Penicillins

Question 1

PCN MOA

Answer 1

Binds to transpeptidases (penicillin binding proteins)

Mimics alanine (d ala d ala) residues

Inactivates enzymes

Bacterial cell wall breakdown>wall creation —> autolysis

PCN BACTERICIDAL

Question 2

Natural PCNs

Answer 2

PCN G- IV and IM
PCN VK- oral

Probenecid- gout drug, inhibits renal secretion of PCN, boosts PCN levels

Question 3

Natural PCN resistance (3)

Answer 3

1. Modified penicillin binding proteins
2. Reduced bacterial cell penetration- GN poor penetration bc protected by outer membrane and bacteria can decrease number of porins
3. Beta lactamase enzyme

Question 4

Beta lactamase (penicillinase)

Answer 4

Bacterial enzymes

Degrade beta lactamase compounds
- PCN G and VK, other PCNs, cephalosporins

GN bacteria- found in PERIPLASM

STAPH AUREUS and GP- beta lactamase a secreted, produce more enzyme than GN

Question 5

B lactamase inhibitors (4)- CAST

Answer 5

Clavulanic acid
Avibactam
Sulbactam
Tazobactam

Added to aminoPCNs and antistaphylococcal PCNs to expand coverage

No effect alone

Question 6

PCN G and VK clinical use (3)

Answer 6

Narrow spectrum

1. GP- GAS (strep throat) and actinomyces
2. Treponema pallidum (syphillis)
3. Only susceptible isolates- N meaning idiots and strep PNA

Question 7

PCN AEs 4, same for cephalosporins and sulfonamides

Answer 7

Type 1- acute, IgE, anaphylaxis, urticaria, bronchospasm

Type 2- direct coombs + hemolytic anemia, IgE (PCN acts as happen, abs against PCN bound to RBCs)

Type 3- serum sickness (days to weeks after exposure, complement activation, IgG, fever, urticaria, LAD, arthritis)

Type 4- maculopapular rash (mc with aminoPCN and EBV pharyngitis), interstitial nephritis (PCN acts as hapten)- fever, oliguria, high BUN/Cr, eosinophils, WBC, WBC casts in urine

Question 8

C diff infection

Answer 8

Diarrhea after abx
Abx depletes normal flora
C diff growth—> pseudomembranous colitis

Frequently caused by

1. CLINDAMYCIN
2. Fluoroquinolones
3. Cephalosporins
4. PCNs

Question 9

Jarisch Herxheimer Reaction

Answer 9

Flu like syndrome (fever, malaise, HA, myalgia, flushing, chills) after PCN for spirochetes (classically: syphilis) d/t killed bacteria releasing toxins

Question 10

Antistaphylococcal PCNs 3

Answer 10

Oxacillin
Nafcillin
Dicloxacillin

Methicillin was prototype

Question 11

Antistaphylococcal PCN use

Answer 11

Remember staph and strep found on skin- Covers NON MRSA staph and most strept
Community acquired cellulitis
Impetigo- honey crusted lesions on skin in peds, caused by s aureus
Staph endocarditis

Question 12

AminoPCN 2

Answer 12

Amoxicillin- oral
Ampicillin- IV

Penetrate porin channel of GN

Sensitive to beta lactamase enzymes

Question 13

Aminopenicillin coverage 6

Answer 13

H influenza
E. coli
Proteus
Salmonella
Shigella
Listeria (GP)

Used for:
Otitis media
Bacterial sinusitis
MENINGITIS- newborns, elderly, Listeria coverage

Question 14

Aminopenicillins and maculopapular rash

Answer 14

MC with viral infection

Classic- EBV infection with sore throat, amoxicillin given for presumed bacterial pharyngitis, maculopapular rash

Question 15

SJS and TEN common with which abx class?

Answer 15

AminoPCNs
Sulfonamides
Cephalosporins

Question 16

Amoxicillin/clavulanic acid, ampicillin/sulbactam

Answer 16

Increases activity against S aureus, H influenza, and anaerobes (B FRAGILIS)

Used in-
Otitis media/sinusitis (Broad spectrum)
Bite wounds (polymicrobial with anaerobes)

Question 17

Antipseudomonal PCNs 2

Answer 17

Ticarcillin
Piperacillin

Greater porin penetration

Effective against P aeroginosa and more GN

Broad spectrum when used with b lactamase inhibitors
1. Most GP, GN (Psuedomonas) and anaerobes
NOT MRSA

