Penicillins Flashcards
Penicillin Mechanism of Action
binds to transpeptidases aka “Penicillin binding proteins” which cross-link alainine resideues in bacterial cell walls to make it functional.
Mimics alanine (“D-alanyl-D-alanine”) residues • Inactivates enzymes • Wall breakdown > wall creation → Autolysis • Enzymes that hydrolyze cell wall continue to work • Cell death (bactericidal)
2 Natural Penicillins
& special feature:
Penicillin G (IM and IV)
Penicillin VK (oral)
Probenecid • Gout drug • Inhibits renal secretion PCN • Boosts PCN levels → co-administered in special circumstances
3 mechanisms of Resistance to Natural Penicillins
Modified penicillin binding proteins
May result from genetic mutations • Example: S. pneumonia often produces altered PBPs
Reduced bacterial cell penetration
Gram negative bacteria: poor penetration • Porins: gram negative proteins that transport nutrients/waste • Bacteria may decrease number of porins
Beta lactamase enzyme
whats Beta Lactamase? who has it?
Bacterial enzymes that Degrade beta lactam compounds • Penicillin G and VK • Some other penicillins • Some cephalosporins
Many gram negative bacteria & Staphylococcus aureus
Beta Lactamase in (-) bacteria found in:
in (+) bacteria:
Gram negative bacteria • Beta lactamase found in periplasm
Gram positive bacteria (S. Aureus) • No periplasm - Beta lactamase secreted • Generally produce more enzyme than GN
3 β-Lactamase Inhibitors:
Clavulanic Acid
Sulbactam
Tazobactam
β-Lactamase Inhibitors effectivness:
• Little/no effect used alone therefore Added to some penicillins to expand coverage • Aminopenicillins • Antistaphylococcal penicillins
Clinical Uses for Penicillin G and VK
Narrow spectrum – few specific modern uses
Gram positives • Strep pyogenes (strep throat) • Actinomyces
Treponema Pallidum (syphilis)
Rare uses: (only in susceptible isolates) • Neisseria meningitides • Strep. pneumonia
Penicillin Adverse Effects:
acute:
immediate:
skin:
Acute (“immediate”) • Type I, IgE-mediated • Usually within 1 hour of taking drug
“Non-immediate” reaction • Most common with aminopenicillins • Maculopapules • Itchy or may be non-pruritic • Absence of fever, wheezing, joint pain • Days or weeks after starting drug • Type-IV (T-cell-mediated) mechanism
Stevens-Johnson Syndrome • Fever, necrosis • Sloughing of skin • Dermal-epidermal junction • Vesicles, blisters • Toxic epidermal necrolysis • Severe form SJS (>30% skin) Immune mediated • CD8 T-cells play important roll
Penicillin Adverse Effects: Interstitial Nephritis
Drug acts as hapten → immune response in kidneys • Hypersensitivity (allergic) reaction • Complex mechanism • Considered a Type IV hypersensitivity reaction • T cells, Mast cells
Classic presentation • Fever • Oliguria • Increased BUN/Cr** • **Eosinophils** in urine • White cells and **WBC casts (“sterile pyuria”)
Penicillin Adverse Effects: Hemolytic Anemia
High doses can lead to extrinsic hemolytic anemia • PCN binds to surface RBCs (hapten**) • Elicits immune response • **Antibodies against PCN bound to RBCs • Direct Coombs test: positive • Type II hypersensitivity
Penicillin Adverse Effects: Serum Sickness
• Immune complex disorder (IgG) • Days/weeks after exposure • Complement activation • Type III hypersensitivity reaction • Urticaria, fever, arthritis, lymphadenopathy
Penicillin Immunology:
types 1-4:
Penicillin Adverse Effects: C. Difficile Infection?
Frequent associations
Clindamycin* classicallly • Fluoroquinolones • Cephalosporins • Penicillins
3 Antistaphylococcal Penicillins:
mechanism of action:
Oxacillin, nafcillin, dicloxacillin
Side chain protects β-lactam from staph penicillinase
Covers Staph Aureus (non-MRSA) and most strep
Common uses for Antistaphylococcal Penicillins
Community acquired cellulitis • Impetigo
Staph endocarditis based on culture data(never empirically tho)
2 Aminopenicillins
what do they do:
coverage:
Amoxicillin (oral) • Ampicillin (IV) • (Poor bioavailability when given orally)
Penetrate porin channel of gram-negative bacteria • Sensitive to beta lactamase enzymes
Covers penicillin bacteria plus some gram negatives
6 bugs commonly treated by Aminopenicillins Amoxicillin/Ampicillin
Bacteria:
H. Influenza
E. Coli
Proteus
Salmonella
Shigella
Listeria (gram +)
3 main clinical uses for Aminopenicillins Amoxicillin/Ampicillin:
Otitis Media
Bacterial sinusitis
Meningitis • Newborns, elderly • Listeria coverage
Aminopenicillins Maculopapular Rash:
classic case:
Most common with aminopenicillins
More common in viral infection • Classic case • EBV infection with sore throat • Amoxicillin given for presumed bacterial pharyngitis • Maculopapular rash
β-Lactamase Inhibitors Clavulanic Acid, Sulbactam, Tazobactam • Commonly used with
aminopenicillins
2 Common uses of β-Lactamase Inhibitors (Clavulanic Acid, Sulbactam, Tazobactam) • + aminopenicillins:
Otitis media/sinusitis (Broad-spectrum) • Bite wounds (Polymicrobial with anaerobes)
2 Antipseudomonal Penicillins:
Ticarcillin, Piperacillin
Antipseudomonal Penicillins:
greater:
more - coverage than_
susceptible to:
broad spectrum b/c:
usually given to:
Greater porin channel penetration • Effective against Pseudomonas aeruginosa • More gram (-) coverage vs. aminopenicillins
Susceptible to β-lactamases
Given with β-lactamase inhibitor
Broad-spectrum antibiotics • Most gram-positive (not MRSA) • More gram-negative (pseudomonas) • Most anaerobic bacteria
Hospitalized patients with sepsis/PNA