DR. MABANAG - BETA LACTAMS + OTHER CELL WALL & MEMBRANE ACTIVE ANTIBIOTICS

Question 1

4 Major categories of Bacterial targets

Answer 1

1. Cell Wall
   ● Beta lactams, Vancomycin
2. Outer cell membrane
   ● Polymyxins
3. Nucleic acid
   ● Fluoroquinolone, Trimethoprim
4. Ribosomes
   ● Aminoglycosides, Spectinomycin, Tetracyclines, Macrolides, Chloramphenicol, Linezolid

Question 2

○ Buy AT 30
- Aminoglycoside
- Tetracycline

○ SCEL at 50
- Streptogramins
- Chloramphenicol, Clindamycin
- Erythromycin (Macrolides)
- Linezolid

Answer 2

● There are two subfamilies:
○ Those that attack 50S Subunit
○ Attack 30S Subunit

Question 3

● Antibiotics also attack Nucleic acid synthesis, like in
folate synthesis

Answer 3

C-S-T
cotrimoxazole
sulfonamides
trimethoprim

Question 4

attack the DNA gyrase.

Answer 4

QUINOLONES

Question 5

attacks the RNA polymerase.

Answer 5

RIFAMPIN

Question 6

______bactericidal by inhibiting bacterial cell wall synthesis leading to loss of cell wall integrity and eventually cell lysis

Answer 6

BETA LACTAMS

Question 7

most complex subclasses of beta-lactams

Answer 7

P-C
PENICILLIN
CEPHALOSPORINS

Question 8

All beta-lactams inhibit synthesis of the ___________found on the bacterial cell wall

Answer 8

PEPTIDOGLYCAN LAYER

Question 9

● A heteropolymer component of bacterial cell wall that provides rigid mechanical stability
● It maintains bacterial cell shape and integrity and prevents bacterial cell lysis from high osmotic pressure.

Answer 9

PEPTIDOGLYCAN LAYER

Question 10

PEPTIDOGLYCAN LAYER
Composed of alternating chains of:
?
?

Answer 10

○ N-acetylglucosamine (NAG)
○ N-acetylmuramic acid (NAM)

● They are pentaglycine cross-linked by peptide
chains

Question 11

● If peptidoglycan is weakened or synthesis is inhibited, cell lysis occurs or the cell would not be able to replicate.

Answer 11

PEPTIDOGLYCAN LAYER COMPOSITION

Question 12

OLD BETA LACTAMS ARE MORE ACTIVE AGAINST GRAM + THAN GRAM-

Answer 12

○ Gram-positive = Very thick peptidoglycan layer
○ Gram-negative = Thin peptidoglycan layer

Question 13

inhibit synthesis of the peptidoglycan layer by binding to and inhibiting the action of TRANSPEPTIDASE involved in the cross-linking of peptidoglycan chains.

Answer 13

ALL BETA-LACTAMS

Question 14

○ Involved in the cross-linking of
peptidoglycan chains
○ It represents one of the multiple types of
penicillin-binding proteins (PBPs).
○ Inhibitory action on the transpeptidase
enzyme has a bactericidal effect as the impaired peptidoglycan synthesis leads to loss of bacterial shape and integrity thus leading to cell lysis and cell death.

Answer 14

TRANSPEPTIDASE

Question 15

1. Porin Mutations (e.g., Klebsiella spp.)
   ● Decreases entry of beta-lactams.
2. Action of B-Lactamases
   ● Degradation of antibiotics once inside the cell.
   ● Combat against antibiotics.
3. Efflux Pumps (e.g., P. aeruginosa)
   ● Removal of antibiotic once inside the cell.
4. PBP mutations
   ● Not allowing binding of beta-lactam.
   ● So that the drug cannot attach.

Answer 15

Major mechanisms of beta-lactam resistance:

Question 16

Resistance for beta-lactams in G(-) bacilli are usually due to

Answer 16

BETA LACTAMASE PRODUCTION

Question 17

encode plasmids (which are passed from bacterium to bacterium by horizontal transfer) or encoded by the bacterial chromosome itself.

Answer 17

Beta-lactamases (anti-beta lactam enzymes)

Question 18

BETA LACTAMASE:

Inactivate penicillins

Answer 18

Penicillinases

Question 19

BETA LACTAMASE:

• Inactivate most beta-lactams except carbapenems.
• Mostly found in E. coli and Klebsiella spp.

Answer 19

○ Extended-spectrum beta-lactamases (ESBLs)

Question 20

BETA LACTAMASES:

• Inactivate carbapenems
• Used as treatment of last resort for
  multi-drug resistant G(-) infections.

Answer 20

Carbapenemases

Question 21

more commonly observed among G(+) pathogens.

● Confers resistance to all beta-lactam antibiotics with one exception, Ceftaroline which is a newer cephalosporin.

Answer 21

ALTERED PENICILLIN BINDING PROTEINS (PBPs)

Question 22

one of the most complex subclasses of beta-lactam antibiotics.

● All have the same basic structure: the 6-aminopenicillanic acid nucleus - a thiazolidine ring attached to a beta-lactam ring that carries a secondary amino-group.

