G3: Beta-Lactam Antibiotics: Penicillins

What are the types of beta-lactam antibiotics?

• Penicillins

• Cephalosporins

• Carbapenems

• Monobactam

What is MOA of penicillins?

Inhibit cell wall synthesis at Penicillin Binding Proteins (PBP)

What are the general characteristics of penicillins?

• Time dependent (T > MIC), bactericidal activity

• Gram (+) → Gram (-)

• Short half-lives

• Nearly exclusive renal elimination & dose-adjustment for renal dysfunction

What are the ADRs common to all penicillins?

• Gastrointestinal upset

• Allergic reaction, rash

• Thrombocytopenia, neutropenia

• Seizures (rare)

What are the drug interactions of penicillins?

• Warfarin (mild)

• Birth control (mild, controversial)

What are the agents of natural penicillins?

• Penicillin G (IV)

• Penicillin G Benzathine (IM)

• Penicillin G procaine (IM)

• Penicillin V(K) (PO)

What is the spectrum of natural penicillins?

Some Streptococci, Enterococci, some mouth anaerobes, Treponema pallidum

What are the notes of natural penicillins?

• Narrow spectrum

• DOC for syphilis, some streptococci

• Caution w/ K+ salt in renal failure

• IM repository forms should NOT be given IV

What are the agents of aminopenicillins?

• Ampicillin (IV)

• Amoxicillin (PO)

What are the spectrum of aminopenicillins?

Adds enhanced Enterococcus, H. influenzae, Neisseria, E. coli, Proteus, Klebsiella, Listeria monocytogenes

What are the notes on aminopenicillins?

• Increased gastric acid stability

• DOC for enterococci & listeria

• Some S. Pneumoniae coverage

What are the agents of antistaphylococcal (penicillinase-resistant) penicillins?

• XX methicillin (IV)- interstitial nephritis

• Nafcillin (IV)

• Oxacillin (IV)

• XX Cloxacillin (PO)

• Dicloxacillin (PO)

What are the spectrum of antistaphylococcal (penicillinase-resistant) penicillins?

Staphylococci & some Streptococci ONLY

What are the notes of antistaphylococcal (penicillinase-resistant) penicillins?

• DOC for Methicillin Susceptible Staphylococcus aureus (MSSA)

• Unique monitoring: interstitial nephritis, hypokalemia, LFTs

• No dose adjustment needed for renal insufficiency

What is the chief of “Staph”?

• Methicillin-Resistance Staphylococcus aureus (MRSA)

• Methicillin-Resistance Staphylococcus epidermidis (MRSE)

• Characteristics:

  • Encoding of mec A gene

  • Altered PBP to PBP2a

  • Low binding affinity

  • MRSE often a contaminant of blood cultures

What are the agents of beta-lactam/BLI combinations?

• Aminopenicillins:

  • Ampicillin/sulbactam (Unasyn) (IV)

  • Amoxicillin/clavulanic acid (Augmentin) (PO)

• Extended spectrum:

  • XX ticarcillin/clav acid (Timentin) (IV)

  • Piperacillin/tazobactam (Zosyn) (IV)

What are the spectrum of beta-lactam/BLI combinations?

• Adds MSSA, H. Influenzae, N. Gonorrhoeae, E. coli, Klebsiella, Proteus, Bacteroides

• Extended spectrum w/ SPACE coverage including P. Aeruginosa

What are the notes of beta-lactam/BLI combinations?

• BLI= enhanced Gm (-) & anaerobic coverage

• BLI increases GI side effects

What is penicillin allergy?

Mild rash to anaphylaxis

• Immediate (w/in 1 hour)

  • IgE mediated: anaphylaxis, angioedema, bronchoconstriction

• Accelerated (1-72 hours)

  • IgE mediated: rash, itching, fever, laryngospasm, hypotension

• Delayed (>48-72 hours)

  • Not IgE mediated: rash

What is the book definition of penicillin allergy?

Cross reactivity <10%

What is the true cross-allergenicity b/w PCN allergy & other beta-lactams likely less than historical reports?

• PCNS & most cephalosporins: ~1-2%

• PCNS & carbapenems: ~1-2%

• PCNS & aztreonam: <1%