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Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis
  1. Manju Bala1,
  2. Monika Kakran1,
  3. Vikram Singh1,
  4. Seema Sood2,
  5. V Ramesh1,
  6. Members of the WHO GASP SEAR Network
  1. 1Apex Regional STD Teaching, Training & Research Centre, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India
  2. 2Department of Microbiology, AIIMS, New Delhi, India
  1. Correspondence to Dr Manju Bala, Apex Regional STD Teaching, Training & Research Centre, 5th Floor, New OPD Building, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, 110029, India; manjubala_2{at}hotmail.com

Abstract

Objective The aim of the present study was to retrospectively analyse the data reported on antimicrobial resistance (AMR) in Neisseria gonorrhoeae in six South-East Asia Region countries from 2009 to 2012 following the revitalisation of the WHO global Gonococcal Antimicrobial Surveillance Program (GASP).

Methods AMR data were generated for 7 antibiotics of 4675 isolates in 18 focal point laboratories using the calibrated dichotomous sensitivity (CDS) or Clinical and Laboratory Standards Institute (CLSI) methods and minimal inhibitory concentration testing by Etest in some of the centres. The results were interpreted using the breakpoints recommended.

Results High-level resistance to traditional antibiotics, penicillin (25% to 100%) and tetracycline (10% to 100%) and the previously recommended ciprofloxacin (38% to 100%) was observed in all the countries. Overall, >90% of less susceptible and resistant isolates to penicillin and ciprofloxacin were identified from 15 laboratories. Decreased susceptibility to ceftriaxone and cefpodoxime was reported by nine and eight centres, respectively. Resistance to spectinomycin (0.6% to 10.5%) and azithromycin (<5%) was reported only by three centres. The increasing trends of resistance towards penicillin, tetracycline and ciprofloxacin were demonstrated in Bhutan, India, Sri Lanka and Thailand, and no large intercountry variations were evident. Insignificant trends in decreased susceptibility towards ceftriaxone were reported.

Conclusions Expansion of the WHO GASP facilitated enhanced AMR surveillance to meet the ongoing challenges of control of gonococcal AMR. The results highlight that the emergence of decreased susceptibility to ceftriaxone and resistance to spectinomycin and azithromycin will unavoidably lead to loss of therapeutic options, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.

  • Antibiotic Resistance
  • Surveillance
  • Neisseria Gonorrhoea
  • Syndromic Management
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Introduction

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious threat to public health, contributing to health and economic losses worldwide. Systematic AMR surveillance of N gonorrhoeae at local, regional, national and global levels helps to detect the emergence of new resistance, monitor changing patterns of susceptibility and allows treatment recommendations to be updated on a regular basis. The WHO, therefore, established the Gonococcal Antimicrobial Surveillance Program (GASP) in 1990.1 Establishment of global WHO GASP across all regions assists in generating AMR data, and compiling and disseminating the information. GASP is important in assisting national programmes and healthcare providers in making recommendations regarding effective antibiotics for treatment.

WHO GASP was established in the South-East Asia Region (SEAR) in 1997. The Regional STD Teaching, Training and Research Centre at Safdarjung Hospital, New Delhi, India was recognised as the Regional Reference Laboratory (RRL) for WHO GASP in SEAR in 1999. Almost all SEAR countries have limited data, but there are some areas where continuous data are available and some countries where only intermittent data are available.2–11

There was a revitalisation of GASP by WHO Headquarters, Geneva in 2009 following the emergence of resistance to and treatment failures in the use of extended spectrum cephalosporins (ESCs), currently the recommended first-line treatment. Quality-assured systems for collection, storage and transportation of clinical specimens, N gonorrhoeae cultures and antimicrobial susceptibility testing (AST) were implemented in more centres in SEAR countries after the training in GASP techniques in 2009, 2010 and 2012. Subsequently, the WHO has published the ‘Global Action Plan to Control the Spread and Impact of AMR in N gonorrhoeae’.12 ,13 The main components of the global action plan are to enhance AMR surveillance worldwide, facilitate early detection and verification of resistance and treatment failure to recommended treatment (particularly ESCs), advocacy for increased awareness on correct use of antibiotics among healthcare providers and the consumers and research to identify alternative effective treatment strategies.

In response to this developing situation, this study was conducted to analyse the AMR profile of N gonorrhoeae in selected SEAR countries, based on retrospective AMR data communicated by the focal point laboratories participating in the WHO GASP during the period 2009 to 2012. It also describes the trends in resistance to various antimicrobials during the period mentioned.

