Antibacterial Therapy

Question 1

MOA of beta-lactams

Answer 1

MOA: inhibition of cell wall synthesis by binding to PBPs in cell wall and preventing cross-linking of peptide chains. Activates bacterial autolytic system -> cell death. Not active if bacteria doesn’t have cell wall (mycoplasma), or intracellular. Poor bioavailability (need empty stomach). Bactericidal, time-dependent. Allergy is related to R-side chains, not the ring. 1% risk with carbapenems if confirmed allergy.

Question 2

MOR of beta-lactams

Answer 2

Alteration in PBP, prevent access to binding sites, beta-lactamase (cleave beta-lactam ring). Overcome with beta-lactamase inhibitors (clavulanic acid, tazobactam): little activity on their own, but contain beta-lactam ring which binds to and inhibits beta-lactamases.

Question 3

AmpC cephalosprinases

Answer 3

Resistant to penicillins, clavulanic acid, 1st/2nd gen. cephalosporins. Use with caution: pip/tazo, 3rd/4th gen. cephalosporins.

Question 4

Extended spectrum beta-lactamase (ESBL)

Answer 4

Resistant to penicillins and cephalosporins. Use carbapenems.

Question 5

Penicillin V (PO), Penicillin G (IV)

Answer 5

Streptococci, An G+B/C. Dental infections, endocarditis (IV). Syphilis: intramuscular benzathine penicillin.

Question 6

Amoxicillin PO, Ampicillin IV.

Answer 6

Streptococcus. Amoxicillin: 1st line for S. pneumoniae.

Question 7

Cloxacillin

Answer 7

Methicillin susceptible S. aureus (MSSA). IV for bacteremia, endocarditis, bone/joint infections.

Question 8

Amoxicillin/clavulanate PO

Answer 8

G+, MSSA, Enterobacteriacae, H. influenza, Anaerobes. Polymicrobial infections (bites, diabetic foot ulcer). Extended spectrum when adding beta lactamase inhibitor (not effective against ESBL, AmpC.

Question 9

Piperacillin/tazobactam IV

Answer 9

G+, MSSA, Enterococcus, Pseudomonas, Enterobacteriaciae, Anaerobes. Febrile neutropenia, polymicrobial infections, sepsis. Not effective against ESBL.

Question 10

Ticeracillin/clavulanate IV

Answer 10

Same as pip/tazo, but less effective against Pseudomonas.

Question 11

Cephalosporins

Answer 11

No activity vs. Enterococci or MRSA. 3rd gen: extended G- activity, but less S. aureus activity. Ceftazidime IV (3rd) and Cefepime IV (4th): Pseudomonas.

Question 12

1st generation cephalosporins (2)

Answer 12

Cephalexin PO, Cefazolin IV

Question 13

2nd generation cephalosporins (3)

Answer 13

Cefuroxime IV, Cefuroxime axetil PO, Cefprozil PO

Question 14

3rd generation cephalosporins (4)

Answer 14

Cefotaxime IV, Ceftriaxone IV, Cefixime PO, Ceftazidime IV

Question 15

4th generation cephalosporins (1)

Answer 15

Cefepime IV

Question 16

Carbapenems (3)

Answer 16

Broad spectrum, but not 1st line for community acquired infections. Reserved for serious infections with multidrug resistant pathogens. Only IV. Ertapenem is narrowest. Meropenem: Pseudomonas but no Enterococcus. Imipenem: Pseudomonas and Enterococcus.

Question 17

Glycopeptide (1)

Answer 17

Vancomycin. MOA: Inhibits cell wall synthesis (earlier phase than beta-lactams). MOR: Alterations in target. Slowly tidal. IV: G+ and MRSA. PO: C. difficile.

Question 18

Lipopeptide (1)

Answer 18

Daptomycin. Disrupts cell wall membrane. Calcium dependent depolarization, disrupts RNA, DNA, and protein synthesis. Spectrum is same as Vancomycin IV + VRE. Not effective for pneumonia (inactivated by surfactant).

Question 19

Aminoglycosides (2)

Answer 19

Binds 30s ribosomal subunit to inhibit protein synthesis. G- Enterobacteriaceae, Pseudomonas. Tobramycin has no G+ synergy with beta-lactams, but better than Gentamicin for Pseudomonas.

Question 20

Macrolides (1)

Answer 20

Azithromycin. Inhibit protein synthesis by binding to 23S rRNA in 50S RSU. Prophylaxis and treatment for MAC in HIV patients. Broad spectrum against IC (eg. Chlamydia). 2nd line for STI, combined with beta-lactam for CAP.

Question 21

Lincosamide (1)

Answer 21

Clindamycin. Inhibit protein synthesis by binding to 50S RSU. Streptococci, S. aureus, MRSA (must confirm susceptibility), anaerobes, combo for polymicrobial. Increasing resistance.

Question 22

Tetracyclines & Glycylcyclines (3)

Answer 22

Inhibit protein synthesis by binding to 30S and 50S RSU. Doxy: MRSA + IC. Tetra: Narrow spectrum, QID on empty stomach. TIge: last line for polymicrobial and multi-drug resistant. Broad spectrum.

Question 23

Fluoroquinolones (3)

Answer 23

Inhibit DNA gyrase/topoisomerase. Responsible for G- resistance, therefore not 1st line. Cipro: only PO for Pseudomonas. Levo/Moxi: IC

Question 24

Anti-folates (2)

Answer 24

Inhibit purine synthesis (block enzymes, reactive intermediates to cause damage). Nitrofurantoin PO: 1st line for cystitis. TMP/SMX: MRSA, S. pneumonia, PJP treatment and prophylaxis.

Question 25

Nitromidazole (1)

Answer 25

Inhibit protein synthesis. Metronidazole PO/IV: Anaerobes, C. difficile, Protozoa, combo for polymicrobial infections.

Question 26

Oxazolidinones (1)

Answer 26

Inhibit protein synthesis by binding 23S rRNA in 50S RSU. Linezolid PO/IV: MRSA, VRE, Streptococci, Staphylococci, Anaerobes, Enterococci.

Question 27

Anti-tuberculous drugs (4)

Answer 27

Rifampin: binds RNAPol to inhibit mRNA synthesis. Isoniazid + pyrazinamide: inhibit mycolic acid synthesis. Ethambutol: inhibit polymerization in mycobacterial wall.

Question 28

MOA: Inhibit cell wall synthesis (2)

Answer 28

beta-lactams, glycopeptide

Question 29

MOA: inhibit cell wall membrane (1)

Answer 29

lipopeptide

Question 30

MOA: inhibit protein synthesis (5)

Answer 30

Aminoglycoside, macrolide, lincosamid, nitromidazole, oxazolidione.

Question 31

MOA: Disrupt DNA synthesis (2)

Answer 31

Anti-folates, fluoroquinolones.