Penicillin

Question 1

What is the mechanism of action of penicillins?

Answer 1

Penicillins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), which are enzymes involved in peptidoglycan synthesis.

Question 2

What is the role of penicillin-binding proteins (PBPs)?

Answer 2

PBPs are enzymes that act as catalysts in the synthesis of the peptidoglycan cell wall in bacteria.

Question 3

What happens when PBP1a and PBP1b in E. coli are inhibited?

Answer 3

Inhibition of PBP1a and PBP1b causes cell elongation and rapid cell lysis.

Question 4

What is the effect of inhibiting PBP2 in E. coli?

Answer 4

Inhibition of PBP2 results in stable round forms that grow for several generations before lysing.

Question 5

What is the effect of inhibiting PBP3 in E. coli?

Answer 5

Inhibition of PBP3 leads to filamentous forms that grow for 5-6 generations before becoming deformed and dying.

Question 6

What are the four main mechanisms of bacterial resistance to β-lactams?

Answer 6

1) Production of β-lactamases, 2) Reduced affinity of PBPs for β-lactams, 3) Impermeability of the cell membrane, 4) Efflux pumps.

Question 7

What is the function of β-lactamase?

Answer 7

β-lactamase breaks the β-lactam ring of penicillin, rendering the antibiotic ineffective.

Question 8

What are natural penicillins?

Answer 8

Natural penicillins include Penicillin G and Penicillin V.

Question 9

What is the spectrum of activity of Penicillin G?

Answer 9

Penicillin G is most active against non-β-lactamase producing Gram-positive bacteria, some anaerobes, and selected Gram-negative cocci like Neisseria meningitidis.

Question 10

What bacteria are typically resistant to Penicillin G?

Answer 10

Staphylococci, PRSP (penicillin-resistant Streptococcus pneumoniae), Neisseria gonorrhoeae, H. influenzae, Enterobacteriaceae, and Pseudomonas.

Question 11

What is MRSA, and how does it resist penicillins?

Answer 11

MRSA (Methicillin-resistant Staphylococcus aureus) produces altered PBPs (PBP2a) that have reduced affinity for β-lactams, making them resistant to most penicillins.

Question 12

What percentage of S. aureus isolates in Edmonton were MRSA in 2019?

Answer 12

25% of S. aureus isolates in Edmonton were MRSA in 2019.

Question 13

What is the resistance mechanism in Streptococcus pneumoniae?

Answer 13

Resistance in Streptococcus pneumoniae is due to altered PBPs.

Question 14

What is the susceptibility of Enterococcus faecalis to ampicillin/amoxicillin in 2019?

Answer 14

100% of Enterococcus faecalis isolates were susceptible to ampicillin/amoxicillin in 2019.

Question 15

Why are Enterobacteriales intrinsically resistant to penicillins?

Answer 15

Enterobacteriales are intrinsically resistant due to β-lactamase production, reduced affinity for PBPs, and cell wall impermeability.

Question 16

What is the mechanism of resistance in Neisseria gonorrhoeae?

Answer 16

Resistance in Neisseria gonorrhoeae is due to β-lactamase production and decreased affinity of PBPs.

Question 17

What are penicillinase-resistant penicillins?

Answer 17

Penicillinase-resistant penicillins, such as cloxacillin, have bulky side chains that protect the β-lactam ring from being broken by β-lactamases.

Question 18

What is the spectrum of activity of cloxacillin?

Answer 18

Cloxacillin is active against β-lactamase-producing staphylococci but not MRSA or MRSE. It is usually used for skin infections caused by S. aureus and S. pyogenes.

Question 19

What are aminopenicillins?

Answer 19

Aminopenicillins, such as ampicillin and amoxicillin, have an amino group added to the side chain, which increases their spectrum of activity against Gram-negative bacteria.

Question 20

What is the spectrum of activity of ampicillin and amoxicillin compared to Penicillin G?

Answer 20

Ampicillin and amoxicillin are more active against S. pneumoniae, Enterococcus, Listeria monocytogenes, and some Gram-negative bacteria like H. influenzae and E. coli.

Question 21

What is the role of clavulanic acid?

Answer 21

Clavulanic acid is a β-lactamase inhibitor that irreversibly binds to β-lactamase, protecting the β-lactam ring of penicillins from being broken.

Question 22

What is the spectrum of activity of amoxicillin/clavulanic acid?

Answer 22

Amoxicillin/clavulanic acid has an expanded spectrum that includes Enterococci, H. influenzae, Moraxella catarrhalis, many Enterobacteriaceae, and Bacteroides spp.

Question 23

What are antipseudomonal penicillins?

Answer 23

Antipseudomonal penicillins include carboxypenicillins (e.g., ticarcillin) and ureidopenicillins (e.g., piperacillin).

Question 24

What is the spectrum of activity of piperacillin/tazobactam?

