Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2007–2008

The Australian Gonococcal Surveillance Programme is funded by the Federal health department to provide laboratory analysis of gonococcal isolates in Australia. The Programme produces an annual report on its findings as well as a report on the WHO Western Pacific Region Gonococcal Antimicrobial Surveillance Programme. This annual report for 2007/08 also includes data on the South East Asian Region.

Page last updated: 19 April 2010

The WHO Western Pacific and South East Asian Gonococcal Antimicrobial Surveillance Programmes

Abstract

Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as ‘resistant’, ‘less susceptible’ or ‘non-susceptible’ gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007–2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be maintained and potentially expanded. Commun Dis Intell 2010;34:1–7.

Top of page

Introduction

The World Health Organization (WHO) Western Pacific (WPR) and South East Asian Regions (SEAR) have a continuing high incidence of gonorrhoea, but treatment and public health management of gonococcal disease in both regions have been severely compromised over many years by increasing antimicrobial resistance (AMR) in Neisseria gonorrhoeae. Currently, treatment of gonorrhoea in the public sector of ‘Asian’ countries in the WHO WPR and in the WHO SEAR is substantially based on the use of third-generation cephalosporin agents, most notably the injectable ceftriaxone, although there are a wide range of dosing regimens used.1 The oral third-generation cephalosporin most commonly used is cefixime, but dosing regimens are more uniform.1 These antibiotics are employed as single-dose treatments. Other injectable and oral cephalosporins are also used in some jurisdictions.1 There is also widespread resistance to penicillins, early generation cephalosporins and quinolones in the ‘Asian’ group of WPR and in SEAR countries.2,3 In the ‘Pacific Island’ or ‘Oceania’ group of countries within the WHO WPR, the penicillin group of agents remains the recommended treatment in a number of settings.2 Other antibiotics such as spectinomycin and azithromycin are also recommended and used in some countries, although drug availability and cost limit their wider use. There are few reliable data on antibiotic usage and availability in the private sector in the WHO WPR and SEAR, but anecdotally, a wide variety of antibiotics are used, often in suboptimal doses.1

The WHO4 and others5,6 recommend that treatment options be refined by data from surveillance of AMR in N. gonorrhoeae and that use of an antibiotic for routine treatment be discontinued when therapeutic failure and/or AMR reaches a level of 5%. The WPR Gonococcal Antimicrobial Surveillance Programme (GASP) has documented the emergence and spread of AMR in N. gonorrhoeae in the WHO WPR since 19922,7 to provide information for action and to optimise the antibiotic treatment for gonorrhoea. The WHO SEAR GASP has published similar data intermittently.3 Considerable concerns have been expressed following the appearance and spread of gonococci ‘non-susceptible’ to the later-generation cephalosporins in the WHO WPR.8–11 Their recognition followed documentation of treatment failures with several oral third-generation cephalosporins.8,10,12 The gonococci involved were usually also resistant to other antibiotics, including penicillins and quinolones and would be classified as ‘multi-drug resistant gonococci’ by recently proposed criteria.4

This report provides an analysis of antimicrobial resistance in N. gonorrhoeae in the WHO WPR derived from the results of the WPR GASP surveillance for the calendar years 2007 and 2008, and is augmented by equivalent data in a number of centres in the WHO SEAR. The difficulties currently experienced with reliable detection and reporting of cephalosporin ‘non-susceptible’ gonococci4 are discussed.

Top of page

Methods

The methods used by the WHO WPR GASP have been published7 and provide full details of the source of isolates, sample populations, laboratory test methods and quality assurance programs (EQAS) used to generate data. These general principles were unaltered in 2007–2008 and were also applied to centres in the WHO SEAR. However, there has been a continuing expansion of the N. gonorrhoeae comprising the panel strains used in WHO WPR and SEAR EQAS programmes so as to reflect the impact of emerging resistance initially to the quinolones and, latterly, the third-generation cephalosporins and issues related to the detection of these forms of resistance.13,14

