Medication Summary
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 recommended 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. [26] 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. [41]
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, and widespread resistance limits the use in many areas (especially in the Pacific Northwest).
Doxycycline may be an option for patients who refuse parenteral therapy or who have penicillin allergy.
Antibiotics
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. 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, with limited data to support its use. It is a third-generation cephalosporin. 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.
Uricosuric agents
Class Summary
Uricosuric agents are 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.
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Syphilis. These photographs depict the characteristic chancre observed in primary syphilis. Used with permission from Wisdom (Left) A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989. (Right) Centers for Disease Control and Prevention
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Syphilis. These photographs show the disseminated rash observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. These photographs show close-up images of gummas observed in tertiary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. This photograph depicts primary syphilis "kissing" lesions. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. Palmar lesions observed in secondary syphilis. Used with permission from Wisdom (Left) A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989. (Right) Centers for Disease Control and Prevention
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These photographs illustrate examples of condylomata lata. The lesions resemble genital warts (condylomata acuminata). Fluids exuding from these lesions are highly infectious. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. These photographs illustrate typical facies of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.
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Syphilitic chancre
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Secondary syphilis - Exanthem
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Secondary syphilis - Exanthem
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Lues hematoxylin and eosin stain. Histopathological examination shows a lichenoid infiltrate that is stereotypical of the secondary stage of syphilis. Note that vacuolar alteration of the superjacent epithelium can be seen much like a noninfectious form of lichenoid dermatitis. The subjunctional infiltrate is rich in histiocytes and plasmacytes. At times, an overtly granulomatous lichenoid infiltrate can be seen.
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Lues TP stain. Immunoperoxidase staining for T pallidum highlights many slender coiled organisms residing in the perijunctional zone. Occasionally, organisms can also be found in the upper dermis or around adnexal structures.
