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SYMPOSIUM ON INFECTIOUS AGENTS IN A MULTIDRUG RESISTANT GLOBE Table of Contents   
Year : 2010  |  Volume : 2  |  Issue : 3  |  Page : 284-290
Cephalosporin resistance in Neisseria gonorrhoeae


1 Regional STD Teaching Training and Research Centre, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi, India
2 Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication17-Aug-2010
 

   Abstract 

Gonorrhea, a disease of public health importance, not only leads to high incidence of acute infections and complications but also plays a major role in facilitating human immunodeficiency virus (HIV) acquisition and transmission. One of the major public health needs for gonorrhea control is appropriate, effective treatment. However, treatment options for gonorrhea are diminishing as Neisseria gonorrhoeae have developed resistance to several antimicrobial drugs such as sulfonamides, penicillin, tetracyclines and quinolones. Antimicrobial resistance (AMR) surveillance of N. gonorrhoeae helps establish and maintain the efficacy of standard treatment regimens. AMR surveillance should be continuous to reveal the emergence of new resistant strains, monitor the changing patterns of resistance, and be able to update treatment recommendations so as to assist in disease control. Current treatment guidelines recommend the use of single dose injectable or oral cephalosporins. The emergence and spread of cephalosporin resistant and multi drug resistant N. gonorrhoeae strains, represents a worrying trend that requires monitoring and investigation. Routine clinical laboratories need to be vigilant for the detection of such strains such that strategies for control and prevention could be reviewed and revised from time to time. It will be important to elucidate the genetic mechanisms responsible for decreased susceptibility and future resistance. There is also an urgent need for research of safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate).

Keywords: Antimicrobial resistance, Cephalosporin resistance, Gonorrhea management, Neisseria gonorrhoeae

How to cite this article:
Bala M, Sood S. Cephalosporin resistance in Neisseria gonorrhoeae. J Global Infect Dis 2010;2:284-90

How to cite this URL:
Bala M, Sood S. Cephalosporin resistance in Neisseria gonorrhoeae. J Global Infect Dis [serial online] 2010 [cited 2017 Jul 24];2:284-90. Available from: http://www.jgid.org/text.asp?2010/2/3/284/68537



   Introduction Top


Sexually transmitted infections (STIs), both ulcerative and non ulcerative, constitute one of the major public health problems. There has been increasing world wide incidence of these infections because of several socioeconomic factors like women's emancipation, permissiveness, homosexuality, population migration and technical factors like increased availability of better diagnostic facilities. The World Health Organization (WHO) estimates that approximately 340 million new cases of the four main curable STIs (gonorrhea, chlamydial infection, syphilis and trichomoniasis) occur every year, majority of them in developing countries. [1]

Gonorrhea caused by  Neisseria More Details gonorrhoeae (N. gonorrhoeae), is one of the most common STIs and is a global health problem. [2] Gonorrhea is an easily curable STI. However, undetected, untreated infections can lead to complications like pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, adverse pregnancy outcomes in females, and testicular and prostate infections and infertility in males. Also, asymptomatic patients, unaware of their infection, may serve as a reservoir of infection to their partners.

Gonorrhea has gained tremendous importance in the last few decades because of its role as a co-factor in increasing HIV infections. This is thought to result from an increase in the viral load in the semen or cervico-vaginal fluids from those co-infected with gonorrhea and HIV, and to an increase in the number of target cells for HIV in the inflammatory exudates present in symptomatic bacterial sexually transmitted diseases (STDs). [3],[4],[5],[6] This new association provides an important reason for proper and timely treatment of gonorrhea.

The incidence/prevalence rates of gonorrhea are difficult to ascertain because resources are mostly lacking where the disease is concentrated. [2] Some available estimates of incidence suggest that approximately 62 million new cases of gonorrhea occur globally each year. [2] Despite a high prevalence of gonorrhea, no regular monitoring of antimicrobial susceptibility of N. gonorrhoeae is carried out in many countries, the reasons being invasive specimen collection procedures, fastidious nature of the organism, need for specialized culture media and trained personnel. [7] Moreover, as a consequence of emphasis on syndromic management of STDs and the introduction of nonculture-based diagnostic tests, there is decreased availability of N. gonorrhoeae isolates for susceptibility testing.

A major contributing factor to the continued spread of gonococcal infections is the remarkable ability of N. gonorrhoeae to acquire resistance to antibiotics. Over the last two decades, N. gonorrhoeae strains have developed high level of resistance against several antimicrobial agents like penicillin, tetracycline and quinolones in different countries, [8],[9],[10],[11],[12],[13] The emergence of strains resistant to extended-spectrum cephalosporins, the antibiotics used as the first line treatment for uncomplicated gonococcal infections, is now a serious concern worldwide as it may pose a problem in the management of gonorrhea. This review is aimed at analyzing the problem of antimicrobial resistance in N. gonorrhoeae, particularly to currently recommended cephalosporins.


   Materials and Methods Top


A Medline search was conducted in July (2009), using PubMed, for articles published under the major headings of "antimicrobial resistance in N. gonorrhoeae0", "Surveillance of antimicrobial/drug resistance in N. gonorrhoeae" and "gonorrhea treatment/therapy,". Additional searches were performed for related reports posted on the internet by internationally recognized public health agencies. The articles identified through the methods described above were compiled.

