Penicillin Flashcards
Natural Penicillins Examples with Routes
Penicillin G (IV)
Benzathine Penicillin (IM)
Penicillin V Potassium (PO)
Natural Penicillins MOA
Bind to penicillin binding proteins (PBPs)
Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
Natural Penicillins Mechanism of Resistance
Beta-lactamase enzymes -> destruction of antibiotic (more common for Gram-negative)
Failure to penetrate outer membrane of bacteria and reach binding site (Gram-negative)
Pumped out of the cell via efflux pump (Gram-negative)
Alteration of binding site (Gram-positive)
Natural Penicillins
Gram-positive Aerobes
Good against: ___
Limited activity against___
Treatment of Choice for ___
Good against: Enterococcus faecalis
Limited activity against: Staphylococcus aureus
TOC: for susceptible Streptococcus spp.
Group A streptococcus
strep pyogenes
skin flora –> cellulitis
Group B Streptococcus
Strep agalactiae
Skin and vaginal flora
Group C, F, G Streptococcus
Skin flora –> cellulitis
Streptococcus pneumoniae
Respiratory flora –> pneumonia
Viridans Streptococcus
oral flora –> dental infections, endocarditis
Natural Penicillins
Gram Negative Aerobes
Minimal Activity
Some activity against: Neisseria Meningitidis
Natural Penicillins
Atypical
No activity
Natural Penicillins
Anaerobes
Good activity against:
TOC:
Limited activity:
Good activity: Gram + anaerobes (oral flora)
- Actinomyces spp.
- -Peptostreptococci
- -Propionibacterium acnes (Cutibacterium acnes)
TOC: Clostridium perfringens
Limited activity: Gram - anaerobes
- -Bacteroides fragilis
- -Prevotella spp.
- -Fusobactierium necrophorum
Natural Penicillins
Other organisms
TOC against spirochete, Treponema pallidum, which causes syphilis
Natural Penicillins
Metabolism
Substrate of organic transporters (OAT) 1/3
Poor penetration across BBB but with inflamed meningitis, does exceed MIC of susceptible organisms with new breakpoints (Streptococcus)
Natural Penicillins
Elimination: Half life
Half-life in normal renal function is only 30-60 minutes -> leading to frequent dosing
–> often seen dosed as 2-3 million units q4hr
Natural Penicillins
Elimination: Excretion
Excreted in urine, mostly as unchanged drug -> requires dose adjustment in renal dysfunction
Natural Penicillins
Adverse effects: CNS
Seizures at very high doses (40-100 million units/day)
Natural Penicillins
Adverse effects: hematologic
Neutropenia
Natural Penicillins
Adverse effects: Hypersensitivity
Ranges from rash/hives to anaphylaxis
Serum sickness can occur but is uncommon
Natural Penicillins
Adverse effects: Renal
Acute interstitial nephritis
Renal tubular disease
Natural Penicillins
Drug Interactions
Drugs that interact with the organic anion transporters 1/3
–Pretomanid, Teriflunomide, Fexinidazole
Probenecid
- -Increases plasma levels of penicillin by competitively inhibiting renal tubular secretion
- -Used as alternative dosing strategy to extend half-life and increase drug concentrations
Penicillinase-resistant Penicillins
Examples with Routes
Nafcillin (IV)
Oxacillin (IV)
Dicloxacillin (PO)
Penicillinase-resistant Penicillins
MOA
Bind to penicillin binding proteins (PBPs)
Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
Acyl side chain prevented disruption of the beta-lactam ring
Penicillinase-resistant Penicillins
Gram + Aerobes
No activity:
Good activity:
TOC:
No activity: Enterococcus faecalis or MRSA
Good activity: penicillin-susceptible Streptococcus spp.
