Gonococcal infection, antibiotic resistance, and its wane on the introduction of ceftriaxone and Cefixime

Gonococcal infection, antibiotic resistance, and its wane on the introduction of ceftriaxone and Cefixime

01 Sep 2023

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This informal CPD article ‘Gonococcal infection antibiotic resistance and its wane on the introduction of ceftriaxone and Cefixime’ was provided by Nwaobia Hope Olileanya from The Edge Medical Writing, an organisation that provides high quality medical writing support, tailored to meet the needs of medical education, product development, and the dissemination of medical information.

Most bacterial infections keep emerging and re-emerging as one choice of antibiotic has been used in combating them; Gonorrhea is one of them. Gonorrhea is a sexually transmitted disease caused by infection with the Neisseria gonorrhoeae bacterium. Neisseria gonorrhoeae is a Gram-negative diplococci bacterium.


Gonococci selectively attaches to specific non-ciliated epithelial cells of the body, notably those of the urethra, uterine cervix, pharynx, and conjunctiva. Infection begins when the fimbriae from their surface attach specifically to receptors on host cells(1). These pilli(fimbriae), and other surface proteins such as Opa protein, possessed by Gonococcus express different surface antigens which allow them to attach different kinds of cell receptors and also will enable them to escape the effects of antibodies formed against them(2).

Like other pathogens, Gonococcus produces an enzyme that destroys IgA antibodies found on mucosal surfaces. Opa proteins of the outer membrane of Gonococcus represent another important pathogenicity(1). These proteins attach specifically to receptors on CD4 T lymphocytes, thereby preventing activation and proliferation of the lymphocytes and impairing the immune response to the infection(3).

Gonococcus epidemiology in Africa

The World Health Organization (W.H.O) estimates that in 2020, 82.4 million new cases were infected among adolescents and adults aged 15-49 years world-wide, with a global incident rate of 19 per 1000 women and 23 per 1000 men(1). Sequel to the estimate, The W.H.O noted that 7.5 million people in Africa had Gonorrhea(6). The prevalence was higher among females, with about 4.3 million people infected, whereas the number of males affected was 3.2 million(1). The WHO has estimated that every year in Africa there are 16 million cases of Gonorrhea-about 1.5 million case per year in Nigeria (College of Medicine, University of Ibadan)(7).

Diseases associated with gonococcus infection

Sexually transmitted diseases in pregnant women can result in pre-maturity, stillbirth and neonatal infections which Gonorrhea is among them. Gonorrhea follows a different course in women(1). Besides infecting the urethra, gonococci thrive in the cervix and fallopian tubes, as well as in glands in the vaginal wall and other areas of the genital tract(1). 15% to 30% of untreated infections progress upward through the uterus into the fallopian tubes, causing pelvic inflammatory disease (PID)(1). In some cases, the infection exists in the fallopian tube and passes into the abdominal cavity, which attacks the surface of the liver or other abdominal organs(9).

Though the movement of gonococcus to the uterus is not well understood there is a possibility that the organism attaches to the sperm(2). When the fallopian tube is scarred, the passage of the ova is blocked, which causes sterility and dangerous complications in which the embryo develops in the fallopian tube or even in the abdominal cavity outside the uterus (ectopic pregnancy)(9). Gonorrhea in most women can be asymptomatic as the organism attaches to the wall of the birth canal(10). During the time of labor, the baby picks the gonococcus from the birth canal, which leads to Ophthalmia neonatorum: blindness in new born babies(10).

In men, Urethritis leads to a burning sensation during urination and the production of purulent discharge from the urethra(10). The discharge may be foul smelling, if untreated can result to scarring of the urethra. It can transmit to the testes, causing orchitis and high chances of prostate cancer(10).

Gonorrhea in most women can be asymptomatic

Ceftriaxone as a single therapy: for the treatment of gonorrhea 

As earlier said that gonococcus possesses Opa proteins, pilli, and surface antigens, which hide them from the immune system and its mechanism(2). They also confer the bacterium with resistance to many antibiotics ranging from the penicillin family to aminoglycosides, to beta-lactam drugs; and even the first to the second family of cephalosporin drugs. Cephalosporins like ceftriaxone and cefixime are used today to handle their infection though some antibioticresistant gonorrhea is also emerging. Ceftriaxone is not recommended in newborns with high blood bilirubin(1). In updated guidance, the CDC recommended a 500mg intramuscular dose of ceftriaxone to treat uncomplicated gonorrhea(1).

The emergence of antibiotic resistant gonococcus: and the need for dual therapy

In most cases, gonorrhea can be treated with a single dose of antibiotics. However, as with many other bacteria, the emergence of antibiotic resistant gonorrhea (ARG) has been recorded. The bacteria are coming up with ways of resisting the bactericidal activities of cephalosporin drugs. The Antibiotic Resistant Gonococcus is not frequent(1). Morgan 2016 said that data collected over the years recorded that ARG emerges every 10-20 years. The Centers for Disease Control and Prevention (CDC), recorded that gonorrhea has become resistant to nearly all the antibiotics used to treat it. Ceftriaxone, one class of cephalosporins, is still effective but has yet to be compared when the antibiotics are combined(1).

The quest to treat gonococcal infection has given room for dual therapy recommendation. The CDC treatment guidelines recommend dual therapy with two different antibiotics: ceftriaxone (a cephalosporin) and azithromycin. Each antibiotic has a different mechanism of action against Neisseria gonorrheae (the microorganism that causes gonorrhea)(1). This dual therapy approach increases the chances that the treatment will be effective. Since cephalosporin works against gonorrhea, adding azithromycin will help greatly slow the emergence of antibiotic resistant gonococcus(15).

