Syphilis Treatment
Benzathine penicillin G is the recommended treatment for syphilis, with dosing based on disease stage: 2.4 million units IM as a single dose for primary, secondary, and early latent syphilis, or 7.2 million units total (administered as 3 doses of 2.4 million units IM at 1-week intervals) for late latent syphilis or latent syphilis of unknown duration. 1
Treatment Regimens by Stage
Early Syphilis (Primary, Secondary, Early Latent)
- First-line treatment: Benzathine penicillin G 2.4 million units IM as a single dose 1
- Alternative treatments (for penicillin-allergic non-pregnant patients):
Late Latent Syphilis or Latent Syphilis of Unknown Duration
- First-line treatment: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
- Alternative treatments (similar to early syphilis but longer duration):
Neurosyphilis
- First-line treatment: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
Special Populations
Pregnant Women
- Only penicillin is proven effective for treating syphilis during pregnancy 1
- Pregnant women with penicillin allergy must undergo desensitization and receive penicillin therapy 1
- The full course of therapy must be completed without missing any doses 1
HIV-Infected Patients
- Same regimens as HIV-negative patients but with closer follow-up 1
Treatment Administration Considerations
- For high-dose IV penicillin G (above 10 million units), administer slowly due to potential electrolyte imbalance from potassium content 2, 3
- If a patient misses a dose in the weekly therapy schedule for late latent syphilis, an interval of 10-14 days between doses might be acceptable before restarting the sequence, except in pregnant women who must repeat the full course if any dose is missed 1
Monitoring and Follow-up
- Quantitative nontreponemal serologic tests (RPR or VDRL) should be repeated at 6,12, and 24 months 1
- Treatment success is indicated by a fourfold decline in titers within 12-24 months 1
- Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment 1
Treatment Failure
Treatment failure should be suspected when:
- Signs or symptoms persist or recur
- There is a sustained fourfold increase in non-treponemal tests
- The expected fourfold decrease in titers is not observed within the established period 1
Partner Management
- All sexual partners should be evaluated clinically and serologically for syphilis 1
- Partners exposed within 90 days of diagnosis should be treated presumptively even if seronegative 1
- Partners exposed >90 days before diagnosis should be treated based on clinical and serological evaluation 1
Common Pitfalls and Caveats
Penicillin allergy management: For patients with severe allergic reactions (anaphylaxis, angioedema, bronchospasm), all β-lactams should be avoided. Skin testing with major determinant and penicillin G can identify ~90-97% of allergic patients 1
Jarisch-Herxheimer reaction: Patients should be warned about this potential reaction, which typically occurs within 24 hours of treatment
Missed doses: Critical to avoid, especially in pregnant women where the full course must be repeated if any dose is missed 1
Laboratory test interference: After treatment with penicillin G, false-positive reactions for glucose in urine may occur with certain tests (Benedict's solution, Fehling's solution, CLINITEST) but not with enzyme-based tests 2, 3
Drug interactions: Bacteriostatic antibiotics (chloramphenicol, erythromycins, sulfonamides, tetracyclines) may antagonize penicillin's bactericidal effect and should be avoided concurrently 2, 3