Cell Wall Inhibitors

Question 1

Describe the mechanisms of resistance to beta-lactams

Answer 1

Transpeptidase won’t bind the drug (low affinity for it), impermeability of outer membrane, efflux of drug, beta-lactamases inactivate drug via hydrolysis

Question 2

Key points and adverse effects of penicillin

Answer 2

Inactivated by gastric acid so only absorb like 25% from PO. Poor CNS penetration, renal excretion, low toxicity (we don’t have cell walls). Rare but high doses impact CNS (tremors, seizure); superinfection, hypersensitivity.

Question 3

What do you give to someone allergic to penicillin?

Answer 3

A macrolide (e.g. erythromycin)

Question 4

Talk to me about nafcillin

Answer 4

It is a penicillinase-resistant penicillin, effective against Gram + bacteria that produce penicillinase (e.g. S. aureus). Used mostly IV. Biliary excretion.

Question 5

Talk to me about amoxicillin

Answer 5

Works against Gram + and Gram - organisms. It’s acid-stable so well absorbed (unlike penicillin G). B/c of better GI absorption, can give w/ food.

Question 6

Talk to me about piperacillin

Answer 6

Only given IV, enhanced activity against some Gram - organisms, specifically pseudomonas

Question 7

Why is amoxicillin sometimes combined with clavulanic acid?

Answer 7

The clavulanic acid inhibits beta-lactamase so amoxicillin can still work. This drug is aka Augmentin.

Question 8

Basics of cephalosporins

Answer 8

Work just like penicillins, but less readily inactivated by beta-lactamases (though resistance still results from this). 1st gen txs Gram +, as you go up they tx Gram - more and less +. 3rd gen penetrates CNS. Renal excretion.

Question 9

Adverse effects of cephalosporins

Answer 9

Cross-allergenicity with other cephalosporins and penicillins. Mild nephrotoxicity that enhances w/ aminoglycosides.

Question 10

First generation cephalosporins

Answer 10

Gram + effective.
Cefazolin: parenteral; preferred pre-op prophylaxis.
Cephalexin: PO

Question 11

Second generation cephalosporins

Answer 11

More Gram - activity, some Gram +.
Cefotixin: particularly resistant to beta-lactamases, given IV. Tx for lung abscesses, pelvic inflammatory dz, and pre-op prophylaxis for Gram - organisms.

Question 12

Third generation cephalosporins

Answer 12

Often combined w/ aminoglycosides for severe, resistant Gram - infections.
Ceftriaxone: penetrates CNS (good for meningitis)
Ceftazidime: penetrates CNS (good for pseudomonas)
*Can have resistance via extended spectrum beta-lactamases (ESBLs)

Question 13

Fourth generation cephalosporins

Answer 13

Cefepime: penetrates CNS (good for bacterial meningitis), extended spectrum of activity compared to 3rd gen

Question 14

Basics of Imipenem-cilastatin

Answer 14

New class of beta-lactam, type of carbapenem, highly resistant to beta-lactamases. Broadest activity of all antibiotics! Given together b/c cilastatin prevents breakdown. *Imipenem has highest propensity to cause seizures.

Question 15

Aztreonam

Answer 15

A monobactam. Resistant to beta-lactamases. Limited to aerobic Gram - organisms (good for enterobacteriaceae and pseudomonas).
***The one exception- you can give this to patients w/ hx of penicillin allergy b/c very low cross-allerginicity.

Question 16

Mechanism of action and resistance of vancomycin

Answer 16

Effective against Gram + bacteria. Inhibits peptidoglycan synthetase (enzyme responsible for adding disaccharide to cell wall) –> weakens cell wall.
*Resistance when D-ala-D-ala mutates to D-ala-D-lactate and vanc can’t bind.

Question 17

ADME of vancomycin

Answer 17

Always IV (except for pseudomembranous colitis from C. diff- give PO). 
Thrombophlebitis at injection site, ototoxicity, flushing, and nephrotoxicity.

Question 18

Describe the mechanism of action of beta-lactams

Answer 18

Binds peptidoglycan transpeptidase so that when it tries to cross-link D-ala-D-ala, the beta-lactam becomes covalently bound inactivating it (suicide inhibition). Cell tries to repair w/ a lytic enzyme that goes crazy and leads to cell lysis.