcus pneumoniae; S. maltophilia; Moraxella;
Haemophilus influenzae; Enterobacteriaceae; Shigella; ?Listeria; Burkholderia; Brucella; Pneumocystis.

Question 28

Timethoprim alone

Answer 28

Same as bactrim but no moraxella

Staph, Strep, haemophilus, enterobacteriaceae

Question 29

Clindamycin MOA, adverse effects and coverage

Answer 29

Protein synthesis inhibition through binding of 50S ribosomal subunit (similar to macrolides). Lincomycin group of antibiotics
Staphylococci;
Streptococci; many oral anaerobes. Unreliable MRSA
Deranged LFTs. Rare: leukopenia, thrombocytopenia. Higher risk of Clostridium
difficile than other agents.

Question 30

Metronidazole MOA, adverse effects and coverage

Answer 30

Disrupts DNA of bacterial cells. Bactericidal. Coverage: most anaerobes, including anaerobic protozoa.

neuropathy if long-term use (e.g. > 6 wks)
Reaction with alcohol - nausea vomiting rash

Question 31

Nitrofurantoin MOA, adverse effects and coverage

Answer 31

Damages bacterial DNA/proteins (bacteria convert nitrofurantoin into reactive forms).
Coverage: Staphylococci; E. coli; Enterococcus faecalis; Citrobacter; Klebsiella.
Concentrated in the urine and turns urine a brownish colour.

Question 32

Fosfomycin MOA and coverage

Answer 32

Inhibits cell-wall formation by inactivating the enzyme UDP-N-acetylglucosamine-3-enolpyruvyltransferase, also known as MurA. Bactericidal. Coverage: ?Staphylococci; Enterococci; Enterobacteriaceae

Question 33

Linezolid MOA and coverage

Answer 33

Inhibits bacterial protein synthesis through disruption of mRNA. Usually bacteriostatic, but bactericidal against Streptococci. Its also a weak, non-selective, reversible monoamine oxidase inhibitor

Streptococci; Enterococci (including VRE); Staphylococci (including MRSA)

First line in Enterococcus faecium (VRE)

Question 34

Probenicid use and mechanism of action

Answer 34

Prolongs penicillin levels by competitively inhibiting their excretion. Give 30-45min prior to IV penicillin dose
Also increases uric acid excretion by interacting with the organic anion transporter.

Question 35

Vancomycin MOA and coverage

Answer 35

Inhibits cell-wall formation by binding to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis
Coverage: The only oral use is for treatment of Clostridium difficile colitis (drug of
choice if severe infection, or if second recurrence of C. diff infection
Also coverage of MRSA (and MSSA), strep,and enterococcus.

Question 36

Carbapenums Coverage

Answer 36

Gram-positives: Generally very good, but does miss MRSA and Enterococcus faecium.
Gram-negative coverage:
Overall excellent (including pseudomonas, ESBL and Amp-C multi-drug resistant species).
Some carbapenem resistance is starting to emerge among enterobacteriaceae (especially among Klebsiella pneumoniae);
Anaerobic coverage: Excellent (but doesn’t cover Clostridium difficile)

Question 37

Ertopenum vs. Meropenum coverage

Answer 37

Main differences compared to meropenem:
1) Lacks coverage of pseudomonas and acinetobacter.
2) Limited ertopenum activity against enterococci.
May be superior for non-pseudomonal gram-negatives

Question 38

Carbapenum MOA

Answer 38

Bactericidal beta-lactam antibiotics that bind to penicillin-binding proteins (PBPs). By binding and inactivating these proteins, carbapenems inhibit the synthesis of the bacterial cell wall. Much the same as other beta-lactams.

Question 39

Steven-Johnson Syndrome causative agents

Answer 39

Allopurinol > Antiepileptics > Sulfonoamides > NSAIDs