Inpatients with GN sepsis/PNA

Question 18

Beta lactam abx 3

Answer 18

Carbapenems
Aztreonam
Cephalosporins

All bind transpeptidases, prevents peotidoglycan cross linking, bacterial cell autolysis, bactericidal

Susceptible to beta lactamase enzymes

Question 19

Carbapenems 4

Answer 19

Imipenem
Meropenem
Ertapenem
Doripenem

Most resistant to most beta lactamase enzymes

DRUG OF CHOICE FOR ESBL BACTERIA

Broad spectrum- GP, GN, Psuedomonas, Enterobacter, anaerobes, B fragilis

Question 20

Extended Spectrum Beta Lactamases

Answer 20

Plasmid mediated

Confer R to most beta lactam abx

Found in only GN:
Pseudomonas
Klebsiella
E. coli
Enterobacter
Salmonella
Serration
Shigella

Question 21

Imipenem

Answer 21

Metabolized by kidneys

MUST admin with CILASTATIN to inhibit PCT enzyme dihydropeptidase I to decrease renal tox

Question 22

Carbapenems AES

Answer 22

N/V/D
Skin rash
NEUROTOXICITY at high doses or renal failure - seizures dt inhibition of GABA RECEPTORS

lowest seizure risk with MEROPENEM

Question 23

Aztreonam (monobactam)

Answer 23

Binds PENICILLIN BINDING PROTEIN 3- prevents peptidoglycan cross linking

PBP3 only in GN

Aztreonam only active against GN (incl pseudomonas)

Question 24

Aztreonam use

Answer 24

IV only- inpatients

Synergistic with aminoglycosides

NO CROSS REACTIVITY IN PCN ALLERGIC PTS

Can use in PCN allergic patients

Question 25

1st gen cephalosporins 2 (+PeCK)

Answer 25

Cefazolin Cephalexin Cefazolin used pre op to prevent S aureus wound infection GP Proteus E. coli Klebsiella

Question 26

2nd gen cephalosporins 3 (HENS PeCK)

Answer 26

Cefuroxime Cefoxitin Cefotetan ``` Hib Enterobacter Neisseria Serratia Proteus E. coli Klebsiella ``` B fragilis (anaerobe)

Question 27

Cefuroxime use

Answer 27

``` Otitis media (S PNA, H flu) UTI in peds (e coli, no fluoroquinolones in peds) ```

Question 28

Cefoxitin/cefotetan use

Answer 28

IV PID- cover Neisseria, give with doxycycline for Chlamydia coverage Pre op in peds with appendicitis- covers E. coli, GN, some anaerobes, usually given with metronidazole

Question 29

3rd gen cephalosporins 3

Answer 29

Ceftriaxone Cefotaxime Ceftazidime- covers pseudomonas More resistance to beta lactamase enzymes Good CSF penetration- meningitis

Question 30

Ceftriaxone

Answer 30

Used for N gonorrhea Commonly used in meningitis - active against S PNA, N meningiditis - good CSF penetration

Question 31

Cefepime

Answer 31

4th gen cephalosporin Hospital patients with serious GN infections

Question 32

Ceftaroline

Answer 32

5th gen cephalosporin Active against MRSA and VRSA Binds PBP2a- MRSA specific PBP No Psuedomonas coverage

Question 33

Cephalosporin resistance mechanisms 3

Answer 33

1. Modified PBPs 2. Altered cell permeability 3. Beta lactamase

Question 34

Cephalosporin AES 6

Answer 34

``` HYPERSENSITIVITY RXN SIMILAR TO PCN: Anaphylaxis Maculopapular rash Serum sickness- fever, rash, arthritis Hemolytic anemia- drug addiction hapten Interstitial nephritis SJS/TEN ``` Some cross reactivity with PCNs

Question 35

Vitamin K deficiency and abx

Answer 35

Gut bacteria produce vitamin k2 Necessary for proper clotting Abx reduce bacterial vit k production—> increased INR and potential bleeding Common problem for pts on WARFARIN

Question 36

Hypoprothrombinemia

Answer 36

Cefotetan and cefazolin inhibit epoxied reductse (same as warfarin) Decreased liver synth of clotting factors Can prolong PT/INR Reversible with vitamin K Mostly in malnourished pts

Question 37

Special cephalosporin AEs 3

Answer 37

1. Nephrotoxic with aminoglycosides 2. Hypoprothrombinemia 3. Disulfiram reaction- EtOH with cephalosporins Warmth, flushing, sweating Inhibition of acetaldehyde dehydrogenase -> accumulation of acetaldehyde