Primary Care Corner with Geoffrey Modest MD: Gonorrhea Resistance Increasing?

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By Dr. Geoffrey Modest

A rather disturbing MMWR just came out finding that gonorrhea is becoming increasingly resistant to pretty much all of our current antibiotics (see http://www.cdc.gov/mmwr/volumes/65/ss/pdfs/ss6507.pdf ).

Details:

  • The Gonococcal Isolate Surveillance Project (GISP) has been around since 1986 and does sentinel surveillance of antimicrobial sensitivity for N. gonorrhoeae (GC). They check GC cultures and antibiotic susceptibility from the first 25 men with gonococcal urethritis attending each of the participating STD clinics at 27 sites in the US.
  • They are able to extract selected demographic and clinical data
  • Mean age 28, 58% Black/22% white/13%Hispanic-Latino; 37% MSM or MSMF (men who have sex with men, or both men and women)

Results:

  • 5093 isolates were collected in 2014 (all of the resistance patterns were more common in MSM)
    • 3% resistant to tetracyclines
    • 2% resistant to ciprofloxacin (increasing, though there was an initial dip after the CDC stopped recommending its use to treat GC)
      • 2% resistant to penicillin (plasmid-based, chromosomal, or both) — though CDC has not recommended using it for treatment of GC since 1989
    • But of major significance:
      • 5% had reduced susceptibility to azithromycin (0.6% in 2013):
        • In all geographic areas of the US, but most in the Midwest (Midwest about 4%, Northeast about 2.7%, rest about 2%)
        • In all groups of sex partners (MSM about 4.3%, MSMW about 3.2%, and MSW about 1.5%)
        • None of these azithro-resistant isolates had reduced ceftriaxone or cefixime susceptibility
      • 8% had reduced susceptibility to cefixime (0.4% in 2013)
      • 1% had reduced susceptibility to ceftriaxone (no change from 2013), though highest in Northeast (about 0.4%).
      • 38% of isolate exhibited resistance to some antibiotic;  and 10% to 2, 7% to 3 and 0.5% to 4 antibiotics

Commentary:

  • Gonorrhea is the 2nd most commonly reported notifiable disease in the US, with 350,062 cases reported in 2014
  • The role of GISP is especially important, since we have mostly gone to NAAT testing (nucleic acid amplification tests) instead of GC culture, and one needs to grow the GC in culture to test susceptibility
  • Though the numbers of resistant isolates to the azithro and ceftriaxone are still pretty low, it is important to remember that there is a critical threshold (inflection, or tipping point), where the prevalence leads to a dramatic increases in their transmission (which, from my rather distant memory is on the order of 8%). So the 4-fold increase in azithro resistance to 2.5% may be really foreboding
  • Limitations of the study: a big one is that only men with urethritis were tested (and MSM,MSMW were disproportionately represented); another is that we do need to see infectious diseases more and more through a global perspective. What is happening in the US is not isolated from the rest of the world. And though the resistance level to ceftriaxone is still relatively low in the US, in other areas the levels are much higher (the WHO report in 2014 found >25% resistance to 3rd generation cephalosporins in 3 of the 6 regions of the world. See https://stg-blogs.bmj.com/bmjebmspotlight/2014/07/11/primary-care-corner-with-geoffrey-modest-md-whos-remarkable-scary-report/ for details.)  Also, with such low numbers of resistance reported by GISP (especially for ceftriaxone), sampling error could lead to rather large % changes in the numbers (only about 1% of the reported cases were actually sampled, and my guess is that there are many more cases of GC than those reported….)
  • CDC recommendations remain the same: treat GC with ceftriaxone 250mg IM plus azithro 1gm orally (the combined meds are synergistic and cover for each other’s resistance for now, since there are no reported cases of resistance to both). Use azithro 2g plus gentamicin or gemifloxacin if intolerant of cephalosporins. Cefixime had been considered an acceptable cephalosporin to use until 2012, when recommendations changed because of increasing cefixime The decreasing cefixime resistance reported now may not be significant, since it is not simultaneously decreasing in other areas of the world. It is still not recommended by the CDC.
  • And, the striking increase in azithromycin is very concerning because if it continues to increase, the mainstay of GC treatment will become increasingly ineffective, especially in the context of increasing cephalosporin resistance in much of the world. GC may become effectively resistant to all meds we currently have….

For a slew of blogs on antimicrobial resistance, see https://stg-blogs.bmj.com/bmjebmspotlight/category/antimicrobial-resistance/

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