An Insight Into The Drug Resistance Profile And Mechanism Of Drug Resistance In Neisseria Gonorrhoeae

Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neisseria Gonorrhea is considered to be most important, because of emerging antibiotic resistance strains that compromise the effectiveness of treatment of the disease.

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Title Page                                                                 i

Certification                                                     ii

Acknowledgement                                            iii

Abstract                                                           IV


1.0   Introduction


2.0   Characteristic of Neisseria Gonorrhea


3.0   Epidemiology

3.1   Mechanism of Drug Resistance


4.0   Conclusion

4.1   Recommendation



        Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neisseria Gonorrhea is considered to be most important, because of emerging antibiotic resistance strains that compromise the effectiveness of treatment of the disease. Gonococci infections are usually treated with single – dose therapy with an agent found to cure above 95 percent of each case, but unfortunately Neisseria gonorrhea has developed resistance to most of the antibiotic used against it, which can be categorized into pre-quinolone, quinolone and post – quinolone era.

Among the anti-biotic available so far, the third generation “cephalosporin has also be safely recommended as first line therapy for gonorrhea globally;


Despite the recent advances in diagnosis, surveillance and treatment, sexual transmitted disease (STDs) remain one of the leading diseases throughout the world. Increased promiscuity and onset of sexual activity at an early age are two important contributing factors to the spread of sexual transmitted disease.  Neisseria gonorrheae (also known as the gonococcus) colonizes primarily in the human genital urinary tract, giving rise to the sexually transmitted infection gonorrhea.  It cause both symptomatic and asymptomatic genital and extra genital tract infections.  Disease caused by this organism is a significant public health problem despite continual advances in treatment (Tanaka and Reyn et al, 2004).

World wide, there is an estimated 62million new cases a year, with an average of 22miilion cases at any given time (WHO, 1992).  N. gonorrhea inhabits mainly mucosal surface of the urethra in males and the cervix in females.  As the signs and symptoms of infection are often absent or obscure complication such as pelvic inflammatory disease (PID), infertility, entopic pregnant woman may lead to crucial perforation and blindness in the newborn. Gonococci infection have also been documented to facilitate acquisition and transmission of HIV and HPV infection (Hunter et al. 1990).  Asymptomatic infections by N. gonorrhoeae largely contribute to the persistence and transmission of disease in a community. (Hunter et, al.1990).

Therefore, to eliminate N. gonorrhea infection and in turn to control HIV and HPV infection it is important not only to screen high – risk population but also to treat them immediately with most effective drugs.  Control of gonococci infection has relied on effective single – dose antibiotic therapy given at the initial clinical visit, prior to any knowledge of the organism’s susceptibility pattern.  In the recent past, there has been an alarming increase in the number of isolate of N. gonorrhea resistance to commonly used drugs.  (Chaudhry et al, 2002).  Surveillance is therefore, necessary to understand on going resistance trends and to ensure the success of any therapy.

The irrational and injudicious use of antibacterial agents especially in the developing countries is encouraging this trend and the situation is expected to worsen unless appropriate steps are initiated. This resistance of the gonococcus to antibiotics has been the cause of much concern in recent years and has been the subject of extensive investigation.  The present review summarizes and trends to drug resistance in N. gonorrhoeae, mechanism of drug resistance and discusses the treatment regime.  In addition, the need to look for new and alternative antibacterial agent is also emphasized.


Neisseria gonorrhoeae is a gram – negative diplococci and is know to infect human only.  It is closely related to and probably derived from Neisseria meningitides, but has because highly adapted to survival in the genital tract.  It is transmitted by human-to- human contact and survives poorly outside the human   body.  Neisseria gonorrhoea is a very successful pathogen as it can evade or adapt to host defenses persist without severally damaging the host, and be transmitted to and infect other hosts, thereby maintaining itself.

Particularly in women, gonococci may produce only mildly symptomatic or asymptomatic disease.  This adaptation allows the organism to persist and disseminate over long periods (Brunham and Plummer 1993).