Materials and methods

Participating laboratories and study population

In the present study, AMR data from January 2009 to December 2012 from 18 focal point laboratories in 6 SEAR countries (namely Bhutan, Indonesia, India, Myanmar, Sri Lanka and Thailand) were analysed. There were 9 focal point laboratories for GASP in 2009, 15 in 2010 and 18 in 2011 and 2012 (table 1). As the present report describes the results reported from different focal-point laboratories in different countries, the study populations differed in each setup, as shown in table 1.

Table 1

Details of 18 focal point laboratories in the 6 countries of the South-East Asia Region

Isolation and identification of N gonorrhoeae

N gonorrohoeae cultures were grown and identified by all the laboratories following the standard procedures.14–17

Antimicrobial susceptibility testing

The disc-diffusion method for AST using either the calibrated dichotomous sensitivity (CDS) technique or the Clinical and Laboratory Standards Institute (CLSI), was the only feasible system suitable for widespread use in the GASP SEAR Network because of the cost and complexity of minimal inhibitory concentration (MIC) determination. MIC testing was performed by the Etest method (AB Biodisk, Sweden) only at the RRL and three other centres (table 1). Consecutive isolates were subjected to AST in all the laboratories. AST was carried out for penicillin, tetracycline, ciprofloxacin, third-generation cephalosporin (ceftriaxone and cefpodoxime), azithromycin and spectinomycin (Oxoid Basingstoke, UK/Himedia Laboratories Ltd., India) using concentrations recommended.14–17 The susceptibility testing was performed on chocolate agar with a Columbia agar base for the CDS technique, and GC agar base+haemoglobin/sheep blood and Isovitalex/Vitamino growth supplement was used for the CLSI method. The source of media components was either from BBL (now Becton Dickinson, Sparks, Maryland, USA), Difco or HiMedia. The interpretive criteria used for analysis were those recommended by the CDS and CLSI guidelines.16 ,17 Analysis of multidrug-resistant N gonorrhoeae (MDR-NG) was carried out according to the definition proposed by Tapsall et al.18

Trends in the proportion of strains resistant to penicillin, tetracycline, ciprofloxacin and ceftriaxone for the period 2009–2012 were determined from aggregated national data from four centres in Bhutan, from two centres in India (RRL and Delhi, AIIMS) and one each from Sri Lanka and Thailand.

β Lactamase testing

β Lactamase production was identified by chromogenic cephalosporin method using nitrocefin freeze-dried powder (Oxoid) or nitrocefin discs (Cefinase discs; Becton Dickinson), according to the manufacturer's instructions.

Preservation of clinical isolates and quality control (QC) strains

Details regarding the methods used by the participating laboratories for preservation of clinical isolates and QC strains are provided in table 1.

Quality assurance among SEAR countries: QC strains, control strains and external quality assurance scheme (EQAS)

QC strains such as WHO reference strains or ATCC 49226 were used as controls for disc diffusion and MIC testing. Details about the reference strains used by each centre for quality assurance (QA) and QC of gonococcal AMR surveillance and the control strains having in stock in the year 2012 are listed in table 1.

Comparability of data was obtained by the uniformity of methods and the QC and EQAS programmes. Participation in EQAS programmes and appropriate use of the WHO reference panel by GASP focal point laboratories is a necessary requirement for the validation of gonococcal AMR data. The Inter-RRL, located at the WHO Collaborating Centre for sexually transmitted infections (STIs) in Sydney (WHO CC-Sydney), Australia, provided technical support, reference panels of gonococci for use in internal QC and organised the EQAS every year for these laboratories. In India, RRL organised the EQAS in collaboration with WHO CC-Sydney since 2000 and provided the above-mentioned support for nine laboratories. The WHO EQAS programme included dispatching a panel of six QA strains each year as unknowns to each participating laboratory. Participating laboratories in SEAR countries sent EQAS data to the WHO CC-Sydney and in India to RRL, where data were analysed and feedback was provided to the participating laboratories.19 Focal point laboratories from India (RRL), Thailand, Myanmar and Sri Lanka have participated in the programme since its inception. Bhutan has participated since the year 2009.

Treatment guidelines for gonococcal infections in participating countries

In Bhutan, Indonesia, Myanmar and Thailand, injectable third-generation cephalosporin (ceftriaxone 250 mg intramuscularly) or oral third-generation cephalosporin (cefixime 400 mg) is being used for the management of gonococcal infections. In India, as per National AIDS Control Organisation guidelines, syndromic management (cefixime 400 mg+azithromycin 1 g) is recommended in all STI clinics while in Sri Lanka, cefuroxime axetil 1 g is used (table 1).