TOC: methicillin-susceptible Staphylococcus aureus (MSSA)
Penicillinase-resistant Penicillins
Gram - Aerobes
No activity
Penicillinase-resistant Penicillins
Anaerobes
No activity
Penicillinase-resistant Penicillins
Atypical
No activity
Penicillinase-resistant Penicillins
Metabolism: Nafcillin/Oxacillin
Nafcillin is moderate CYP3A4 inducer
Widely distributed with increased CSF penetration with meningeal inflammation
90-95% protein bound
Penicillinase-resistant Penicillins
Elimination: Nafcillin/Oxacillin
Half-life only 20-60 min -> dosed every 4 hours
Excreted primarily through feces (nafcillin) and bile/urine (oxacillin) -> no renal dose adjustments
Penicillinase-resistant Penicillins
Metabolism: Dicloxacillin
Moderate CYP2C19, weak CYP2C9, and weak CYP3A4 inducer
Rapid and incomplete absorption that is affected by food
Low CSF penetration
95-99% protein bound
Penicillinase-resistant Penicillins
Elimination: Dicloxacillin
45 min half-life - > dosed every 6 hours
Excreted in feces and urine as unchanged drug -> no renal dose adjustments
Penicillinase-resistant Penicillins
Adverse Effects: GI
Dicloxacillin
Abdominal pain, diarrhea, nausea
Penicillinase-resistant Penicillins
Adverse Effects: Hepatic
nafcillin/oxacillin
Increased serum transaminases
Hepatotoxicity
Penicillinase-resistant Penicillins
Adverse Effects: Hematologic
nafcillin/oxacillin
Neutropenia
Penicillinase-resistant Penicillins
Adverse Effects: Renal
nafcillin/oxacillin
Acute interstitial nephritis
Renal tubular disease
Penicillinase-resistant Penicillins
Adverse Effects: Local
nafcillin/oxacillin
injection site reactions
phlebitis
Penicillinase-resistant Penicillins
Drug interactions
CYP3A4 substrates will be affected by Nafcillin and should be monitored
Antifungal azoles, anti-epileptics, statins, transplant medications, etc.
Dicloxacillin Transplant medications (sirolimus, tacrolimus, mycophenolate) CYP3A4 Carbamazepine CYP3A4 Fosphenytoin/Phenytoin CYP2C19 Omeprazole CYP2C19
Aminopenicllins
Examples and Routes
Ampicillin (IV)
Amoxicillin (PO)
Aminopenicllins
MOA
Bind to penicillin binding proteins (PBPs)
Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
Aminopenicllins
Gram + aerobes
TOC:
Limited activity:
Same as penicillin against:
TOC: Enterococcus Faecalis and Listeria Monocytogenes
Limited Activity: Staphylococcus aureus
Same as penicillin against: Streptococcus spp. but broader
Aminopenicillins
Gram - Aerobes
Limited activity:
Limited activity overall - > expanded activity compared to natural penicillins
Not active if beta-lactamase producing
E. coli and P. mirabilis can be susceptible, especially in younger patients without prior antibiotic exposure
H. influenzae is covered if beta-lactamase negative (otitis media or sinusitis)
Aminopenicillins
Atypical
no activity
Aminopenicillins
Gram + Anaerobes
Good activity against Gram-positive anaerobes (oral flora)
Actinomyces spp.