The most important characteristic of Neisseria gonorrhoeae, in the content of antimicrobial resistance pattern are its phenotypic and genotypic variability which enable it to evade the host response.  Phenotypic variability occurs through differential expression of existing parts of the genome.  Genotypic variation is achieved by incorporation of new genetic material, which can be acquired either by conjugation are transformation.

It is because of this feature that N. gonorrhoeae has acquired penicillin’s producing plasmids. Another important feature of N. gonorrhoeae is its antigenic variability.  This helps the bacterium to survive in its limited host i.e. human.  Antigenic variability of N. gonorrhoeae is partially due to its ability to acquire genetic material from related organism.  (Sarafian and Knapp 1989).


Single dose therapy for Neisseria gonorrhoeae infection bas become the norm in most of the countries through out the world.  The basic reason behind this is that single close therapy is most effective and assures adequate treatment.  World Health Organization (WHO) recommendations for selecting any treatment for gonorrhoea.  States that the antimicrobial prescribed should be such that the cure rate is about 95 percent (Quinn, 1996). More over, during the past few year N. gonorrhoeae has started developing resistance against most of the antimicrobials that are described for its therapy.  Therefore, surveillance of the antimicrobial resistance becomes very important in monitoring the emergence and spread of resistance and in planning appropriate treatment regimens.     

Gonorrhea is a disease mainly found in resource poor settings where laboratory facilities are limited or unavailable. Due to this reason, culture and antimicrobial susceptibility testing of N. gonorrhoeae is hardly done in developing countries. Developed countries had collected the data in a proper manner due to availability of adequate resources which help in monitoring resistance data obtained from developing countries are mainly from point presence studies, which can not be use to follow the trends.  Such epidemiological study need to be done at a regular basis because the prevailing strains of the bacteria and their antimicrobial susceptibility profiles keep on changing. (Tapsall 2001).


Neisseria gonorrhea is a bacteria which cause sexual transmitted disease in human being, this bacteria   was discovered in the early 1930s. Sulphanilamide was introduced as an anti-microbial against Neisseria gonorrhea as early as in 1837. (Dees and colston, 1937).

However, the bacteria became resistant quickly against the antimicrobial “sulphanilamide” within a span of two years. At the same time, when sulphanilamide were given as treatment for gonorrhea. Alexander Fleming also documented the ability of penicillin to inhibit the growth of Neisseria gonorrhea (Fleming 2001). There after penicillin became the choice of antimicrobial for treatment of gonorrhea.

The susceptibility profit of N. gonorrhea against penicillin (and other antimicrobials) was monitor through out the world, in Vitro resistance to penicillin was expressed in a uniform manner in terms of minimum inhibitory concentration (MIC). During the initial years of treatment of gonorrhea with penicillin, all the isolate had an MIC of < 0.0125mg/l and were considered to be sensitive to the treatment. Gradually the bacteria began to develop high resistance to penicillin as the value for the MIC increase rapidly.

Coincident with the development of resistance to penicillin, gonococci also developed resistance to several other antibiotic including, tetracycline, chloramphenicol, erythromycin and streptomycin. (Ison et al, 1988). Tetracycline was also considered as another important antimicrobial since it’s in expensive. It was not possible to evaluate the contribution of tetracycline in management of gonorrhea. This is thesame for azithromycin, although it is more expensive. (Whittington and knapp 1999).

During the quinolone era in the treatment of gonorrhea in response to the increasing frequency of isolation of penicillin, tetracycline, streptomycin resistance strain of N. gonorrhea thought the whole world. The centre for diseases control and prevention (CDC) recommend the use broad spectrum cephalosporin or fluoroquinolones for the treatment of gonorrhoeae. But as time goes on the bacteria become resistant to the drug and it is not more suitable for the  treatment of gonoeehoea.

Consequent to the increase in the resistance profile of Neisseria gonorrhea towards quinolones, Third generation cephalosporin, both injection (ceftriaxone) and oral (cefixime and cefdinir), this treatment were the only available treatment recommended by CDC and national organization  ( Ray et all, 2005)


Neisseria gonorrhea, originally high susceptible to antibiotic can adapt to adverse condition. (Johnson and Morse 1988). A hostile environment in which antibiotic are present may select; for the multiple change which result in resistance and treatment failure.

