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Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) program

CDC Releases Update: 2020 Treatment Guidelines for Gonococcal Infections

In December 2020, the CDC updated recommendations for the treatment of uncomplicated gonorrhea in adolescents and adults: two-drug approach no longer recommended; treat with just one 500 mg injection of ceftriaxone. Further details are outlined below:

Regimen for uncomplicated gonococcal infections of the cervix, urethra, or rectum:

Ceftriaxone 500 mg IM as a single dose for persons weighing <150 kg (300 lb)

  • For persons weighing ≥150 kg (300 lb), 1 g of IM ceftriaxone should be administered.
  • If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally twice daily for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.

Alternative regimens for uncomplicated gonococcal infections of the cervix, urethra, or rectum if ceftriaxone is not available:

Gentamicin 240 mg IM as a single dose plus azithromycin 2 g orally as a single dose OR

Cefixime 800 mg orally as a single dose. If treating with cefixime, and chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally twice daily for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.

Recommended regimen for uncomplicated gonococcal infections of the pharynx:

Ceftriaxone 500 mg IM as a single dose for persons weighing <150 kg (300 lb)

  • For persons weighing ≥150 kg (300 lb), 1 g of IM ceftriaxone should be administered.
  • If chlamydia coinfection is identified when pharyngeal gonorrhea testing is performed, providers should treat for chlamydia with doxycycline 100 mg orally twice a day for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.
  • No reliable alternative treatments are available for pharyngeal gonorrhea. For persons with a history of a beta-lactam allergy, a thorough assessment of the reaction is recommended.*
  • For persons with an anaphylactic or other severe reaction (e.g., Stevens Johnson syndrome) to ceftriaxone, consult an infectious disease specialist for an alternative treatment recommendation.

Follow-Up

A test-of-cure is not needed for persons who receive a diagnosis of uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens; however, any person with pharyngeal gonorrhea who is treated with any regimen should return 14 days after treatment for a test-of cure using either culture or NAAT. All positive cultures for test-of-cure should undergo antimicrobial susceptibility testing.

Symptoms that persist after treatment should be evaluated by culture for N. gonorrhoeae (with or without simultaneous NAAT), and any gonococci isolated should be tested for antimicrobial susceptibility. Persistent urethritis, cervicitis, or proctitis also might be caused by other organisms (see Urethritis, Cervicitis, and Proctitis sections).

A high prevalence of N. gonorrhoeae infection has been observed among men and women previously treated for gonorrhea (86,480,481,577). Rather than signaling treatment failure, most of these infections result from reinfection caused by failure of sex partners to receive treatment or the initiation of sexual activity with a new infected partner, indicating a need for improved patient education and treatment of sex partners. Men or women who have been treated for gonorrhea should be retested 3 months after treatment regardless of whether they believe their sex partners were treated. If retesting at 3 months is not possible, clinicians should retest whenever persons next present for medical care within 12 months following initial treatment.

More information on treatment failures can be found at the bottom of this page, under "Treatment Failures". 

Abbreviation: IM = intramuscular.

* CDC. Sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 2015;64(No. RR-3). https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm.

Further information can be found on the CDC's website, by clicking here.


 

History of Resistance

Antibiotic resistance is bacteria’s ability to resist the effects of the drugs used to treat them. Bacteria that become resistant are no longer able to be killed by previously used drugs. Gonorrhea has developed resistance to nearly all of the antibiotics used for its treatment. We are currently down to one last recommended and effective class of antibiotics, cephalosporins, to treat this common infection. This is an urgent public health threat because gonorrhea control in the United States largely relies on our ability to successfully treat the infection.

Gonorrhea is skilled at outsmarting the antibiotics that are used to kill it. For this reason, we must continuously monitor for antibiotic resistance and encourage the research and development of new drugs for gonorrhea treatment.

Here is a short video for that details the history of drug-resistant gonorrhea in the United States, the dangers of untreatable gonorrhea, and why this issue must remain a top public health priority. https://www.youtube.com/watch?v=iFwlnljV2Go


Since the 1940’s, there has been a shift in front-line medication recommendations about every decade.
This figure shows the main medications used to treat gonorrhea for the past three decades.
This highlights how limited our options have become for standard treatment therapy.

Source: https://www.cdc.gov/std/stats18/STDSurveillance2018-full-report.pdf

 

Treatment Guidelines

For a thorough explanation of CDC-recommended treatment guidelines for gonorrhea, including alternative therapy for patients with drug allergies, visit the CDC website: https://www.cdc.gov/std/tg2015/gonorrhea.htm.

 

Antimicrobial Resistance Trends

In order to monitor trends in antimicrobial resistance, the CDC-supported Gonococcal Isolate Surveillance Project (GISP) compiles antimicrobial susceptibility testing results from gonorrhea isolates collected in funded jurisdictions across the United States. Gonorrhea isolates are obtained from symptomatic men with genital infections who visit an STD clinic for screening and treatment. These isolates are then tested for susceptibility to recommended antibiotics, including ceftriaxone, cefixime and azithromycin.

Over the past decade, Neisseria gonorrhoeae has started developing resistance to Azithromycin—as seen in the figure below. Ongoing discussions at the CDC about updates to the treatment guidelines are actively occurring, but at this time, the dual therapy of ceftriaxone and azithromycin are still recommended by the CDC for treatment of gonorrhea.

