Antimicrobial Resistance of Neisseria gonorrhoeae in Selected World Health Organization Southeast Asia Region Countries: An Overview : Sexually Transmitted Diseases

Secondary Logo

Journal Logo

Article

Antimicrobial Resistance of Neisseria gonorrhoeae in Selected World Health Organization Southeast Asia Region Countries: An Overview

Ray, Krishna MD*; Bala, Manju MD*; Kumari, Sudarshan MD; Narain, Jai P. MD, MPH

Author Information
Sexually Transmitted Diseases 32(3):p 178-184, March 2005. | DOI: 10.1097/01.olq.0000154490.40381.15
  • Free

Background and Objectives: 

A Gonococcal Antimicrobial Susceptibility Program (GASP) under the World Health Organization South East Asia Region (WHO SEAR) is continuing in India and neighboring countries and is being coordinated by the WHO Regional Reference Laboratory (RRL), Vardhman Mahavir Medical College, and Safdarjung Hospital, New Delhi.

Goal: 

The present communication describes the current status and trends of antimicrobial resistance patterns of Neisseria gonorrhoeae, isolated in different focal-point laboratories under GASP, as presented in WHO SEAR intercountry consultative meeting conducted in December 2001.

Study: 

Seven laboratories from India and 1 each from Bangladesh, Sri Lanka, and Nepal presented their data for the year 2000/2001. In addition, RRL Delhi, Bangladesh, and Sri Lanka presented data for the years 1995 to 2001, 1997 to 2001, and 1996 to 2000, respectively. Either National Committee for Clinical Laboratory Standards or calibrated dichotomous sensitivity technique was used in the different laboratories for determining antimicrobial susceptibility.

Results: 

It was observed that in the Indian laboratories, penicillin resistance varied from 20% to 79%, tetracycline resistance from 0% to 45.6%, and ciprofloxacin from 10.6% to 100%. Chromosomal, as well as plasmid-mediated resistance, was observed. The strains were reported to be less sensitive to ceftriaxone in 5 out of 7 laboratories, while none reported spectinomycin resistance. The reasons for wide variation in the results could be due to geographical strain difference in different parts of this vast country.

At Sri Lanka, gonococci showed resistance towards penicillin (96.8%) and ciprofloxacin (8.2%). Bangladesh reported N. gonorrhoeae with ciprofloxacin (76%), penicillin (33%), and tetracycline (50%) resistance and decreased susceptibility to ceftriaxone (1.5%). Both the laboratories did not report any spectinomycin resistance. The resistance trends in these 2 centers and the RRL, New Delhi, showed different patterns.

Conclusion: 

The report indicates the necessity for continuous surveillance of antimicrobial resistance pattern in this region of WHO for establishing antimicrobial policy guidelines for management of this common but important sexually transmitted infection (STI) pathogen, known to facilitate human immunodeficiency virus (HIV) infection. It also highlights the importance of ensuring quality assurance in the techniques in order to generate uniform data.

GONORRHEA IS ONE OF the classical sexually transmitted diseases (STDs) with human as the only host for the causative agent, Neisseria gonorrhoeae. The estimated number of cases globally is 200 million every year. There are several problems in compilation of data, as clinical presentation is not specific enough and laboratory-based diagnosis is not attempted in many areas because of inadequate facilities, material, or personnel. Besides, there is a lack of reporting mechanism in developing countries. The prevalence rate of the disease varies greatly among countries in the developed and developing world, the highest being in south and southeast Asia, followed by sub-Saharan Africa and Latin America, where it continues to be a major public health problem.1 The Regional STD Teaching, Training and Research Centre at New Delhi showed an increasing trend from 14% to 19.4% between 1990 and 2001.2,3 Overall, it varies between 4.2% and 16.2% in the other STD clinics of the country. In Bangladesh, the incidence is around 35.5%.4 The success of the HIV Control Programme in Thailand has led to decline in gonorrhea by more than 80%.5

Emergence of resistance to antimicrobial agents has made the treatment of gonorrhea expensive and prolonged, as well as unpredictable. The organism acquires resistance by spontaneous mutation or it acquires new DNA via conjugation and transformation, and thus resistance may be chromosomal or extrachromosomal.6,7 A single organism can have both the mechanisms of resistance, and resistance to multiple antibiotics is often seen. Antimicrobial resistance against almost all the antimicrobial agents is spreading now in southeast Asian region (SEAR) countries.8–10 Surveillance was therefore considered mandatory to develop strategy and policy for proper therapy.