Statistical analysis

The differences in percentages were statistically compared, tested for significance using the χ2 test, and then p values were determined.

Results

N gonorrhoeae isolates from most of the centres were mainly from male patients, except from Myanmar where the isolates were from female sex workers (table 1). During the study period, 4675 isolates were tested by 18 centres. The total number of isolates from each country varied from 24 (Indonesia) to 2496 (Thailand) during these 4 years. The number of consecutive isolates that were subjected to AST increased from 1136 in 2009 to 1224 in 2012 (table 1).

Status of overall resistance profile and trend of AMR for various antimicrobials in different SEAR countries

Penicillin

The percentages of resistant isolates in the reporting laboratories ranged from 25% (Pune) to 100% (ERRH Mongar, GH (General Hospital) Phuentsholing, Delhi Maulana Azad Medical College (MAMC)). Three and nine laboratories reported figures of 25% to 50% and 50% to 90%, respectively, while the remaining five laboratories reported resistant percentages above 90% (figure 1). Indonesia did not carry out testing for penicillin. Resistant isolate data in figure 1 includes penicillinase producing N gonorrhoeae (PPNG) and chromosomally-mediated resistance N gonorrhoeae (CMRNG), except from Central Regional Referral Hospital (CRRH) Gelephu, ERRH Mongar, GH Phuentsholing and Vadodra, as these laboratories did not perform β lactamase testing. The PPNG percentage varied from 0% (Pune, Nagpur) to 88.9% (Jigme Dorji Wangchuk National Referral Hospital (JDW/NRH), Bhutan) with University College of Medical Sciences and Guru Tegh Bahadur Hospital (UCMS and GTB), Delhi reporting 19.6%, Myanmar 35%, Hyderabad 41.9%, Chennai 50%, AIIMS Delhi 50.6%, RRL 53.8%, Kolkata 52.6%, Sri Lanka 63.6%, Thailand 84% and Delhi MAMC 88.2% (table 2). Less susceptible isolates ranged from 0% to 75% (table 2). Overall, a high percentage (>90%) of less susceptible and resistant isolates were identified from 15 out of 18 focal point laboratories. Thailand, CRRH Gelephu, RRL, Chennai, Hyderabad and Myanmar reported 0.2%, 1.2%, 5.8%, 10%, 16.1% and 32.5% isolates as susceptible to penicillin, respectively. Vadodra reported one out of two isolates tested to be susceptible.

Table 2

Number of Neisseria gonorrhoeae isolates tested for 7 antimicrobials and the antimicrobial susceptibility profile in 18 participating laboratories

Figure 1

Percentages of Neisseria gonorrhoeae isolates demonstrating overall resistance and decreased susceptibility to the 4 antimicrobials from 2009 to 2012 in 18 focal point laboratories in 6 South-East Asia Region countries. AIIMS, All India Institute of Medical Sciences; Ceft DS, ceftriaxone decreased susceptibility; CRRH, central regional referral hospital; ERRH, eastern regional referral hospital; GH, general hospital; JDW/NRH, Jigme Dorji Wangchuk National Referral Hospital; LS, less susceptible; MAMC, Maulana Azad Medical College; NARI, National AIDS Research Institute; R, resistant; Tet R, tetracycline resistant; UCMS and GTB, University College of Medical Sciences and Guru Tegh Bahadur Hospital.

The trends for the period 2009–2012, for the N gonorrhoeae isolates resistant and less susceptible towards penicillin in the four SEAR countries are shown in figure 2A. Penicillin resistance in Bhutan decreased significantly (χ2=7.27, p<0.05) from 99.4% in 2009 to 94.8% in 2012 with concomitant significant (p<0.05) increase of penicillin less susceptible strains from 0.5% in 2009 to 5.2% in 2012. In contrast, in India, penicillin resistance increased significantly (χ2=9.19, p=0.01) from 49.1% in 2009 to 73.9% in 2012 with concomitant (p>0.05) decrease of penicillin less susceptible strains from 43.8% in 2009 to 25% in 2012. Resistance to penicillin in Sri Lanka decreased insignificantly (χ2=0.49, p>0.05) from 80% in 2009 to 74.4% in 2010 and thereafter, there was increase (χ2=0.61, p>0.05) to 81.2% in 2012. However, penicillin less susceptible isolates increased insignificantly (χ2=3.57, p>0.05) from 6.7% in 2009 to 18.7% in 2011 with subsequent decrease (χ2=1.12, p>0.05) to 10.4% in 2012. In Thailand, 87.7% resistance to penicillin was reported in 2009, which reduced to 80.8% (χ2=12.28, p=0.002) in 2011, with significant (χ2=8.85, p=0.012) increase to 87.1% in 2012. A significant rise (p<0.05) in penicillin less susceptible strains from 12.3% in 2009 to 19.2% in 2011 was observed and it decreased to 12.7% (p<0.05) in 2012.

