Antimicrobial Pharmacology

Question 1

As part of the “start smart, then focus” antimicrobial stewardship programme, when should a clinical review and decision be made about focusing or changing antimicrobial therapy?

Answer 1

At 48 hours

Question 2

Name two (antibiotic) core drugs that have a narrow therapeutic index

Answer 2

Gentamicin and Vancomycin

Question 3

What pathogens are commonly implicated in the aetiology of CAP?

Answer 3

Streptococcus pneumonia
Haemophilus Influenza
Klebsiella pneumonia
S. Aureus
Atypical organisms
Viral (up to 13%)

Question 4

What investigations should be carried out when considering a diagnosis of CAP?

Answer 4

• CXR
• Sputum sample
• Sputum/throat swab for viral culture and immunofluorescence if immunocompromised patient or creatures suggestive of influenza during flu season
• Serum and urine for pneumococcal and legionella testing if atypical features

Question 5

What is the CURB-65 score used for?

Answer 5

To aid decisions regarding treatment of pneumonia

Question 6

What clinical signs are implicated as indicators of pneumonia severity?

Answer 6

CURB-65 score: 1 point for each of the following-
- Confusion (new onset/ AMT < or = 8)
- Urea > 7 mmol/L
- RR > or = 30/min
- BP (SBP < 90 mmHg and/or DBP <60 mmHg)
> or = 65 years old

0-1: PO abx or home tx
2: Hospital tx
3 or >: Severe pneumonia, consider ITU (mortality 15-40%)

Question 7

What factors should be considered when choosing an antibiotic for the tx of CAP?

Answer 7

• Allergies, CURB-65 score (but also clinical picture), previous abx, recent travel, hobbies, renal function, hepatic function.
  Discuss with microbiology if recent flu
  Is there any need to isolate patient? (e.g. flu / TB risk) Discuss with infection team

Question 8

How do you calculate ideal body weight?

Answer 8

IBW male = 50 kg + (2.3 x every inch over 5 ft)

IBW female = 45.5 kg + (2.3 x every inch over 5 ft)

Question 9

What risks are associated with Gentamicin (aminoglycoside)?

Answer 9

Nephrotoxic. Monitor drug levels and serum creatinine. Also ototoxicity, vestibular toxicity.

Question 10

Contraindications of gentamicin

Answer 10

Severe renal or liver failure, ascites, burns, high cardiac output states (e.g. anaemia, Paget’s), children, pregnancy

Question 11

Signs of Gentamicin toxicity

Answer 11

Tinnitus, deafness, nystagmus, vertigo, renal failure

Question 12

What is the trough level of Gentamicin and when is this measured?

Answer 12

Trough level should be <1 mg/L, which should be measured just before the next dose

Question 13

What are the Beta-lactam antibiotics?

Answer 13

Penicillins- Amoxicillin and Flucloxacillin

Question 14

Drug class: Beta lactam antibiotic + Beta-lactamase inhibitor

Answer 14

Co-Amoxiclav

Question 15

Drug class of vancomycin?

Answer 15

Glycopeptide

Question 16

Drug class of Doxycycline?

Answer 16

Tetracycline

Question 17

Drug class of Clarithromycin, Erythromycin?

Answer 17

Macrolide

Question 18

Drug class of Gentamicin?

Answer 18

Aminoglycoside

Question 19

Drug class of Ciprofloxacin?

Answer 19

Quinolones

Question 20

Drug class of Metronidazole?

Answer 20

Nitroimidazole

Question 21

60-80% of cases of uncomplicated Pyelonephritis are caused by what organism?

Answer 21

E.Coli (gram negative)

Question 22

MOA: Inhibition of bacterial cell wall synthesis. Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls

Answer 22

Cephalosporins

Question 23

Interaction: _________________ enhance the coagulation effect of warfarin by killing normal gut flora that synthesise Vitamin K.
Can cause nephrotoxicity if given with Gentamicin, Ibuprofen and celecoxib

Answer 23

Cephalosporins

Question 24

Adverse effects: GI upset is common (abdominal pain, diarrhoea). Less frequently, can cause C.diff. Leukopenia.

Answer 24

Cephalosporins

Question 25

Ceftriaxone is a _____ generation broad spectrum antibiotic

Answer 25

Third (Remember TRI and third)

Question 26

Which of the Cephalosporin drugs can be used to treat Pseudomonas infections?

Answer 26

Ceftazidime

Question 27

Indications: acute pyelophritis, lower UTIs, HAP

Answer 27

Cephalosporins

Question 28

DOC in MRSA infections?

Answer 28

Vancomycin

Question 29

Indication: NARROW SPECTRUM DRUG. Mainly against Gram-positive bacteria, including MRSA.

