Best Evidence Analyses and Commentary

Evolving resistance trends for Neisseria gonorrheae
Lucas Reinhartz, PharmD Candidate; Michael Mueller, PhD

Gonorrhea remains the second most commonly reported sexually transmitted disease in the United States behind chlamydia.1 Prevention and treatment of N. gonorrheae, through safe sex practices and antibiotics, can result in a decrease of male patients with epididymitis and female patients with pelvic inflammatory disease and the possibility of infertility. Historically, several different antibiotic classes have been used to treat N. gonorrheae including sulfonamides, penicillins, tetracyclines and fluoroquinolones, but all have been met with resistant strains. By the 1980s, sulfonamides, penicillin and tetracyclines were no longer seen as first-line options for treatment. In 2007, fluoroquinolone-resistant N. gonorrheae emerged in the United States which left cephalosporins as the only recommended antimicrobial class available for treatment.2 Recently, the CDC’s Gonococcal Isolate Surveillance Project (GISP) is showing an alarming trend of resistance, increased minimum inhibitory concentrations (MICs), and reduced susceptibility to the only orally available agent, cefixime.3 From January 2006 to August 2011, the percentages of isolates with elevated cefixime MICs (≥ 0.25 mcg/mL) have increased from 0.1% to 1.5%.


Percentages of ceftriaxone MIC elevations have also increased but very minimally as compared to cefixime, 0% to 0.4% in the same timeline.4   The highest reported incidence of elevated MICs for cefixime and ceftriaxone isolates are in the Western United States and in men who have sex with men.  In Europe, there have been several reports of gonorrhea treatment failure with cefixime.5  This data is indicative of declining effectiveness of cefixime and therefore, as of August 2012 the CDC no longer recommends the routine use of cefixime as a first-line regimen for the treatment of N. gonorrheae in the United States.  As cefixime is used less for treatment of N. gonorrheae, the increased usage of ceftriaxone will likely hasten the continued development of resistance patterns.  With intramuscular ceftriaxone being the remaining critical treatment for N. gonorrheae and resistance beginning to emerge, there is an increased need for new treatment regimens for N. gonorrheae. 


Based on the new data showing increased resistance for treatment of N. gonorrheae, the CDC has updated their recommendations from the 2010 Sexually Transmitted Diseases Treatment Guidelines.  When looking at the treatment of uncomplicated urogenital, anorectal and pharyngeal gonorrhea, the CDC recommends combination therapy with a single intramuscular dose of ceftriaxone 250 mg plus either a single dose of azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days.4  Patients with persistent infections despite treatment with the recommended combination therapy regimen should have cultures gathered with susceptibility testing of the N. gonorrheae isolates.


Despite changes to the guidelines, cefixime has not been fully removed from treatment regimens.  Cefixime 400 mg orally plus either azithromycin 1 g orally or doxycycline 100 mg orally twice daily for 7 days can be used if ceftriaxone is not readily available.  Azithromycin 2 g orally in a single dose should be the agent used if ceftriaxone cannot be given because of severe allergy. If a patient with gonorrhea is treated with an alternative regimen, the patient should return 1 week after treatment for a test-of-cure at the infected anatomic site.4  Cases of treatment failure with either the first-line or alternative regimens should be reported to the CDC through the local or state health department.  Sexual partners of patients with gonorrhea should be tested for N. gonorrheae and if detected should be treated with a recommended regimen. 



1.     "Gonorrhea." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 17 Nov. 2011. Web. 01 Nov. 2012. <>.

2.     CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 2007;56:332–6.

3.     CDC. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010;59(No. RR-12):1-110.

4.     CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep 2012; 61(31);590-594

5.     Unemo M, Golparian D, Stary A, Eigentler A. First Neisseria gonorrhoeae strain with resistance to cefixime causing gonorrhea treatment failure in Austria, 2011. Euro Surveill 2011;16:pi:19998.


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