Antibiotics- Cell wall synthesis inhibitors

Question 1

Beta-lactam antibiotics include:

Answer 1

Penicillins, cephalosporins, Carbapenems, Monobactams, Glycopeptides and “other drugs”

Question 2

Classes of penicillins and mechanism of action:

Answer 2

Mechanism of action: irreversible inhibition of transpeptidation step of cell wall synthesis in bacteria.
Beta-lactam is structurally similar to D-ala and forms a stable product with transpeptidase enzyme and therefore inhibited the transpeptidation process.

Natural penicillins, Lactamase stable, Broad spectrum, and extended-spectrum
broad and extended-spectrum are combined with lactamase inhibitors.

Question 3

Natural penicillins:

Answer 3

Benzylpenicillin- I.V. 
Phenoxymethylpenicillin- Oral 
Use: gram +, Gram - (only Neisseria) , anaerobes and Spirochetes 
significant resistance 
use for : gram + diseases which are 
skin/wound infections 
RTI 
endocarditis 
Dental inf 
gram - :  first-line for syphilis (Spirochetes)

Question 4

Lactamase stable penicillins

Answer 4

Methicillin - I.V.
Use: obsolete due to MRSA
however, before used for lactamase resistant staphylococcus aureus infections i.e endocarditis and skin/wound infections

Question 5

Broad-spectrum penicillins

Answer 5

Amoxicillin, Ampicillin- oral and I.V.
More effective on Gram -
so spectrum includes : gram +, Gram - including Neisseria, hemophilia, and coliform. only NOT including pseudomonas.
diseases:
skin/wound infections
RTI (S.pneumoniae and neiss. and hemoph.)
endocarditis
UTI ( Coliform)
abdominal and pelvic infections (coliform, anaerobes)
also syphilis
meningitis

Question 6

Broad-spectrum penicillins used with:

Answer 6

Beta-lactamase inhibitors : (irreversible inhibition of beta lactam)
Amoxicillin- Clavulanic acid
Ampicillin- Sulbactam

Question 7

Extended Spectrum Penicillin:

Answer 7

Ureidopenicillins- piperacillin- I.V.
the spectrum includes ALL including Pseudomonas
Use: Nosocomial infections (due to Pseudomonas)

Question 8

Extended Spectrum Penicillin used with:

Answer 8

Beta-lactamase inhibitors : (irreversible inhibition of beta-lactam)
Piperacillin- Tazobactam combination

Question 9

Side Effects of penicillin

Answer 9

Allergy (anaphylaxis, rash, fever) -> IgE mediated
Seizure
Interstitial nephritis
<10% cross reactivity w/ cephalosporins
drug induced autoimmune hemolytic anemia -> IgG binds to RBCs
safe during pregnancy

Question 10

Cephalosporins: first gen

Answer 10

Cefazolin - I.V.
Cefalexin- oral
not used anymore.
spectrum: Gram +, Gram negative (only neisseria), Spiro
UTI’s (PEK: Proteus, E.coli, Klebsiella)
NO ANEROBES ( so no dental inf. or pelvic/stomach infec)

Question 11

Cephalosporins: second gen

Answer 11

Cefuroxime- I.V. 
Cefaclor, Cefuroxime axetil- Oral 
Spectrum: gram +, gram - except pseudomonas, Spirochetes 
Use: gonorrhoea (neisseria) 
RTI 
UTI 
surgical prophylaxis
against HENS: H.infl., Neisseria, Serratia

Question 12

Cephalosporins: third gen

Answer 12

Cefotaxime , Ceftriaxone, - I.V. 
spectrum: gram +, common gram - 
GI bugs, RTI, gono (IM CEFTRIAXONE), meningitis, lyme disease, surgical prophylaxis 
Ceftazidime - I.V. 
Mostly gram - INCLUDING pseudomonas 
so nosocomial infections , UTI RTI etc 
Cefixim- oral
gram -, not as widely used.

Question 13

Cephalosporins - fourth gen

Answer 13

Cefepime - I.V.
balanced gram + and -
spare antibiotics- use in severe infections
broad spectrum
used in Pseudomonas & bacterial meningitis

Question 14

Cephalosporins - fifth-gen

Answer 14

Ceftaroline- I.V.
broad spectrum
usually: MRSA (skin/wound infections)
PRSP( RTI)

Question 15

3rd, 4th gen used for:

Answer 15

First-line for meningitis!

pass the BBB

Question 16

side effects of cephalosporins

Answer 16

Allergy, kidney damage (rare), <10% cross reactivity w/ PENICILLINS

Question 17

Carbapenems include:

Answer 17

Imipenem (-cilastatin)
Meropenem
Ertapenem
Spectrum: Gram -, gram -, anaerobes, spiro

Question 18

Imipenem used with:

Answer 18

degraded via dehydropeptidase enzyme rapidly (human enzyme) so we use it with DHP inhibitor: cilastatin

Question 19

Use of carbapenems

Answer 19

severe infections:
skin/wound
RTI, UTI, abdominal/pelvic, and meningitis
nosocomial inf. (Pseudomonas)

Question 20

glycopeptides

Answer 20

MOC: covers D-ala, D-ala
so inhibits both transglycosylation and transpeptidation
Drugs: Vancomycin, I.V. and oral
Use: ONLY gram + (including gram + anaerobes)
used for severe infections that are resistant to Beta lactams (MRSA, PRSP)
such as: endocarditis, skin/tissue, RTI, meningitis
and pseudomembrane colitis (C.dificile)

Question 21

“Other drugs” include:

Answer 21

Fosfomycin- intracellular
irreversibly inhibit MurA enzyme and inhibit the synthesis of muramic acid.
Spectrum: both gram + and gram -
fosfomycin is hydrophilic that’s why it inhibits gram -
Use: non complicated UTI
safe in pregnancy

Bacitracin-
spectrum: gram +
topical use for skin infections
nephrotoxicity

Question 22

SE of glycopeptides

Answer 22

Red man syndrome (rashes)
thrombophlebitis on the site of injection
ototoxicity
nephrotoxicity

Question 23

monobactams

Answer 23

AZTREONAM

USE:
Pseudomonas (nosocomial inf.)
Gram - (meningitis, pneumonia, sepsis)

No SE
not used in Europe (yet) only in the USA
used in case a patient is allergic to PENICILLIN
resistant to beta-lactamases

Question 24

Membrane damaging antibiotics

Answer 24

COLISTINE (target gram +): polycationic, interacts w/ bacterial outer membrane by displacing Ca & Mg ions from the polysaccharide lipids -> disruption of outer cell membrane -> leakage -> bacterial death
POLYMIXIN (target gram -): bind to polysaccharides in outer membrane