Answer 24

Piperacillin/tazobactam is active against β-lactamase-producing Staphylococci, Streptococci, Enterococci, Pseudomonas aeruginosa, H. influenzae, M. catarrhalis, many Enterobacteriaceae, and Bacteroides fragilis.

Question 25

How are penicillins distributed in the body?

Answer 25

Penicillins are well-distributed to most areas, with good levels in middle ear, pleural, peritoneal, and synovial fluids. In the absence of inflammation, levels in CSF, eye, brain, and prostate are minimal.

Question 26

How are penicillins excreted from the body?

Answer 26

Most penicillins are excreted intact by the kidneys through glomerular filtration and renal tubular secretion.

Question 27

What is the half-life of Penicillin G in patients with normal renal function?

Answer 27

The half-life of Penicillin G is 0.5 hours in patients with normal renal function.

Question 28

What is the most common adverse effect of penicillins?

Answer 28

The most common adverse effect of penicillins is hypersensitivity reactions, ranging from rash to anaphylaxis.

Question 29

What is the incidence of anaphylactic reactions to parenteral penicillin?

Answer 29

The incidence of life-threatening anaphylactic reactions to parenteral penicillin is 0.01-0.02%, with a fatality rate of 0.0015-0.02%.

Question 30

What is the risk of CNS toxicity with penicillins?

Answer 30

CNS toxicity, such as myoclonic seizures, can occur with large doses of penicillin or in patients with renal failure without dosage adjustment.

Question 31

What is interstitial nephritis, and how is it related to penicillins?

Answer 31

Interstitial nephritis is a rare adverse effect of penicillins, characterized by fever, rash, eosinophilia, proteinuria, and hematuria. It is most common with methicillin but can occur with any penicillin.

Question 32

What is the risk of neutropenia with penicillins?

Answer 32

Neutropenia occurs in 1-4% of patients receiving penicillins, especially with large doses. WBC counts usually return to normal after discontinuing the drug.

Question 33

What is Coombs-positive hemolytic anemia?

Answer 33

Coombs-positive hemolytic anemia is a type II reaction where penicillin binds to red blood cells, leading to antibody formation and complement-mediated destruction of RBCs.

Question 34

What are the gastrointestinal adverse effects of penicillins?

Answer 34

Gastrointestinal adverse effects include diarrhea, nausea, and, rarely, hepatic injury with elevated liver enzymes.

Question 35

What is the interaction between allopurinol and ampicillin?

Answer 35

The combination of allopurinol and ampicillin increases the incidence of rash, occurring in up to 14-22.4% of patients.

Question 36

How does probenecid affect penicillin excretion?

Answer 36

Probenecid reduces the renal excretion of penicillins, leading to increased blood levels.

Question 37

What is the absorption rate of Penicillin G?

Answer 37

Penicillin G is 20% absorbed when taken orally.

Question 38

What is the absorption rate of Amoxicillin?

Answer 38

Amoxicillin is 75% absorbed when taken orally.

Question 39

What is the protein binding percentage of cloxacillin?

Answer 39

Cloxacillin is 94% protein-bound.

Question 40

What is the half-life of amoxicillin in patients with normal renal function?

Answer 40

The half-life of amoxicillin is 1 hour in patients with normal renal function.

Question 41

What is the half-life of piperacillin in patients with normal renal function?

Answer 41

The half-life of piperacillin is 1.3 hours in patients with normal renal function.

Question 42

What is the maximum dose of clavulanic acid for children?

Answer 42

The maximum dose of clavulanic acid for children is 10 mg/kg/day.

Question 43

What is the spectrum of activity of ticarcillin?

Answer 43

Ticarcillin is a carboxypenicillin with activity against Pseudomonas aeruginosa and other Gram-negative bacteria.

Question 44

What is the spectrum of activity of piperacillin?

Answer 44

Piperacillin is a ureidopenicillin with activity against Pseudomonas aeruginosa, Enterobacteriaceae, and Bacteroides fragilis.

Question 45

What is the role of tazobactam in piperacillin/tazobactam?

Answer 45

Tazobactam is a β-lactamase inhibitor that protects piperacillin from being broken down by β-lactamases.

Question 46

What is the incidence of skin rash with ampicillin?

Answer 46

The incidence of skin rash with ampicillin is increased, especially when combined with allopurinol.

Question 47

What is the effect of food on the absorption of Penicillin V?

Answer 47

Food does not affect the absorption of Penicillin V.

Question 48

What is the effect of food on the absorption of Amoxicillin?

Answer 48

Food does not affect the absorption of Amoxicillin.

Question 49

What is the effect of renal failure on penicillin excretion?

Answer 49

In renal failure, penicillin excretion is reduced, leading to increased blood levels and potential toxicity.

Question 50

What is the incidence of hepatic injury with penicillins?

Answer 50

Hepatic injury is uncommon (1-4%) and usually reversible upon discontinuation of the drug.