Top of page

Results and discussion

A total of 17,458 N. gonorrhoeae isolates were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by EQAS controlled methods in the 2 years 2007–2008 in 24 reporting centres in 20 countries and jurisdictions: 16 in the WHO WPR and four in SEAR countries. There are important limitations that apply to data generated from surveys of this kind. Inevitably, low sample numbers only were available in some centres. This is for several reasons, including abandonment of laboratory-based diagnostic culture facilities where syndromic management is used and, more recently, substitution of diagnostic nucleic amplification assays for culture based approaches. Additionally, resource limitations restrict the capacity for susceptibility testing based on minimal inhibitory concentration (MIC) methodology, even when gonococcal isolates are available, so that disc testing procedures remain the only practical means of in vitro assessment of gonococcal antibiotic susceptibility in many situations.14 Despite these limitations, in the absence of other data sources, and when surveillance is conducted over extended periods under the same conditions, this series has provided reliable trend data for the WHO WPR as a whole.

The consistent results that have been obtained over time in similar countries in the WPR reinforce the significance of the findings, and these data now include the addition of quality controlled information from the WHO SEAR. This allows inferential extrapolation of the data obtained to countries that are unable to participate fully in each surveillance period.

Top of page

Tables 1–4 show the patterns of resistance to the quinolone and penicillin groups of antibiotics by jurisdiction for each year of the surveillance period. The WHO recommendation that an antibiotic should be removed from standard treatment schedules when the proportion of resistant isolates reaches 5% or more provides guidance for the interpretation of these data. The previously described patterns of resistance to these groups of antibiotics across the WHO WPR2,7 were again evident in 2007–2008. A high proportion of both penicillin and/or quinolone resistance was detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. In 2007, quinolone resistance or reduced susceptibility was in excess of 90% of all N. gonorrhoeae isolates examined in China, the Hong Kong SAR, Mongolia, India, Thailand and Sri Lanka and between 75% and 90% of all isolates in Brunei, Japan, Korea, Malaysia, Singapore and Vietnam. Similarly, high proportions of quinolone resistant gonococci (QRNG) were found in these centres and also in Myanmar in 2008. Lower, but still substantial, proportions of QRNG were present in Australia, the Lao PDR, New Zealand and the Philippines in both years. Penicillin resistance rates were lower than those for the quinolone antibiotics, but followed a similar pattern in WPR and SEAR centres in both years. Not all jurisdictions monitored penicillin resistance because treatment of gonorrhoea with this group of antibiotics has long been discontinued, and even where this surveillance was performed, it was sometimes limited to detection of beta-lactamase production.

Table 1: Quinolone resistance in 8,376 strains of Neisseria gonorrhoeae in the World Health Organization Western Pacific Region and the South East Asia Region, 2007

Country
n Less susceptible Resistant All QRNG
    n % n % n %
Western Pacific Region (n = 7,507)
Australia
3,042
37
1.2
1,456
47.9
1,493
49.1
Brunei
208
50
24.0
120
57.7
170
81.7
China
1,163
41
3.5
1,108
95.3
1,149
98.8
Fiji
320
0
0.0
3
0.9
3
0.9
Hong Kong SAR
1,478
15
1.0
1,437
97.2
1,452
98.2
Japan
329
16
4.9
241
73.3
257
78.1
Korea
56
9
16.1
37
66.1
46
82.1
Lao PDR
9
NS
NS
3
33.0
3
33.0
Malaysia
41
5
12.2
29
70.7
34
82.9
Mongolia
10
4
40.0
6
60.0
10
100.0
New Caledonia
108
0
0.0
0
0.0
0
0.0
New Zealand
301
1
0.3
48
15.9
49
16.3
Papua New Guinea
54
0
0.0
0
0.0
0
0.0
Philippines
99
1
1.0
71
71.7
72
72.7
Singapore
160
12
7.5
122
76.3
134
83.8
Vietnam
129
45
34.9
70
54.3
115
89.1
South East Asian Region (n = 869)
India
36
8
22.2
28
77.8
36
100.0
Sri Lanka
115
12
10.4
94
81.7
106
92.2
Thailand
718
217
30.2
480
66.9
697
97.1

NS Not specified

Top of page

Table 2: Quinolone resistance in strains of Neisseria gonorrhoeae isolated in the World Health Organization Western Pacific Region and the South East Asia Region, 2008