Magnitude of antimicrobial resistance in N. gonorrhoeae

Many antimicrobials were active against N. gonorrhoeae. However, with the emergence of antimicrobial resistance only few antibiotics are effective against N. gonorrhoeae. Single dose therapy is the universal practice of choice in the treatment of uncomplicated gonorrhea. WHO and Center for Disease Control and Prevention (CDC) recommend a change in the treatment regimen when the prevalence of antimicrobial resistance exceeds five per cent for a specific antibiotic. [14],[15]

Sulfonamides were used for gonococcal treatment after their introduction in 1936, but their efficacy was short-lived because of the rapid emergence of resistance by 1945 [16],[17] Penicillin proved highly effective in treating gonorrhea when introduced in the early 1940s. With the emergence and spread of penicillinase producing N. gonorrhoeae (PPNG), in the 1970s, a switch to alternative therapy became a necessity in many locations in the 1980s. [18],[19],[20],[21] Chromosomally mediated resistance N. gonorrhoeae (CMRNG) and PPNG still pose a major problem.

Tetracyclines, being cheap, were widely used in some developing countries. Requirement of a multi-dose regime and compliance with multi-day regimens was usually unsatisfactory. [22],[23] Tetracycline resistant N. gonorrhoeae (TRNG) were first reported in the United States in 1985. [24] Tetracycline resistance, both chromosomal and plasmid mediated, increased and has attained a high prevalence in many countries such as United States, Trinidad and Tobago, India, Thailand and Indonesia. [25-29] Tetracyclines remain important and effective agents in the treatment of other sexually transmitted infections, notably Chlamydia trachomatis.

Fluoroquinolones became popular therapy during the 1980s and were widely used as effective oral therapy against penicillin-resistant N gonorrhoeae. The most widely used quinolone against uncomplicated gonorrhea was ciprofloxacin and the efficacy of this agent was 100% with single dose of 500 mg. On the basis of data regarding high efficacy, safety, and convenience as single-dose therapies, oral fluoroquinolones were recommended for gonorrhea treatment by CDC in 1993. [30] Other quinolones, such as ofloxacin and fieroxacin, also showed good clinical efficacy. [31],[32] Quinolones were effective in eradicating rectal and pharyngeal infection. [33] Resistance to fluoroquinolones was first detected in mid-1980s in Asia, and then it spread to other areas in Europe, Western Pacific, South and South-East Asia, and the Americas. [9],[10],[11],[34],[35],[36],[37]


   Current Treatment Guidelines for Gonorrhea Top


Presently, the recommended first-line treatment for gonorrhea in most countries includes antibiotics such as cefixime, ceftriaxone and in some cases spectinomycin, azithromycin.

Cephalosporins

Cephalosporins, in the form of "third-generation" preparations, have proved highly effective for more than a decade in the treatment of gonorrhea, including PPNG and chromosomally-mediated penicillin resistance and are currently recommended for treatment of gonorrhea. Ceftriaxone is recommended as the drug of choice for gonorrhea as it is safe and effective for the treatment of uncomplicated gonorrhea at all anatomical sites. It has been reported to cure 98.8% of uncomplicated urogenital and anorectal infections in published clinical trials. [38] Ceftriaxone is favored in comparison with other cephalosporins for its long serum half life, and side-effects are infrequent and generally mild. The dose recommended by CDC and WHO is 125 mg intramuscularly (IM). [14],[15] However, many countries recommend 250 mg and in China and Japan, the dose recommended is one gram ceftriaxone. [39],[40],[41] Cefotaxime 500 g IM as a single dose is an alternative preparation of proven efficacy. [30] These cephalosporins regimens have shown good efficacy against rectal and pharyngeal infection. [42] The drawbacks of these highly effective regimens include expense, the necessity to administer them by injection and discomfort at the injection site.

Cefixime is an oral preparation with similar spectrum to that of ceftriaxone. A single oral dose of cefixime 400 mg has been shown to be of equivalent efficacy to ceftriaxone. [43] There is more extensive use of injectable ceftriaxone in comparison to oral cefixime. [41]

Other injectable and oral cephalosporins are available but do not offer any substantial advantages over ceftriaxone and cefixime. Where these specific antimicrobials are not available, a variety of other cephalosporins have proven efficacy in the treatment of urogenital and anorectal gonorrhea. Possible injectable alternatives include cefotaxime, ceftizoxime, and cefodizime. Oral alternatives to cefixime are ceftibuten, cefdinir, cefpodoxime proxetil, cefoperozone, cefditoren and cefuroxime axetil. The pharmokinetics of cefuroxime axetil (one gram oral) are suboptimal as a single dose treatment. [44] Although clinical trial data on cefpodoxime (400mg oral) was very limited in earlier years, [45] cefixime was not available in the USA from 2002 to 2008 and cefpodoxime 400 mg was more widely used during that time. [46] Oral ceftibuten is being used In Hong Kong since 1997 and cefditoren and cefdinir in Japan. [47],[48]

Spectinomycin

Spectinomycin played a central role in the control of gonococcal infection following the emergence of PPNG and higher-level chromosomal resistance. Adoption of spectinomycin as the routinely used drug of choice was soon followed by reports of spectinomycin resistance. [49] Spectinomycin resistance is unstable and reverts once its use is discontinued. It is highly effective as a single intramuscular dose of two grams for urethral and cervical Infection. It has poor efficacy against pharyngeal infection. [33] It remains a useful reserve option for gonococcal therapy and is generally reserved for situations where cheaper alternatives are contraindicated, for example in a pregnant woman who is allergic to cephalosporins. [50] In Japan, where oral cephalosporin resistance is common, it has been shown to be effective for treatment of gonococcal infections. [51] It is, however, expensive and not available in some countries like India. [52] There have been recent reports of occasional spectinomycin resistant isolates from some countries like US, India, WHO Western Pacific region and China. [53],[54],[55],[56]

