Gonorrhea: A Rising Resistance

What are the main issues with Neisseria gonorrhoeae diagnosis?

SS: The best diagnostic assays are molecular tests, but they don’t give us information on antimicrobial sensitivity. Patients often present without symptoms, so physicians don’t take samples for culture – and N. gonorrhoeae is also less likely to culture when the organism load is low. This means that many patients lack sensitivity information. Molecular assays to determine treatment resistance could help, because they are quicker and more sensitive than culture.

TS: Sensitivity and specificity can be a challenge when diagnosing gonorrhea. Microscopy is poorly sensitive in determining the presence of infection, except for perhaps when it occurs in the urethra in men. Specificity can be a problem for molecular tests in extragenital infections due to the presence of other Neiseria species, and confirmatory testing is usually required.

Accurate molecular point-of-care testing can enable immediate treatment, which is important to prevent the spread of gonorrhea. Unfortunately, we don’t have tests available yet that can provide a result within half an hour of taking a sample, which some say is important to them working in the average sexual health clinic. With new technologies, it is important to continue to observe best practices – multi-anatomical-site testing in men who have sex with men, microscopy on Gram stain smears from suspicious cases, good follow-up and partner notification, and test of cure at the right time.

How concerning is the appearance of multidrug-resistant N. gonorrhoeae?

SS: Very. The new guidelines (1) place strong emphasis on the importance of culturing all individuals at relevant sites with suspected or confirmed disease – not only for surveillance purposes, but also to identify highly drug-resistant strains early. They also recommend test of cure in all individuals with gonorrhea, which will be a challenge to implement because it significantly adds to current clinic workloads.

TS: This is very worrying as such cases are emerging internationally. Many have links with Asia, but there are a number of multidrug-resistant strains that have been detected on different continents. Even more concerning is that, for some, there appears to be no direct link with international travel. These strains could quite easily enter deep sexual networks without detection and disseminate. The guidelines put an emphasis on increasing the dose of ceftriaxone to prevent the breakthrough of resistance. This switch to monotherapy was made reluctantly because the value of azithromycin in high doses is questionable – it frequently causes adverse effects and can lead to resistance in other STIs such as syphilis and Mycoplasma genitalium.

In contrast, the concern about empirical treatment with ceftriaxone monotherapy is that it might still accelerate the selection of ceftriaxone resistance, even with the higher dose. These are difficult, conflicting challenges to bring together, reflected in the development of different guidelines internationally. However, the emerging consensus is that ceftriaxone will inevitably be lost as an empirical first-line therapy, regardless of treatment strategy.

Can we combat this issue?

SS: It’s difficult, because gonorrhea is always one step ahead of us. There is an urgent need for newer, more efficacious antimicrobials, but trials take years and there’s not much in the pipeline at present. We need to improve access to genitourinary medicine clinics, encourage frequent testing of high-risk individuals, and ensure test of cure and partner notification.

TS: To prevent STIs, we must promote good sexual health and remain aware of the potential for N. gonorrhoeae infection. Aside from regular testing, this means ensuring the use of culture when there is suspicion of gonorrhea to detect drug-resistant strains; considering the possibility of travel-associated gonococcal infection, particularly if acquired from the Far East; and encouraging the development of good molecular antimicrobial resistance (AMR) testing both in the lab and at the point of care.

What do you foresee happening in the future?

SS: I think we’ll see more multidrug-resistant strains requiring more complex antibiotic regimens and taking up a lot of time and resources. Hopefully, we’ll counter that with better diagnostics, such as rapid point-of-care tests that provide resistance information, but I think those are still some years away.

TS: I predict increased use of molecular and point-of-care AMR testing, as well as more comprehensive surveillance. I hope we’ll have new treatment strategies (although the results of new therapeutic candidates are currently mixed), along with more flexibility in guidelines as the AMR landscape rapidly changes. The advances in diagnostics must be evaluated properly but, given the current economic climate and cuts to sexual health care, they may still be challenging to implement in the near future. We may be forced as a specialty to let go of the idea of directly observed single-dose treatments and accept that we need to work toward deploying longer (less tolerable) treatments. Vaccine development is still in its early stages, but there is some evidence to suggest that a vaccine may reduce the risk of getting gonorrhea by enough to help prevent its spread.