Answer 29

Vancomycin

Question 30

Adverse effects of this drug class include “infusion reaction” (formerly known as “red man syndrome”), nephrotoxicity and ototoxicity

Answer 30

Glycopeptide (Vancomycin)

Question 31

MOA: Inhibits peptidoglycan formation. Prevents incorporation of NAM and NAG peptide units from being incorporated into the peptidoglycan matrix, which forms the major structural component of Gram+ cell walls

Answer 31

Vancomycin

Question 32

MOA: Inhibition of protein synthesis in the 50s subunit of the bacterial ribosome

Answer 32

Clarithromycin (Macrolide) (Also Chloramphenicol has same MOA)

Question 33

Indication: Broad spectrum antibiotic to treat Strep pyogenes, Pneumococcal infections, and cell wall deficient bacteria (Chlamydia). Examples include cellulitis, CAP, HAP, and H.pylori (in combination with other drugs)

Answer 33

Clarithromycin (macrolide)

Question 34

Adverse effects of this drug class include GI effects and PROLONGATION OF QT INTERVAL, which can lead to ARRYTHMIAS

Answer 34

Macrolides (Clarithromycin, Erythromycin)

Question 35

Drug interaction: INHIBITOR of p-450 enzyme

Answer 35

Macrolides (“Sickfaces” inhibit) Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol & grapefruit juice, Chloramphenicol, Erythromycin, Sulfonamides, Ciprofloxacin, Omeprazole, Metronidazole

Question 36

Important adverse effects include “Gray baby syndrome” (vomiting, diarrhoea, flaccidity, low temp, and an ashen-gray colour when prescribed in neonates) and also severe bone marrow depression (PANCYTOPENIA)

Answer 36

Chloramphenicol

Question 37

Interaction: Inhibits CYP3A4 and CYP2C19, preventing the metabolism of drugs

Answer 37

Chloramphenicol

Question 38

Adverse effects include DEPOSITION IN TEETH, bone growth inhibition, phototoxicity, and gastric discomfort

Answer 38

Doxycycline

Question 39

MOA: This drug binds reversibly to the 30s subunit of the bacterial ribosome. This action prevents binding of tRNA to the mRNA- ribosome complex, thereby inhibiting bacterial protein synthesis

Answer 39

Doxycycline

Question 40

Interaction: Enhances anticoagulant effect of Warfarin due to competitive interaction for albumin binding

Answer 40

Doxycycline

Question 41

Which two core antibiotics are given IV as they are not absorbed orally?

Answer 41

Vancomycin and Gentimicin

Question 42

MOA: Inside the cell, they bind the 30s ribosomal subunit and cause 3 effects- block formation of the initiation complex, miscoding of amino acids in the emerging peptide chain d/t misreading of the mRNA, block translocation on mRNA

Answer 42

Gentamicin

Question 43

Adverse effects of Gentamicin?

Answer 43

Nephrotoxic, ototoxic

Question 44

MOA: Inhibition of DNA gyrases- topoisomerase II and IV- which are needed for supercoiling, replication, and separation of circular bacterial DNA —> rapid bacterial cell death

Answer 44

Ciprofloxacin (Quinolones)

Question 45

Interactions: Inhibits CYP1A2-mediated metabolism and may inhibit CYP3A4 metabolism. Should be avoided with dairy products

Answer 45

Ciprofloxacin (Quinolones)

Question 46

Adverse effects: TENDONITIS, TENDON RUPTURE, PROLONG QT INTERVAL, nausea, vomiting, headache, dizziness, CNS effects (hallucinations, anxiety, insomnia, confusion, seizures) peripheral neuropathy, phototoxicity

Answer 46

Ciprofloxacin (Quinolones)

Question 47

Are the following bacteria gram negative or gram positive? E. Coli Klebsiella Proteus Pseudomonas Enterobacter

Answer 47

Gram negative

Question 48

What is the first choice of antibiotic for uncomplicated pyelonephritis?

Answer 48

Cefalexin (Cephalosporin) Other choices include Co-Amoxiclav and Ciprofloxacin, depending on result of MC&S

Question 49

First choice of IV antibiotic in Pyelonephritis if patient is vomiting or extremely unwell?

Answer 49

Co-amoxiclav or Ceftriaxone

Question 50

Choice of antibiotic for pyelonephritis in patient who is pregnant?

Answer 50

Cefalexin (not known to be harmful in pregnancy or breastfeeding)

Question 51

Most common organisms causing cellulitis? (2)

Answer 51

Streptococcus pyogenes and Staph aureus

Question 52

First line choice of drug in cellulitis (oral)?

Answer 52

Flucloxacillin (Penacillin)

Question 53

Which two drug classes bind to the 50s subunit of bacterial ribosomes, blocking transpeptidation?

Answer 53

Macrolides and Chloramphenicol

Question 54

Which of the following sx may be a signal to the physician to stop gentamicin therapy? Eosinophilia, headache, nausea, salivation, tinnitus

Answer 54

Tinnitus

Question 55

MOA of tetracycline antibiotics?

Answer 55

Binds reversibly to the 30s subunit of the bacterial ribosome.

Question 56

Which drug class is contraindicated in children < 8 due to deposition in bone and teeth, as well and stunting growth?

Answer 56

Tetracyclines (Doxycycline)

Question 57

Which of the following antibiotics may have contributed to tendon rupture? Amoxicillin/clavulinic acid Cefalexin Ciprofloxacin Minocycline

Answer 57

Ciprofloxacin (Quinolones)