Azithromycin

Azithromycin is a newer antibiotic belonging to a class of compounds known as azalides, which resemble macrolides. It achieves a high, prolonged, intracellular concentration and has potential as an alternative, effective, oral therapy for gonorrhea. It is effective in single dose therapy against genital infection with C. trachomatis.[57],[58] It is active in vitro against N. gonorrhoeae and recent studies show promising efficacy in vivo using a single oral dose. Single-dose treatment with two grams gave a 98-99% efficacy in uncomplicated gonococcal infection, whereas smaller studies using a single dose of one gram showed marginally lower efficacy. [59],[60] CDC does not recommend one gram dose, as it can cause rapid emergence of antimicrobial resistance. [61],[62],[63],[64],[65] The two gram dose was associated with a high frequency (35%) of gastrointestinal side effects, which were generally mild. [59]

Azithromycin proved highly effective (100%) against pharyngeal infection and penicillin-resistant strains. [59] All co-infections with C. trachomatis were cured. Resistance to two-gram azithromycin is increasing with high-level resistance recently reported in the US, UK and Scotland. [66],[67],[68]

Emergence of cephalosporin resistance in N. gonorrhoeae

Clinical failure with oral cephalosporins was first documented in Japan in two patients with gonococcal urethritis. [69] Subsequently, resistance to oral third generation cephalosporins was reported from many areas in Japan. [70],[71] Therefore, in Japan, cefixime was discontinued as a drug of choice for gonorrhea in 2006. [72] Ceftriaxone and spectinomycin, both injectable, are recommended as first-line therapy for gonorrhea in Japan.

Decrease in susceptibility to cephalosporins was also noted in many countries like India, US, other countries in the WHO Western Pacific Region (Australia, Brunei, China, and Papua New Guinea), Vietnam and Greece. [12],[73],[74],[75],[76],[77] Resistance to oral cephalosporins have been reported from Hong Kong and Taiwan. [47],[78] In Hong Kong, clinical treatment failure rate of empirical ceftibuten was around 3.7%, which is still within the five per cent figure generally considered an acceptable resistance level. [47] All the isolates in this study remained susceptible to ceftriaxone by laboratory testing criteria. So far, no treatment failures with injectable ceftriaxone have been reported. [12],[47],[79] Gonococci may be clinically resistant to orally administered extended spectrum cephaosporins (ECS) while remaining sensitive to the injectable ceftriaxone. It was proposed that the two groups of ESC should be considered separate treatment entities for definitional purposes. [79]

Some of these reports have documented that these ceftrixoneless susceptible strains were multi drug resistant. [12],[73],[77],[80],[81],[82] All these strains were susceptible to spectinomycin.

Problem of multi drug resistant N. gonorrhoeae

Many studies have reported multi drug resistant N. gonorrhoeae (MDR-NG).[12],[73],[77],[80],[81],[82],[83] However, recently, there have been concerns for defining MDR-NG as the term MDR is being used without precise definition. [73],[79] In earlier definitions of MDR, resistance to out-dated or little-used drugs like tetracycline was included and multiresistant isolates were defined as quinolone resistant N. gonorrhoeae (QRNG) and PPNG; QRNG and TRNG; QRNG, PPNG and TRNG; QRNG and azithro resistant. [12],[83] MDR-NG by the revised criteria, are defined as those resistant to one of the antibiotic classes listed in category I (injectable cephalosporins/oral cephalosporins/spectinomycin), plus two or more in category II (Penicillins/ Fluoroquinolones/Azithromycin/Aminoglycosides/Carbapenems). [80] Extensively-drug resistant N. gonorrhoeae (XDR-NG) include those resistant to two or more of the antibiotic classes in category I and three or more in category II. [80] XDR-NG are yet to be reported. [80] If the current guidelines for treatment of gonorrhea and concomitant control of gonococcal disease i.e. the usage of right drugs at the right time in the right dose are not adhered to, will definitely lead to the spread of existing MDR-NG and, presumably, the emergence of XDR-NG.

Mechanism of resistance to cephalosporins and other antimicrobials

Many studies of molecular mechanisms that underlie resistance to various classes of antimicrobial agents have been reported. [84] Mutations in the gyrA and parC genes are responsible for resistance to fluoroquinolones in N. gonorrhoeae.[85],[86] In addition, alterations in drug permeation and drug efflux can contribute to the level of resistance to fluoroquinolones. [87] The latter mechanisms are associated with the development of cross-resistance to structurally unrelated antibiotics. [87] Therefore, the resistance to azithromycin has been linked to the multiple transferable resistance (mtr) efflux system. [88],[89]

Resistance to spectinomycin can be the result of a single step mutation, possibly due to mutations in the 16S rRNA gene. [90] The mechanisms for chromosomally mediated resistance to penicillin G and tetracycline in N. gonorrhoeae involve the penA, penB, and mtr mutations. Mutations in penA causes insertion of a single amino acid into penicillin-binding protein 2 (PBP 2), and this reduces the level of binding of penicillin to PBP 2. [91] The penB mutation, which is a mutation that is linked to the porin gene, reduces porin permeability to hydrophilic antibiotics and plays an important role in the development of resistance to penicillin G, cephalosporins, and tetracycline. [92] mtr increases the level of expression of the MtrCDE efflux pump and confers resistance to multiple hydrophobic agents (i.e.,crystal violet, Triton X-100, and erythromycin) and some hydrophilic antibiotics such as the penicillins. [93]