Figure 2

Trends for Neisseria gonorrhoeae antimicrobial resistance in four South-East Asia Region countries. A. Trends of penicillin resistant and less susceptible isolates. B. Trends of tetracycline resistance and ceftriaxone decreased susceptibility. C. Trends of ciprofloxacin resistant and less susceptible isolates. Ceft DS, ceftriaxone decreased susceptibility; LS, less susceptible; R, resistant; Tet R, tetracycline resistant.

Tetracycline

Resistance to tetracycline varied from 9.8% to 100% and it includes tetracycline resistant N gonorrhoeae (TRNG) and chromosomally mediated resistance (CMR) isolates for some laboratories and only TRNG or CMR isolates from other centres based on the techniques used for AST. UCMS and GTB Delhi, Hyderabad, Kolkata, Nagpur, Vadodra, Myanmar and Sri Lanka only differentiated between TRNG and not-TRNG isolates based on the CDS technique. RRL, AIIMS Delhi and Thailand further characterised not-TRNG isolates as resistant (9.9%, 30.4% and 59.5%, respectively), less susceptible (30.4%, 30.4% and 9.9%) and susceptible (28.6%, 8.9% and 8.1%) by MIC testing (table 2). Resistance of between 50% to 90% was reported by AIIMS Delhi, Chennai, Myanmar and Thailand. All four laboratories in Bhutan and Indonesia reported more than 95% resistance to tetracycline (figure 1).

The trends for tetracycline resistance are shown in figure 2B. In Bhutan, there was a rise (χ2=2.13, p>0.05) in the percentage of resistance to tetracycline from 99.2% in 2009 to 100% in 2011 and this was maintained in 2012. The tetracycline resistance increase from 2009 to 2011 was observed to be highly significant in India (from 28.1% to 58.5% (χ2=10.38, p=0.0056)) and Sri Lanka (8% to 50% (χ2=25.84, p<0.001)) followed by a decrease in 2012 to 55.7% (χ2=0.10, p>0.05) in India and to 12.5% (χ2=14.47, p=0.0007) in Sri Lanka. In Thailand, susceptibility testing for tetracycline was carried out only in 2012. Therefore, a trend for tetracycline resistance is not depicted for Thailand.

Ciprofloxacin

Rates of resistance and less susceptibility to ciprofloxacin, the previously recommended treatment, were very high across SEAR laboratories (90% to 100% for 14 centres and 57% to 74% for 3 centres), indicating that its usage is no longer appropriate (figure 1). High-level resistance based on MIC values (≥4 mg/mL) was reported only by RRL and AIIMS Delhi and was observed to be 49.1% and 57%, respectively.

The antimicrobial susceptibility trends of N gonorrhoeae isolates towards ciprofloxacin are shown in figure 2C. Two out of the four SEAR countries (India (94.7% in 2009 to 97.7% in 2012, χ2=0.93, p>0.05) and Thailand (76.2% to 87%, χ2=27.67, p<0.0001)) had increasing trends of resistance to ciprofloxacin over the last 4 years. In Bhutan, ciprofloxacin resistance increased significantly (χ2=6.38, p<0.05) from 95.8% in 2009 to 98.7% in 2011 followed by a drop in 2012 to 91.8% (χ2=16.69, p<0.001). There was an insignificant reduction (χ2=1.13, p>0.05) in the percentage of ciprofloxacin less susceptible isolates from 2.2% in 2009 to 0.9% in 2010 and a subsequent rise (χ2=1.92, p>0.05) to 2.6% in 2012. In Sri Lanka, ciprofloxacin resistance decreased (χ2=0.77, p>0.05) from 92% in 2009 to 86.8% in 2011 and increased to 95.8% (χ2=2.29, p>0.05) in 2012.