Country
n Less susceptible Resistant All QRNG
    n % n % n %
Western Pacific Region
Australia
3,110
34
1.1
1,651
53.1
1,685
54.2
Brunei
353
92
26.1
168
47.6
260
73.7
China
1,403
53
3.8
1,348
96.1
1,401
99.9
Hong Kong SAR
1,393
12
0.9
1,362
97.8
1,374
98.6
Japan
328
14
4.3
240
73.2
254
77.4
Korea
141
29
20.6
106
75.2
135
95.7
Lao PDR
9
NS
NS
1
11.0
1
11.0
Malaysia
43
6
14.0
29
67.4
35
81.4
Mongolia
91
35
38.5
34
37.4
69
75.8
New Caledonia
152
2
1.3
3
2.0
5
3.3
New Zealand
258
2
0.8
53
20.5
55
21.3
Papua New Guinea
32
0
0.0
0
0.0
0
0.0
Philippines
84
4
4.8
68
81.0
72
85.7
Singapore
160
10
6.3
119
74.4
129
80.6
Vietnam
153
5
3.3
147
96.0
152
99.3
South East Asian Region
India 60 10 16.7 50 83.3 60 100.0
Myanmar 12 4 33.3 6 50.0 10 83.3
Sri Lanka 34 0 0.0 26 76.5 26 76.5
Thailand 754 162 21.5 570 75.6 732 97.1

NS Not specified

Top of page

Table 3: Penicillin resistance in strains of Neisseria gonorrhoeae isolated in the World Health Organization Western Pacific Region and the South East Asia Region, 2007

Country
n PPNG CMRP All Pen R
    n % n % n %
Western Pacific Region
Australia
3,042
369
12.1
796
26.2
1,165
38.3
Brunei
308
119
51.3
79
25.6
198
64.3
China
1,163
435
37.4
NS
ND
NS
NS
Fiji
345
22
6.4
12
3.4
34
9.8
Hong Kong SAR
1,478
498
33.7
384
26.0
882
59.7
Japan
329
4
1.2
53
16.1
57
17.3
Korea
56
7
12.5
24
42.9
31
55.4
Lao PDR
9
NS
NS
NS
NS
7*
78.0
Malaysia
41
11
26.8
5
12.2
25
61.0
Mongolia
10
0
0.0
7
70.0
7
70.0
New Caledonia
108
0
0.0
0
0.0
0
0.0
New Zealand
301
5
1.7
60
19.9
65
21.6
Papua New Guinea
54
40
74.1
0
0.0
40
74.1
Philippines
99
89
89.9
0
0.0
89
89.9
Singapore
160
83
51.9
7
4.4
90
56.3
Tonga
55
NS
NS
NS
NS
9*
16.4
Vietnam
129
48
37.2
0
0.0
48
37.2
South East Asian Region
India
36
13
36.1
4
11.1
17
47.2
Sri Lanka
39
24
61.5
2
5.1
26
66.7
Thailand
815
701
86.0
16/22
72.7
NS
NS

ND Gonococci in China were examined for penicillinase production only.

NS Not specified

* Laos, Tonga – mechanism of penicillin resistance not specified.

† Thailand, a subset of 22 non-PPNG strains were tested for chromosomal resistance.

Top of page

Table 4: Penicillin resistance in strains of Neisseria gonorrhoeae isolated in the World Health Organization Western Pacific Region and the South East Asia Region, 2008

Country
n PPNG CMRP All Pen R
    n % n % n %
Western Pacific Region
Australia
3,110
373
12.0
994
32.0
1,367
44.0
Brunei
351
201
70.5
44
12.5
245
69.8
China
1,403
543
38.7
ND
NS
NS
NS
Fiji
320
20
6.3
11
3.4
31
9.7
Hong Kong SAR
1,393
434
31.2
169
12.1
603
43.3
Japan
328
2
0.6
88
26.8
90
27.4
Korea
141
18
12.8
77
54.6
95
67.4
Lao PDR
9
NS
NS
NS
NS
7*
78.0
Malaysia
43
23
53.5
0
0.0
23
53.5
Mongolia
91
NS
NS
3
3.3
3
3.3
New Caledonia
152
0
0.0
2
1.3
2
1.3
New Zealand
258
6
2.3
57
22.1
63
24.4
Papua New Guinea
32
20
62.5
2
6.3
22
68.8
Philippines
84
76
90.5
0
0.0
76
90.5
Singapore
160
90
56.3
12
7.5
102
63.8
Tonga
14
1
7.1
0
0.0
1
7.1
Vietnam
153
40
26.1
9
5.9
49
32.0
South East Asian Region
India
60
20
33.3
5
8.3
25
41.7
Myanmar
12
2
16.7
8
66.7
10
83.3
Sri Lanka
34
18
52.9
1
2.9
19
55.9
Thailand
733
592
80.8
45/53
84.9
NS
NS

