penicillin G
Brand: Pfizerpen, Bicillin (benzathine formulation)
Prototype Drug
Drug Class: antibiotic
Drug Family: antibiotic
Subclass: natural penicillin / beta-lactam
Organ Systems: infectious-disease
Mechanism of Action
Binds and inhibits PBPs (transpeptidases) on the inner bacterial cell membrane, blocking cross-linking of peptidoglycan strands in the bacterial cell wall; bactericidal; time-dependent killing (efficacy depends on time above MIC).
penicillin-binding proteins (PBPs)transpeptidase
Indications
- syphilis (drug of choice — benzathine penicillin G IM)
- streptococcal pharyngitis
- pneumococcal pneumonia (susceptible strains)
- meningococcal meningitis
- infective endocarditis (streptococcal)
- anthrax
- neurosyphilis (aqueous penicillin G IV)
Contraindications
- penicillin allergy (anaphylaxis — cross-reactivity with cephalosporins ~1–2%)
Adverse Effects
Common
- hypersensitivity reactions (maculopapular rash)
- diarrhea
- injection site pain (IM)
Serious
- anaphylaxis (rare, 0.01–0.05%)
- Jarisch-Herxheimer reaction (syphilis treatment)
- neurotoxicity/seizures (high doses in renal failure)
- interstitial nephritis
Pharmacokinetics (ADME)
| Absorption | Not absorbed orally (penicillin V is the acid-stable oral form); IM/IV only |
| Distribution | Protein binding ~60%; does not cross intact BBB but crosses inflamed meninges (CSF levels ~5–10% of serum) |
| Metabolism | Minimal hepatic metabolism; partially hydrolyzed to penicilloic acid |
| Excretion | Renal via tubular secretion (probenecid blocks and increases levels); dose reduction needed in severe CKD |
| Half-life | 30–60 minutes (aqueous); benzathine: days to weeks |
| Onset | IV: immediate |
| Peak | IV: end of infusion; IM benzathine: 12–24 hours |
| Duration | IV q4–6h; benzathine IM: 2–4 weeks |
| Protein Binding | 60% |
| Vd | ~0.35 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| probenecid | inhibits renal tubular secretion of penicillin, increasing levels and duration | moderate |
| methotrexate | penicillins reduce methotrexate renal excretion; methotrexate toxicity risk | major |
| warfarin | large doses of penicillin may alter gut flora and reduce vitamin K absorption | minor |
Nursing Considerations
- Obtain allergy history before administration; skin testing should be performed in patients with history of severe penicillin reactions when penicillin is required (e.g., syphilis in pregnancy)
- Benzathine penicillin G is only for IM injection — IV administration is fatal; verify formulation and route before administration
- Monitor for Jarisch-Herxheimer reaction 2–8 hours after first syphilis treatment dose: fever, chills, myalgia, headache — self-limited; not an allergic reaction
- For high-dose IV penicillin G (meningitis, endocarditis): monitor serum sodium (penicillin G sodium contains 1.7 mEq Na/million units) and potassium (penicillin G potassium)
Clinical Pearls
- Benzathine penicillin G (Bicillin L-A) and benzathine/procaine combination (Bicillin C-R) look identical — Bicillin C-R is NOT appropriate for syphilis treatment; always verify the correct formulation
- Penicillin remains the drug of choice for syphilis — there is no acceptable alternative for penicillin-allergic pregnant patients with syphilis (desensitization is required)
Safety Profile
Pregnancy generally-safe
Lactation safe
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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