Gonorrhea | Questions & Answers | 2015 STD Treatment Guidelines

General management

Question: Is ceftriaxone 250 mg intramuscularly, plus doxycycline 100 mg orally twice a day for seven days, considered inadequate for the treatment of gonorrhea?

Due to the high proportion (>20%) of Gonococcal Isolate Surveillance Project (GISP) isolates with tetracycline (i.e., doxycycline) resistance and the results of two observational studies which showed inferiority of cephalosporins plus doxycycline (Barbee et al. and Sathia et al.), azithromycin is the preferred second agent to accompany ceftriaxone. All individuals treated for gonorrhea should receive two drugs, both to ensure clinical cure and to prevent the development of resistance.   Persons treated with an alternative regimen for pharyngeal gonorrhea, should receive a test of cure three to four weeks after treatment.

Dual Therapy

Question: What is the purpose of dual treatment for gonorrhea and what is the appropriate timing for administering the medications?

The use of dual therapy for the treatment of gonorrhea is important for two reasons:   the first is to ensure clinical cure in this era of evolving antimicrobial resistance; and, the second is to prevent further development of resistance.   Often in clinical practice, patients are treated with azithromycin for urethritis on one day, and screening tests return positive for gonorrhea on the next.   The goal of dual therapy is to have both drugs active simultaneously.   Because azithromycin’s half-life is 68 hours, it is probably safe to administer ceftriaxone within five days of the azithromycin dose.    However, the converse is not true.  Ceftriaxone’s half-life is much shorter (5.8–8.7 hours), thus, if a patient is given ceftriaxone in a clinic, and fails to pick up azithromycin at the pharmacy for a couple of days, the patient should receive a second dose of ceftriaxone when they take the azithromycin.

Allergy

Question: What is the recommended gonorrhea treatment and follow-up for persons (including pregnant women) who are allergic to cephalosporins?

Patients with IgE-mediated allergies to cephalosporins (e.g., anaphylaxis, Stevens-Johnson syndrome, or toxic epidermal necrolysis) should be treated with an alternative regimen, either 320 mg gemifloxacin, plus 2 g azithromycin orally, or 240 mg gentamicin intramuscularly, plus 2 g azithromycin orally.  Unfortunately, gemifloxacin is currently unavailable, and it is unclear when it might become available again (http://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm?AI=Gemifloxacin%20Mesylate%20(Factive)%20Tablets&st=c&tab=tabs-1).  Gentamicin is available as a 40 mg/mL injection.  The 6 cc injection can be split into two 3 cc injections for administration.  When treating pharyngeal gonococcal infections with any alternate regimens,it is recommended that a test of cure is obtained 14 days using either culture or nucleic acid amplification testing following treatment.  These alternative treatment regimens are contraindicated in pregnant patients.  To treat a pregnant woman with gonorrhea who has a history of an IgE-mediated allergy to cephalosporins, consult with an infectious disease specialist.

Question: Where can I find the latest information on drug shortages (e.g., availability of gemifloxacin)?

http://www.accessdata.fda.gov/scripts/drugshortages/default.cfm#G

EPT

Question: Why is Expedited Partner Therapy (EPT) not recommended for men who have sex with men (MSM)? Where can we find the most current information on which states allow EPT and which diseases EPT can be used to treat?

EPT is not recommended for MSM, as current data from GISP data have consistently shown that gonococcal isolates from MSM are more likely to have reduced susceptibility to cefixime and azithromycin, compared to isolates from heterosexuals.  That means that there is a higher risk of treatment failure for MSM with gonorrhea treated with cefixime and azithromycin; there have been no reports of treatment failures to ceftriaxone in the United States.  Secondly, some MSM whose partners have been diagnosed with a bacterial STI receive an HIV diagnosis upon evaluation.  Therefore, it is important that MSM who are contacts to gonorrhea and/or chlamydia also receive HIV and syphilis testing.

EPT is allowed or permissible in most states for heterosexual patients with chlamydia or gonorrhea.  Please see the CDC EPT website for details on your state.  https://www.cdc.gov/std/ept/legal/default.htm

Treatment Failure/Test of Cure

Question: Will a test of cure for gonorrhea performed with a NAAT seven to fourteen days after treatment have a false positive result?

Documentation in the literature (J Clin Micro 2002; 40:3596) reveals that, most urogenital gonorrhea is cleared within three days, with vaginal specimens remaining positive longer.  All urine specimens were negative by day six, and vaginal specimens by day nine.  However, the large majority of patients had cleared much earlier. These studies were done with LCR testing and, since current NAATS may be somewhat more sensitive, perhaps false positivity results may be of longer duration with such tests.

A recent paper by Bissessor et al. (CID 2015;60:557) shows that persistence is probably longer in pharyngeal and rectal infections, and associated with elevated ceftriaxone and azithromycin MICs.

Question: In the case of treatment failure with cefixime and azithromycin, what is the rationale for treating with 2 g of azithromycin instead of 1 g, in addition to ceftriaxone?

Concern with the cefixime component (thus perhaps indicating reduced efficacy of ceftriaxone) is that treatment would rely more on the azithromycin component when retreating. Recommendations for azithromycin have only been established at the 2 g level for treatment of gonorrhea.

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