ND Gonococci in China were examined for penicillinase production only.

NS Not specified

* Laos – mechanism of penicillin resistance not specified.

† Thailand, a subset of 53 non-PPNG strains were tested for chromosomal resistance.

Top of page

N. gonorrhoeae in the WPR and SEAR have also been shown to have decreased susceptibility to third-generation cephalosporins for a number of years.4,7–12 This altered susceptibility was accompanied by treatment failures following therapy with oral third-generation cephalosporins in a significant number of cases.6,8,10,12 No major changes were evident in these patterns over the 2 years of surveillance reported here. There are however concerns in regard to assessments of the proportion of N. gonorrhoeae that display altered susceptibility to the third-generation cephalosporin antibiotics in the WHO WPR and SEAR. Surveillance of gonococcal susceptibility to ‘third-generation’ cephalosporins has emphasised the assessment of ceftriaxone susceptibility because of its wide use throughout both regions1 so that the MIC data reported here were based mostly on assessment of the in vitro susceptibility of gonococcal isolates to the injectable agent ceftriaxone. Recent investigations have shown that the mechanisms of resistance to the third-generation cephalosporins are multiple and complex and involve the aggregation and expression of a number of different genes within N. gonorrhoeae.15–17 The effects of this polygenic involvement on in vitro susceptibility of the injectable agents such as ceftriaxone and on the oral cephalosporins such as cefixime and ceftibuten differ considerably, meaning that susceptibility data for ceftriaxone cannot be used to predict reliably the outcomes of treatment with the oral drugs.4,12 Further, it would also appear that there is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise and report on the different MIC levels that arise with both the injectable and oral cephalosporins as the various resistance mechanisms aggregate over time in N. gonorrhoeae.4 This process is currently in train through WHO working groups.4 It is also now known that other important mechanisms of gonococcal cephalosporin resistance also exist, but are yet to be fully elucidated.16 In 2007 and 2008, these limitations were evident in reporting and in EQAS data.14 In 2009, a revised panel of WHO control strains was further developed and distributed in the WPR and SEAR. It is anticipated that more widespread use of these controls from 2010 onwards will better define ‘decreased susceptibility’, ‘non-susceptibility’ and ‘resistance’ to the different third-generation cephalosporin antibiotics.13,14,18 This is not an easy task because of the need to define ‘clinical’ as opposed to in vitro resistance through improved and more complete examination of gonococci isolated from documented treatment failures. Additionally, different jurisdictions may employ different treatment doses, especially for ceftriaxone1 that may alter MIC/outcome correlates. It is also established that elimination of N. gonorrhoeae from some infected sites is also more difficult, e.g. extra-genital tract infections are harder to eradicate.19 The following data are therefore indicative of a well documented increase in the MICs of cephalosporins in gonococci found in both regions. Sixteen centres examined N. gonorrhoeae for cephalosporin susceptibility in 2007 and 15 in 2008. The proportions of ‘resistant’, ‘less susceptible’ or ‘non-susceptible’ gonococci lay over a wide range in both years. A large number of centres including Australia, Fiji, India, Japan, Hong Kong, Korea, Laos, Malaysia, New Zealand, Papua New Guinea, the Philippines, Singapore, Thailand, Tonga and Vietnam reported no or very low proportions of strains with altered ceftriaxone susceptibility when tested in large numbers. Most of these centres tested isolates for susceptibility to ceftriaxone only, and i t is not surprising that very few strains exhibited altered susceptibility to this antibiotic. Brunei, China, Myanmar and Mongolia all reported ceftriaxone ‘resistant’ or ‘less susceptible’ gonococci in much larger proportions. The number of strains tested in the countries and jurisdictions mentioned above approximates those shown in Tables 1–4. Very few isolates were tested separately for their susceptibility to the oral cephalosporin agents. It is thus not possible at present to interpret the in vitro data in terms of likely clinical outcome other than in general terms.

