Cefixime and azithromycin

Cure for Gonorrhea

Gonorrhea is a sexually transmitted disease (STD) caused by the bacterium Neisseria gonorrhoeae (1). It is one of the most common sexually transmitted infections in the world (2). The bacteria can infect both men and women, with a higher incidence seen in young adults (age 15-24 years in women and age 20-24 years in men) (1). The risk factors for gonorrheal infection include the following (1):

  • Sexual contact with an infected individual.
  • Sexual contact with an individual from an endemic region.
  • Past history of gonorrheal infection.

Certain demographic groups are at a higher risk of contracting gonorrheal infection (1). These include:

  • HIV positive individuals.
  • Individuals who have multiple sex partners.
  • Sex workers.
  • Homosexual men.

Gonorrheal infections most commonly affect the genital region, followed by the anus and the throat (1). In the initial stages of gonorrheal infection, women can frequently remain without any symptoms (asymptomatic). However, as the disease progresses, women can present with abnormal vaginal discharge, lower abdominal or rectal pain, abnormal bleeding from the uterus, painful urination, pain during sexual intercourse, fever, and sore throat (1). In men, there is an early onset of gonorrheal symptoms. Men can exhibit symptoms such as urethral discharge and itching (the urethra is the tube connecting the bladder to the penis), painful urination, testicular or rectal pain, and sore throat (1).

The diagnosis of gonorrhea is primarily made via the patient’s clinical signs and symptoms, along with, a few investigative tests (3). The two main tests used for diagnosing gonorrhea are a urine test and swab test. In a urine test, the bacterial DNA is detected in the urine sample (3). In the swab test, a swab of the affected area (penis, vagina, rectum, or throat) is taken and tested for the presence of the gonorrhea bacteria (3). In some cases, a bacterial culture may also be required to confirm the diagnosis (3). As individuals with pre-existing STDs are at greater risk of contracting gonorrhea, investigative tests for other STDs may also be recommended for the diagnostic evaluation of gonorrheal infection (3).

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Gonorrhea is a curable infection. This is especially true for uncomplicated cases of gonorrheal infections, where the bacteria have not spread to organs outside of the genital system (1). Once an individual is diagnosed with gonorrhea, it is essential to receive prompt treatment, as the condition can worsen if left untreated (1). Gonorrheal infections are managed using antibiotic therapy. As gonorrhea bacterial strains can develop antibiotic resistance, the Center for Disease Control (CDC) recommends dual therapy for gonorrheal infection (2). Current antibiotic therapy for gonorrhea and future prospects for gonorrhea management are discussed in this article.

Current Treatments for Gonorrheal Infections

Since the mid-1930s, antimicrobials have been used for the treatment of gonorrhea (4). Unfortunately, in the past decades, the bacterium N. gonorrhea has developed resistance to most groups of antimicrobials including, penicillins, sulphonamides, tetracyclines, macrolides, fluoroquinolones, and early generation cephalosporins (4). Thus, antimicrobial resistance is a growing global health concern that jeopardizes the treatment and cure of gonorrheal infections (4).

To combat the rising issue of antibiotic resistance, the CDC recommends using dual therapy for the treatment of gonorrhea (5). Dual therapy refers to a combination therapy consisting of two antibiotic drugs. In general, the two antibiotics used for the treatment of gonorrhea have different mechanisms of action. The underlying principle of using dual therapy in the treatment of gonorrhea is to prevent antibiotic resistance and to improve the overall efficacy of the antibiotic regimen (5).

For all uncomplicated cases of gonorrhea infections in the urethra, cervix, and rectum, the CDC recommends the following antibiotic regimen:

  • An intra-muscular 250 mg single dose of ceftriaxone PLUS 1g single oral dose of azithromycin (5).
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In most cases, both antibiotic doses are administered simultaneously under direct observation of the physician. Ceftriaxone is the preferred antibiotic for gonorrhea treatment, as even a single injection of 250 mg ceftriaxone provides high bactericidal (ability to kill bacteria) levels in the blood (5). Clinical research indicates that ceftriaxone is an effective and safe drug for the treatment of uncomplicated gonorrhea. As per clinical trials, a single dose of 250 mg ceftriaxone injection can cure 99.2% of uncomplicated genital and rectal gonorrhea, and 98.9% of gonorrheal throat infections (5).

Future Treatment Options for Gonorrheal Infections

The current dual antibiotic therapy used for gonorrhea management is an effective treatment method (4). However, some concerns pertaining to antibiotic drugs have been noted in different regions of the world (4). Firstly, in the past decade, it has been seen that the gonorrhea bacterial strain has become less susceptible to ceftriaxone, which is the main drug of dual therapy (4). Secondly, in many countries, azithromycin resistance or concomitant resistance to ceftriaxone and azithromycin in prevalent (4). Thirdly, dual therapy isn’t a cost-effective treatment option in several less-sourced settings (4). Due to these drawbacks, there is a fear of treatment failure using dual therapy in the future (4).

To ensure effective gonorrhea treatment in the future, current clinical research suggests development and testing of affordable monotherapy (single drug) antibiotic drugs (4). A few of the antibiotics that have been suggested for future gonorrhea treatment include spectinomycin, injectable carbapenem ertapenem, injectable aminoglycoside gentamicin, and oral Fosfomycin (4). Disadvantages of these antimicrobials include decreased susceptibility to the gonorrhea bacteria and in vitro (in test tube) resistance (4).

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In recent years, several antimicrobial compounds with novel antimicrobial strategies have been developed (4). These compounds have been found to be effective in vitro gonorrhea bacterial strains (4). Some of the notable compounds include a protein synthesis inhibitor- pleuromutilin BC-3781, boron-containing inhibitor- AN3365, species-specific FabI inhibitors- MUT056399, bacterial topoisomerase inhibitors- VXc-486, and oral spiro pyrimidine trione ETX0914 (most advanced compound).

References

  1. Piszczek J, St Jean R, Khaliq Y. Gonorrhea: Treatment update for an increasingly resistant organism. Can Pharm J (Ott). 2015;148(2):82-9.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366410/

  1. Alirol E, Wi TE, Bala M, Bazzo ML, Chen X-S, Deal C, et al. (2017) Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines. PLoS Med 14(7): e1002366. https://doi.org/10.1371/journal.pmed.1002366.

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002366

  1. Torpy JM, Lynm C, Golub RM. Gonorrhea. 2013;309(2):196. doi:10.1001/2012. jama.10802.

https://jamanetwork.com/journals/jama/fullarticle/1556150

  1. Unemo M. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect Dis. 2015; 15:364. Published 2015 Aug 21. doi:10.1186/s12879-015-1029-2.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546108/

  1. https://www.cdc.gov/std/tg2015/gonorrhea.htm