What if a patient misses their second Penicillin G (Benzathine penicillin G) injection by more than 14 days?

Management of Missed Penicillin G Injections Beyond 14 Days

If a patient misses their second Benzathine penicillin G injection by more than 14 days, the treatment should be resumed without restarting the entire course for non-pregnant patients, but pregnant patients must restart the full treatment course. 1

General Management Principles

For patients receiving treatment for late syphilis or latent syphilis of unknown duration with Benzathine penicillin G:

• Non-pregnant patients:

  • Resume the sequence of injections where it was interrupted
  • No need to restart the entire course of therapy
  • Pharmacokinetic considerations suggest that intervals of 10-14 days between doses are acceptable 2, 1
  • Document the extended interval between injections in the patient's record

• Pregnant patients:

  • Must restart the full course of therapy if any dose is missed 2, 1
  • This more conservative approach is necessary due to the high risk of congenital syphilis
  • No exceptions should be made for pregnant women 2

Pharmacokinetic Rationale

The recommendation to continue the sequence without restarting for non-pregnant patients is based on:

• Benzathine penicillin G maintains treponemicidal serum concentrations for 2-3 weeks after injection 1, 3
• This provides a pharmacological buffer that allows for some flexibility in dosing intervals
• Studies show that subcutaneous administration can extend the half-life even further (20.1 days vs 10.2 days for IM) 4

Follow-Up Recommendations

After completing the treatment course with the delayed injection:

1. Perform quantitative nontreponemal serologic tests at 6,12, and 24 months 2, 1
2. Consider retreatment if:
   • Titers increase fourfold
   • An initially high titer (≥1:32) fails to decline at least fourfold within 12-24 months
   • Signs or symptoms attributable to syphilis develop 2

Special Considerations

Pregnant Patients

• Higher risk of adverse outcomes with incomplete treatment 5
• Research shows that inadequate treatment duration (less than 3 weeks of treponemicidal coverage) results in:
  • Decreased birth weight
  • Increased prematurity
  • Higher perinatal mortality
  • Increased risk of congenital syphilis 5

Monitoring for Treatment Failure

• Document the extended interval between injections
• Be vigilant for signs of treatment failure during follow-up
• Consider CSF examination if treatment failure is suspected 2

Common Pitfalls to Avoid

• Unnecessarily restarting the entire course for non-pregnant patients
• Failing to restart the full course for pregnant patients
• Inadequate follow-up serologic testing
• Not documenting the extended interval between injections
• Switching between different nontreponemal tests during follow-up 1

Remember that the goal of therapy is to maintain adequate serum penicillin levels to effectively treat the infection. For non-pregnant patients, pharmacokinetic data supports resuming the sequence without restarting, while pregnant patients require the more conservative approach of restarting the full course to minimize risks to both mother and fetus.