What is benzoyl penicillin (penicillin G)?

Benzyl Penicillin (Penicillin G)

Benzyl penicillin (penicillin G) is a natural penicillin antibiotic that remains the drug of choice for treating many serious bacterial infections due to its potent bactericidal activity against susceptible organisms, particularly streptococci, pneumococci, meningococci, and certain spirochetes like Treponema pallidum.

Chemical Structure and Properties

Benzyl penicillin is chemically defined as monopotassium (2S,5R,6R)-3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylate 1. It contains:

• A 4-membered beta-lactam ring fused to a 5-membered thiazolidine ring
• A molecular weight of 372.48
• High water solubility
• pH of 6.0-8.5 when reconstituted

Mechanism of Action

Benzyl penicillin works by:

• Inhibiting biosynthesis of bacterial cell wall peptidoglycan
• Rendering the cell wall osmotically unstable
• Exerting bactericidal effects during the stage of active bacterial multiplication 1

Antimicrobial Spectrum

Penicillin G is highly active against:

• Streptococci (groups A, B, C, G, H, L, and M)
• Neisseria meningitidis
• Neisseria gonorrhoeae
• Corynebacterium diphtheriae
• Bacillus anthracis
• Clostridia species
• Actinomyces species
• Listeria monocytogenes
• Treponema pallidum (extremely susceptible) 1

It is not effective against:

• Penicillinase-producing bacteria (many staphylococcal strains)
• Organisms resistant to beta-lactams due to altered penicillin-binding proteins
• Most gram-negative bacilli 1

Formulations and Administration

Benzyl penicillin is available in several formulations:

1. Aqueous Penicillin G (Potassium or Sodium salt)

   • For intravenous or intramuscular administration
   • Available in vials of 1 million, 5 million, or 20 million units 1
   • Short half-life requiring frequent dosing

2. Benzathine Penicillin G (Bicillin L-A)

   • Long-acting intramuscular formulation
   • Provides antibiotic blood levels for several weeks after a single injection
   • Standard dose: 1.2 million units IM every 4 weeks (for prophylaxis) 2, 3
   • Used for treatment of syphilis and rheumatic fever prophylaxis

Clinical Applications

Rheumatic Fever Prophylaxis

• Benzathine penicillin G 1.2 million units IM every 4 weeks is the recommended regimen for secondary prevention 2
• In high-risk populations, administration every 3 weeks may be justified 2
• For patients with rheumatic carditis, prophylaxis should continue well into adulthood and possibly for life 2

Syphilis Treatment

• Benzathine penicillin G remains the preferred drug for all stages of syphilis 4
• Primary and secondary syphilis: 2.4 million units IM in a single dose 4
• Late latent syphilis: 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 4

Group A Streptococcal Pharyngitis

• Intramuscular benzathine penicillin G: 1.2 million units as a single dose for adults 2
• For children who weigh <27 kg: 600,000 units as a single dose 2

Pharmacokinetics

• Serum half-life varies with age and renal function (1.4-3.2 hours in normal renal function)
• Distributed to most body areas including lung, liver, kidney, muscle, bone, and placenta
• Penetrates poorly into CSF unless inflammation is present
• Actively secreted into bile
• Eliminated primarily by renal excretion
• Probenecid blocks renal tubular secretion, prolonging elimination and increasing serum concentrations 1

Management of Penicillin Allergy

For patients with suspected penicillin allergy who require penicillin therapy:

1. Skin Testing:

   • Test with major determinant (benzylpenicilloyl poly-L-lysine/Pre-Pen) and minor determinants
   • Patients who are skin-test negative can receive conventional penicillin therapy
   • Skin-test positive patients should be desensitized 2

2. Desensitization:

   • Required for patients with positive skin tests
   • Should be performed in a hospital setting
   • Can be done orally or intravenously, with oral route considered safer 2
   • Takes approximately 4 hours to complete

Special Considerations

• Dosage adjustment: Required in patients with severe renal impairment, with additional modifications when hepatic disease accompanies renal impairment 1
• Pregnancy: Pregnant women with penicillin allergy should undergo desensitization if penicillin is required 4
• Jarisch-Herxheimer reaction: May occur within 24 hours after treatment, particularly in early syphilis 4

Advantages and Limitations

Advantages:

• Potent bactericidal activity
• Low toxicity
• Excellent tissue distribution
• Long history of effective use
• Cost-effective compared to newer antibiotics 5

Limitations:

• Increasing bacterial resistance
• Risk of allergic reactions
• Short half-life of aqueous formulations requiring frequent dosing
• Limited gram-negative coverage 5

Benzyl penicillin remains a cornerstone antibiotic despite the development of numerous alternatives, particularly for susceptible streptococcal, pneumococcal, and spirochetal infections.