Mechanism of antibiotic resistance in gonococcus may be conveniently group as those that involve alteration of the target site. Access of antibiotic to the target site may be limited by reduce permeability of the cell envelope caused by change in porin proteins; active export of antibiotic from the cell by means of efflux pumps; and destruction of the antibiotic before it can interact with the target site. (Sparling  2005).

Alteration or deletion of the target site of the antibiotic result in a reduction of its affinity for the antibiotic. Generally, these changes may be mediated by either chromosomal or extra-chromosomal elements (plasmids). Multiple resistance determination may co-exist in a single organism so that level of resistance can increase incrementally and a single strain can be resistant to a number of different antibiotics.

In Neisseria gonorrhea, the process of genetic transformation is known to be responsible for acquiring drug resistance. But such a change is visible only if many such acquisitions of the determinant take place. (Johnson and Morse, 1998). Plasma mediation resistance, at present limited to penicillin and tetracycline, is transmitted by means of conjugation. This process requires the presence of a conjugative plasmid to mobilize the plasmid carrying the resistance determinants.

Since not all strain posses conjugative plasmids, the rate of spread of resistance may be limited to some extent. However, conjugative plasmids are also transferable during conjugation, so that some recipient strain then becomes donor themselves. Among non-quinolone drugs, several studies have been carried out to understand the mechanism of penicillin resistance in N. gonorrhea, this is summarized below.


Penicillin was widely used from the treatment of gonorrhea for many years (and is still in use in some regions). Originally, Neisseria gonorrhea was extremely sensitive to almost all the drugs known so far, and treatment with 150,000 units of penicillin was effective in most instances. Later on decreased in Vitro susceptibility towards penicillin appeared and it was thought to be associated with treatment failure (Reyn et al, 1958). Increasing the recommendation dose of penicillin temporarily alleviated the clinical problem resulting from infection with these strain, but almost inexorably levels of resistance increased and large number of treatment failure occurred again even with high-dose regimens(Sparling 2005).

A vivid example is the targets of B-lactum agents are the Penicillin Binding Protein (PBPs), enzyme located in the cell envelops that participate in cell wall metabolism. Alteration in PBPs-2 and PBP-1 decrease their affinity for the penicillin’s and thus, the susceptibility of the organism. PBP-2 is encoded by the PenA locus (Sparling et al, 1999). Change in other locci such as mtr and PenB produce additive effect. The mtr locus mediates resistance to a wide rage of antibiotics, detergents and dye through an active efflux system.

Neisseria gonorrhea is also resistance to some other drugs apart from penicillin; some of which include tetracycline, quinolone and cephalosporin, in which the access of quinolones to their target is reduced by changes in cell permeability and possibly by efflux mechanisms. The target of quinolone are topoisomerase in the organism (Neisseria gonorrhea), these include DNA gyrase. (Weidman and Heisig, 2008).


Despite a high prevalence of uncomplicated gonorrhea and an increasing incidence of resistant isolate of N. gonorrhea throughout the world, a standardized monitoring of the antimicrobial susceptibility profile has been resisted to gonococcus isolated surveillance project (GISP) in unites state and other association in other countries.  There is a need for better control of gonococci disease including enhanced global surveillance of resistance and improved treatment.

It has been observed that the single dose approach has also contributed to the ability of N. gonorrhea to develop resistance to common used, inexpensive and effective drugs. The transmissibility of resistance genes has made the development of new antibiotics a challenging area of research but the laboratory base surveillance and susceptibility would be useful not only in deciding the correct treatment but also help to detect the emergence of new antibiotic resistant trait and to monitor the treatment. (Van Embden  et al, 1999).

Since the infection caused by Neisseria gonorrhea is prevalent to all antibiotic produces against it, therefore it has become imperative to initiate sustained national and international effort to reduce the infections and misuse of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimism treatment regimens, but also to gain insight into how gonococcus develops drug resistance.


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