Neisseria gonorrheae has over time developed resistance to sulfonamides, penicillin, tetracyclines and fluoroquinolones. There have now been reports of resistance to oral third-generation cephalosporins in Asian, Australia and elsewhere. Strains with altered cephalosporin susceptibility have caused clinical failures after treatment with oral third generation cephalosporins (cefixime), especially with infection of the pharynx and recent data demonstrates rising MICs of GC to cefixime.
Treatment for Gonorrhea should be:
Ceftriaxone 250 mg IM x 1 (note: higher than standard 125 mg dose)
PLUS azithromycin 1000 mg PO x 1 regardless of concurrent Chlamydia.
Azithromycin 1 gram PO X 1
doxycycline 100 mg PO BID for 7 days
General observations on HIV-infected patients with syphilis:
- Case reports suggest that the unusual clinical manifestations of syphilis may be more common (e.g. overlap of primary & secondary manifestations) and the course more rapid in patients with HIV infection.
- Though above not corroborated in prospective studies, case reports have largely driven the hypotheses that among patients coinfected with HIV and T pallidum:
- Mucocutaneous lesions may be more severe or numerous,
- Symptomatic neurosyphilis may be more likely to develop,
- Latency period before the development of meningovascular syphilis may be shorter,
- Efficacy of standard therapy for early syphilis may be reduced.
- HIV-infected patients can have atypical serologic responses. More typical is higher-than-expected RPR titers (e.g. 1:128). More rare: false negative and delayed onset of seroreactivity. Biologic false positives can occur (treponemal test negative), esp. if polyclonal gammopathy present.
- The “serofast” state is not uncommon among HIV-infected persons. It is the persistence of a reactive nontreponemal syphilis test, usually 1:16 or less, with variation no greater than 1 to 2 dilutions over time, despite adequate therapy and no evidence of reexposure.
- NOTE: Reinfection may be difficult to rule out in some patients, and reactivation or relapse of a previously treated infection is also possible in a person with HIV infection.
General treatment principles – areas of consensus [ CDC STD 2010 Guidelines]
- Long-acting penicillin G is treatment of choice:
- Benzathine penicillin G (Bicillin LA) 2.4 million U intrasmuscularly x 1 should be used in all cases for incubating, primary, secondary or early latent syphilis with no evidence of neurologic involvement.
- For late latent or syphilis of unknown duration:
- For late latent or syphilis of unknown duration without neurologic symptoms and/or negative CSF examination, then benzathine PCN G should be given as 7.2 million IU IM as 3 doses of 2.4 million IU in successive weeks.
- If CSF without evidence of neurosyphilis (CSF WBC>20/μL or reactive CSF VDRL), then benzathine PCN G should be given as 7.4 million IU IM as 3 doses of 2.4 million IU in successive weeks.
- Neurosyphilis (or syphilitic eye or auditory disease):
- Aqueous crystalline penicillin G 18-24 million U IV per day, dosed as continuous infusion or q4h, x 14 days
- Procaine penicillin 2.4 million U per day IM + Probenecid 500 mg PO QID x 14 days
- Doxycycline is an oral alternative and reserved only for patients who are truly penicillin-allergic – oral agents should never be used for neurosyphilis or pregnant patients with syphilis.
- Azithromycin, though it has shown promise in early syphilis, should not be used because of reported resistance.
- Confirmation of post-treatment serologic response:
- NOTE: Nontreponemal test antibody titers (RPR or VDRL) usually correlate with disease activity. Sequential serologic tests should be performed by same testing method (RPR or VDRL) & preferably by same lab.
- Follow-up of RPR or VDRL titer recommended at 3, 6, 9, 12 and 24 months after therapy.
- Appropriate response to treatment = 4-fold decrease in titer (2 dilutions) in 6 months.
- When do you perform a lumbar puncture to examine CSF?
- Any patient with syphilis who has neurologic complaints (includes ophthalmic or otologic complaints as well as cranial nerve palsy, meningitis, stroke, altered mental status or loss of vibratory sensation).
- Evidence of active tertiary syphilis (e.g., aortitis and gumma);
- All patients with treatment failure defined as:
- Recurrence or persistence of symptoms
- Lack of a 4-fold decrease in RPR titers after 12 months in early syphilis, 24 months in late syphilis
- 4-fold increase in RPR titers at any time after treatment
- More controversial: any asymptomatic HIV+ patient with RPR titer >1:32 or CD4 count <350.
- If you think your patient needs an LP, contact Trudy Jones, ARNP who can perform the LP and enroll patient in Christina Marra’s syphilis study [link]. Need UW ID to log in.
MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1-110. Sexually transmitted diseases treatment guidelines, 2010, Workowski KA, Berman S; Centers for Disease Control and Prevention (CDC).
MMWR Morb Mortal Wkly Rep. 2011 Jul 8;60(26):873-7. Cephalosporin susceptibility among Neisseria gonorrhoeae isolates--United States, 2000-2010. Centers for Disease Control and Prevention (CDC).
Syphilis and HIV infection: an update. Zetola , NM and Klausner JD. Clin Infect Dis 2007; 44:1222-8.