Recently, ponA1 and another resistance locus, termed penC, were shown to be involved in penicillin resistance. ponA1 encodes altered PBP 1 and penC mutations now named as pilQ2 mutations, is required to transform an intermediate-level penicillin-resistant strain with ponA1 to high level resistance. [94] The reduced susceptibility of N. gonorrhoeae strains to broad spectrum cephalosporins such as cefixime and ceftriaxone has been proposed to be associated with polymorphisms in several of these genes and especially with certain penA mosaic alleles. [81],[95] These mosaic sequences are thought to have evolved from recombination events involving penA gene sequences from several Neisseria species, including N. perflava, N. sicca, and N. cinerea.[95],[96] Therefore, reduced susceptibility to newer cephalosporins is attributed to the acquisition of genetic material from resistant commensal Neisseria spp. by originally susceptible gonococci. However, thorough knowledge regarding these molecular mechanisms is still lacking. All these genes need to be systematically sequenced in more numerous and evidently diverse clinical N. gonorrhoeae strains with reduced susceptibility to broad-spectrum cephalosporins. [97]

Future options in treatment of N. gonorrhoeae infections

The worldwide increase in resistance of N. gonorrhoeae to all classes of antimicrobials is of serious concern and necessitates the search of alternative remedies for the treatment of gonorrhea. There is an urgent need for safe, alternative anti-gonococcal compounds that can be administered orally and have effective potency, allowing high therapeutic efficacy (greater than 95.0% cure rate) with preferably a single-dose regimen. However, very little research regarding this is being carried out. Recently, activities of some medicinal plants have been evaluated against N. gonorrhoeae which seems to have a promising future. [98],[99],[100] Among the compounds evaluated, eugenol, a compound from Ocimum sanctum was also found to be active against multi resistant isolates of N. gonorrhoeae.[101]

Two studies evaluated the activities of topical microbicides. [102],[103] In one of these studies, a polyherbal cream (Basant) inhibited the growth of WHO strains and clinical isolates of N. gonorrhoeae, including those resistant to penicillin, tetracycline and ciprofloxacin. [103]

Research is needed to evaluate the activity of other antimicrobials or combinations of antimicrobials that may be efficacious for the treatment of urogenital and anorectal gonorrhea.


   Conclusion Top


Increase in N. gonorrhoeae isolates which are resistant to multiple antimicrobial agents including oral cephalosporins and the emergence of intermediate-level resistance to the injectable ephalosporins is now a serious problem. If this form of resistance evolves further, it will pose a major threat to public health. Therefore, efficient methods for its detection and control will need to be in place. This has led to renewed calls for better control of gonococcal disease, including enhanced global surveillance of resistance. [104],[105] Although considerable technical and logistical difficulties are associated with this approach, the WHO has already expanded its regional surveillance programs and consolidated the reporting and analysis of data generated. [80] This also underscores the importance of the cautious use of antibiotics, and there is a need for the development of a wider range of antimicrobial options.

