Antibacterial Agents 2: Cell-Wall Synthesis Inhibitors Flashcards
3 Components of the B-lactam drugs
Side chain, B-lactam ring, and thiazolidine ring
Penicillin G
High activity against Gram (+), low against (-)
Destroyed by B-lactamase (resistance mech)
Acid labile
Prototypical penicillin
Oxacillin/cloxacillin/dicloxacillin/flucloxacillin
Aka isoxazoyl penicillins
Acid stable
Can be taken orally
Highly protein-bound
Safe with pts w/ renal insufficiency
Narrow Spectrum (cocci)
Nafcillin
Similar to isoxazolyl penicillins, but not as strongly bound
Resistant to staph B-lactamase
More efficacious that Oxacillin fam
Narrow spectrum (cocci)
Ampicillin
Similar to penicillin G
Susceptible to B-lactamase
Acid stable, and better gram (-) activity
Extended spectrum (additional activity against g(-) bacilli)
Ticarcillin
Like carbenicillin, but higher blood levels
Active against gram (-) aerobes
Anti-pseudomonal
Not penicillinase resistant
Amoxicillin
Similar to ampicillin but higher blood levels
Extended spectrum (additional activity against g(-) bacilli)
Penicillin R Groups
Can alter function of of atbx, like
Acid stability
Renal excretion
Bacterial resistance
Spectrum variation
What is Stage 1 of wall formation and what atbx inhibits it
Synthesis of cell wall subunits in cytosol
Fosfomycin and cycloserine
What is Stage 2 of wall formation and what inhibits it
Linear polymerization of subunits at cell membrane
Bacitracin and vancomycin
What is Stage 3 of cell wall formation and what inhibits it
Cross-linking of peptidoglycan polymers at the cell wall
Penicillin and cephalosporins
How does penicillin interfere with the cross-linking?
Penicillin mimis D-al-D-al, the terminal end of the peptide that crosslinks adjacent N-actylmuramic acids
Penicillins are ________ to growing organisms
Bactericidal
Penicillin Binding Proteins
Bacterial proteins targetted by B-lactams for acetylation
Penicillin Mech of action:
Effect on autolytic enzymes
Depresses inhibitors of natural autolysins
Covalently binds to them, thus effect persist when drug is gone
B-lactamase
Generic term for enzymes that hydrolyze B-lactams, including penicillinases and cephalosporinases
Production via plasmids in response to penicillin
MRSA and Penicillin resistance in pneumococci resistance
They alter their penicillin-binding proteins
Penicillin:
Absorption characteristics
Highly water soluble (moderately acidic)
Best taken on empty stomach (lots of penicillins are acid-labile)
Oral needs higher dosage than parenteral
Penicillin:
Distribution characteristics
Throughout body
Poor tissue penetration (ionized at physiological pH)
Can enter inflamed tissues or membranes
Penicillins:
Metabolism and Excretion
Ecreted as active drug
90% tubular excretion
Excreted in breast milk
B-Lactamase Inhibitors
Clavulanic Acid, Sulbactam, Tazobactam
Irreversible inhibitors
Clavulanic acid combines with this amoxicillin
Augmentin
Calvulanic acid combines with this ticarcillin
Timentin
Sulbactam combines with this ampicillin
Unasyn
Tazobactam combines with this piperacillin
Zosyn
Streptococci
Clinical atbx uses
Penicillins
Penicillin G
Penicillin V
Amoxicillin
Enterococci
Clinical atbx uses
Penicillins
Penicillin G and Ampicillin for bacteremia
Ampicillin for UTI
Staphylococcus aureus
Clinical atbx uses
Penicillins
MSSA: Oxacillin
MRSA: No penicillins
Neisseria meningititis
Clinical atbx uses
Penicillins
Penicillin G
Moraxella catarrhalis
Clinical atbx uses
Penicillins
Amoxicillin combined with Clavulanate
Bacillus anthracis
Clinical atbx uses
Penicillins
Penicillin G
Corynebacterium diphtheria
Clinical atbx uses
Penicillins
Penicillin G
All gram negative bacilli
Clinical atbx uses
Penicillins
Ampicillin
Amoxicillin +/- Calvulanate
(Includes: H-flu, E. coli, klebsiella, H. pylori)
Pseudomonas aeruginosa
Clinical atbx uses
Penicillins