WHO recommended establishing a global surveillance program in 1978 and 1990.11,12 Gonococcal Antimicrobial Susceptibility Programme (GASP) became functional in SEAR in 1997. Two regional reference laboratories (RRL), 1 each in India and Thailand, were identified to provide technical and material support to 5 countries each of the regions. The Inter Regional Reference Laboratory, located at Sydney, Australia, provides technical support and organizes the external quality-assessment scheme for these 2 laboratories. Laboratories from India, Bangladesh, and Sri Lanka have participated in the program since its inception. Although isolated studies have been done in Sri Lanka to understand the susceptibility of N. gonorrhoeae strains towards penicillin, only in 1997 was a systematic monitoring system established with the introduction of GASP.

The present communication compares the current status of the antimicrobial susceptibility pattern of N. gonorrhoeae, isolated in different GASP focal-point laboratories, and also attempts to assess the trend of antimicrobial resistance of N. gonorrhoeae in 3 selected laboratories, based on the data presented by the in-charges of these laboratories in the WHO-SEAR intercountry consultative meeting conducted in December 2001 at RRL, Regional STD Teaching, Training and Research Centre, Vardhman Mahavir Medical College, and Safdarjung Hospital, New Delhi, India. The data could be used by the public health managers to change the national management guidelines, if necessary.

Materials and Methods

There are 10 functional focal point laboratories for GASP under RRL, New Delhi, 7 from India, and 3 from other countries (eg, Bangladesh, Sri Lanka, and Nepal). As the present communication describes the results reported from different focal-point laboratories, the study populations differed in each setup, as shown in Table 1. Standard methods for transport, isolation, presumptive and confirmatory identification, subculture, and storage were adopted by all the laboratories under GASP, according to the WHO manual.13 Antimicrobial susceptibility testing was carried out following either National Committee for Clinical Laboratory Standards (NCCLS) method14 or calibrated dichotomous sensitivity (CDS) technique,13 using high- and low-potency discs, respectively (Himedia Laboratories Ltd., India/Oxoid). All the laboratories used the same panel of antibiotics. The discs used in the 2 techniques were penicillin (10 and 0.5 IU), tetracycline (30 μg and 10 μg), ciprofloxacin (5 μg and 1 μg), ceftriaxone (30 μg and 0.5 μg), and spectinomycin (100 μg in both), respectively. For the NCCLS method, media used was GC agar base + hemoglobin/blood and Isovitalex/Vitamino growth supplement, and for the CDS technique, chocolate agar having Columbia agar base was used. The source of media components was either from BBL, now Becton Dickinson, Sparks, MD; or HiMedia. The interpretive criteria were according to CDS and NCCLS guidelines.13,14 The RRL at New Delhi compared the CDS technique with NCCLS in 50 strains of N. gonorrhoeae before adopting it for use. The results were in 98% agreement. WHO N. gonorrhoeae strains A to E were used as control strains. RRL, New Delhi, Bangladesh, and Sri Lanka received the control strains from WHO Neisseria Reference Laboratory, Sydney, Australia. These strains were distributed to focal-point laboratories in India. Interpretation of antimicrobial susceptibility and breakpoints for resistance were as reported earlier.13,14 β Lactamase testing for detection of penicillinase-producing N. gonorrhoeae (PPNG) was performed by a paper acidometric method in Bangladesh, Chennai, Nagpur, and by chromogenic cephalosporin method using nitrocefin freeze-dried powder (Oxoid) in RRL, New Delhi, and nitrocefin disc (BBL) in Maulana Azad Medical College (MAMC), New Delhi.

T1-8
TABLE 1:
Details of Laboratories Under GASP in India and Other Selected SEAR Countries

TRNGs were defined as plasmid-mediated tetracycline-resistant N. gonorrhoeae with tetracycline MIC ≥16 μg/mL. Chromosomally mediated resistant strains for tetracycline (TetR) were defined as non-TRNG with tetracycline MIC of ≥2 μg/mL.9 Presumptively, in the NCCLS technique,14 TRNGs were identified when the zone of inhibition (diameter) was ≤19 mm and in the CDS technique when the zone of inhibition (annular radius) was ≤1 mm.