Peptostreptococci
Propionibacterium acnes (Cutibacterium acnes)
Aminopenicillins
Gram - Anaerobes
Limited activity against Gram-negative anaerobes due to resistance
Bacteroides fragilis is considered resistant
Prevotella spp. and Fusobacterium necrophorum have high likelihood of producing beta-lactamases and being resistant
Aminopenicillins
Gram - Anaerobes
Limited activity against Gram-negative anaerobes due to resistance
Bacteroides fragilis is considered resistant
Prevotella spp. and Fusobacterium necrophorum have high likelihood of producing beta-lactamases and being resistant
Aminopenicllins
Metabolism and Elimination
Ampicillin
Distributes well into bile, penetration into CSF with inflamed meninges
10-18% Protein bound
Half-life 1 to 2 hours, extended up to 20 hours in anuric patients
Primarily excreted in urine as unchanged drug (∼90%) -> requires renal dose adjustment
Aminopenicllins
Metabolism and Elimination
Amoxicillin
Widely distributed
20% Protein bound
Half-life 2 hours
Primarily excreted in urine as unchanged drug (∼60%) -> requires renal dose adjustment
Aminopenicllins
Adverse Effects: GI
Amoxicillin
Abdominal pain, diarrhea, nausea
Aminopenicllins
Adverse Effects: Dermatologic
ampicillin
Erythema multiforme
Exfoliative dermatitis
Skin rash
Urticaria
Aminopenicllins
Adverse Effects: Hematologic
ampicillin
Neutropenia
Leukopenia
Anemia
Eosinophilia
Aminopenicllins
Adverse Effects: Renal
Ampicillin
Acute interstitial nephritis (rare)
Aminopenicllins
Drug Interactions
No significant drug interactions
Penicillin + Beta-Lactamase Inhibitor
Examples and Routes
Ampicillin/sulbactam (IV)
Amoxicillin/clavulanate (PO)
Piperacillin/tazobactam (IV)
Penicillin + Beta-Lactamase Inhibitor
MOA
Bind to penicillin binding proteins (PBPs)
Inhibit cross-linking of peptidoglycan in the cell wall -> autolysis -> cell death
___ was the first beta-lactamase inhibitor
Clavulanic acid
Penicillin + Beta-Lactamase Inhibitor
Gram + Aerobes
No added activity:
Added activity:
No activity:
No added activity: Enterococcus or Streptococcus spp.
Added Activity: S.aureus (methicillin susceptible)
No activity: MRSA
Penicillin + Beta-Lactamase Inhibitor
Gram - Aerobes
TOC:
Activity against:
TOC: Amox/clav and Amp/sulb are TOC for Haemophilus influenza, Moraxella catarrhalis, Pasteurella multocida & Capnocytophaga species
Activity against: Acinetobacter baumannii, E.coli, Klebsiella, Proteus spp., psedomonas aeruginosa
Penicillin + Beta-Lactamase Inhibitor
Gram + anaerobes
TOC: anaerobes that cause oral infections
Actinomyces spp.
Peptostreptococci
Propionibacterium acnes (Cutibacterium acnes)
Penicillin + Beta-Lactamase Inhibitor
Gram - anaerobes
TOC:
Bacteroides fragilis,
Prevotella spp.
Fusobacterium necrophorum
Intra-abdominal infections
Diabetic foot infections
Penicillin + Beta-Lactamase Inhibitor
Metabolism and Elimination
Sulbactam
Widely distributed
Protein binding: 38%
Half-life elimination: 1 to 1.3 hours
Excretion: Urine (~75% to 85% as unchanged drug) within 8 hours
Penicillin + Beta-Lactamase Inhibitor
Metabolism and Elimination
Clavulanic Acid
Protein binding: ~25%
Half-life elimination: 1 hour
Excretion: Urine (25% to 40% as unchanged drug)
Penicillin + Beta-Lactamase Inhibitor
Metabolism and Elimination
Piperacillin/tazobactam
Widely distributed
Protein binding: Piperacillin: ~26% to 33%; Tazobactam: 31% to 32%
6 – 9% of Piperacillin is metabolized to desethyl metabolite (weak activity)
22% of tazobactam is metabolized to an inactive metabolite
Half-life elimination: Piperacillin and tazobactam’s half-lives are 45 minutes to 1.5 hours
Piperacillin and tazobactam are primarily excreted into the urine (68% for piperacillin and 80% for tazoactam as unchanged drug)
Penicillin + Beta-Lactamase Inhibitor
Adverse Effects: GI
amox/clav
Abdominal pain, diarrhea, nausea
Penicillin + Beta-Lactamase Inhibitor
Adverse Effects: Dermatologic
Skin Rash
Urticaria
Pruritis
Penicillin + Beta-Lactamase Inhibitor
Adverse Effects: Hematologic
Pancytopenia
Thrombocytopenia
Penicillin + Beta-Lactamase Inhibitor
Adverse Effects: Hepatic
Increased LFTs
Hepatitis
Penicillin + Beta-Lactamase Inhibitor
Adverse Effects: Renal
Interstitial nephritis
Penicillin + Beta-Lactamase Inhibitor
Drug Interactions
Piperacillin-tazobactam + Vancomycin increases risk of nephrotoxicity