 
   References Top

1.WHO. Global prevalence and incidence of selected curable sexually transmitted infections: Overviews and estimates. WHO/HIV_AIDS/2001-02. Geneva: WHO; 2001.  Back to cited text no. 1      
2.Gerbase AC, Rowley JT, Heymann DH, Berkley SF, Piot P. Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect 1998;74:12-6.  Back to cited text no. 2      
3.Cohen MS, Hoffman IF, Royce RA, Kazembe P, Dyer JR, Daly CC, et al. Reduction of concentration of HIV - 1 in semen after treatment of urethritis: implications for prevention of transmission of HIV- 1. Lancet 1997;349:1848-73.  Back to cited text no. 3      
4.Ghys PD, Fransen K, Diallo MO, Ettiegne-Traore V, Coulibaly IM, Yeboue KM, et al. The association between cervicovaginal HIV shedding, sexually transmitted diseases and immunosupression in female sex workers in Abidjan, Cote d′Ivoire. AIDS 1997;11:85-93.  Back to cited text no. 4      
5.Mostad SB, Overbaugh J, DeVange DM, Welch MJ, Chohan B, Mandaliya K, et al. Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina. Lancet 1997;350:922-7.  Back to cited text no. 5      
6.Levine WC, Pope V, Bhoomkar A, Tambe P, Lewis JS, Zaidi AA, et al. Increase in endocervical CD4 lymphocytes among women with non-ulcerative sexually transmitted diseases. J Infect Dis 1998;177:167-74.  Back to cited text no. 6      
7.Tapsall JW. Antimicrobial resistance in N. gonorrhoeae. WHO/CDS/DRS/ 2001.3. Geneva: World Health Organization, 2001. Available from: http://www.who.int/csr/resources/publications/drugresist/WHO_CDS_CSR_DRS_2001_3/en/ . [cited on 2009 Jul 23].  Back to cited text no. 7      
8.Stathi M, Flemetakis A, Miriagou V, Avgerinou H, Kyriakis KP, Maniatis AN, et al. Antimicrobial susceptibility of Neisseria gonorrhoeae in Greece: Data for the years 1994 - 2004. J Antimicrob Chemother 2006;57:775-9.  Back to cited text no. 8      
9.Wang B, Xu JS, Wang CX, Mi ZH, Pu YP, Hui M, et al. Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Jiangsu Province, China, with a focus on fluoroquinolone resistance. J Med Microbiol 2006;55:1251-5.  Back to cited text no. 9      
10.Enders M, Turnwald MA, Regnath T. Antimicrobial resistance of Neisseria gonorrhoeae isolates from the Stuttgart and Heidleberg areas of Southern Germany. Eur J Clin Microbiol Infect Dis 2006;25:318-22.   Back to cited text no. 10      
11.Bala M, Ray K, Kumari S. Alarming increase in ciprofloxacin and penicillin resistant Neisseria gonorrhoeae isolates in New Delhi, India. Sex Transm Dis 2003;30:523-5.  Back to cited text no. 11      
12.Bala M, Ray K, Gupta SM, Muralidhar S, Jain RK. Changing trends of antimicrobial susceptibility patterns of Neisseria gonorrhoeae in India and the emergence of ceftriaxone less susceptible N.gonorrhoeae strains. J Antimicrob Chemother 2007;60:582-6.  Back to cited text no. 12      
13.Tapsall JW. Antibiotic resistance in Neisseria gonorrhoeae. Clin Infect Dis 2005;41:S263-8.  Back to cited text no. 13      
14.World Health Organization. Guidelines for the management of sexually transmitted infections. Geneva, Switzerland: 2003.   Back to cited text no. 14      
15.Newman LM, Moran JS, Workowski KA. Update on the management of gonorrhea in adults in the United States. Clin Infect Dis 2007;44:S84-101.  Back to cited text no. 15      
16.Nelson NA. The treatment of syphilis and gonorrhea as of today. Am J Nurs 1944;44:737-41.  Back to cited text no. 16      
17.Kampmeier RH. Introduction of sulfonamide therapy for gonorrhea. Sex Transm Dis 1983;10:81-4.   Back to cited text no. 17      
18.Phillips I. β-lactamase-producing, penicillin resistant gonococcus. Lancet 1976;2:656-7.  Back to cited text no. 18      
19.Jaffe HW, Biddle JW, Johnson SR, Weisner PJ. Infections due to penicillinase-producing Neisseria gonorrhoeae in the United States: 1976-1980. J Infect Dis 1981;144:191-7.   Back to cited text no. 19      
20.Faruki H, Kohmescher RN, McKinney WP, Sparling PF. A community-based outbreak of infection with penicillin resistant Neisseria gonorrhoeae not producing penicillinase (chromosomally mediated resistance). N Engl J Med 1985;313:607-11.  Back to cited text no. 20      
21.Rice RJ, Thompson SE. Treatment of uncomplicated infections due to Neisseria gonorrhoeae. JAMA 1986;255:1739-46.  Back to cited text no. 21      
22.Judson FN, Rothenberg R. Tetracycline in the treatment of uncomplicated male gonorrhoea. Y Am Ven Dis Assn 1976;3:56-8.   Back to cited text no. 22      
23.Katz BP, Zwickl BW, Caine VA, Jones RB. Compliance with antibiotic therapy for Chlamydia trachomatis and Neisseria gonorrhoeae. Sex Transm Dis 1992;19:351-4.   Back to cited text no. 23      
24.Knapp JS. Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid-mediated high-level resistance to tetracycline. J Infect Dis 1987;155:819-22.   Back to cited text no. 24      
25.Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 1997. Division of STD Prevention, Centers for Disease Control and Prevention [CDC], September 1998.   Back to cited text no. 25      
26.Swanston WH. Antibiotic susceptibility of Neisseria gonorrhoeae in Trinidad and Tobago. West Indian Med J 1997;46:107-10.   Back to cited text no. 26      
27.Bhalla P, Sethi K, Reddy BSN, Mathur MD. Antimicrobial susceptibility and plasmid profile of Neisseria gonorrhoeae in India [New Delhi]. Sex Transm Inf 1998;74:210-2.  Back to cited text no. 27      
28.Knapp JS, Wongba C, Limpakarnjanarat K, Young NL, Parekh MC, Neal SW, et al. Antimicrobial susceptibility of strains of Neisseria gonorrhoeae in Bangkok, Thailand: 1994-1995. Sex Transm Dis 1997;24:142-8  Back to cited text no. 28      
