1. Clinical Overview
Penicillin G (Benzylpenicillin) is a narrow-spectrum, bactericidal, natural penicillin antibiotic. It is the first clinically used antibiotic and remains a drug of choice for infections caused by susceptible Gram-positive cocci (except penicillinase-producing staphylococci), Gram-positive rods, and certain Gram-negative cocci. In the Indian context, it is a critical, low-cost agent for severe streptococcal and pneumococcal infections, syphilis, and certain clostridial infections. Its use is primarily in hospital settings due to its poor oral bioavailability, necessitating parenteral administration (IV/IM).
| Onset | Duration | Bioavailability |
|---|---|---|
| Rapid; bactericidal action begins within 30-60 minutes of administration. Peak serum concentrations are reached within 15-30 minutes after an IV dose and 30-60 minutes after an IM dose. | Short; requires frequent dosing (every 4-6 hours) due to a short half-life. Procaine Penicillin G and Benzathine Penicillin G formulations provide longer durations (12-24 hours and 2-4 weeks, respectively). | Oral: 15-30% (acid-labile, degraded in stomach). Intramuscular: ~100%. Intravenous: 100%. |
2. Mechanism of Action
Penicillin G is a beta-lactam antibiotic that inhibits bacterial cell wall synthesis. It binds to and inactivates specific penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. This inactivation prevents the final transpeptidation step of peptidoglycan synthesis, a critical component of the bacterial cell wall. The resulting defective cell wall cannot withstand internal osmotic pressure, leading to cell lysis and death, especially during active bacterial growth and division.
3. Indications & Uses
- Severe Streptococcal Infections (e.g., Streptococcal pharyngitis, cellulitis, erysipelas, necrotizing fasciitis)
- Pneumococcal Pneumonia and Meningitis (penicillin-susceptible strains)
- Syphilis (all stages)
- Meningococcal Meningitis (as an alternative)
- Clostridial Infections (e.g., Gas gangrene due to Clostridium perfringens)
- Actinomycosis
- Rat-bite fever (Streptobacillus moniliformis)
4. Dosage & Administration
Adult Dosage: Highly variable based on infection severity. Moderate infections: 1-4 million IU IV every 4-6 hours. Severe infections (meningitis, endocarditis): 18-24 million IU/day IV in divided doses every 4 hours. Syphilis: Varies by stage (e.g., Neurosyphilis: 18-24 million IU/day IV as 3-4 million IU every 4 hours for 10-14 days).
Administration: For IV use: Reconstitute powder with Sterile Water for Injection or 0.9% Sodium Chloride. Further dilute in 50-100 mL of compatible IV fluid (NS, D5W) and infuse over 30-60 minutes to avoid CNS toxicity. For IM use: Reconstitute with Sterile Water for Injection or 1% Lidocaine HCl (without epinephrine) to reduce pain. Administer deep IM into a large muscle mass. NEVER administer intrathecally without specific expertise due to risk of arachnoiditis and seizures.
5. Side Effects
Common side effects may include:
- Pain and inflammation at IM injection site
- Thrombophlebitis at IV site
- Mild diarrhea
- Oral or vaginal candidiasis (thrush) due to altered flora
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Probenecid | Competitively inhibits renal tubular secretion of Penicillin G, increasing and prolonging serum concentrations. | Moderate |
| Methotrexate | Penicillins may reduce renal clearance of methotrexate, increasing risk of methotrexate toxicity. | Major |
| Warfarin | May potentiate anticoagulant effect, increasing INR and risk of bleeding. Mechanism may involve altered gut flora affecting vitamin K. | Moderate |
| Oral Contraceptives | Theoretical risk of reduced efficacy due to altered enterohepatic circulation; advise backup contraception. | Minor |
| Aminoglycosides (e.g., Gentamicin) | In vitro synergistic against some organisms (e.g., Enterococcus), but physical incompatibility occurs if mixed in same IV line/solution. | Moderate |
7. Patient Counselling
- DO complete the full course of therapy even if you feel better.
- DO inform all healthcare providers (doctors, dentists) about your penicillin allergy if applicable.
- DO report any rash, itching, swelling, or difficulty breathing immediately.
- DONT skip doses.
- DONT use leftover antibiotic for a future illness.
8. Toxicology & Storage
Overdose: Neurological toxicity: Myoclonus, hyperreflexia, seizures (especially with renal impairment). Electrolyte imbalance: Hyperkalemia (with Potassium salt) leading to cardiac arrhythmias, or hypernatremia (with Sodium salt). Nausea, vomiting.
Storage: Store unopened vials at controlled room temperature (15-25°C), protected from light and moisture. After reconstitution: Stability varies with diluent. For IV infusion in NS or D5W, use within 24 hours if refrigerated (2-8°C). For IM use, use immediately after reconstitution. Do not freeze. Keep out of reach of children.