Cephalosporins

Decreased susceptibility to the injectable third-generation cephalosporin, ceftriaxone, was reported from 9 out of 18 laboratories and varied between 0.1% and 84.2% (figure 1). The rate of decreased susceptibility was less than 10% from six of the centres. In Sri Lanka in 2012, 12.5% and 6.2% isolates, respectively, were found to be resistant and less susceptible to the second-generation cephalosporin, cefuroxime, recommended for treatment. In 2009, only 1 isolate out of 74 had been observed to be resistant to cefuroxime. All these strains were susceptible to ceftriaxone and the patients were treated either with ceftriaxone 250 mg intravenously or with cefixime 400 mg.

Testing for oral third-generation cephalosporin, cefpodoxime started in RRL, AIIMS Delhi, JDW/NRH Bhutan in 2009, 2009, 2011, respectively. A total of 5.8%, 7.6%, 0.9% isolates, respectively, were found to have decreased susceptibility to cefpodoxime and ceftriaxone from the above centres. In other centres in India such as Chennai, Delhi MAMC, Hyderabad, Kolkata and Nagpur, testing for cefpodoxime was initiated in 2012 and 0/2, 0/17, 0/14, 11/19 and 2/5 isolates, respectively, showed decreased susceptibility to cefpodoxime (table 2).

Insignificant trends in decreased susceptibility towards ceftriaxone were reported from the four SEAR countries during the study period (figure 2B). This increased from 2009 to 2011 in Bhutan (0 to 1.9% (χ2=3.49, p>0.05)) and India (5.3% to 9.4% (χ2=0.70, p>0.05)) and thereafter, in 2012, decreased to 0.4% (χ2=2.80, p>0.05) in Bhutan and 1.1% (χ2=5.60, p>0.05) in India.

Spectinomycin

Resistance to spectinomycin was reported only from JDW/NRH Bhutan, CRRH, Gelephu and Kolkata and it was observed to be 0.6%, 1.2% and 10.5%, respectively. Testing for spectinomycin was not carried out in Indonesia. Only 1 isolate out of 2898 tested in Thailand was found to be less susceptible (table 2).

Azithromycin

The number of isolates with relevant AST information for azithromycin reported by the 11 participating laboratories ranged from 2 to 2893 (table 2). Azithromycin testing in AIIMS Delhi, RRL and Thailand was carried out throughout the study period by CDS and Etest and <5% (3.8%, 2.3% and 0.3%, respectively) isolates were observed to be resistant. Testing by CDS technique was established in five laboratories (UCMS and GTB Delhi, Chennai, Delhi MAMC, Kolkata, Vadodra) in 2011 and in three centres (JDW/NRH Bhutan, Hyderabad, Nagpur) in 2012, and all the isolates were susceptible to azithromycin except in Vadodra, where one out of two isolates tested was reported to be resistant.

No strain was observed to be MDR-NG in the present study.

Discussion

The origins and procedures of the GASP and early outcomes of the programme have been published previously.4 ,8 The first study for surveillance of AMR trends in selected SEAR countries was carried out between 1996 and 2000.4 Thereafter, annual surveillance results for antibiotic resistance were reported from 2007 onwards.9–11 Of the 11 WHO SEAR member states (Bangladesh, Bhutan, DPR Korea, Indonesia, India, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste), 6 countries (Bhutan, Indonesia, India, Myanmar, Sri Lanka and Thailand) are at present participating in the AMR surveillance programme. Bangladesh and Nepal participated initially but later discontinued their involvement.4 ,8

This report provides an insight into the AMR data reported to RRL by 18 focal point laboratories and further analyses of trends in AMR in gonococci isolated during the period 2009 to 2012. Some of the participating centres reported very low numbers of isolates; such findings that are not truly representative of the country data. One factor that may be responsible is that STI doctors do not collect the specimens before management. Laboratory capacities for culture are also decreasing as more laboratories are using nucleic acid amplification tests for diagnosis.

In the present study, the high percentages of resistance reported towards penicillin, tetracycline and ciprofloxacin and increasing trends of resistance to these antibiotics in SEAR countries reinforce the fact that these antimicrobials should not be used for the treatment of gonorrhoea. These findings are consistent with the recent data from the GASP in other WHO regions (the Western Pacific Region, Latin America and the Caribbean, Russia, Europe and Africa).9–11 20–23 It also demonstrates that penicillin, tetracycline and ciprofloxacin resistance has continued to increase in spite of these drugs not being used for treatment of gonococcal infections, indicating ongoing selective pressure produced by the use of these antimicrobials to treat other infections.

