New Assay Targets Susceptibility to Ciprofloxacin in Gonorrhea

Researchers from the University of California, Los Angeles (UCLA) Fielding School of Public Health (FSPH) recently introduced an important new assay that identifies susceptibility to ciprofloxacin for the treatment of Neisseria gonorrhoeae, a type of infection that is quickly becoming untreatable. The gyrase A (gyrA) is a rapid assay that successfully genotyped two-thirds of patients with N gonorrhoeae tested, resulting in more targeted use of ciproxofloxacin, a drug previously considered unreliable in gonorrhea treatment, according to a recent brief in Clinical Infectious Diseases, published by the Infectious Disease Society of America (IDSA).¹

The worldwide spread of gonorrhea has reached crisis proportions, the investigators stated, resulting in the Centers For Disease Control and Prevention (CDC) designating the infection in 2013 as 1 of the 3 top public health threats.² Multiple sources have reported the resistance of N gonorrhea to all the first-line antimicrobial agents used to treat it, setting the stage for the extensive global spread of multidrug-resistant strains.^3-7

The investigators, led by Jeffrey D. Klausner, MD, MPH, professor of medicine and public health at the UCLA David Geffen School of Medicine and FSPH, reviewed records from 251 patients who presented to the UCLA health center with 314 N gonorrhoeae infections between January 2015 and July 2016. Samples were collected during 2 periods, before and after assay implementation in November of 2015.

A total of 176 infections were recorded during the period after the assay was introduced, of which 121 (68.8%) were successfully genotyped. The majority of infections were identified as wild-type gyrA (59.5%), with a mutation rate of 40.5%. Providers were sent electronic reminders of individual results, which the investigators felt contributed to an observed increase in treatment with ciprofloxacin. There was also a corresponding decrease in treatment with ceftriaxone, a drug that has also demonstrated evolving resistance and is currently the last available option for monotherapy.³

In the wake of continuing evolution of drug-resistant N gonorrhoeae, a range of novel approaches to therapy are being considered, and through targeting of susceptible patients, the new assay helps to reintroduce a previously less effective treatment for patients who are most likely to benefit. “Rapid molecular assays that predict antibiotic treatment outcomes are the future of infectious disease therapy,” Dr Klausner told Infectious Disease Advisor. “We have had similar assays for HIV, tuberculosis, and staphylococcal infections for a few years. Our assay is the first to be created and used for gonorrhea, one of the world’s most common STDs [sexually transmitted diseases] and one that has become resistant to all our current antibiotics.”

An assay-driven targeted approach can also open the door to identifying other known therapies, such as ciprofloxacin, that may be effective for specific subsets of patients with N gonorrhoeae, as part of the overall campaign to combat antimicrobial resistance. Dr Klausner explained that this approach is “highly adaptable and could be used to predict treatment outcomes to older drugs like penicillin, tetracycline, or erythromycin and new drugs we don’t even know about yet. Because in new drug development we often know exactly how the drug works at the molecular level, we can use that information to create lab tests that can predict whether gonorrhea would be successfully treated or not,” he stated.

References

1. Allan-Blitz LT, Humphries RM, Hemarajata P, et al. Implementation of a rapid genotypic assay to rromote targeted ciprofloxacin therapy of Neisseria gonorrhoeae in a large health system. Clin Infect Dis. 2017;64(9):1268-1270. doi:10.1093/cid/ciw864
2. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/drugresistance/threat-report-2013/index.html Updated April 10, 2017. Accessed June 16, 2017.  
3. Unemo M, GolparianD, Shafer WM, et al. Challenges with gonorrhea in the era of multi-drug and extensively drug resistance—are we not on the right track? Expert Rev Anti Infect Ther. 2014;12:653-656. doi:10.1586/14787210.2014.906902
4. World Health Organization (WHO), Department of Reproductive Health and Research. Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva, Switzerland: WHO;2012:1-36.
5. Tapsall JW, Ndowa F, Lewis DA, Unemo M. Meeting the public health challenge of multidrug and extensively drug resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther. 2009;7:821-834. doi:10.1586/eri.09.63
6. Unemo M, Nichola RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012;7:1401-1422. doi:10.2217/fmb.12.117
7. Unemo M, Shafer WM. Antibiotic resistance in Neisseria gonorrhoeae: origin, evolution and lessons learned for the future. Ann NY Acad Sci. 2011;1230:E19-E28. doi:10.1111/j.1749-6632.2011.06215.x