Antibiotics II Flashcards
MOA of penicillins
Bactericidal and time-dependent action.Disrupts cross-linking of the cell wall by irreversible inhibition of transpeptidase.
1) Disinhibition (activation) of autolysins also occurs due to cytosolic accumulation of peptidoglycan precursors; promotes cell wall degradation.
2) Bacterial cell lysis is end result.
3) Most effective against bacteria in the log phase of growth.
Beta lactam Antibiotics class
Penicillins
Targets of penicillins known collectively as what
Penicillin-binding proteins and include proteins other than transpeptidase
3 Mechanisms of resistance of penicillins
1) Inability of lipophilic penicillins to penetrate the G- outer membrane.
2) Acquired mutations in penicillin-binding proteins that lower the binding affinity for the B-lactam.
3) B-Lactamases
Standard,narrow spectrum penicillins (2)
Penicillin G, Penicillin V
True/False: PenG and Pen V are active against G-»>G+, also effective against anaerobic bacteria.
False: G+»>G-
T/F: Pen G is unstable in stomach acid; pen v is acid-stable and thus orally effective
True
penicillinase-resistant, narrow spectrum (anti-staph) prototype
nafcillin
T/F: Nafcillin is used only against pen G-resistant staph (MSSA) due to altered PBPs with lower binding affinities
True
Aminopenicillins, broad spectrum prototype
Amoxicillin, ampicillin
Antipseudomonal, extended-spectrum drugs
Ticarcillin, piperacillin
What characterizes amoxicillin?
Aditional activity agaisnt G- bacteria due to increased penetration. Susceptible to beta lactamases
Characteristics of ticarcillin and piperacillin
Spectrum includes organisms susceptible to aminopenicllins plus Pseudomonas aeruginosa. Given IV for serious hospital acquired G- infections. Susceptible to B-lactamases
Fixed-dose combination with B-lactamase inhibitors:
Clavulanic acid-no bactericidal activity of their own; not all B-lactamases are inhibited.
T/F: Penicillins have relatively short half-live (30-90 min) and most are orally well absorbed.
False: Not orally well absorbed (diarrhea)
Respiratory preparation of penicillin
pen G benzathine
Adverse reactions of penicillins
Least toxic Antibiotics.
1) Jarisch-Herxheimer reaction during therapy for syphilis.
2) CNS toxicity (seizures) in pts with high IV doses.
3) Repository prep can be fatal if given IV
4) Amox/Amp can produce rashes not allergy related.
5) Ticarcillin- large IV doses can cause sodium overload
First generation cephalosporin
Cefazolin
Activity of cefazolin
High activity against G+ MSSA (not MRSA) and strep; less active against G-
Second generation Cephalosporin
Cefoxitin
Activity of cefoxitin:
More activity against G- bacteria due to higher affinity for PBPs, greater cell envelope penetration and greater resistance to G- B-lactamases, less active than 1st gen against G+ organisms.
3rd generation cephalosporin
Ceftriaxone
Activity of ceftriaxone
Higher activity against G- and good penetration into CNS. Used for treating meningitis and gonorrhea+empiric chlamydia
Fourth generation cephalosporin
Cefepime
Activity of cefepime
Highly resistant to B-lactamases and broad antibacterial spectrum; good CNS penetration.
Adverse reactions of Cephalosporins
Hypersensitivity, Diarrhea, Potentially nephrotoxic
Drug selections of cephalosporins
3rd generation (ceftriaxone) is most widely used.
Carbapenems
Imipenem/cilastatin
T/F: Imipenem/cilastatin is highly resistant to inactivation by most B-lactamases
True
Pharmcokinetics of imipenem/cilastatin
Given parenterally and eliminated predominantly by the kidneys; imipenem is in fixed-dose combination with cilastatin to prevent renal inactivation.
Monobactam
Aztreonam- contains a B-lactam ring but it is not fused with a second ring- little cross reactivity for allergies to other B-lactam groups
T/F: Aztreonam has a broad spectrum of activity.
False: Narrow spectrum- only against G- aerobic bacteria. Highly resistant to B-lactamases
Other cell wall synthesis inhibitors besides B-lactams: Prototype glycopeptide
Vancomycin
MOA of vancomycin
Prevents polymerization of cell wall precursors; binds to D-Ala-A-Ala terminus of NAM monomer, blocking addition of NAM-NAG to the NAM-NAG polymer chain (bactericidal).
T/F: Vancomycin cannot penetrate G- envelope due to large molecular size; active only against G+ bacteria- S. aureus and S. epidermis
True
What is the change that caused VRSA?
Variations in peptide terminus (D-Ala-D-lactate) producing 1000-fold decrease in binding affinity
What is VRSA treated with?
Linezolid, daptomycin, or quinupristin/dalfopristin
What do you combine Vancomycin with to treat meningitis?
3rd gen cephalosporin (ceftriaxone)
What drug has the adverse effects of Ototoxic, “red man syndrome”, and Thrombophlebitis with IV infusion?
Vancomycin
What drug is a bactericidal phosphenolpyruvate analogue that is used in treatment of uncomplicated G- urinary tract infections
Fosfomycin
Drug that inhibits production of murein monomers in the cytosol by inhibiting the synthesis of UDP-NAM from UDP-NAG covalently binds to the active site (-SH group) of the enzyme enolpyruvate transferase
Fosfomycin
T/F: Fosfomycin enters the bacterium via a glycerophosphate transporter; mutations to this transporter render the microbe resistant
TRUE
What drug is a bactericidal cyclic polypeptide isolated from Bacillus subtilus?
Bacitracin
What drug does this MOA belong to: Inhibits bactoprenol dephosphorylation (bactophrenol is a lipid carrier that transfers murein monomers across the inner membrane to the cell wall)
Bacitracin
Bacitracin is active against G+/G- bacteria?
G+, much less effective against G-. Acquired resistance is unknown
Bacitracin is usually available topically in fixed-dosembination with what 2 drugs?
Neomycin/polymyxin B
T/F: Bacitracin is highly nephrotoxic if administered systemically
True
