Issues to consider about repurposing ertapenem
As reported earlier in this issue of TreatmentUpdate, Dutch researchers have found preliminary evidence that the antibiotic ertapenem has the potential for use as a treatment for gonorrhea. However, the Dutch trial, code-named Nabogo, was relatively small and had limitations. These limitations must be kept in mind when planning future research with ertapenem as a treatment for gonorrhea.
Ceftriaxone susceptibility
Lab testing in the Dutch study confirmed that all strains of gonorrhea in participants were susceptible to ceftriaxone. Over the past two decades, there have been increasing reports of cases of gonorrhea resistant to ceftriaxone. Will ertapenem work against such strains?
A decade ago, scientists in Sweden conducted lab experiments with four strains of gonorrhea that were resistant to ceftriaxone. They found that ertapenem was able to stop the growth of these four strains of gonorrhea-causing bacteria. Note that as promising as these test-tube results are, they require confirmation in a clinical trial with people who have gonorrhea resistant to ceftriaxone. Many lab experiments that seem promising do not always have the same results when tested in people. Also, in cases of ceftriaxone-resistant gonorrhea, it may be necessary to use doses of ertapenem that are higher than what was used in the present Dutch study. It is even plausible that multiple doses of ertapenem (rather than a single dose) might be required for the treatment of ceftriaxone-resistant gonorrhea. These are issues that could be explored in future clinical trials.
Women
The proportion of women in the Dutch trial was small, limiting its relevance to this population. Furthermore, one woman with cervical-vaginal gonorrhea was not cured when treated with ertapenem. More research needs to be done with ertapenem in this population.
Throat infection
Gonorrhea in the throat can be difficult to cure, perhaps because antibiotics have difficulty reaching high concentrations in throat tissue. The main purpose of Nabago was to assess the effectiveness of treatment on anorectal or urogenital gonorrhea. A minority of participants had gonorrhea in the throat. Among these people, most who were treated with ceftriaxone (90%) or ertapenem (88%) were cured.
This finding is promising, but the Dutch researchers called for more randomized trials to assess the ability of antibiotics to cure gonorrhea in the throat.
Other issues
Participants in Nabago had uncomplicated gonorrhea. Future studies need to assess ertapenem’s effectiveness at treating gonorrhea-causing bacteria that has spread to tissues beyond the anorectal and urogenital tracts and/or throat. This is called disseminated gonorrhea.
It is possible that ertapenem could be used in combination with another antibiotic in a clinical trial to enhance its effect on gonorrhea or to help wipe out coinfections (such as chlamydia or Mycoplasma genitalium). However, additional research is needed to select a drug that could fulfill such a potential role.
Cost
The Dutch researchers stated that “the costs of ertapenem are considerably higher than ceftriaxone.” This may limit its potential use against gonorrhea in the future.
Recruitment
Nabago encountered challenges in recruitment. Such challenges may bedevil future clinical trials for antibiotics that target gonorrhea and may therefore slow the pace of research.
Reserved for rescue
Due to some of the previously mentioned issues, it is likely that, for the foreseeable future, clinics and hospitals will reserve the use of ertapenem in cases where ceftriaxone has failed.
Although the Dutch study is an important step forward, research remains to be done to uncover ertapenem’s full potential against gonorrhea and to determine the best dose and duration of therapy.
—Sean R. Hosein
REFERENCES:
- de Vries HJC, de Laat M, Jongen VW, et al. Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial. Lancet Infectious Diseases. 2022 Jan 19:S1473-3099(21)00625-3.
- Kong FYS, Hocking JS. Treating pharyngeal gonorrhoea continues to remain a challenge. Lancet Infectious Diseases. 2022 Jan 19:S1473-3099(21)00649-6.