By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Antibiotic-resistant gonorrhea threatens to make the infection untreatable in some patients.

SOURCE: Wi T, Lahra MM, Ndowa F, et al. Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action. PLoS Med 2017;14:e1002344.

The Global Gonococcal Antimicrobial Surveillance Programme (GASP) is a World Health Organization (WHO) activity designed to monitor antimicrobial resistance (AMR) trends and to identify newly emerging AMR to provide the necessary information for adjustments to treatment guidelines and public health policy. In 2016, WHO set a goal of a 90% reduction in the global incidence of gonorrhea a target that cannot be achieved in the absence of the control of the spread of antibiotic resistance in this sexually transmitted infection.

Globally widespread resistance to penicillin, tetracycline, and ciprofloxacin persisted in 2009 to 2014, along with increasing resistance to azithromycin and the emergence of resistance to extended-spectrum cephalosporins (ESC), such as cefixime and ceftriaxone. Among countries reporting antimicrobial susceptibility results for at least one year, 97% had detected ciprofloxacin resistance or reduced susceptibility, 81% to azithromycin, and 66% to ESCs — mostly to cefixime. While resistance rates are significantly higher in some other regions, resistance to ceftriaxone remains infrequent in North America, with a 1% rate in Canada and 0.4% in the United States.

COMMENTARY

Global susceptibility data are somewhat compromised by a lack of data from many developing countries, as well as by the use of nucleic acid amplification testing for the diagnosis of infection in more economically developed countries, meaning that no isolate is available for antimicrobial susceptibility testing.

In 2010, CDC dropped its recommendation for use of cefixime in the treatment of gonorrhea because of increasing resistance and associated treatment failures. The current CDC recommendation for the treatment of uncomplicated genital, rectal, or oropharyngeal gonorrhea is the administration of a single 250 mg dose of ceftriaxone given intramuscularly together with either a single 1 gram oral dose of azithromycin or the oral administration of 100 mg doxycycline twice daily for seven days. If unable to administer ceftriaxone, CDC recommends substitution of a single 400 mg dose of cefixime together with either azithromycin or doxycycline as above. If the patient has a severe allergy to cephalosporins, a single 2 gram dose of azithromycin may be administered orally. In the absence of ceftriaxone administration, however, a one week test of cure should be performed.

While the use of combination therapy may slow the further emergence of resistance, this progression is likely to be inevitable. Other available antibiotics (at least in developed countries) that could play a role in therapy include ertapenem, fosfomycin, spectinomycin, and gentamicin — each of which, if used, should be administered with a second antimicrobial. The authors point out that several potentially effective antibiotics are under investigation, including a fluoroketolide, solithromycin, and the gyrase/topoisomerase inhibitors gepotidacin and zoliflodacin.

Prevention is better than treatment. In addition to various public health measures, including promotion of condom use, novel interventions will be necessary. These may include technical approaches such as point-of-care rapid antimicrobial susceptibility testing. Since oropharyngeal gonorrhea is prevalent but also often asymptomatic, the regular use of antiseptic mouthwashes may be beneficial, as suggested by evidence that Listerine significantly reduces the pharyngeal bacterial load of Neisseria gonorrhoeae.1 The ultimate goal is the development of an effective vaccine. The recent report that a group B outer membrane vesicle meningococcal vaccine (MeNZB) produced modest protection against gonorrhea may help provide a pathway to a vaccine against this sexually transmitted infection.2 Of note is that MeNZB is not available, but the membrane vesicle group B immunogen is included in a group B vaccine available in the United States.

REFERENCES

  1. Chow EP, Howden BP, Walker S, et al. Antiseptic mouthwash against pharyngeal Neisseria gonorrhoeae: A randomised controlled trial and an in vitro study. Sex Transm Infect 2017;93:88-93.
  2. Petousis-Harris H, Paynter J, Morgan J, et al. Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: A retrospective case-control study. Lancet 2017; (published online July 10). Available at: http://dx.doi.org/10.1016/S0140-6736(17)31449-6. Accessed July 12, 2017.