29.Djajakusumah T, Sugigduadi S, Mehens A, Van Dyck E. Plasmid patterns and antimicrobial susceptibilities of Neisseria gonorrhoeae in Bandung, Indonesia. Trans Royal Soc Trop Med Hyg 1998;92:105-7.   Back to cited text no. 29      
30.Centers for Disease Control and Prevention. 1993 sexually transmitted diseases treatment guidelines. MMWR Recomm Rep 1993;42:1-102.  Back to cited text no. 30      
31.Rajakumar MK, Ngeow YF, Khor BS, Lirn KF. Ofloxacin, a new quinolone for the treatment of gonorrhoea. Sex Transm Dis 1988;15:25-6.  Back to cited text no. 31      
32.Smith BL, Mogabgab WJ, Dalu ZA, Jones RB, Douglas JM, Handsfield HH, et al. Multicenter trial of fleroxacin vs ceftriaxone in the treatment of uncomplicated gonorrhoea. Am J Med 1993;94:81-4.   Back to cited text no. 32      
33.Moran JS. Treating uncomplicated Neisseria gonorrhoeae infections: is the anatomic site of infection important? Sex Transm Dis 1995;22:39-47.  Back to cited text no. 33      
34.Tanaka M, Kumazawa J, Matsumoto T, Kobayashi I. High prevalence of Neisseria gonorrhoeae strains with reduced susceptibility to fluoroquinolones in Japan. Genitourin Med 1994;70:90-3.  Back to cited text no. 34      
35.Centers for Disease Control and Prevention. Fluoroquinolone resistance in Neisseria gonorrhoeae-Colorado and Washington, 1995. MMWR Morb Mortal Wkly Rep 1995;44:761-4  Back to cited text no. 35      
36.Tapsall JW, Phillips EA, Shultz TR, Thacker C. Quinolone-resistant Neisseria gonorrhoeae isolated in Sydney, Australia, 1991 to 1995. Sex Transm Dis 1996;23:425-8.  Back to cited text no. 36      
37.Centers for Disease Control and Prevention (CDC). Increases in fluoroquinolone-resistant Neisseria gonorrhoeae-Hawaii and California, 2001. MMWR Morb Mortal Wkly Rep 2002;51:1041-4.  Back to cited text no. 37      
38.Moran JS, Handsfield HH. Neisseria gonorrhoeae. In: Yu VL, Weber R, Raoult D, editors. Antimicrobial therapy and vaccines. 2 nd ed. New York: Apple Trees Productions; 2002. p. 457-69.  Back to cited text no. 38      
39.BASHH (British Association for Sexual Health and HIV). National Guidelines on the Diagnosis and Treatment of Gonorrhoea in Adults 2005.   Back to cited text no. 39      
40.Treatment Guidelines of STD. In: Sharma VK, editor. Sexually Transmitted Diseases and AIDS. WHO/CDC/NACO, Appendix II. New Delhi: 2003. p. 489-98.  Back to cited text no. 40      
41.Tapsall JW. Implications of current recommendations for third-generation cephalosporin use in the WHO Western Pacific Region following the emergence of multiresistant gonococci. Sex Transm Inf 2009;85:256-8.  Back to cited text no. 41      
42.Judson FN, Ehret JM, Handsfield HH. Comparative study of ceftriaxone and spectinomycin for treatment of pharyngeal and anorectal gonorrhoea. JAMA 1985;253:1417-9.  Back to cited text no. 42      
43.Plourde PJ, Tyndall M, Agoki E, Ombette J, Slaney LA, D′Coasta J, et al. Single-dose cefixime vs single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection. J Infect Dis 1992;166:919-22.  Back to cited text no. 43      
44.Ison CA, Mouton JW, Jones K, Fenton KA, Livermore DA. Which cephalosporin for gonorrhoea? Sex Transm Infect 2004;80:386-8.  Back to cited text no. 44      
45.Novak E, Paxton LM, Tubbs HJ, Turner LF, Keck CW, Yatsu J. Orally administered cefpodoxime proxetil for the treatment of uncomplicated gonococcal urethritis in males: a dose-response study. Antimicrob Agents Chemother 1992;36:1764-5.  Back to cited text no. 45      
46.Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2006 Supplement: Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2006. Atlanta, GA: US Department of Health and Human Services; 2008. Available from: http://www.cdc.gov/STD/gisp2006/GISPSurvSupp2006Complete.pdf./. [cited on 2009 Jul 28].   Back to cited text no. 46      
47.Lo JYC, Ho KM, Leung AO, Felisa ST, Grand KL, Angus CT, et al. Ceftibuten resistance and treatment failure of Neisseria gonorrhoeae infection. Antimicrob Agents Chemother 2008;52:3564-7.  Back to cited text no. 47      
48.Barry PM, Klausner JD. The use of cephalosporins for gonorrhea: The impending problem of resistance. Expert Opin Pharmacother 2009;10:555-77.  Back to cited text no. 48      
49.Boslego JW, Tramont EC, Takafuji E, Diniega BM, Mitchell BS, Small JW, et al. Effect of spectinomycin use on the prevalence of spectinomycin-resistant and of penicillinase-producing Neisseria gonorrhoeae. N Engl J Med 1987;317:272-8.  Back to cited text no. 49      
50.Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006;55:1-94.  Back to cited text no. 50      
51.Kojima M, Masuda K, Yada Y, Hayase Y, Muratani T, Matsumoto T. Single-dose treatment of male patients with gonococcal urethritis using 2 g spectinomycin: Microbiological and clinical evaluations. Int J Antimicrob Agents 2008;32:50-4.  Back to cited text no. 51      
52.Centers for Disease Control and Prevention. Notice to readers: Discontinuation of spectinomycin. MMWR Morb Mortal Wkly Rep 2006;55:370.  Back to cited text no. 52      
53.Centers for Disease Control and Prevention (CDC). Gonococcal Isolate Surveillance Project (GISP) annual report-2004. Atlanta: CDC; 2005.   Back to cited text no. 53      
54.Bala M, Ray K, Salhan S. First case of spectinomycin resistant Neisseria gonorrhoeae isolate in New Delhi, India. Sex Transm Inf 2005;81:186-7.  Back to cited text no. 54      
55.WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2006. Commun Dis Intell 2008;32:48-51.  Back to cited text no. 55      
56.Guoming L, Qun C, Shengchun W. Resistance of Neisseria gonorrhoeae epidemic strains to antibiotics: Report of resistant isolates and surveillance in Zhanjiang, China: 1998 to 1999. Sex Transm Dis 2000;27:115-8.  Back to cited text no. 56      
