Other Beta Lactam Inhibitors

Question 1

What is the MOA of Beta-Lactams?

Answer 1

Potent inhibitor of most (not all) Beta-lactamases

Question 2

What are the spectrum of inhibition?

Answer 2

Staphylococci, H. Influenzae, N. Gonorrhoeae, Salmonella, Shigella, E.coli

Question 3

What is the indications of beta-lactamases?

Answer 3

Clavulanic acid + amoxicillin
Sulbactam + ampicillin
Tazobactam + Pipericillin, Ceftolozane

Question 4

What is the spectrum of activity for beta-lactams?

Answer 4

Gram- only, E.Coli, Pseudomonas, Serratia.
Unique spectrum similar to aminoglycosides

Question 5

What is the indications of Beta-lactams?

Answer 5

Gonorrhoea, pseudomonas, cystitis. Gaps are gram + organisms and anaerobes.

Question 6

What is the MOA and Spectrum of Carbapenems?

Answer 6

Very broad spectrum, similar to penicillins. Used to for serious resistant infections. Beta-lactam drug of choice for enterobacter infections

Question 7

What is the major gap in the spectrum?

Answer 7

None are active against MRSA

Question 8

What are the clinical uses?

Answer 8

Complicated UTIs, Lower URTIs skin, soft tissue, bone and joint infections. Empirical therapy in hospitalised patients.

Question 9

What is the spectrum of imipenem?

Answer 9

Active against G+ and G- organisms, but not MRSA. Excellent coverage against Enterobacteriacae.

Question 10

Summarize the pharmacokinetics of imipenem?

Answer 10

Hydrolyzed by dehydropeptidases, combined with cilastatin. Half life of 1 hour.
Standard dose 500mg-1g 6-8H IVI daily. Nausea, vomiting common, low-risk of cross-reactivity.

Question 11

What is special about doripenem?

Answer 11

In Europe - increased mortality risk in nosocomial pneumonia patients

Question 12

What are the adverse reactions of imipenem?

Answer 12

GI disturbances, Skin rashes Reactions at infusion sites, Toxicity: seizures (imipenem)

Question 13

How does the interaction occur between carbapenems and valproic acid?

Answer 13

Valproic acid gets metabolized to VPA-glucuronide, which gets excreted in urine and bile. Carbapenems inhibit acylpeptide hydrolase, which increases VPA-glucuronide, and decreases valproic acid. This can predispose the patient to seizures.

Question 14

Name 3 mechanisms of carbapenem resistance.

Answer 14

Reduced penetration of outer membrane, efflux pumps, altered carbapenem-binding proteins.

Question 15

Categorize CSF penetration

Answer 15

Doripenem - good penetration
Imipenem and Meropenem - high penetration
Ertapenem - poor penetration.