The resistance patterns of consecutive isolates of N. gonorrhoeae in different focal-point laboratories in 2001 were summarized and compared. The trends of antimicrobial resistance in Sri Lanka, Bangladesh, and New Delhi (RRL), India, from 1996 to 2000 were also compared. Data for penicillin and tetracycline resistance from Bangladesh were available only from 1997 to 1999. Trend data were analyzed statistically using χ2 test, and P value was determined.

Results

Current Status of Antimicrobial Resistance of N. gonorrhoeae in India

Table 2 summarizes and compares the resistance patterns of N. gonorrhoeae in 2001, as reported from 7 focal-point laboratories in India.

T2-8
TABLE 2:
Percent Resistance of N. gonorrhoeae to Various Antimicrobials in India and Other Selected SEAR Countries

Penicillin

Resistance to this antibiotic continues to be a problem in India. Resistance was reported from all 7 laboratories but varied between 20% and 79%. PPNGs were reported from Delhi-MAMC (10%), Nagpur (13.5%), and RRL, New Delhi (26.8%).

Tetracycline

Resistance to tetracycline was reported from all the laboratories except Chennai and Kolkata. In Pune (data communicated after the meeting) and Hyderabad, percent resistance was 97.2% and 45.6%, respectively. A total of 33.8% of strains were reported from Nagpur as TRNG. From both the laboratories in Delhi, percent of resistance varied from 7.4% to 10%.

Ciprofloxacin

Resistance to ciprofloxacin was reported from all the laboratories and varied considerably. Delhi (RRL 88.4% and MAMC 100%) and Hyderabad (57%) reported very high percent resistance.

Ceftriaxone

The RRL, New Delhi, did not report any strain having reduced susceptibility to ceftriaxone. However, it was reported from 5 laboratories and varied between 5% and 20%. MAMC, Delhi, reported decreasing zone diameters from 50 mm to 40 mm (NCCLS) for this antibiotic.

Spectinomycin

No spectinomycin resistance was reported from India, so far.

Current Status of Antimicrobial Resistance of N. gonorrhoeae in Other SEAR Countries

Table 2 summarizes and compares the resistance patterns of N. gonorrhoeae, as reported from Bangladesh, Sri Lanka, and Nepal.

Bangladesh

The resistance to penicillin and tetracycline continued to be a problem, and the isolates from FSWs had 33% resistance and 66% reduced susceptibility to penicillin and 57% resistance and 35% reduced susceptibility to tetracycline in 1999. High percent resistance (76%) against ciprofloxacin and reduced susceptibility to ceftriaxone, only in 1.5% of the isolates, were reported in 2000.

Sri Lanka

Resistance to penicillin and ciprofloxacin was reported to be 96.8% and 8.2%, respectively, in 2000. No resistance was reported against the other antibiotics.

Nepal

The report was based only on 9 isolates in 2001 and showed 4 PPNGs, 4 TRNGs, and only 1 isolate resistant to ciprofloxacin. No resistance was reported to ceftriaxone and spectinomycin.

Antimicrobial Resistance Trends in 3 SEAR Countries

Penicillin.

The trends of antimicrobial susceptibility of N. gonorrhoeae strains towards penicillin in the 3 SEAR countries are shown in Fig. 1a and the trends of PPNG in Figure 1b. In Sri Lanka, a highly significant (P < 0.001) rise in the percentage of chromosomally mediated resistance to penicillin from 37% in 1996 to 96.8% was observed in 2000. The rest of the strains were low sensitive. β Lactamase testing has been done since 1980. Since then, the percentage of β lactamase–positive strains gradually increased to 20% in 1989. However, with the withdrawal of penicillin as the first line of therapy, detection of PPNG strains decreased, and in 1995, no PPNG strains were isolated. During the past few years, the percentage of PPNG isolates was reported to increase to 10% to 15%. In Bangladesh, 65.0% resistance to penicillin was reported in 1997, which reduced to 33% (P < 0.001) in 1999, with highly significant (P < 0.001) increase in less-sensitive strains from 35% to 66% during the same period. However, the PPNG isolates rose from 10% in 1999 to 31% (P < 0.001) in 2000. In RRL, New Delhi, a very low level of chromosomal penicillin resistance was maintained till 1999, which increased significantly (P < 0.001) to 42.4% in 2000. A significant (P < 0.01) increasing trend was also observed in the percent of PPNG isolates from 3.4% in 1996 to 17.6% in 2000.