Since 2010, the CDC has recommended a single 250mg dose of intramuscular ceftriaxone and 1g of oral azithromycin as a strategy for preventing ceftriaxone resistance and treating possible co-infection with Chlamydia trachomatis(15).The updated guidance now recommends adding 100mg of oral doxycycline, not azithromycin, twice daily for 7 days if Chlamydial co-infection has not been ruled out(15).

Emergence of antibiotic resistant gonorrhea

Are there other reasons for using dual therapy in combating the gonococcal infection?

Another reason for using azithromycin in combination with ceftriaxone is that many people infected with gonorrhea are also infected with Chlamydia, a sexually transmitted infection. Azithromycin is effective in treating Chlamydia(14). The two antibiotics are each given as a single dose simultaneously. After treatment, the patient must abstain from sexual activity for at least 7 days to prevent transmission. If a patient is treated for gonorrhea, they should be re-tested 3 months later. The person should also be tested for other STIs such as Chlamydia, Syphilis, and HIV. Any of your recent sexual partners should be treated due to the risk of complications from untreated gonorrhea and the risk of spread(14).

How to administer ceftriaxone

This medication is given by injection into a muscle or vein, usually once or twice daily. The dosage is based on the patient’s medical condition and response to treatment. Drink plenty of fluids while using this medication unless directed otherwise by your healthcare provider(15). Avoidance of Intra Vesicular fluids with calcium in them, such as Ringer’s and Hartmann’s solutions should be seriously observed. Check for discoloration and the presence of particles before use. Thaw at room temperature or in the refrigerator using the frozen pre-mixed solution. Shake well and squeeze the bag to check for leaks. Remember to continue using this antibiotic for the entire time prescribed, even if the symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection(15).

How long does treatment take to work?

Though the dual antibiotics are effective at treating gonorrhea, unfortunately, they cannot reverse any damage; such as scarring, that the infection may have caused. After treatment, it takes a few days for the symptoms to resolve completely. Early treatment is recommended, and if the symptoms persist after a few days, you should consult your healthcare provider(14).

How to prevent gonorrheoa

The best way to avoid gonorrhea is by abstaining from sex with multiple individuals or you indulge in safe sex practices, including the use of condoms.

Important precautions for doctors and health-care providers

  • Their patients keep the appropriate dosage and the time the antibiotics should be taken.
  • Their patients conduct their test for confirmation in an accredited laboratory.
  • They should adopt effective drug regulation.
  • Pregnant women should be screened for gonococcus before allowing vaginal child delivery.

We hope this article was helpful. For more information from The Edge Medical Writing, please visit their CPD Member Directory page. Alternatively, you can go to the CPD Industry Hubs for more articles, courses and events relevant to your Continuing Professional Development requirements.


(1).  Edwards JL, Apicella MA. The molecular mechanisms used by Neisseria gonorrhoea to initiate Infection differ between men & women. Clin Microbiol Rev.2004:17(4):965-981.doi:10.1128/CMR.17.4.965-981.2004

(2).  Quillin SJ, Seifert HS. Neisseria gonorrhoea host adaptation and pathogenesis. Nat Rev Microbiol.2018:16(4):226-240.doi:10.1038/nrmicro.2017.169

(3).  Mistry D, Stockley RA. IgA1 protease. Int J Biochem cell. Biol.2006:38(8):1244-8.doi:10.1016/I.biocel.2005.10.005

 (4). Griffiss JM, Lammel CJ, Wang J, Dekker NP, Brooks GF. Neisseria gonorrhoea co-ordinately uses pili & opa to activate HEC-1-B Cell Microvilli which causes engulfment of the gonococci: Infect Immune. 1999:67(7):3469-3480 doi:10.128/iai.67.7.3469-3480.1999

 (5). Plant JL, Jonsson AB. Type IV pillow of Neisseria gonorrhoea influence the activation of human CD4+ T Cell. Infect Immu.2006;74(1):442-448.doi.10:1128/iai.74.1.442-448-2006

 (6). World Health Organization. Multi-drug-resistant-gonorrhea. https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea 

 (7). Statists Research Department. Prevalence of gonorrhoea in Africa 2020 by gender. https://www.statista.com/statistics/1128557/prevalence-of-gonorrhoea-in-africa-by-gender/

 (8). World Health Organization. Sexually transmitted Infections (STIs). https://www.who.int/news-room/fact-sheets/detail/sexually-transmitted-infections-(stis)

 (9). Lenz JD, Dillard JP. Pathogenesis of Neisseria gonorrhoea and the host defense in ascending Infection of human fallopian tube. Front Immunol.2018:9:2710.doi.10.3389/fimmu.2018.02710

 (10). Krywko DM, Jennings LK. Pelvic Inflammatory Disease. https://www.ncbi.nlm.nih.gov/books/NBK499959/

 (11). Hile GB, Musick KL, Dugan AJ, Bailey AM, Howington GT. Occurrence of hyperbilirubinemia in neonates given a short-term course of ceftriaxone versus cefotaxime for sepsis. J. Pediat. Pharmocl There.2021.26(1)99-103.doi 10.5863/1551-6776-26.1.99

 (12). Morbidity and Mortality Weekly Report. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020. https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6950a6-H.pdf

 (13). Creighton S. Gonorrhoea BMJ Clin Evid.2014.1604. PMID: 24559849

 (14). Richa C. Gonorrhoea treatment: ceftriaxone and azithromycin. Reviewed by Tzvi Doron Do: last updated Aug 22, 2019. https://ro.co/health-guide/gonorrhea-treatment/ 

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