Answer 22

PENICILLINS

Question 23

Natural Penicillins (Penicillin Sensitive)

Have the greatest activity against gram-positive (+) organisms, gram-negative (-) cocci, and non-beta-lactamase-prod ucing anaerobes

Answer 23

Penicillin G
Penicillin V

Question 24

Antistaphylococcal Penicillins (Penicillinase- Resistant)

Resistant to staphylococcal beta-lactamases

Answer 24

Cloxacillin
Oxacillin

Question 25

Antistaphylococcal Penicillins (Penicillinase- Resistant) Only active against staphylococcus and staphylococci but not against other gram-negative (-) rods.

Answer 25

Nafcillin Methicillin (Con-MD)

Question 26

Extended-Spectrum Penicillins Aminopenicillin Relatively susceptible to hydrolysis by beta-lactamases

Answer 26

Aminopenicillins: - Ampicillin - Amoxicillin

Question 27

Extended-Spectrum Penicillins antipseudomonal penicillins Most commonly formulated and administered in combinations with beta-lactamases inhibitors.

Answer 27

Antipseudomonal: - Carbenicillin - Ticarcillin - Piperacillin

Question 28

used in the ICU, there are aggressive pathogens and use stronger antibiotics.

Answer 28

ANTIPSEUDOMONALS - Carbenicillin - Ticarcillin - Piperacillin

Question 29

Anti-staphylococcal PCNs Resistant against β-lactamases Only active vs Staphylococci and Streptococci

Answer 29

Penicillin-Resistant PCNs Cloxacillin Oxacillin Dicloxacillin Nafcillin Methicillin

Question 30

● Retain the same antibacterial activity of natural PCNs, w/ added activity vs G(-) rods. ● Retain susceptibility to hydrolysis by β-lactamases

Answer 30

Extended-SpectrumPCNs ○ Aminopenicillins: Ampicillin, Amoxicillin ○ Antipseudomonal PCNs: Carbenicillin, Ticarcillin, Piperacillin

Question 31

Give oral penicillins, except_________, in between meals. Should be administered at least 1-2 hours before or after a meal.

Answer 31

amoxicillin

Question 32

PCNs are rapidly excreted by the kidneys via 1. 2.

Answer 32

1. TUBULAR SECRETION 2. GLOMERULAR FILTRATION

Question 33

an anti-staphylococcal PCN, is primarily cleared by biliary excretion.

Answer 33

NAFCILLIN

Question 34

● Drug of choice (DOC) for infections caused by: ○ Streptococci ‐ E.g. “Strep throat” (Streptococcus pyogenes) ○ Meningococci ‐ E.g. Meningococcemia (Neisseria meningococci) ○ Penicillin-susceptible Pneumococci ‐ E.g. Pneumonia (Streptococcus pneumoniae) ○ Non-β-lactamase-producing Staphylococci ○ Treponema pallidum ‐ E.g. Syphilis ‐ In the 1950s, it was also the first line of treatment for syphilis. ○ Actinomyces ○ Clostridium sp.

Answer 34

PENICILLINASE-SENSITIVE PENICILLINS (NATURAL PCNs)

Question 35

are considered DOCs for serious staphylococcal infections such as endocarditis (infection of the heart muscles or valves)

Answer 35

-OXACILLIN -NAFCILLIN

Question 36

-PNEUMOCOCCI -TX BACTERIAL SINUSITIS,OTITIS AND LRTIs -Shigella, Listeria monocytogenes, E. coli, Salmonella, and Haemophilus influenzae -treatment of Gram(-) bacilli infections caused by Pseudomonas aeruginosa and Klebsiella pneumoniae.

Answer 36

EXTENDED-SPECTRUM PENICILLINS (AMINOPENICILLINS [Ampicillin & Amoxicillin], ANTIPSEUDOMONAL PCNs)

Question 37

PCN ADVERSE EFFECT

Answer 37

MC= ALLERGY / HYPERSENSITIVITY *ANAPHYLACTIC SHOCK ○ PCN and their breakdown products of alkaline hydrolysis act as haptens after covalent reaction with proteins → PENICILLOIC ACID

Question 38

if the patient is allergic to one of the penicillins, especially if there is severe reaction, it should be presumed that all penicillins are contraindicated and the entire group should be avoided.

Answer 38

Complete (Absolute) Cross-Allergenicity

Question 39

if allergic to penicillin, patients can be given cephalosporin. They are both β-lactams, but not exactly penicillin formulations. However, a better choice would be not to use any β-lactam antibiotics. ‐ If a patient is allergic, it is safer to give non-β-lactam antibiotics.

Answer 39

Partial Cross-Allergenicity

Question 40

Gastrointestinal disturbance (i.e. nausea, vomiting, and diarrhea)

Answer 40

large PO doses of PCNs

Question 41

Pseudomembranous colitis

Answer 41

AMPICILLIN

Question 42

Myoclonic jerks and seizures

Answer 42

high doses of PenG or patients with renal failure

Question 43

Interstitial nephritis

Answer 43

Nafcillin, Methicillin (Antistaphylococcal Penicillins;

Question 44

Neutropenia

Answer 44

NAFCILLIN

Question 45

HEPATITIS

Answer 45

OXACILLIN (Antistaphylococcal Penicillin)

Question 46

○ Occurs several hours after 1st injection of PCN ○ Symptoms: chills fever, headache, myalgias, arthralgias

Answer 46

Jarisch Herxheimer Reaction