57.Martin DH, Mroczkowski TF, Dalu ZA, McCarty J, Jones RB, Hopkins SJ, et al. A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. N Engl J Med 1992;327:921-5.  Back to cited text no. 57      
58.Stamm WE, Hicks CB, Martin DH, Leone P, Hook III EW, Cooper RH, et al. Azithromycin for empirical treatment of the non-gonococcal urethritis syndrome in men: a randomized double-blind study. JAMA 1995;274:545-9.  Back to cited text no. 58      
59.Handsfield HH, Dalu ZA, Martin DH, Douglas JM, McCarty JM, Schlossberg D, et al. Multicenter trial of single-dose azithromycin vs. ceftriaxone in the treatment of uncomplicated gonorrhoea. Sex Transm Dis 1994;21:107-11.  Back to cited text no. 59      
60.Waugh MA. Open study of the safety and efficacy of a single oral dose of azithromycin for the treatment of uncomplicated gonorrhoea in men and women. J Antimicrob Chemother 1993;25:109-14.  Back to cited text no. 60      
61.Centers for Disease Control and Prevention. Updated recommended treatment regimens for gonococcal infections and associated conditions - United States, April 2007. Available from: http://www.cdc.gov/std/treatment/2006/updated-regimens.htm. [cited on 2009 Jul 24].  Back to cited text no. 61      
62.Young H, Moyes A, McMillan A. Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin. Int J STD AIDS 1997;8:299-302.  Back to cited text no. 62      
63.Tapsall JW, Schultz TR, Limnios EA, Donovan B, Lum G, Mulhall BP. Failure of azithromycin therapy in gonorrhoea and discorrelation with laboratory parameters. Sex Transm Dis 1998;25:505-8.  Back to cited text no. 63      
64.Tapsall J. Current concepts in the management of gonorrhoea. Expert Opin Pharmacother 2002;3:147-57.  Back to cited text no. 64      
65.Waters LJ. Efficacy of azithromycin 1 g single dose in the management of uncomplicated gonorrhoea. Int J STD AIDS 2005;16:84.  Back to cited text no. 65      
66.Wang SA, Harvey AB, Conner SM, Zaidi AA, Knapp JS, Whittington WL, et al. Antimicrobial resistance for Neisseria gonorrhoeae in the United States, 1988 to 2003: the spread of fluoroquinolone resistance. Ann Intern Med 2007;147:81-8.  Back to cited text no. 66      
67.Health Protection Agency. Health Protection Report 2008;2:No 14 (4 April).  Back to cited text no. 67      
68.Palmer HM, Young H, Winter A, Dave J. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother 2008;62:490-4.  Back to cited text no. 68      
69.Akasaka S, Muratani T, Yamada Y, Inatomi H, Takahashi K, Matsumoto T. Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce beta-lactamase. J Infect Chemother 2001;7:49-50.  Back to cited text no. 69      
70.Muratani T, Akasaka S, Kobayashi T, Yamada Y, Inatomi H, Takahashi K, et al. Outbreak of cefozopran (penicillin, oral cephems, and aztreonam)-resistant Neisseria gonorrhoeae in Japan. Antimicrob Agents Chemother 2001;45:3603-6.  Back to cited text no. 70      
71.Ito M, Yasuda M, Yokoi S, Ito S, Takahashi Y, Ishihara S, et al. Remarkable increase in central Japan in 2001-2002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones. Antimicrob Agents Chemother 2004;48:3185-7.  Back to cited text no. 71      
72.Yokoi S, Deguchi T, Ozawa T, Yasuda M, Ito S, Kubota Y, et al. Threat to cefixime treatment for gonorrhea. Emerg Infect Dis 2007;13:1275-7.  Back to cited text no. 72      
73.Wang SA, Lee MVC, O′Connor N, Iverson CJ, Ohye RG, Whiticar PM, et al. Multi-drug resistant Neisseria gonorrhoeae with decreased susceptibility to cefixime-Hawaii, 2001. Clin Infect Dis 2003;37:849-52.  Back to cited text no. 73      
74.WHO Western Pacific Gonococcal Antimicrobial Surveillance Programme. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific Region, 2004. Commun Dis Intell 2006;30:129-32.  Back to cited text no. 74      
75.Whiley DM, Limnios EA, Ray S, Sloots TP, Tapsall JW. Diversity of penA alterations and subtypes of Neisseria gonorrhoeae less susceptible to ceftriaxone from Sydney, Australia. Antimicrob Agents Chemother 2007;51:3111-6.  Back to cited text no. 75      
76.Cao V, Ratsima E, Tri DV, Bercion R, Fonkoua MC, Richard V, et al. Antimicrobial susceptibility of Neisseria gonorrhoeae strains isolated in 2004-2005 in Bangui, Central African Republic; Yaounde, Cameroon; Antananarivo, Madagascar; and Ho Chi Minh Ville and Nha Trang, Vietnam. Sex Transm Dis 2008;35:941-5.  Back to cited text no. 76      
77.Tzelepi E, Daniilidou M, Miriagou V, Siatravani E, Pavlidou E, Flemetakis A. Cluster of multi drug-resistant Neisseria gonorrhoeae with reduced susceptibility to the newer cephalosporins in Northern Greece. J Antimicrob Chemother 2008;62:637-9.  Back to cited text no. 77      
78.Wong WW, Huang CT, Li LH. Molecular epidemiology of gonorrhea identified clonal clusters with distinct susceptibilities associated with specific high-risk groups. J Clin Microbiol 2008;46:3931-4.  Back to cited text no. 78      
79.Tapsall J. Multidrug-resistant Neisseria gonorrhoeae. CMAJ 2009;180:268-9.  Back to cited text no. 79      
80.Tapsall JW, Unemo M, Lewis D, Ndowa F. Meeting the public health challenge of multi- and extensively-drug resistant Neisseria gonorrhoeae. Expert Rev Anti-Infect Ther 2009 in press.  Back to cited text no. 80      
81.Tanaka M, Nakayama H, Huruya K, Konomi I, Irie S, Kanayama A, et al. Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype. Int J Antimicrob Agents 2006;27:20-6.  Back to cited text no. 81      
