Syphilis Medication

The goal of pharmacotherapy is to eradicate the causative organism of syphilis, T pallidum. Penicillin is the mainstay of treatment, the standard by which other modes of therapy are judged, and the only therapy that has been used widely for neurosyphilis, congenital syphilis, or syphilis during pregnancy.

Penicillin

The drug of choice is parenteral penicillin G for all stages of syphilis. According to the 2010 CDC STD treatment guidelines, penicillin G is the only therapy that is clinically documented to be effective against syphilis during pregnancy.^[18] Since the dividing time of T pallidum is slow (days), penicillin G benzathine is the only penicillin effective for single-dose therapy because it is in depo form and levels remain therapeutic in the blood for up to 30 days. Avoiding Bicillin C-R (combination procaine and benzathine), which remains in blood for only 7 days, is essential.

On rare occasions, T pallidum has been found to persist after adequate penicillin therapy; however, no indication exists that T pallidum has acquired resistance to the drug.

According to the Centers for Disease Control and Prevention (CDC; see current CDC recommendations), patients with known penicillin allergies should undergo penicillin allergy skin testing and penicillin desensitization, if necessary.^[25]

Alternatives to penicillin

Since T pallidum resistance to penicillin has not emerged, the primary need for alternative drugs in treating syphilis is reserved for penicillin-allergic patients.

Researchers are studying the efficacy of ceftriaxone and azithromycin in treating syphilis. Central nervous system (CNS) penetration and its similarity to penicillin support the use of ceftriaxone in the treatment of syphilis. Studies are presently inconclusive, and CDC guidelines neither support nor refute its use. Given the limited data available to support its efficacy, prudence dictates a 5- to 7-day course of treatment for early syphilis.

The long half-life of azithromycin and its clinical efficacy in vitro against syphilis support its use in treating early syphilis. At present, however, clinical data remain insufficient to recommend its use.

No good evidence indicates that the non–beta-lactam antibiotics, which are used as alternatives to penicillin, are clinically effective in syphilis. Erythromycin has been associated with high failure rates. Doxycycline may be an option for patients who refuse parenteral therapy.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Penicillin G benzathine (Bicillin L-A)

Benzathine penicillin G is the first-line agent for primary and secondary syphilis infection. It is a spirocheticide with in vivo activity against T pallidum. It interferes with cell wall mucopeptide synthesis during replication.

Penicillin G procaine

Penicillin G procaine is the first-line agent for treating late latent syphilis.

Doxycycline (Doryx, Vibramycin)

Doxycycline is used as alternative therapy for syphilis infection. It inhibits bacterial growth by binding to the 30S ribosomal unit, preventing protein synthesis.

Tetracycline (Sumycin)

Tetracycline is used as alternative therapy for syphilis infection. It inhibits bacterial growth by binding to the 30S ribosomal unit, preventing protein synthesis.

Erythromycin (E.E.S., E-Mycin)

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dosage. When twice-daily dosing is desired, half of the total daily dose may be taken q12h. For more severe infections, double the dose.

Ceftriaxone (Rocephin)

Ceftriaxone is an alternative agent for penicillin-allergic patients. It is a third-generation cephalosporin with broad-spectrum, gram-negative activity; it has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin binding proteins.

Azithromycin (Zithromax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Azithromycin concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. This drug is used to treat mild-to-moderate microbial infections.

Class Summary

Uricosuric agentsare used to increase serum concentration of certain antibiotics and other drugs.

Probenecid

Probenecid inhibits tubular secretion of penicillin and usually increases penicillin plasma levels by any route the antibiotic is administered. A 2- to 4-fold elevation has been demonstrated for various penicillins. Probenecid is used as an adjunct to penicillin in late latent and neurosyphilis.