Antibiotics

Question 1

Beta-lactams (structure and 4 types)

Answer 1

-4-membered lactam ring
- penicillins
cephalasporins
carbapenems
monobactams
beta-lactamase inhibitors

Question 2

penicillin (structure and 4 types)

Answer 2

• 5-member thiazolidine ring + beta-lactam ring, types differ by R group
  -natural penicillins
  anti-staphylococcal
  extended spectrum (amino-, carboxy-, ureido-)
  beta-lactamase inhibitor combinations

Question 3

penicillin MOA, pharm properties and toxicity

Answer 3

MOA:inhibits transpeptidase by mimicking th terminal chain on peptidoglycan chain ( acyl-D-Ala-D-Ala); therefore prevent cross linking of peptidoglycan; not effective in non-dividing phase.

Pharm: short half life 30-60 min; water soluble and passively diffuses into tissue; protein bound upon oral administration; can’t passively diffuse due to tight junctions into CSF, brain, prostate, ocular fluid and phagocytes; metabolized in the liver but excreted in urine though glomerula filtration (passive) and tubular secretion (active)

Tox: hypersensitivity; seizure in pts with renal failure; GI disturbances with large doses
nafcillin-bone marrow suppression and neutropenia
oxacillin-hepatatis

Question 4

natural penicilling (2 drugs, SoA)

Answer 4

pen G and V
SOA:
-Syphillis
-GP:
strep (drug of choice)
most enterococcus faecalis sensitive
most staph resistant
most enterococcus faecium ressitant
- GN
minimal

Question 5

aminopenicillins (2 drugs, SoA)

Answer 5

Amoxicillin/Ampicillin (GP similar to natural pen, more GN)

GP:
strep
entero faecalis
entero faecium often resistant
no staph
no MRSA

GN:
minimal
H. influenzae

• GP Listeria(memimgitis) -Ampicillin

Question 6

Anti-staph penicillins (4 drugs, SoA)

Answer 6

Methicillin/Nafcillin/Oxacillin/Dicloxacillin
GP: (same as 1st gen cephalosporins)
staph (coagulase negative staph resistant)
strep
no entero
no MRSA

GN: minimal

Question 7

Extended Spectrum Penicillins (2 drugs, SoA)

Answer 7

PIPERCILLIN/ TICARCILLIN

GP:
strep
min staph
entero faecalis
entero faecium resistant
no MRSA

GN:
improved +PSA

Anaerobes: some

Question 8

Beta lactamase inhibitors combines (4 drugs and SoA)

Answer 8

Amoxicillin/Clavulanate
Ampicillin/Sulbactam
Piperacillin/Tazobactam
Ticarcillin/Clavulanate

-GP: 
staph
strep
entero faecalis
entero faecium resistant
no MRSA

-Anaerobes

-GN:
P/T; T/C- broad includes PSA
A/C; A/S: PEK (proteus, E.coli, klebsiella), Morexella, Niesseria, H. influenzae, no PSA; * acinetobacter by A/S

Question 9

beta-lactam resistance (4 types)

Answer 9

• altered PBP and lower affinity for AB ( staph, strep, H. influenzae, E.coli, PSA)
• reduces permeability only in GN, because of the cell wall, down regiulation of sporins (PSA, Enterobacter, Serratia, Klabsiella
• beta lactamase: )staph, entero, PSA, Neisseria, E.coli, Klebsiella)
• Efflux pump (GN only)

Question 10

Beta-lactamases (4 types)

Answer 10

T1-chromosmal cephalosporinase
T2-beta lactamase
T3-metallo-beta-lactamase
T4-beta lactamase (not commonly used)

Question 11

T1-chromosomal cephalosporinase

Answer 11

SPPEMC ( Serratia, PSA, Providencia, Entero, Morganella, Citrobacter); plasmid tratransfer to E.coli and Klebsiella

Effected: beta-lactamases inhibitors and combinations; penicillins, 1-3 generations cephalosporins, monobactams

Tx: imipenem, Fluoroquinelones, cefepime

Question 12

T2-beta -lactamase

Answer 12

E.coli and Klebsiella

Effected: cephalosporins (exs. cefoxitin, cefmetazole, cefotetan); aztreonam, extended spectrum penicillins,beta-lactamases inhibitors and combinations effective but sensitive to inoculum effect

Tx: carbapenems, non-beta lactams, cephamycins,beta-lactamases inhibitors and combinations shoudl not be used as single agents

Question 13

T2-metallo-beta -lactamase

Answer 13

Stenattrophomonas maltophilia, aeromonas, PSA

effected: carbapenems, older penicillins, cefotaxime, ceftriaxone

Tx: piperacillin, ceftazidime,beta-lactamases inhibitors and combinations

Question 14

cephalosporins (structure, MOA, pharmac properties)

Answer 14

• beta lactam ring+ 6 member sulfar containing dihydrothiazine ring (R1-change in activity, R2-change in pharmacokinetics)
• inhibit transpeptidaze an dlinkage of peptidoglycan
• some metabolized in liver, all eliminated in urine (glomerula filtration -all, tubular secretion-1, 2 only); good CSF penetration in 3 and 4

Question 15

1st gen cephalosporins( 3)

Answer 15

Cefazolin, Cephalexin, Cefadroxil
- GP: same as anti-staphiloc: staph, strep, no entero, no MRSA, coag negative staph frequently resistant
GN: PEK

Question 16

2nd gen cephalosporins( 7)

Answer 16

cefuroxime, cefaclor, cefprozil, cefoxitin , cefotetan, cefmetazole, cefimandole

GP: same as 1st gen, a little less (staph, strep, no enter, no MRSA
GN: HENPEK
anaerobes: cefoxetin, cefotetan,cefmetazole
MTT side chain(platelet disfunction, antabuse reaction): cefotetan, cefmetazole, cefimandole

Question 17

3rd gen cephalosporins( 7)

Answer 17

ceftriaxone, ceftazidine, cefoperazone, cefixime, cefdinir, Cefpodoxime, ceftibuten

GP: same as 1 and 2nd gen , a little less: staph, strep, no entero, no MRSA

GN: HENPEK = serratia, citrobacter, acinetobacter, morganella, providencia

PSA: ceftazidime, cefoperazole

Question 18

4th gen cephalosporins (1)

Answer 18

cefepime
GP: same as 1,2, 3: staph, strep, no entero
GN: broad +PSA

Question 19

5th gen cephalosporins (1)

Answer 19

Ceftaroline( specifically designed for MRSA(

GP: Staph, MRSA, strep
GN: same as 3rd gen, less than 4( HENPAK)

Question 20

Combination cephalosporins (2)

Answer 20

Ceftolozane/Tazobactam
Ceftazidime/Avibactam (covers carnapenem resistant entero)

GP:Staph-only MSSA, strep
GN: Broad+ ESBL