By Rebecca Bowers

EXECUTIVE SUMMARY

Newly released research indicates that a certain combination of drugs, gentamicin and azithromycin, may work as well as ceftriaxone alone for cases of drug-resistant gonorrhea.

  • Scientists are pressing to find a reliable and affordable oral treatment option for gonorrhea since the bacteria has become increasingly antibiotic-resistant.
  • Gonorrhea is on the rise around the world. Following a decline in notification rates in 2016, the number of gonorrhea cases rose 17% in the European Union and associated countries, with more than 89,000 confirmed diagnoses in 2017. The United States saw a similar rise, with a total of 555,608 cases of gonorrhea reported in 2017, an 18.6% increase since 2016.

Gonorrhea is on the rise around the world. Following a decline in notification rates in 2016, the number of gonorrhea cases rose 17% in the European Union and associated countries, with more than 89,000 confirmed diagnoses in 2017.1 The United States saw a similar rise, with a total of 555,608 cases of gonorrhea reported in 2017, an 18.6% increase since 2016.2

Current numbers do not even show the true extent of the sexually transmitted infection’s (STI) epidemic in Europe, says Gianfranco Spiteri, MD, MPH, STI expert at the European Centre for Disease Prevention and Control.

“Many infections are not diagnosed due to lack of symptoms or limited access to diagnostics or simply are not reported,” Spiteri said in a press statement.

Newly released research indicates that a certain combination of drugs, gentamicin and azithromycin, may work as well as ceftriaxone alone for cases of drug-resistant gonorrhea.3 Scientists are pressing to find a reliable and affordable oral treatment option for gonorrhea since the bacteria has become increasingly antibiotic-resistant. (Read the October 2018 Contraceptive Technology Update article on investigation efforts, “Research Strides May Offer Keys to Battling Gonorrhea,” at https://bit.ly/30a5IDM.)

Check the Research

The new study is the first randomized controlled trial to compare the use of gentamicin and azithromycin amid concerns about growing resistance to ceftriaxone. For the trial, investigators recruited participants from 14 sexual health clinics in England and randomly assigned 720 participants to receive either injections of gentamicin or ceftriaxone, with both groups also receiving a single dose of oral azithromycin.

The results indicate that 98% of participants who received ceftriaxone were cleared of infection, compared to 91% of those who received gentamicin. Among the study participants, gentamicin achieved a 94% cure rate for genital gonorrhea, making it a possible useful choice if ceftriaxone is not available or inappropriate to use, scientists concluded.3

“Our current antibiotic treatment for gonorrhea is beginning to fail and experience with previous drugs strongly suggests that this could become a widespread problem,” says Jonathan Ross, MD, professor of sexual health and HIV at the University of Birmingham. “Our trial has found that gentamicin combined with azithromycin works almost as well as ceftriaxone with azithromycin for genital gonorrhea, but did not clear throat or rectal gonorrhea as effectively.”

Ceftriaxone should remain the first-line treatment for gonorrhea, with gentamicin as an alternative, particularly for patients with genital infection and for those who are allergic or intolerant to ceftriaxone, notes Ross, who served as chief investigator of the Birmingham trial. However, further research is required to identify and test new alternatives to ceftriaxone for the treatment of the STI, he states.

On the Hunt for More Options

Scientists are looking for multiple alternatives for treatment-resistant gonorrhea, since cases are appearing across the globe. Public health institutions such as the National Institute for Health Research (NIHR), the largest national clinical research funder in Europe, are committed to research in areas of the greatest health need, such as antimicrobial resistance. The current research is one of a number of studies the NIHR has funded over the last few years in its sustained effort to tackle this worldwide threat, says Hywel Williams, PhD, professor of dermato-epidemiology at the University of Nottingham and director of the NIHR’s Health Technology Assessment Programme.

Investigators say further research into developing a preventive or therapeutic vaccine is crucial because of increasing resistance and limited future antibiotic options. The samples collected in the current trial will help to develop a greater understanding of the immune response to infection, they note. Also, scientists plan to examine the frequency of multiple infections and their potential role in the spread of resistance. By using genome sequencing, investigators could identify genetic markers of gonorrhea resistance and provide insights into the mechanisms and predictors of resistance, they conclude.

Scientists recently have completed proteomic profiling on all the proteins produced by 15 gonorrhea strains; among the isolates were World Health Organization-maintained reference strains that show all known profiles of gonococcal antimicrobial resistance.4 Nine new potential vaccine candidates were identified as a result of the research.

The National Institutes of Health recently awarded a $5.1 million grant to a team of Johns Hopkins University (JHU) scientists to develop a device that rapidly tests for gonorrhea and detects if a particular bacterial strain is resistant to antibiotics. Researchers from JHU’s Whiting School of Engineering and School of Medicine, the World Health Organization, GE Global Research, and Stanford University also are involved in the inquiry.

REFERENCES

  1. European Centre for Disease Prevention and Control. Gonorrhoea: Annual Epidemiological Report for 2017. Stockholm: ECDC; 2019. Available at: https://ecdc.europa.eu/sites/portal/files/documents/gonorrhoea-annual-epidemiological-report-2017.pdf. Accessed May 28, 2019.
  2. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2017. Atlanta: U.S. Department of Health and Human Services; 2018.
  3. Ross JDC, Brittain C, Cole M, et al. Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): A randomised non-inferiority trial. Lancet 2019. doi: 10.1016/S0140-6736(18)32817-4.
  4. El-Rami FE, Zielke RA, Wi T, et al. Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants. Mol Cell Proteomics 2019;18:127-150.