What is the protocol if a patient misses their second Penicillin (Penicillin G) injection by a week, when they require a series of 3 injections?

Protocol for Missed Penicillin G Injection in a 3-Injection Series

If a patient misses their second Penicillin G injection by a week in a 3-injection series, they should resume the sequence of injections without restarting the entire course, as pharmacologic considerations suggest that an interval of 10-14 days between doses is acceptable for late syphilis or latent syphilis of unknown duration. 1

Management Algorithm for Missed Penicillin G Injection

Assessment of Patient Factors:

1. Determine if the patient is pregnant

   • If pregnant: The entire course of therapy must be repeated 1
   • If not pregnant: Continue with protocol below

2. Determine type of syphilis being treated

   • Early latent syphilis: Single dose regimen (not applicable to this scenario)
   • Late latent or unknown duration syphilis: Three-dose regimen (applicable to this scenario)

Protocol for Non-Pregnant Patients:

• Administer the missed second dose immediately
• Schedule the third dose to be given 1 week after the second dose
• Document the extended interval between first and second doses
• Ensure close follow-up with appropriate serologic testing

Rationale and Evidence

The CDC guidelines specifically address this scenario, stating: "If a patient misses a dose of penicillin in the course of weekly therapy for late syphilis, the appropriate course of action is unclear. Pharmacologic considerations suggest that an interval of 10-14 days between doses of benzathine penicillin for late syphilis or latent syphilis of unknown duration might be acceptable before restarting the sequence of injections." 1

This recommendation is based on the pharmacokinetics of benzathine penicillin G, which maintains treponemicidal serum concentrations for 2-3 weeks after injection. The goal of therapy is to maintain adequate serum penicillin levels to treat the infection effectively.

Special Considerations

For Pregnant Patients:

• Missed doses are not acceptable for pregnant patients receiving therapy for late latent syphilis
• Pregnant women who miss any dose must repeat the full course of therapy 1
• This more conservative approach is due to the risk of congenital syphilis

Follow-Up Recommendations:

• Quantitative nontreponemal serologic tests should be repeated at 6,12, and 24 months 1
• Monitor for signs of treatment failure:
  • Fourfold increase in titer
  • Failure of initially high titer (>1:32) to decline at least fourfold within 12-24 months
  • Development of signs or symptoms attributable to syphilis

Common Pitfalls to Avoid

• Unnecessarily restarting the entire course for non-pregnant patients
• Failing to recognize that pregnant patients require a complete restart of therapy
• Inadequate follow-up serologic testing
• Not documenting the extended interval between injections
• Switching between different nontreponemal tests during follow-up, which can complicate interpretation

By following this protocol, clinicians can ensure appropriate management of patients who miss a dose in their penicillin G treatment series while minimizing the risk of treatment failure and disease progression.