Spectinomycin resistance has been only infrequently found in earlier reports in this series. A form of high level resistance due to a single-step ribosomal mutation has been described,20 and other reports of unexplained low level resistance or decreased susceptibility also occur. Fourteen centres examined gonococci for spectinomycin susceptibility in each year. Only a few sporadic cases of resistance to spectinomycin were found and in a limited number of settings in 2007–2008. Low numbers of isolates (10 or less) with in vitro resistance or decreased susceptibility to spectinomycin were found in Brunei, China, Japan, Laos, New Caledonia, Papua New Guinea and Thailand. The number of strains tested in the countries and jurisdictions mentioned above approximates those shown in Tables 1–4. The availability of spectinomycin as a treatment option has been significantly reduced following lack of reliable supplies of the drug. However, spectinomycin is still used as a first line and second line treatment in a number of WPR jurisdictions. Korea is one such country, and an outbreak of spectinomycin resistant N. gonorrhoeae was reported there many years ago. Notably, no spectinomycin resistance has been detected there for many years and overall resistance has remained low to this antibiotic in both regions.

Top of page

Tetracyclines are not a recommended treatment for gonorrhoea in the WHO WPR or SEAR, but historical data on the spread of 1 form of tetracycline resistance, namely a high level plasmid mediated type (TRNG), continues to be monitored in some countries. Eleven centres tested gonococci for this form of resistance in 2007 and 12 in 2008. In 2007 and 2008, up to 50% of gonococci examined exhibited this form of resistance. The proportion of TRNG has been high in some parts of the WPR for many years and between 35% and 55% of all strains in China, Hong Kong, Malaysia, the Philippines, Papua New Guinea, Singapore, Sri Lanka and Vietnam were TRNG, with proportions between 10% and 34% in Australia, India, Korea and New Zealand. The number of strains tested in the countries and jurisdictions mentioned above approximates those shown in Tables 1–4.

The complexities associated with surveillance in the WHO WPR and SEAR GASP have increased as the need for more and better quality surveillance of gonococcal antibiotic resistance has become more obvious.4–6 Resistance to other antibiotics, such as azithromycin, that are being used either as a primary treatment for gonorrhoea or as adjunctive treatment for other pathogens, is known to occur in the WHO WPR, but substantive data are not yet available. Of concern are recent reports elsewhere of high level azithromycin resistance following widespread use of this antibiotic.21

Given the past history of emergence and spread of antibiotic resistant gonococci identified in the WHO WPR and SEAR to other parts of the world,4 there is a high likelihood that, unless better disease control becomes a reality, new forms of resistance will continue to appear and spread. A suggested approach to the closely related issues of gonococcal disease control and AMR control in N. gonorrhoeae has recently been published from WHO sources.4 Implicit in these recommendations is the availability of reliable and verifiable antibiotic resistance surveillance data.

Top of page

Acknowledgement

This project was supported by means of a Technical Services Agreement between the WHO Collaborating Centre for STDs, Sydney and the WHO Western Pacific Regional Office, Manila.

Author details

Members of the WHO Western Pacific and South East Asian Gonococcal Antimicrobial Surveillance Programmes for 2007–2008: JW Tapsall and EA Limnios, Australia; Hjh Mahani Hj Abu Bakar, Brunei Darussalam; Yin Yue Ping, China; EM Buadromo, P Kumar and S Singh, Fiji; J Lo, Hong Kong; M Bala and A Risbud, India; T Deguchi, M Tanaka and Y Watanabe, Japan; K Lee and Y Chong, South Korea; S Noikaseumsy and T Phouthavane, Lao PDR; I-Ching Sam, Malaysia; O Tundev, Mongolia; KM Lwin and PH Eh, Myanmar; C Goarant and R Goursaud, New Caledonia; T Bathgate and M Brokenshire, New Zealand; L Latorre and E Velemu, Papua New Guinea; C Carlos, S Leano and EO Telan, Philippines; SS Goh, ST Koh, C Ngan and AL Tan, Singapore; S Mananwatte, Sri Lanka; N Piyanoot, S Lokpichat and P Sirivongranson, Thailand; M Fakahau and H Sitanilei, Tonga; Le Van Hung, Vietnam.