F1-8
Fig. 1:
Trend of antimicrobial resistance in SEAR countries. a, Resistance trend to penicillin. b, Trend of PPNG. c, Resistance trend to tetracycline. d, Resistance trend to ciprofloxacin.

Tetracycline.

The trends of antimicrobial susceptibility of N. gonorrhoeae strains towards tetracycline in the 3 SEAR countries are shown in Figure 1c. In Sri Lanka, TRNG isolates were 13.5% in 1997, which reduced to 0% (P < 0.001) in 2000. In Bangladesh, between 1997 and 1999, tetracycline resistance varied from 57% to 72%, and the TRNG isolates increased significantly (P < 0.001) from 6.5% to 21%. In RRL, New Delhi, resistance was maintained between 1.7% and 12.3% from 1996 to 2000.

Ciprofloxacin.

The trends of antimicrobial susceptibility of N. gonorrhoeae isolates towards ciprofloxacin in the 3 SEAR countries are shown in Figure 1d. In Sri Lanka, resistance to ciprofloxacin varied from 10.3% to 13.7% from 1996 to 1998 and showed a declining trend to 7.7% and 8.2% in 1999 and 2000, respectively. Monitoring of ciprofloxacin resistance from 1997 onward in Bangladesh had shown a highly significant (P < 0.001) increase in resistant strains from 9% in 1997 to 76% in 2000. A steady rise was observed in the percent resistance in the isolates from RRL, New Delhi, from 1996 to 1999, increasing significantly (P < 0.001) from 19.3% in 1999 to 76% in 2000.

Ceftriaxone.

No ceftriaxone less-susceptible strain was isolated till 2000 in Sri Lanka and at RRL, New Delhi, whereas Bangladesh reported reduced susceptibility to ceftriaxone from 1.0% in 1997 to 1.5% in 2000.

Spectinomycin.

Spectinomycin resistance was not reported from these countries till the time of the meeting.

Discussion

Penicillin was widely used for the treatment of gonorrhea for many years and is still being used in many countries. Appearance of chromosomal resistance produced a slow stepwise decline in penicillin sensitivity until clinically significant levels were reached.15

In the current report, different Indian laboratories showed varying penicillin resistance patterns and also fluctuating trends in some of them. Since 1990, use of penicillin for treatment of gonorrhea was discontinued in India, with the result that penicillin resistance (both chromosomal and plasmid mediated), as reported from New Delhi till 1999,8 was quite low. The resistance showed a steep rise to 42.4% and 66.7% in 2000 and 2001,3 respectively, along with increasing isolation of PPNGs. The low level of PPNGs, maintained during 1995 to 1999, could also be due to the widespread use of fluoroquinolones, which are able to cure strains of plasmids, as speculated earlier.16 However, the sudden rise in penicillin resistance, as well as PPNG, in the same laboratory in New Delhi,3 although difficult to explain, could be because of discontinuation of fluoroquinolones in the management of gonorrhea in this center. Penicillin resistance was also reported to be quite high in Hyderabad (79%) and Chennai (62.5%), whereas it was at a comparatively lower level (20% to 33%) in Kolkata, Nagpur, and Pune.

The alarming (96.8%) penicillin resistance reported from Sri Lanka in 2000 prompted the authorities to discontinue its use as the first line of treatment, and cefuroxime was reported to be in use, although a decline in the PPNG was earlier reported from the same city.10 In Bangladesh, a decreasing trend in penicillin resistance, along with a similar trend of PPNG isolates during 1997 to 1999, was reported. However, the subsequent rise in the incidence of PPNG isolates up to 2001 is a matter of concern.

PPNG, in particular, has the potential to spread rapidly within a community, increasing in Nigeria, for example, from 0% of isolates to 70% over a 5-year period.17 Ever since its first isolation18 in 1981, its prevalence in India has been variable. In 1999, Divekar and Gogte19 reported 94% of their isolates as PPNG, and 71% were Asian plasmids. In limited studies from Delhi20,21 also, presence of Asian plasmid could be confirmed. In other SEAR countries like Thailand,22 penicillin resistance was very high in 1997, with 17.8% of the isolates being PPNG, whereas in Indonesia,23 a high rate of PPNG without CMRNG was reported in 1998.