82.Takahashi K, Muratani T, Kobayashi T, Yamada Y, Inatomi H, Matsumoto T. Emergence and prevalence of multi-drug resistant Neisseria gonorrhoeae (fluoroquinolones, tetracyclines, penicillins, 1 st and 2 nd generation cephems, and oral 3 rd generation cephems) in Japan [abstract 882]. In: Program and abstracts of the 2001 Interscience Conference on Antimicrobial Agents and Chemotherapy (Chicago).Washington, DC: American Society for Microbiology, 2001.  Back to cited text no. 82      
83.Martin IM, Hoffmann S, Ison CA. European Surveillance of Sexually Transmitted Infections (ESSTI): The first combined antimicrobial susceptibility data for Neisseria gonorrhoeae in Western Europe. J Antimicrob Chemother 2006;58:587-93.  Back to cited text no. 83      
84.Ito M, Deguchi T, Mizutani KS, Yasuda M, Yokoi S, Ito SI, et al. Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in central Japan. Antimicrob Agents Chemother 2005;49:137-43.  Back to cited text no. 84      
85.Deguchi T, Yasuda M, Asano M, Tada K, Iwata H, Komeda H, et al. DNA gyrase mutations in quinolone-resistant clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother 1995;39:561-3.  Back to cited text no. 85      
86.Deguchi T, Yasuda M, Nakano M, Ozeki S, Ezaki T, Saito I, et al. Quinolone-resistant Neisseria gonorrhoeae: Correlation of alterations in the GyrA subunit of DNA gyrase and the ParC subunit of topoisomerase IV with antimicrobial susceptibility profiles. Antimicrob Agents Chemother 1996;40:1020-3.  Back to cited text no. 86      
87.Nikaido H. Prevention of drug access to bacterial targets: Permeability barriers and active efflux. Science 1994;264:382-8.  Back to cited text no. 87      
88.Johnson SR, Sandul AL, Parekh M, Wang SA, Knapp JS, Trees DL. Mutations causing in vitro resistance to azithromycin in Neisseria gonorrhoeae. Int J Antimicrob Agents 2003;21:414-9.  Back to cited text no. 88      
89.Zarantonelli L. Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations. Antimicrob Agents Chemother 1999;43:2468-72.  Back to cited text no. 89      
90.Maness MJ. Ribosomal resistance to streptomycin and spectinomycin in Neisseria gonorrhoeae. J Bacteriol 1974;120:1293-9.  Back to cited text no. 90      
91.Brannigan JA, Tirodimos IA, Zhang QY, Dowson CG, Spratt BG. Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae. Mol Microbiol 1990;4:913-9.  Back to cited text no. 91      
92.Gill MJ, Simjee S, Al-Hattawi K, Robertson BD, Easmon CS, Ison CA. Gonococcal resistance to beta-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus. Antimicrob Agents Chemother 1998;42:2799-803.  Back to cited text no. 92      
93.Hagman KE, Pan W, Spratt BG, Balthazar JT, Judd RC, Shafer WM. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system. Microbiology 1995;41:611-22.  Back to cited text no. 93      
94.Ropp, PA, Hu M, Olesky M, Nicholas RA. Mutations in ponA, the gene encoding penicillin-binding protein 1, and a novel locus, penC, are required for high-level chromosomally mediated penicillin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2002;46:769-77.  Back to cited text no. 94      
95.Ameyama S, Onodera S, Takahata M, Minami S, Maki N, Endo K, et al. Mosaic-like structure of penicillin-binding protein 2 gene (penA) in clinical isolates of Neisseria gonorrhoeae with reduced susceptibility to cefixime. Antimicrob Agents Chemother 2002;46:374-9.  Back to cited text no. 95      
96.Spratt BG. Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature 1988;332:173-6.  Back to cited text no. 96      
97.Lindberg R, Fredlund H, Nicholas R, Unemo M. Neisseria gonorrhoeae isolates with reduced susceptibility to cefixime and ceftriaxone: Association with genetic polymorphisms in penA, mtrR, porB1b, and ponA. Antimicrob Agents Chemother 2007;51:2117-22.  Back to cited text no. 97      
98.Shokeen P, Bala M, Tandon V. Evaluation of activity of sixteen medicinal plants against Neisseria gonorrhoeae. Int J Antimicrob Agents 2009;33:86-91.  Back to cited text no. 98      
99.Shokeen P, Bala M, Ray K, Tandon V. Preliminary Studies on Activity of Ocimum sanctum, Drynaria quercifolia and Annona squamosa against Neisseria gonorrhoeae. Sex Transm Dis 2005;32:106-11.   Back to cited text no. 99      
100.Silva O, Ferreira E, Vaz PM, Canica M, Gomes ET. In vitro anti-Neisseria gonorrhoeae activity of Terminalia macroptera leaves. FEMS Microbiol Lett 2002;217:271-4.  Back to cited text no. 100      
101.Shokeen P, Bala M, Singh M, Tandon V. In-vitro activity of Eugenol, an active component from Ocimum sanctum against multiresistant and susceptible strains of Neisseria gonorrhoeae. Int J Antimicrob Agents 2008;32:174-9.  Back to cited text no. 101      
102.Spencer SE, Valentin-Bon IE, Whaley K, Jerse AE. Inhibition of Neisseria gonorrhoeae genital tract infection by leading-candidate topical microbicides in a mouse model. J Infect Dis 2004;189:410-9.  Back to cited text no. 102      
103.Talwar GP, Dhar SA, Rai MK, Reddy KV, Mitra D, Kulkarni SV, et al. A novel polyherbal microbicide with inhibitory effect on bacterial, fungal and viral genital pathogens. Int J Antimicrob Agents 2008;32:180-5.  Back to cited text no. 103      
104.Workowski KA, Berman SM, Douglas JM Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: Urgent need to strengthen prevention strategies. Ann Intern Med 2008;148:606-13.  Back to cited text no. 104      
105.Deguchi T, Yasuda M. Lack of nationwide surveillance of antimicrobial resistance in Neisseria gonorrhoeae in Japan. Ann Intern Med 2008;149:363-4.  Back to cited text no. 105      

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Correspondence Address:
Manju Bala
Regional STD Teaching Training and Research Centre, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi
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DOI: 10.4103/0974-777X.68537

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