Antibiotic_Cell Wall and Mycobacterium Flashcards Preview

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Flashcards in Antibiotic_Cell Wall and Mycobacterium Deck (71)
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1

Broad Spectrum Antibiotics

Drugs that work against both classes of bacteria.

2

Extended Spectrum Antibiotic

Drug whose selectivity is broadened by chemical modification.

3

Gm- outer membrane characteristics. (2)

1) Relatively impervious
2) Transport of drugs through TRANSMEMBRANE PORES
a. favor small hydrophilic drugs

4

What two drugs are too big to be effective against Gm- bacteria?

Vancomycin and Daptomycin
- cannot pass through Gm- transmembrane pores

5

Molecular make up of the Peptidoglycan layer. (2)

1) Polysaccharide chain made up of
- N-acetyl-glucosamine (NAG)
- N-acetylmuramic acid (NAM)
2) Five peptide units hanging off of Polysaccharide chain
- Last two peptides are usually D-Ala - D-Ala

6

Enzyme that joins the sugars of the polysaccharide chain.

Transglycosylase

7

Enzyme that joins the sugar-linked peptides to x-linked polysaccharide chains.

Transpeptidase/Penicilin Binding Protein (PBP)/Ser-Enzyme

8

Penicillin mimics what two AA of the peptide bridge precursor?

D-Ala-D-Ala

9

Core structure of primary Beta-lactam antibiotics

Beta-lactam ring

10

Mechanism: Synthesis of peptidoglycan x-link. (2)

1) Transpeptidase (Ser-Enzyme) binds D-Ala-D-Ala ---> D-Ala-Ser-Enzyme + D-Ala (the last D-Ala got kicked out)
2) Glycine comes in forming a peptidoglycan x-link
a. Ser-enzyme is recycled

11

Mechanism: B-lactam antibiotic action.

Penicillin binds Transpeptidase (PBP/Ser-Enzyme)
- Ser-Enzyme is NOT recycled
- Bacteria can no longer form Peptidoglycan x-links

12

Characteristic: B-lactam antibiotic. (3)

1) Irreversible Rxn
2) Effective against GROWING bacteria
3) Bacteriocidal (during peptidoglycan production)
- without peptidoglycan wall, cells burst due to osmotic pressure

13

Mechanism and Result: B-lactamase action (3)

Hydrolysis of B-lactam ring
1) Serine B-lactamase binds penicillin
2) Forms a complex that allows H2O to hydrolyze B-lactam ring of penicilin
3) A hydrolyzed B-lactam can no longer bind PBP
- Has no therapeutic effect

14

Genomic characteristics: B-lactamase (2)

Encoded in both chromosomal genes and plasmids
1) Chromosomal B-lactamase genes show INDUCIBLE expression
- Genes are either amplified or expression was upregulated due to environmental changes
2) Plasmid B-lactamase genes are typically expressed constitutively
- Can be transferred from one organism to another
- Responsible for spread of resistance

The genetic origins of B-lactamases will determine whether or not it is effected by B-lactamase inhibitors such as Clavulanic acid.

15

1) Many Cell Wall drugs work selectively against ___
2) Fewer Cell Wall drugs work selectively against ___
Choices: (Gm+ or Gm-)

1) Gm+
2) Gm-

16

Clavulanic acid - Most active against:
(Detail not important for exam)

PLASMID encoded B-lactamases
- Staphylococci
- Salmonella
- Shigella
- H. influenza
- N. gonorrhoae
- E. coli
- K. pneumoniae

17

Calvulanic acid - Least effective against:

Chromosomally encoded B-lactamases
- Pseudomonas
- Enterobacter
- Serratia
- Citrobacter

18

Characteristic: B-lactamase inhibitor. (2)

Clavulanic acid
1) By itself has NO antibacterial activity
- ONLY effective if combined with other B-lactam antibiotics
2) Bind B-lactamases covalently and inactivate irreversibly

19

Characteristics: Common Penicilin

Penicillin G
1) Acid labile
2) B-lacatamase susceptible
3) Suitable for Gm+, Gm- cocci

20

Characteristics: Anti-staphlococcal penicillins

Cloxacillin
1) Acid STABLE
2) B-lacatamase resistant
3) NOT suitable for:
- enterococci
- anaerobic bacteria
- Gm- cocci
- Gm- rods

21

Characteristics: Extended-spectrum penicillins

Amoxicillin
1) Acid STABLE
2) Inactivated by lactamases
3) Greater activity against Gm-
- highly effective in penetrating the outer membrane

22

Uses of Amoxicillin (4)
(Not emphasized in lecture)

1) Sinusitis
2) Otitis
3) UTI
4) Lower respiratory tract infections

23

Adverse reactions: Penicillin (2)

1) Superinfection with other microbes
- Oppotunistic microbes such as candidiasis can invade post antibiotic therapy

2) Allergic Reaction
- All penicillins are cross reacting, hence past claims of reactivity are frequently unreliable.

Generally non-toxic at grams/day dose

24

Substitution for patients allergic to Penicillin

Cephalosporin (2nd generation or higher)

25

Resistance: Penicillin (3)

1) Upregulation of chromosomally encoded B-lactamases
2) Acquisation of B-lactamases by horizontal gene transfer from other bacteria
3) Mutation of the primary PBP

26

Cephalosporin Generations (4)

1st: Cefazollin
2nd: Cefamandole
3rd: Ceftazidime
4th: Cefepime

27

Cephalosporin:
1) Broad spectrum but better for Gm+
2) Restricted to surgical prophylaxis
3) Does NOT penetrate CNS

Cefazolin (1st generation Cephalosporin)

28

Cephalosporin:
1) Extended coverage of Gm-
2) No allergic cross-reactivity with penicillin

Cefamandole (2nd Generation Cephalosporin)

29

Cephalosporin:
1) Extended gm- activity at the expense of Gm+
2) Effective against inducible B-lactamase but not against constitutive B-lactamase
3) Some cross blood brain barrier

Ceftazidime (3rd generation Cephalosporin)

30

Cephalosporin:
1) More resistant to chromosomal B-lactamases
2) True broad spectrum drugs (Both Gm+ and Gm-)
3) Penetrate CNS
4) Appropriate for MRSA

Cefepime (4th generation Cephalosporin)