What is Neisseria gonorrhoeae and which
antimicrobial therapies have been used?

What is Neisseria gonorrhoeae

The prevalence of gonorrhea (Neisseria gonorrheae) in the United States and abroad, especially under-developed and developing countries, has decreased in the last two decades.  As of recently, though, higher rates of infection have been reported due to the increase of antimicrobial -resistant gonococci (Knapp et al., 1994). Gonorrhea is a very common infectious bacterium, a Gram negative, fastidious,  diplococci, that can grow and rapidly multiply in the mucous membranes, especially the mouth, throat, and anus of males and females, and the cervix, fallopian tubes, and uterus of the female reproductive tract.  Uncomplicated gonorrhea  affects approximately 650,000 persons per year (WebMD, 1999).  This bacteria can be passed through sexual contact (vaginal, oral, or anal), even without ejaculation, or spread from the mother to child at birth.  However, the spread and transmission of gonorrhea, along with other sexually transmitted diseases, can be prevented using condoms and other safe sexual practices.

Intracellular Gram negative diplococci

In females, mild symptoms are usually present that resemble a bladder or vaginal infection; or sometimes they are not even present, making it difficult to treat in an efficient fashion.  Symptoms can appear within 2-5 days for males, but may not be present in females for over 30 days.  The following include painful urination and bloody or yellow vaginal or penile discharge, which if left untreated can develop into pelvic inflamatory disease (PID) for females, and swollen and painful testicles in males (epididymitis) (WebMD).  The presence of gonorrhea can be be diagnosed using a Gram stain test, which will turn red for Gram negative bacteria.

Antibiotics used to treat it

Gonnorrhea is easily treated through antibiotics; however, the estimated cost of treating gonorrhea in the United States is $56 million each year (CDC Update, 2000).  Small amounts of penicillin, and later on tetracycline, was the standard treatment for gonorrhea since the emergence of antibiotics in the 1940s.  During the Vietnam War, the use of penicillin and tetracycline used to treat uncomplicated gonorrhea became more and more resistant as new strains mutated (WebMD, 1999).

In 1963, the first quinolone antibiotic, nalidixic acid, was approved by the Food and Drug Administration for the treatment of urinary tract infections; however, it had several limitations, such as it had a narrow spectrum of activity, and bacteria quickly developed resistance to it (CTR, 1997).  Modifications to nalidixic acid were made based on structure activity relationships in the 1980s and these revisions, through adding a fluorine to the 6 carbon, were responsible for improving activity of this newly formed fluoroquinolone to include Gram positive organisms and more Gram negative speices, such as Pseudomonas aeruginosa and Neisseria gonorrhoeae (CTR, 1997).  These have become an increasingly important addition to antibiotic resources, unfortunately, the United States has now declared this development and spread of bacterial resistance a major public health threat.

The Centers for Disease Control and Prevention (CDC) currently recommend an antibiotic regime of 500mg single-dose ciprofloxacin and 400mg ofloxacin as broad-spectrum fluoroquinolones and cephalosporins, respectively, to treat uncomplicated gonorrhea (CDC, 2000).  Unfortunately, prior to  2000, N. gonorrhoeae's resistance to ciprofloxacin was documented in Canada, Australia, United Kingdom, Hong Kong, and the United States; fluoroquinolone resistance has also been reported in the United States, but isolate frequently in the Far East (CDC, 2000).  In order to monitor and track the susceptibility of N. gonorrhoeae strains, the CDC has instituted the Gonococcal Isolate Surveillance Project (GISP), which is a cooperative group of twenty-six sexually transmitted disease clinics across the United States that collect gonorrhea specimens and send them to regional offices for resistance diagnosis (CDC Update, 2000).  This program has detected resistance cases in Hawaii and Missouri; for example, in 1999, a group of twelve patients in Kansas City, MO became infected with gonorrhea that had increased resistance to azithromycin.