Two’s a party: Gonorrhoea treatment needs antimicrobial stewardship

The sexual health nurse comes to see me, “Doctor, just a quick question before you start your clinic, please.” My readers should know the drill by now – deep breath, then, “Sure, fire away.”

“Do you remember the woman last week with vaginal discharge who we treated empirically for bacterial vaginosis while the swabs were pending? Well, they came back positive for both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)”.

My personal record is someone who had five different sexually transmitted infections at the same time (CT, NG, Trichomonas vaginalis, a herpes simplex virus type 2 flare, and secondary syphilis), so it can’t be any worse than that.

The sexual health nurse continues, “I am calling her back for treatment today. I was reading the new guidelines, but I’m a bit confused – before, I would have given her just ceftriaxone 500mg plus azithromycin 1g for NG, and we were told that would take care of CT as well. But now that doxycycline is recommended for CT rather than azithromycin, what should I do? Give her three antibiotics – ceftriaxone, azithromycin and doxycycline?”

You will know my answer by the end of the article.

Optimising the dose of one antibiotic to spare an unnecessary one is definitely one of the cornerstones of antimicrobial stewardship

The sexual health nurse is not the only one who is a bit confused. Unlike CT, NG is a master in the art of developing resistance to antibiotics, so much so that the state of untreatable disease due to a lack of effective antimicrobials is actually a possibility if we do not use carefully the few options we have left.

Unfortunately, international coordination is patchy; hence, different jurisdictions are opting for diverse solutions for NG infections:

• The British Association for Sexual Health and HIV now recommends ceftriaxone 1g monotherapy (bashh.org/guidelines).
• The US Centers for Disease Control and Prevention recommend ceftriaxone 500mg monotherapy, but ceftriaxone 1g if body weight is >150kg (tinyurl.com/CDCgonococcal).
• The European guideline recommends ceftriaxone 1g plus azithromycin 2g, or ceftriaxone 1g monotherapy only in certain (essentially specialist) settings (Int J STD AIDS 2020 29:956462420949126).
• In Australia, ceftriaxone 500mg plus azithromycin 1g (but azithromycin 2g for pharyngeal infections) is recommended (sti.guidelines.org.au).

When we (the New Zealand Sexual Health Society) approached this topic, we had very robust discussions, also because the New Zealand data on NG antibiotic resistance are very patchy and skewed towards specific subsets.

Essentially, primary care testing for NG is limited to PCR, which does not (yet) give the antibiotic susceptibilities. Therefore, only patients presenting to sexual health clinics (which are limited in number and coverage of the motu) also get a swab for culture and susceptibilities. This introduces a very significant bias towards the major cities and men who have sex with men in our antibiotic resistance data.

The conclusion of our discussions was, for now (subject to early review if and when more data become available), to keep recommending ceftriaxone 500mg plus azithromycin 1g stat for the majority of NG cases, but in the case of NG/CT coinfections, to move to ceftriaxone 1g for NG plus doxycycline 100mg twice daily for seven days for CT (click on “gonorrhoea” at sti.guidelines.org.nz).

This approach gives us confidence that:

• NG is effectively covered by the increased ceftriaxone dose, as per British guidelines
• CT is optimally covered by doxycycline for seven days, which is superior to azithromycin in many circumstances (see “Sexual health”, New Zealand Doctor, 2 February)
• some good antimicrobial stewardship (AMS) principles have been introduced, as optimising the dose of one antibiotic to spare an unnecessary one is definitely one of the cornerstones of AMS.

If I can disclose a personal viewpoint (not representing NZSHS), my opinion was to bring this AMS principle to the extreme consequences, as the British guidelines did; hence, stepping up the ceftriaxone dose and getting rid of the azithromycin for NG monoinfections.

So, you should be able to guess my answer now. I advised to treat the woman with the NG/CT coinfection with two antibiotics rather than three – ceftriaxone 1g via intramuscular injection stat (diluted with 3.5ml lignocaine 1 per cent) plus doxycycline 100mg orally twice daily for seven days. Contact tracing and notification were already being done by the sexual health nurse.

Early test of cure at four weeks after treatment is now only recommended in specific scenarios: pregnancy or pharyngeal infection for NG, and pregnancy or rectal infection for CT. All other patients should be offered a test for reinfection at three months after treatment.

Are there any indications for doing NG culture and susceptibilities in primary care?

You need to discuss this with your local microbiology lab as they might have local policies and protocols. In general, the NZSHS recommends performing an NG culture regardless of the setting in these circumstances (sti.guidelines.org.nz/sexual-health-check):

Females (endocervical swab) – if suspected pelvic inflammatory disease, profuse cervical discharge, or a contact of an NG case.

Males (urethral swab) – if frank urethral discharge is present (the swab does not need to be inserted into the urethra as long as pus is easily accessible in the meatus).

Transgender and non-binary people – as per the genital organs that are present (ie, endocervical swab as above if there is a uterus and cervix, urethral swab as above if there is a penis).

Massimo Giola is an infectious disease and sexual health physician, and clinical lead of the sexual health services for Bay of Plenty and Lakes DHBs