Source: https://www.cdc.gov/std/stats18/STDSurveillance2018-full-report.pdf

 

SURRG in Indiana


 

In order to expand the antimicrobial resistance surveillance conducted by GISP, the CDC created the Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) project in 2016. Similar to GISP, funded jurisdictions across the United States collect gonorrhea isolates that are tested for antimicrobial susceptibility. One of the new objectives for SURRG is to collect gonorrhea isolates from women and extra-genital infections, which were previously missed in GISP. In 2016, Indiana was chosen as one of eight sites to participate in the SURRG project.

Project Aims

The Indiana SURRG project aims to:

  • Strengthen community coordination for identification of resistant gonorrhea through increasing culture collection and antibiotic susceptibility testing (AST) via partnerships with clinical sites and the public health laboratory;
  • Enhance timely surveillance and communication between government agencies, community organizations and medical facilities for rapid detection of resistant gonorrhea strains;
  • Conduct in-depth disease intervention specialists (DIS) interviews with patients identified as having gonorrhea with increased resistance to develop social and sexual networks for analysis; enhance DIS case investigations to identify the transmission dynamics of resistant gonorrhea within local networks and create innovative intervention activities; and
  • Increase community engagement and participation in gonorrhea prevention and control with outreach disease intervention related to social network analyses.

Partnerships

In partnership with the Marion County Public Health Department in Indianapolis, IN, Neisseria gonorrhoeae isolates are collected from five testing sites around the city:

  • Bell Flower STD Clinic (Marion County Public Health Department);
  • The Damien Center;
  • Community Hospital East Infectious Disease Clinic;
  • Community Hospital East Emergency Department; and
  • Eskenazi Hospital Emergency Department.

Screening tests for gonorrhea are available at all the above locations. If you test positive, a DIS may contact you to come in for treatment and a SURRG culture sample could be collected at that time. Opting in to this test will allow a more comprehensive look at a patient’s infection and ensure the appropriate medication is being used to clear the infection. Speaking with the DIS will also help us understand how resistant gonorrhea is spreading through sexual networks and could aid public health workers in stopping disease transmission in the future.

Updated Data Trends

Since May 2017, Indiana has collected 1,664 SURRG gonorrhea isolates for antimicrobial susceptibility testing. As of October 2019, less than 0.001 percent of the isolates have shown increased resistance to ceftriaxone and cefixime. Most of the increased resistance that is being detected is to Azithromycin, with six percent of isolates having increased resistance to the drug. An increasing proportion of these (29 percent) were from extra-genital infections.

Below is a figure of the antibiotic resistance Indiana has detected so far through SURRG. Most of the isolates with increased resistance, those on which the DIS conducts expanded interviews, are at or just above the breakpoint of susceptibility (MIC ≥ 2.0 µg/mL). There was also a cluster of 14 cases that were completely resistant to Azithromycin. All of these cases were properly treated and cleared their infection upon test-of-cure. Through genomic sequencing, all of these cases were determined to be genetically similar—supporting the hypothesis that gonorrhea spreads in a close network of sexual partners.


Source: Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) Project, Indiana, May 2017-October 2019

 

When looking at seasonality of the Azithromycin resistance, it is also worth noting the spikes in the fall and winter months.


Source: Strengthening the U.S. Response to Resistant Gonorrhea (SURRG) Project, Indiana, May 2017-October 2019

 

Taking a Sexual History

One of the most important components of SURRG is collecting gonorrhea samples from all sites of exposure in both men and women. In order to assess what anatomic sites have been exposed, healthcare providers should take a comprehensive sexual history with their patients. This includes asking the patients, sometimes in terminology/slang that they understand, if they give or receive oral or anal sex. This can be a difficult topic to approach for some, but since local SURRG data suggest gonorrhea with increased resistance may be more commonly found in throat and rectum, it is imperative that providers discuss sexual practices with their patients.

Treatment Failures

The CDC’s website discusses the definition of a treatment failure and the questions you need to ask your patients to determine if they have a treatment failure or have simply been re-infected:

“Cephalosporin treatment failure is the persistence of N. gonorrhoeae infection despite appropriate cephalosporin treatment and is indicative of infection with cephalosporin-resistant gonorrhea in persons whose partners were adequately treated and whose risk for reinfection is low. Suspected treatment failure has been reported among persons receiving oral and injectable cephalosporins. Treatment failure should be considered in 1) persons whose symptoms do not resolve within 3–5 days after appropriate treatment and report no sexual contact during the post-treatment follow-up period and 2) persons with a positive test-of-cure (i.e., positive culture >72 hours or positive NAAT ≥7 days after receiving recommended treatment) when no sexual contact is reported during the post-treatment follow-up period. Treatment failure should also be considered in persons who have a positive culture on test-of-cure (if obtained) if there is evidence of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the post-treatment follow-up period.”

“Most suspected treatment failures in the United States are likely to be re-infections rather than actual treatment failures. However, in cases where reinfection is unlikely and treatment failure is suspected, before retreatment, relevant clinical specimens should be obtained for culture (preferably with simultaneous NAAT) and antimicrobial susceptibility testing if N. gonorrhoeae is isolated.

  • If you suspect a treatment failure, or have questions about a case, contact the SURRG Epidemiologist, Jamie Black, MPH: 317-234-8981 or jamblack@isdh.in.gov.