What is the recommended use of Penicillin G (Benzathine) for treating bacterial infections?

Penicillin G Benzathine: Recommended Uses for Bacterial Infections

Benzathine penicillin G is the first-line treatment for syphilis at all stages (except neurosyphilis) and for group A streptococcal pharyngitis when single-dose intramuscular therapy is preferred. 1, 2

Primary Indications

Syphilis Treatment (Primary Indication)

Early Syphilis (Primary, Secondary, and Early Latent)

• Single dose of 2.4 million units IM is the definitive treatment 2, 3
• Recent high-quality evidence confirms one dose is noninferior to three doses, with 76% serologic response at 6 months regardless of HIV status 4
• This applies to primary syphilis (painless chancre), secondary syphilis (diffuse rash, mucocutaneous lesions), and early latent syphilis (acquired within preceding year) 2, 5

Late Latent Syphilis or Syphilis of Unknown Duration

• Three doses of 2.4 million units IM at weekly intervals (total 7.2 million units) 1, 2
• This extended regimen is necessary when infection duration exceeds one year 2

Tertiary Syphilis (Gummatous and Cardiovascular)

• Three doses of 2.4 million units IM at weekly intervals (total 7.2 million units) 1, 2
• CSF examination should be performed before treatment to exclude neurosyphilis 1

Important Exclusion: Benzathine penicillin G should never be used for neurosyphilis—aqueous crystalline penicillin G IV is required for CNS disease 1, 2

Congenital Syphilis

• 50,000 units/kg IM as a single dose for infants meeting specific criteria (normal exam, appropriate maternal treatment, stable low titers) 1
• For older children with acquired syphilis: 50,000 units/kg IM (up to adult dose of 2.4 million units) as single dose for early syphilis 2
• For late latent syphilis in children: 50,000 units/kg IM for three doses at weekly intervals (up to adult total of 7.2 million units) 2

Group A Streptococcal Pharyngitis

When Single-Dose Therapy is Preferred

• Adults and adolescents: 1.2 million units IM as single dose 1
• Children weighing <27 kg: 600,000 units IM as single dose 1
• This is particularly valuable when compliance with 10-day oral therapy is uncertain 1
• Mixtures of benzathine and procaine penicillin G can be used, but dose must be calculated based on benzathine component 1

Moderately Severe Streptococcal Infections

• Upper respiratory tract infections, scarlet fever, erysipelas, and skin/soft tissue infections due to susceptible streptococci (Groups A, C, G, H, L, M) 6
• Moderately severe pneumonia and otitis media due to susceptible Streptococcus pneumoniae 6

Critical Caveat: Severe pneumonia, empyema, bacteremia, pericarditis, meningitis, peritonitis, and arthritis require aqueous penicillin G sodium or potassium IV, not benzathine penicillin G 6

Absolute Contraindications

Do NOT use benzathine penicillin G for:

• Neurosyphilis (requires IV aqueous penicillin G) 1, 2
• Venereal diseases other than syphilis (gonorrhea, yaws, bejel, pinta) 6
• Severe invasive infections requiring high sustained serum levels 6
• Any infection requiring immediate bactericidal levels—benzathine formulation provides low but sustained levels over weeks 7

Special Populations

Pregnant Women

• Penicillin is the ONLY proven effective therapy for preventing congenital syphilis 2
• Pregnant women with penicillin allergy must undergo desensitization followed by penicillin treatment 2, 5
• Never substitute with alternatives in pregnancy—only penicillin prevents congenital transmission 2
• Jarisch-Herxheimer reaction during second half of pregnancy may precipitate premature labor or fetal distress; patients should seek immediate care if they notice changes in fetal movements or contractions 2

HIV-Infected Patients

• Same treatment regimens as non-HIV-infected patients 2
• Recent evidence shows single-dose therapy for early syphilis is equally effective in HIV-positive patients (76% serologic response) 4
• Closer follow-up is mandatory to detect potential treatment failure 2

Penicillin-Allergic Patients (Non-Pregnant)

• For early syphilis: doxycycline 100 mg orally twice daily for 14 days 2, 5
• For late latent syphilis: doxycycline 100 mg orally twice daily for 28 days 1, 2
• Tetracycline 500 mg orally four times daily is an alternative (14 days for early, 28 days for late) 2
• These alternatives have not been proven to prevent rheumatic fever or congenital syphilis 1

Follow-Up and Monitoring

Syphilis

• Quantitative nontreponemal tests (RPR or VDRL) at 6 and 12 months for primary/secondary syphilis 2
• For latent syphilis: repeat at 6,12, and 24 months 2
• Expected response: fourfold decline in titer within 6 months for early syphilis, 12-24 months for late syphilis 2, 5
• Re-treat if: persistent/recurring symptoms, sustained fourfold increase in titers, or failure of initially high titer (>1:32) to decline fourfold within expected timeframe 2

Congenital Syphilis

• Serologic testing every 2-3 months until nonreactive or fourfold decrease 1
• Titers should decline by 3 months and be nonreactive by 6 months if adequately treated 1

Critical Pitfalls to Avoid

• Never use oral penicillin preparations for syphilis—they are ineffective 2
• Do not switch between VDRL and RPR when monitoring—results cannot be directly compared 2
• Do not rely on treponemal antibody titers to assess treatment response—they correlate poorly with disease activity and remain positive despite cure 2
• Do not use azithromycin in the United States—widespread macrolide resistance and documented treatment failures 2
• Do not delay treatment beyond 9 days of symptom onset if rheumatic fever prevention is the goal 1

Jarisch-Herxheimer Reaction

• Acute febrile reaction occurring within 24 hours after treatment, especially in early syphilis 2, 5
• Characterized by fever, headache, myalgia, and other constitutional symptoms 2
• Patients should be informed about this possible reaction before treatment 2
• This is not an allergic reaction and does not contraindicate future penicillin use 7

Advantages of Benzathine Penicillin G

• Only antibiotic providing therapeutic levels for several weeks after single IM injection 7
• Ideal for single-session therapy when compliance is uncertain 7
• Sensitivity reactions are less frequent and less severe than with aqueous or procaine penicillin G 7
• Remains the gold standard after 30+ years with no superior alternative 7, 8