Correspondence: Associate Professor John Tapsall, WHO Collaborating Centre for STD, Department of Microbiology, The Prince of Wales Hospital, RANDWICK NSW, Australia 2031. Facsimile: +61 2 9398 4275. Email: j.tapsall AT unsw.edu.au

Top of page

References

1. 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 Infect 2009;85(4):256–258.

2. The 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(1);32:48–51.

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(6):523–525.

4. Tapsall JW, Ndowa F, Lewis DA, Unemo M. Meeting the public health challenges of multi- and extensively-drug resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther 2009;7(7):821–834.

5. Workowski KA, Berman SM, Douglas JM Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. [Erratum in Ann Intern Med 2008;148(11):888.] Ann Intern Med 2008;148(8):606–613.

6. Deguchi T, Yasuda M, Maeda S. Lack of nationwide surveillance of antimicrobial resistance in Neisseria gonorrhoeae in Japan. Ann Intern Med 2008;149(5):363–364.

7. WHO Western Pacific Region Gonococcal Surveillance Programme. Surveillance of antibiotic susceptibility of Neisseria gonorrhoeae in the WHO Western Pacific Region 1992–4. Genitourin Med 1997;73(5):355–361.

8. 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(12):3744–3749.

9. Ito M, Deguchi T, Mizutani KS, Yasuda M, Yokoi S, Ito S, 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(1):137–143.

10. 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(8):1275–1277.

11. Tapsall JW, Ray S, Whiley D, Lo JY, Lo AC, Deguchi T. Widespread distribution in the Asia-Pacific of a cephalosporin-resistant sequence type of Neisseria gonorrhoeae associated with treatment failure and with a mosaic PBP2. 2008; 16th International Pathology Neisseria Conference; Abstract. P052.

12. Lo JY, Ho KM, Leung AO, Tiu FS, Tsang GK, Lo AC, Tapsall JW. Ceftibuten resistance and treatment failure in gonococcal infection. Antimicrob. Agent Chemother. 2008;52(10):3564–3567.

13. Unemo M, Fasth O, Fredlund H, Limnios A, Tapsall J. Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J Antimicrob Chemother 2009; 63(6):1142–1151.

14. Bala M, Tapsall JW, Limnios A, Sood S, Ray K. Experience with an external quality assurance scheme for antimicrobial susceptibility testing of Neisseria gonorrhoeae in India, 2001–2007. Epidemiol Infect 2010;138(1):69–75.

15. 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(6):2117–2122.

16. Zhao S, Duncan M, Tomberg J, Davies C, Unemo M, Nicholas RA. Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2009;53(9):3744–3751.

17. 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. Inter J Antimicrob Agents 2006;27(1):20–26.

18. World Health Organization GASP. Rationale and applications for the current (2008) WHO panel of Neisseria gonorrhoeae for antimicrobial resistance surveillance for public health purposes, and instructions for their use. 2008. Technical document D007-0408-1, WHO Collaborating Centre for STD, Sydney.

19. Tapsall J, Read P, Carmody C, Bourne C, Ray S, Limnios A, et al. Molecular microbiological methods used to verify two cases of failed ceftriaxone treatment in pharyngeal gonorrhoea. J Med Microbiol 2009;58(Pt 5):683–687.

20. Galimand M, Gerbaud G, Courvalin P. Spectinomycin resistance in Neisseria spp. due to mutations in 16S rRNA. Antimicrob Agents Chemother 2000;44(5):1365–1366.

21. Palmer HM, Young H, Winter A, Dave J. Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother 2008;62(3):490– 494.

Communicable Diseases Intelligence subscriptions

Sign-up to email updates: Subscribe Now

This issue - Vol 34 No 1, March 2010