Wide variation in the prevalence of penicillin resistance in the same country could be due to its widespread availability, especially in subtherapeutic doses,24 as well as use of this antimicrobial as prophylaxis by CSWs25. However, the syndromic management being in use in the community, use of penicillin for therapy of STDs was limited during the period of study. In spite of this, the increasing resistance towards this antibiotic, as observed in India, could be due to the widespread use of penicillin derivatives in the treatment of unrelated illnesses. But reduction in penicillin resistance in gonococcal isolates from Bangladesh could be due to the discontinuation of the drug in treatment of many diseases, including gonorrhea. However, increase in the PPNG strains within the gonococcal isolates from the same city does not correlate with the above observation.

Tetracycline, a cheap and widely used antimicrobial, is an adjunct therapy for Chlamydia trachomatis in syndromic management of STDs, as well as in some other illnesses. High-level tetracycline resistance was first reported in 1985 from CDC Atlanta.26 In a study conducted in 1085 gonococcal isolates from prostitutes over a period of 30 months in Kinshasa, Zaire, 30% were TRNG.27 Tetracycline resistance was reported to be high in Indonesia in 1998 (100% with 94% TRNG)23 and Thailand in 1999 (55% with 7.9% TRNG).22 However, the resistance pattern reported in N. gonorrhoeae under GASP in different SEAR countries showed variable results. In spite of its frequent use, the prevalence of resistance is low in most of the focal-point laboratories in India, as well as in Sri Lanka. High percentage resistance was shown by only 3 centers in India (Hyderabad, Nagpur, and Pune, being adjacent states) and also from Dhaka, Bangladesh. Presence of TRNG was reported from Nagpur (33.8%) and Dhaka (21%). It is interesting to note that in Kolkata, which is the capital of West Bengal, and the adjacent Indian state of Bangladesh, the N. gonorrhoeae strains isolated from female CSWs did not show any tetracycline resistance.

Significant quinolone resistance, exclusively chromosomally mediated, has emerged in the WHO Western Pacific region28 and SEAR8 and has spread to many countries with a high burden of gonorrhea. Emergence may be accelerated by use of quinolones for treatment of other diseases, and rapid spread through domestic transmission seems to have occurred in Bangladesh, reporting a very high prevalence of resistance with treatment failure.29 Over a third of the isolates in 1997 here were QRNG.9 In contrast, ciprofloxacin resistance in Sri Lanka, already reported to have emerged,10 was observed to vary between 10.3% and 13.7% between 1996 and 1998 and declining to 8.2% in 2000. In other SEAR countries like Indonesia,23 the quinolone resistance was reported to be nil, while in Thailand30 it increased from 13.8% in 1998 to 25.4% in 1999. Self-prescribed prophylactic antimicrobial use and inconsistent condom use could be important factors in the continued emergence of gonococcal antimicrobial resistance in Philippines, reporting substantial increase in the proportion of N. gonorrhoeae, highly resistant to ciprofloxacin.31 Although low prevalence8 was reported earlier from Delhi, India, it has assumed an alarming proportion recently.3 The trend is also evident from Delhi (MAMC) and Hyderabad. In spite of the National AIDS Control Organisation (NACO) guidelines for management of gonorrhea with ciprofloxacin, the RRL, New Delhi, had to discontinue its use in 1996 because of treatment failure and has been using injectable ceftriaxone for the last few years to manage the clinical cases.

Very high level of activity of the broad spectrum cephalosporin (ie, ceftriaxone) against gonococci was observed in most of the laboratories. Reduced susceptibility towards ceftriaxone reported by some laboratories in India and neighboring countries should be considered with caution as this antimicrobial is used as a drug of choice in most of the centers for management of acute gonorrhea. It is important to correlate these observations with treatment efficacy. In countries like China,32 the Philippines,33 and Thailand,34N. gonorrhoeae strains having MIC ≥1 μg/mL for ceftriaxone have been reported. Two strains, isolated from one of the focal-point laboratories in India, showing reduced susceptibility towards ceftriaxone could not be confirmed at the RRL, New Delhi. The strains showed sensitive results following both NCCLS and CDS technique, but the zone sizes were close to cutoff (ie, 36 and 7 mm, 40 and 6 mm, respectively). Ceftriaxone less-sensitive strains (unconfirmed by MIC) from other laboratories were not received in RRL for confirmation. The results highlight the importance of quality assurance in the antimicrobial susceptibility techniques in different laboratories before deciding on antimicrobial policy of this important organism. Close monitoring of cephalosporin sensitivity is required, as recommended earlier from Western Pacific regional office experience.28

Spectinomycin resistance has not so far been reported from SEAR countries,16,18–20,22,23 although reports from the Philippines33 and China32 showed emergence of resistance to this antimicrobial.

