California Guidelines for Suspected Gonorrhea Treatment Failure

If symptoms are present 7 days following initial antibiotic treatment, then treatment failure should be suspected.  Depending on the original site of infection, symptoms may include:

• Persistent urethral discharge, dysuria, and/or pyuria (positive leukocyte esterase on urine dipstick) 
• Persistent pharyngitis or odynophagia 
• Persistent rectal discharge, pain, bleeding, pruritis, tenesmus, or painful defecation 
• Persistent vaginal discharge, dysuria, or post-coital spotting
  

Patients with persistent or recurrent symptoms who report interim sexual exposure to untreated or new partners may have been reinfected.  Patients suspected of having a reinfection should be retreated with a recommended antibiotic regimen (see Current Gonorrhea Treatment Recommendations section below).

For patients with suspected treatment failure, the following steps should be taken to ensure adequate testing, treatment, partner management, and follow up:

1. Obtain a specimen for culture and antibiotic susceptibility testing at sites of sexual exposure (i.e., genital, rectal, pharyngeal).  If gonorrhea culture is not available at your local laboratory, contact the California STD Control Branch clinician warm line at (510) 620-3400, M-F 8am-5pm for assistance.
2. Retreat the patient with ceftriaxone 500 mg intramuscular (IM) and azithromycin 2 g orally in a single dose. 
3. Inform your local health department of the case within 24 hours, and please call the California STD Control Branch clinician warm line at (510) 620-3400. 
4. Ensure that all of the patient’s partners in the last 60 days return to the clinic for testing and empiric treatment with ceftriaxone 500 mg IM and azithromycin 2 g orally in a single dose.
5. Instruct the patient to abstain from oral, vaginal, or anal sex until one week after the patient and all of his/her partners are treated. 
6. Ask patient to return for a test-of-cure one week after treatment, preferably with culture, or, if culture is not available, with a nucleic acid amplification test (NAAT). 

Background: Cephalosporin Susceptibility Patterns

The Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report (MMWR) published on July 8, 2011 reported decreased cephalosporin susceptibility among isolates of Neisseria gonorrhoeae in the United States, specifically in California and other western states.  Antibiotic susceptibility was measured by the minimum inhibitory concentration (MIC), or the minimum concentration of antibiotic that inhibits visible bacterial growth.  CDC utilized thresholds for cefixime MICs ≥0.25 µg/mL and ceftriaxone MICs ≥0.125 µg/mL for surveillance purposes; actual MIC thresholds for cefixime and ceftriaxone resistance in N. gonorrhoeae have not yet been defined.  Based on an analysis of 5,865 N. gonorrhoeae isolates between 2000 and 2010, the percentage of isolates with cefixime MICs ≥0.25 µg/mL increased from 0.2 percent to 1.4 percent.  In California this difference was even more prominent (0 percent in 2000 and 4.5 percent in 2010).  An increase in the percentage of isolates with ceftriaxone MICs ≥0.125 µg/mL also was observed in California (0 percent in 2000 and 0.6 percent in 2010).  Updated California gonorrhea resistance data is available on the STD Control Branch program page. 

In light of these epidemiologic patterns in cephalosporin susceptibility, the CDC recommends the following for gonorrhea treatment:  

1. Dual antibiotic treatment with ceftriaxone 250 mg by IM injection and azithromycin 1 g orally is now the preferred treatment for uncomplicated urogenital and pharyngeal gonorrhea.  
2. Azithromycin is preferred over doxycycline for dual antibiotic treatment due to high rates of co-existing tetracycline resistance among gonococcal isolates with elevated cefixime MICs.
3. Dual antibiotic treatment should be given regardless of any chlamydia test result.

Click here (PDF) to link to a table of recommended antibiotic treatments for gonorrhea in California or consult the CDC STD Treatment Guidelines for national gonorrhea treatment recommendations.  

Recommendations for Performing Tests-of-Cure

Currently in California, tests-of-cure after treatment are routinely recommended only for 1) pregnant women; 2) cases where an antibiotic other than a recommended or alternative regimen was used (click here (PDF) for recommended/alternative treatment); 3) cases of suspected treatment failure.

Per the July 8,  2011 CDC Morbidity and Mortality Weekly Report (MMWR), clinicians caring for patients with gonorrhea in California, particularly men who have sex with men, may consider having these patients return one week after treatment for a test-of-cure, preferably with culture, or, if culture is not available, with a NAAT.

Clinical sites interested in implementing and evaluating an expanded test-of-cure protocol for gonorrhea are encouraged to contact the STD Control Branch clinician warm line at (510) 620-3400 for assistance.

For more information about STDs, please visit the STD Control Branch website.

Date Last Revised: 08/24/2011