Amoxicillin-Clavulanate
Piperacillin-Tazobactam
Ticarcillin-Clavulanate
Clostridium perfringens
Clinical atbx uses
Penicillins
Penicillin G
Bacteroides fragilis
Clinical atbx uses
Penicillins
Pipercillin - tazobactam
Ticarcillin - clavulanate
Treponema pallidum (syphilis)
Clinical atbx uses
Penicillins
Penicillin G
Borelia burgdorferi (Lyme)
Clinical atbx uses
Penicillins
Amoxicillin
Penicillin G
Clinical atbx uses
Streptococci
Enterococci
- Neisseria meningititis*
- B. anthracis*
- C. diphtheria*
- C. perfringens*
- T. pallidum*
Amoxicillin
Clinical atbx uses
- Streptococci*
- Morazella catarrhalis* (with Calvulanate)
Gram Negative Bacilli (+/- Calvulanate)
- P. aeruginosa*
- Borrelia burgdorferi*
Penicillins:
Toxicity and Adverse Reactions
Virtually non-toxic except hypersensitivity
10% of patients report penicillin allergy, but only 10-20% actually experience a reaction (1-2% of population)
Commonly an idiopathic reaction, with a rash, type I reactions are life threatening
Vancomycin
Mechanism of Action
Inhibits cell wall synthesis at site different than penicillin (Stage 2)
Vancomycin
Pharmacokinetics (absorption and excretion)
Poor oral, IV preferred unless for GI infection
Excreted by kidneys (6-10 days if renal failure)
Vancomycin
Clinical Uses
MRSA
Staphylococci and streptococci
Ampicillin resistant enterococci
C. diff
Vancomycin
Adverse Effects
Chill-Fever-Skin rash
Ototoxity for most severe
Daptomycin
MOA
At bacterial membrane leading to loss of intracellular ions causing lysis
Cephalosporins
Similar to penicillins but key differences:
Broader specturm v. G(-)
Less suscetible to B-lactamase
LEss cross-reactivity in penicillin sensitive patients
Cephalosporins
Absoprtion
Some oral, some parenteral, depending on acid staiblity
Cephalosporins
Distrubution
Tissue penetrant, including placenta
3rd Gen can go into CSF
Cephalosporins
Metabolism and Excretion
Primarily renal
Dose appropriately if renal insufficiency
Cephalosporin
Generation I
Cefazolin (IV) and Cephalexin (po)
Many G(+) cocci, some g(-) bacillli
Spectrum like amoxicillin
Great activity against MSSA
Cephalosporin
Generation 2
Ceruroxime
Greater against g(-) bacteria than Gen I
Little to no activity agaisnt pseudomonas
Activate against anaerobes (Bacteroides fragilis)
Cephalosporin
Generation 3
Cefdinir, Ceftriaxone, Ceftazidime
Comapred to gen 2, more activate agaisnt enteric g(-) bacilli (lkike eneterobacter)
Ceftazidime has moderate antipseudomonal activity
Cephalosporin
Generation 4
Cefepime
Like gen 3 covers pseudomonas and s. pneumoniae
Cephalosporin
Generation 5
Ceftaroline
MRSA coverage
Cephalosporin
Generation I
Clinical uses
MSSA, Streptococci [cephalexin, cefazolin]
- Klebisella* [cephalexin]
- E. coli* [cephalexin]
Cephalosporin
Generation II
Clinical uses
Resistant E. coli
- H. influenza* [ceruoxime for meingitis and Cefaclor for sinusitis]
- M. catarrhalis* [Cefaclor]
Cephalosporin
Generation III
Clinical uses
- Streptococcus pneumoniae* [Cefotaxime, ceftriaxome]
- Neisseria gonorrheae* [Ceftriaxome]
- Pseudomonas aeruginosa* [Ceft]
- H-flu* [Ceft]
- E. coli* [Cefo, ceft]
- Klebsiella* [ceft]
Sespis [Ceft]
Cephalosporin
Generation IV
Clinical uses
(All Cefepime)
- S. pneumoniae*
- P. aeruginosa*
- Klebsiella*
Cephalosporins
Adverse Reactions and Toxicity
Well tolerated
Do not give to patients with history of immeidate sensitivity to Penicillin
Can intensify oral anticoags
Carbapenems
MOA
Interact with penicillin binding porteins responsible for elongation
B-lactamase resistance
Carbapenems
Pharmacokinetics
Parenteral
Tissue penetrant, including CSF
imipenem- renal metabolism and excretion
Meropenem and ertapenem not ensitive to renal dipeptidase
Carbapenems
Clinical Uses
Active to both G(+) and G(-)
Reserved for multiple resistance
P. aeruginosa, E. coli, C. perfringens, and Becteroides
