Penicillins Flashcards
MOA
Inhibit cell wall synthesis by inhibiting PBP located in bacterial cell walls (transpeptidase)
PBP are primarily expressed during cell division
MOR
B-lactamase: hydrolyzes B-lactam inactivating antibiotics
Production:
Gram (+): Penicillin-resistant staphylococcus aureus
Gram (-): H. influenza, Moraxella, Neisseria, E.coli, Klebsiella, enterobacter
Gram (-) anaerobes: bacteroides fragilis
PBP alterations: leads to decreased binding affinity
- PRSP–>chromosomally mediated mutation that codes for PBP
- MRSA–> PBP–>PBP2A (mecA)
Decreased permeability/penetration
Pharmacodynamic properties
Time-dependent and bactericidal except Enterococcus spp.
T>MIC
PK
Absorption: degraded by gastric acid
-Lower concentration of PO vs IV–>PO only for mild-moderate infections
Distribution:
-Widely distributed into tissues and fluids: do not get into eye or prostate
-Adequate CSF concentrations of high-dose parenteral administration only in the presence of inflamed meninges
-Protein binding is variable: 97% of dicloxacillin (highest)
T1/2: < 2 hours except some cephalosporins and one carbapenem
Elimination: unchanged in the kidneys except NAFCILLIN, OXACILLIN
- Probenecid blocks tubular secretion due to both being anions
-Piperacillin undergoes duel elimination
Cross-allergenicity
YES except Aztreonam
Structure
B-lactam ring + 5-membered thiazolidine ring
Dosing
Maintain serum concentration > MIC of bacteria for 50% of dosing interval
Due to short half-life, requires frequent dosing or continuous infusion
Rate of killing
medium grade
Sodium load
Some parenteral administered penicillin’s contain sodium
Sodium Penicillin G–> 2.0 mEq/1 million units
Nafcillin–>2.9 mEq/g
Ticarcillin–>5.2 mEq/g
Piperacillin–>1.85 mEq/g
Must be used with caution in CHF or renal insufficiency
Adverse effects
Hypersensitivity: rash or anaphylaxis
- haptens produce antibodies that give rise to allergic reactions
Neurologic–> direct toxic effect
-if patients are receiving high IV doses with RI then DOSE ADJUST
- Irritable, jerking, confusion, tonic-clonic seizures
Hematologic
- anemia, thrombocytopenia, neutropenia, leukopenia
- prolonged infusion > 2 weeks reversible when D/C
GI: N/V/D
- diarrhea is high with clavulanate
- pseudomembranous colitis
Interstitial Nephritis
- Immune-mediated damage to renal tubules as penicillin acts as hapten when bound to tubular cells
- Increased SCr, eosinophilia
- Most common with nafcillin and methicillin
Others:
-Phlebitis (nafcillin)
-Hypokalemia (carbenicillin and ticarcillin)
-Na Overload/Fluid retention (piperacillin and ticarcillin)
Synergy
Viridans streptococcus–> penicillin/amoxicillin + gentamicin
Enterococcus spp.–> ampicillin + gentamicin/streptomycin
Staphylococcus spp.–> nafcillin + gentamicin
Gram (-)–> ticarcillin/piperacillin + AGS
Penicillin G (aqueous, benzathine, procaine)
natural penicillin
Spectrum:
-Penicillin susceptible S. pneumoniae
-Penicillin-susceptible S. aureus
-Treponema pallidum (syphilus)
Penicillin V
natural penicillin
Spectrum:
-Penicillin-susceptible S. pneumoniae
-Penicillin-susceptible S. aureus
-Treponema pallidum (syphilus)
Methicillin
Developed in response to penicillinase-production Staphylococcus aureus
parenteral
Nafcillin
penicillinase-resistance penicillin
developed in response to penicillinase-production Staphylococcus aureus
parenteral
Spectrum: MSSA
Oxacillin
penicillinase-resistance penicillin
developed in response to penicillinase-production Staphylococcus aureus
parenteral
Cloxacillin
penicillinase-resistant penicillin
developed in response to penicillinase-production Staphylococcus aureus
ORAL
Dicloxacillin
penicillinase-resistant penicillin
developed in response to penicillinase-production staphylococcus aureus
ORAL
Ampicillin
aminopenicillin
developed in response to have gram (-) activity
oral and parenteral
Spectrum: Enterococcus spp., Listeria monocytogenes
SHEP
Amoxicillin
aminopenicillin
developed in response to have gram (-) activity
oral
Spectrum: Enterococcus spp., Listeria monocytogenes
SHEP
Ticarcillin
developed in response to more gram (-) activity
parenteral
Spectrum: Enterococcus spp., Pseudomonas aeruginosa
SHEPMEPP
Piperacillin
ureidopenicillin
developed in response to more gram (-) activity
parenteral
Spectrum: Pseudomonas aeruginosa–> Penicillin of choice, BDA (bacteroides fragilis and B. fragilis group
Ampicillin-Sulbactam (Unasyn)
Developed to enhance activity against B-lactamase producing bacteria
B-lactamase inhibitors irreversible bind to catalytic site of B-lactamase
Parenteral
MSSA, BDA (bacteroides fragilis and B. fragilis group)
Piperacillin-Tazobactam (Zosyn)
Developed to enhance activity against B-lactamase producing bacteria
B-lactamase inhibitors irreversible bind to catalytic site of B-lactamase
parenteral
Spectrum: MSSA, Pseudomonas aeruginosa, BDA (bacteroides fragilis and B. fragilis group)
Amoxicillin-Clavulanate (Augmentin)
Developed to enhance activity against B-lactamase producing bacteria
B-lactamase inhibitors irreversible bind to catalytic site of B-lactamase
ORAL
Spectrum: MSSA, BDA (bacteroides fragilis and B. fragilis group)
Clinical uses:
- otitis media
- sinusitis
- bronchitis
- lower RTI
- human or animal bites
Clinical uses of B-lactamase combination products
Due to expanded activity against gram + and gram - bacteria including anaerobes they can be used to treat intraabdominal infections, gynecological infections, diabetic foot infections
