When should Benzathine penicillin G (Benzathine penicillin G) therapy be restarted if a dose is missed?

Benzathine Penicillin G Therapy Restart Guidelines

For non-pregnant patients with late syphilis or latent syphilis of unknown duration who miss a dose of Benzathine penicillin G, therapy should be resumed by continuing the sequence of injections where it was interrupted, without restarting the entire course, as intervals of 10-14 days between doses are acceptable. 1

Different Recommendations Based on Patient Population

Non-Pregnant Patients

• Resume the sequence of injections where it was interrupted
• An interval of 10-14 days between doses is acceptable before continuing the sequence 2, 1
• Pharmacological considerations suggest that an interval of 7-9 days between doses may be more optimal, if feasible 3
• No need to restart the entire course of therapy

Pregnant Patients

• Pregnant women who miss any dose of therapy must repeat the full course of therapy 2, 1
• This stricter approach for pregnant women is due to:
  • High risk of congenital syphilis
  • Evidence showing inadequate treatment with a single dose can result in adverse pregnancy outcomes 4
  • Potential for treatment failure in pregnancy 5

Follow-Up Recommendations After Treatment

• Quantitative nontreponemal serologic tests should be performed at 6,12, and 24 months 2, 1
• A CSF examination should be performed if:
  1. Titers increase fourfold
  2. An initially high titer (≥1:32) fails to decline at least fourfold within 12-24 months
  3. Signs or symptoms attributable to syphilis develop 2

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 1

Treatment Completion Challenges

Recent data from Maricopa County, Arizona (2023) showed that only 42.9% of patients with late latent or unknown duration syphilis completed all three injections of Benzathine penicillin G within the recommended timeframe 6. This highlights the importance of addressing barriers to treatment completion and ensuring proper follow-up after the first injection.

The distinction between pregnant and non-pregnant patients is critical in management decisions, as the consequences of inadequate treatment during pregnancy can be severe, including increased risk of adverse pregnancy outcomes such as premature birth, low birth weight, and congenital syphilis 4, 5, 7.