3 - Pharm: Beta Lactams

Question 1

Describe the mechanism of action of the beta lactam antibiotics.

Answer 1

Bactericidal
They are structural analogs of natural substrates that allow them to covalently bind to the active site of Penicillin Binding Proteins (PBPs)
They inhibit bacterial growth by inhibiting transpeptidation reactions that mediate peptide cross-linking in cell wall synthesis

Question 2

Describe the clinical uses for beta lactamase resistant penicillins

Answer 2

Indicated for staph and susceptible strains of strep and pneumo

Question 3

Which penicillins are beta lactamase resistant and what are their indications?

Answer 3

“OCD” - oxacillin, cloxacillin, dicloxicillin are indictated for mild to moderate localized staph infections

Naficillin and oxacillin (IV) are both indicated for serious systemic staph infections

Methicillin is indicated for most staph infections except MRSA of course

Question 4

Which penicillins are known as extended spectrum, and what are their individual indications?

Answer 4

Ampicillin and Amoxicillin have identical spectrum and activity. Indicated for penicillin resistant pneumococci

Ticarcillin and piperacillin - are the antipseudomonals, often given in combo with other antibiotics (aminoglycosides/flouroquinones) for infections outside the urinary tract

Question 5

Which extended spectrum penicillin would be indicated if you needed excellent oral absorption?

Answer 5

Amoxicillin is better absorbed orally than ampicillin

Question 6

What penicillin is the drug of choice for Listeria ?

Answer 6

Ampicillin

Question 7

Which penicillin is most indicated for a pseudomonas infection?

Answer 7

Ticarcillin and Piperacillin are both indicated

Question 8

Give some examples of drugs that use beta lactamase inhibitors in combination with beta lactams to make a lactamase resistant antibiotic

Answer 8

Inhibitors include: Clavulanic acid, sulbactam, and tazobactam

Amoxicillin + Clavulanic acid = Augmentin

Piperacillin + Tazobactam = Zosyn

Question 9

How to beta lactamase inhibitors do the job of inhibiting beta lactamases?

Answer 9

They resemble a ring portion of beta lactamases, but lack the functionality. So, they bind the beta lactamase substrates and inhibit the action through competitive mimicry

Question 10

List some adverse effects of Penicillins

Answer 10

Hypersensitivity (Anaphylaxis, serum sickness, skin rashes)
Diarrhea
Nephritis
Neurotoxicity
Hematologic Toxicity
Cation toxicity

Question 11

Describe the possible resistance mechanisms agains penicillins.

Answer 11

Most common - inactivation via beta lactamases
Modification of the PBPs - (e.g. MRSA and penicillin resistant pneumo)
Efflux from Gram negs

Question 12

What types of bugs are inherently resistant to penicillins? 2 examples

Answer 12

Most gram negatives are resistant due to their outer membrane that acts as a permeability barrier

Most intracellular bugs (e.g. chlamydia) due to certain penicillins’ inability to penetrate mammalian cell membranes

Question 13

What makes cephalosporins more desirable than penicillins?

Answer 13

They have a broader spectrum of activity

More resistant to beta lactamases

Question 14

What is the spectrum of activity of the 1st generation cephalosporins?

Answer 14

Gram negatives: “PEcK” - Proteus, E. coli, and Klebsiella Pneumo

Anaerobes: peptococcus and peptostreptococcus
NOT bacteriodes

Question 15

What is the spectrum of activity of the second generation of cephalosporins?

Answer 15

Active against organisms that inhibit 1st generations PLUS they have extended gram negative activity

Question 16

What type of bug do the cephamycins have activity against?

Answer 16

anaerobes

Question 17

Describe some of the clinical uses of the second generation cephalosporins

Answer 17

Cefuroxime - sinusitis, otitis, and lower resp. tract infections

Cefoxitin, cefotetan - mixed anaerobic infections, peritonitis and diverticulitis (INCLUDING bacteriodes <– not covered by 1st gen cephalosporins)

Question 18

Describe the spectrum of activity of the 3rd generation cephalosporins

Answer 18

Have expanded gram neg coverage compared to 2nd, (cefotaxime, cetriaxone can cross BBB)
Active against beta-lactamase + haemophilus and nisseria
LESS active against gram positives

Question 19

What are the clinical uses of the third generation cephalosporins?

Answer 19

emperical therapy for sepsis of unknown cause in the immunocomprimised and regular people

treatment of infection where cephalosporins are least toxic drug available

in neutropenic, febrile, immunocomprimised patients

used in combo with aminoglycosides

Question 20

If cephalosporins appear to be the least toxic drug available, which generation would you prescribe?
Names?

Answer 20

Third

• Cefotaxime
• Ceftazidime
• Ceftriaxone

Question 21

Which (2) cephalosporins are known as cephamycins?

Answer 21

Both are second gen

• Cefoxitin
• Cefotetan

Question 22

Describe the clinical role of 3rd generation cephalosporins.

Answer 22

Similar to 3rd gen
Cefepime - more resistant to B-lactamases
Good activity against pseudomonas, staph, and strep
Highly active against haemophilus and neisseria
Penetrates CSF

Question 23

What drug would you use to treat an infection that is in the CSF?

Answer 23

Cefepime (4th gen cephalosporin)

Question 24

Describe how cephalosporins are excreted

Answer 24

Most cephalosporins are excreted in the urine

Ceftriaxone - bile

Question 25

What bugs aren’t generally covered by cephalosporins?

Answer 25

"LAME"
Listeria
Atypicals (chlamydia, mycoplasma)
MRSA
Enterococci

Question 26

Name a drug that has similar action to penicillins, with a spectrum similar to 3rd gen cephalosporins, and is resistant to beta-lactamases?

Answer 26

Aztreonam - can be given to patients who are penicillin allergic

treat pneumonia, meningitis, and sepsis caused by gram negative pathogens

Question 27

Describe Imipenem

Answer 27

Acts like a penicillin, resistant to beta lactamases
Inactivated by dehydropeptidase in renal tubules (administered with cilastatin to inhibit dehydropeptidase)

Not necessarily safe in penicillin allergic patients

Question 28

What is the most important side effect of impenem?

Answer 28

MUST MONITOR RENAL FUNCTION

Skin rashes and reactions at infusion sites are also seen

Question 29

Describe the mechanism of action of vancomycin

Answer 29

Binds the D-Ala-D-ala terminus preventing peptidoglycan elongation and cross-linking

Question 30

Describe possible mechanisms of resistance to vancomycin?

Answer 30

The terminal D-ala is transformed to D-lactate, which modifies the binding site for vancomycin

• seen in VRSA (vanco resistant staph aureus

Question 31

Describe the clinical uses of vancomysin

Answer 31

Sepsis or endocarditis caused by MRSA
In combo with cefotaxime or ceftriaxone for the treatment of meningitis caused by highly penicillin-resistant pneumococcus

Very expensive and IV, so generally an antibiotic of last resort

Question 32

Why are penicillins given PO at least 2 hrs before or after food? Which is the exception?

Answer 32

Absorption is impaired by food

Amoxicillin is the exception to this rule

Question 33

Give 2 prominent mechanisms of resistance to penicillins

Answer 33

FINISH