To conclude, gonococcus has developed resistance to the older, as well as the newly introduced, agents, compromising the efficacy of individual case management and the control programs, highlighting the importance of the fact that the data should be generated in different parts of the globe, based on culture and antimicrobial susceptibility. Often the data are sketchy and based on single-point prevalence study, which does not indicate trend. The problem of inability to compare data from different areas arises because of use of different laboratory techniques for determining the antimicrobial susceptibility and absence of proper quality assurance in different laboratories, both internal and external. It is important that formulation of country-specific treatment guidelines for this disease be based on quality-assured antimicrobial susceptibility data collected by reference laboratories from different countries, under such programs as GASP, in order to follow the rationale recommended that a standard treatment regimen is expected to cure 95% or more of gonorrhea cases and an antibiotic should not be used when more than 5% are resistant to it.35 Once antibiotic resistance has emerged in a community and the treatment policy is not altered, the resistant strains become endemic, specially when CSWs, the high-frequency transmitters, have been infected.

References

1. Cohen MS, Sparling PF. Mucosal infection with Neisseria gonorrhoeae: bacterial adaptation and mucosal defences. J Clin Invest 1992;89:1699–1705.
2. Ray K, SM Gupta, Manju Bala. Changing trends in STD Profile at STD Centre, Safdarjang Hospital, New Delhi. GASP Newsletter (A SEARO Newsletter on Gonococcal Antibiotic Susceptibility Programme) 2000;4.1:2–3.
3. Bala M, Ray K, Kumari S. Alarming increase in ciprofloxacin and penicillin resistant Neisseria gonorrhoeae isolates in New Delhi, India. Sex Transm Dis 2003;30:523–525.
4. Motiur Rahman, et al. Etiology of sexually transmitted infections among street-based female sex workers in Dhaka, Bangladesh. J Clin Microbiol 2000;38:1244–1246.
5. Hanenberg RS, et al. Impact of Thailand’s HIV control programme as indicated by the decline of sexually transmitted diseases. Lancet 1994;344:243–245.
6. Uma Chaudhary, K Ray, Manju Bala, Daman Saluja. Mutation patterns in GyrA and ParC genes of ciprofloxacin resistant isolates of Neisseria gonorrhoeae from India (New Delhi). Sex Transm Inf 2002;78:440–444.
7. Dillon JR, Yeung KH. β Lactamase plasmids and chromosomally mediated antibiotic resistance in pathogenic Neisseria species. Clin Microbiol Rev 1989;2:S125–S133.
8. Ray K, Bala M, Kumar J, Misra RS. Trend of antimicrobial resistance in N. gonorrhoeae at New Delhi, India. Int J STD AIDS 2000;11:115–118.
9. Bhuiyan BU, Rahman M, Miah MRA, et al. Antimicrobial susceptibility and plasmid contents of Neisseria gonorrhoeae isolates from commercial sex workers in Dhaka, Bangladesh: emergence of high level resistance to ciprofloxacin. J Clin Microbiol 1999;37:1130–1136.
10. Abeyewickereme I, Seneratne L, Prithiviraj VB. Rapid emergence of 4 fluoroquinolone resistance with associated decline in penicillinase producing Neisseria gonorrhoeae in Colombo, Sri Lanka. Genitourin Med 1996;72:302.
11. World Health Organization. Report of a Scientific Working Group: Neisseria gonorrhoeae and Gonococcal Infection. Geneva: World Health Organization, 1978. Technical Report series 616:134–135.
12. World Health Organization. Management of Sexually Transmitted Diseases. World Health Organization, WHO/UNAIDS 1997:WHO/GPA/ 94.1Rev 1.
13. World Health Organization. Laboratory Diagnosis of Gonorrhoea. WHO Regional Publication, South East Asia series no 33: Geneva: World Health Organization, 1999 (http://w3.whosea.org/book33/).
14. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disc Susceptibility Testing: Approved Standard. Villanova, Pa: NCCLS, 2001:M2-A7 (Vol. 21, no. 1).
15. Ross JDC, Moyes A, McMillan A, Young H. Temporal changes in the sensitivity of Neisseria gonorrhoeae to penicillin in Edinburg, Scotland. Int J STD AIDS 1995;6:110–113.
16. Kam KM, Lo KK, Ng KYH, Cheung MM. Rapid decline in penicillinase producing Neisseria gonorrhoeae in Hong Kong associated with emerging 4-fluoroquinolone resistance. Genitourin Med 1995;71:141–145.
17. Osoba AO. Overview of penicillinase producing N. gonorrhoeae in Africa. Afr J Sex Transm Dis 1986;2:51–55.
18. Vijaylakshmi K. First case of β lactamase producing N. gonorrhoeae isolates from Madras. Indian J Sex Transm Dis 1982;3:13–14.
19. Divekar A, Gogte A. Ciprofloxacin resistance in N. gonorrhoeae isolated in Mumbai [formerly Bombay], India. Sex Transm Inf 1999;75:122.
20. Bhalla P, Sethi K, Reddy BSN, Mathur MD. Antimicrobial susceptibility and plasmid profile of N. gonorrhoeae in India, New Delhi. Sex Transm Inf 1998;74:210–213.
21. Uma Chaudhary, K Ray, Manju Bala, Daman Saluja. Prevalence of African type of β lactamase plasmid from the penicillin resistant isolates of N. gonorrhoeae from New Delhi, India. Under communication with Sex Transm Dis.
22. Knapp JS, Wongra C, Limpa Karnjanarat KZ, et al. Antimicrobial susceptibility of strains of N. gonorrhoeae in Bangkok, Thailand: 1994–1995. Sex Transm Dis 1997;24:142–148.
23. 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;92:105–107.
24. Barnes RC, Holmes KK. Epidemiology of gonorrhoea: current perspectives. Epidemiol Rev 1984;6:1–30.
25. Goh CL, Meija P, Sng EH, Rajan VS, Thirumoorthy T. Chemoprophylaxis and gonococcal infection in prostitutes. Int J Epidemiol 1984;13:344–346.
26. Centers for Disease Control and Prevention. Tetracycline resistant N. gonorrhoea: Georgia, Pennsylvania, New Hampshire. MMWR Morb Mortal Wkly Rep 1985;34:563–570.
27. Van Dyck E, Laga M, Manoka AT, Behets F, Piot P. Epidemic spread of plasmid mediated tetracycline resistant N. gonorrhoeae in Zaire. Int J STD AIDS 1995;6:345–347.
28. Surveillance of antibiotic susceptibility of Neisseria gonorrhoeae in the WHO Western Pacific Region 1992–4: WHO Western Pacific Region Antimicrobial Surveillance Programme. Genitourin Med 1997;73:355–361.
29. Rahman M, Alam A, Nessa K, et al. Treatment failure with the use of ciprofloxacin for gonorrhoea correlates with the prevalence of fluoroquinolone resistant Neisseria gonorrhoeae strains in Bangladesh. Clin Infect Dis 2001;32:884–889.
30. Trees DL, Sirvirongrangson P, Schultz AJ, et al. Multiclonal increase in ciprofloxacin resistant Neisseria gonorrhoeae, Thailand, 1998–1999. Sex Transm Dis 2002;29:668–673.
31. Klausner JD, Aplasca MR, Mesola VP, Bolan G, Whittington WL, Holmes KK. Correlates of gonococcal infection and of antimicrobial-resistant Neisseria gonorrhoeae among female sex workers, Republic of the Philippines, 1996–1997. J Infect Dis 1999;179:729–733.
32. Li Guoming, Chen Q, Wang S. Resistance of Neisseria gonorrhoeae epidemic strains to antibiotics: report of resistant isolates and surveillance in Zhanjiang, China: 1998–1999. Sex Transm Dis 2000;27:115–118.
33. Clendennen TE, Hames CS, Kees ES, et al. In vitro antibiotic susceptibility of Neisseria gonorrhoeae isolates in the Philippines. Antimicrob Agents Chemother 1992;36:277–281.
34. Clendennen TE, Echeverria P, Saengeur S, et al. Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand. Antimicrob Agents Chemother 1992;36:1682–1688.
35. Van de Laar MJW, Van Duyenhoven YTHP, Dessens M, Van Santen M, Van Klingeren B. Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the Netherlands, 1977–1995. Genitourin Med 1997;73:510–517.
© Copyright 2005 American Sexually Transmitted Diseases Association