Decreased susceptibility to the third-generation cephalosporin, ceftriaxone, continued to increase in Bhutan and India from 2009 to 2011 but decreased for the first time in 2012. It has also been reported in England and Wales that decreased susceptibility to another third-generation cephalosporin, cefixime, declined in 2011 for the first time since 2007.24 This may be indicative of the benefits of treating gonorrhoea with a combination treatment under syndromic management. The current SEAR GASP data suggests no immediate threat to the efficacy of the currently recommended treatment, third-generation cephalosporins, in SEAR countries. However, ceftriaxone treatment failures have been reported in Japan, France and Spain.25–27 The emergence of decreased susceptibility to ceftriaxone and cefpodoxime threatens the future use of this class of antimicrobials for gonorrhoea treatment. The recommended combination of cefixime along with azithromycin in syndromic management should delay development and dissemination of resistance to third-generation cephalosporins, but it should be noted that high-level azithromycin resistance has been reported from some countries. Resistance to azithromycin was reported from three centres in the present study. Emergence of high-level azithromycin resistance in isolates showing decreased susceptibility or resistance to ceftriaxone would present a major public health challenge.

Spectinomycin resistance, although less than 5%, was demonstrated in two laboratories in Bhutan and the emergence of spectinomycin resistance is worrisome. One of the focal point laboratories in India reported 10.5% (2/19) of strains as being resistant to spectinomycin. However, these two strains and strains having decreased susceptibility to ceftriaxone and cefpodoxime (unconfirmed by MIC) from some laboratories were not received in RRL for confirmation. The results highlight the importance of QA in AST in different laboratories and validation of AMR data.

In summary, AMR monitoring requires close attention as the percentages of isolates resistant to many antimicrobials continue to increase throughout SEAR countries. Especially worrisome is the emergence of decreased susceptibility to third-generation cephalosporins and resistance to spectinomycin and azithromycin. The emergence of resistance to cefuroxime (12.5%), recommended for treatment in Sri Lanka, highlights that cefuroxime should be removed from treatment guidelines.

AMR surveillance data are absent from SEAR countries such as DPR Korea, Maldives, Nepal and Timor-Leste. There is, therefore, an urgent need to include these countries in the GASP network and to strengthen and expand GASP in existing centres to provide valid and comparable data. Moreover, increased emphasis on translating data into action calls for concerted efforts at the member state level, but also close international cooperation in order to preserve antimicrobial effectiveness and access to effective treatment, is needed. In future, more centres from each country and more countries should be involved to ensure continuous local, regional and national surveillance of antibiotic susceptibility, and efforts are being made for the same by WHO headquarters and regional offices, RRL, WHO CC-Sydney and other national-level organisations, as is evident from the ever-increasing GASP network of laboratories from the year 2000 onwards. This should encourage the implementation, maintenance and improvement of national AMR surveillance programmes and should provide timely AMR data that constitute a basis for policy decisions to modify the national treatment guidelines from time to time. At the same time, a search for new effective agents should be initiated in important centres in collaboration with the national reference centres.

Key messages

  • This study reports high-level resistance to penicillin, tetracycline and ciprofloxacin in 15 focal point laboratories in 6 South-East Asia Region (SEAR) countries, emphasising their future unsuitability for use.

  • The emergence of decreased susceptibility to third-generation cephalosporins and resistance to alternative treatment options, spectinomycin and azithromycin, in SEAR countries is a cause of concern.

  • Emergence of cefuroxime resistance (12.5%) in Sri Lanka indicates that this antimicrobial should be removed from treatment guidelines for gonorrhoea.

  • Expansion of the WHO Gonococcal Antimicrobial Surveillance Program in other SEAR countries and its strengthening in existing focal point laboratories would contribute to the control of gonorrhoea.

Acknowledgments

The authors are indebted to the late Professor John W Tapsall, Dr Monica M Lahra and Ms Athena Limnios, WHO collaborating centre for STD, Department of Microbiology, The Prince of Wales Hospital, Sydney, Australia for supplying WHO reference strains, low concentration antibiotic discs and technical guidance. The authors thank the Medical Superintendent, VMMC and Safdarjung Hospital for permitting us to carry out this study. We are thankful to Leelamma Peter, Naveen Chandra Joshi, Rajinder Singh (India), Hemali hattanayake (Sri Lanka), Ratana Lawung, Angkana Charoenwatanachokchai, Jirayu Caskey (Thailand) and to the staff of all the focal point laboratories for their contribution to these studies.

References

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Footnotes

  • Handling editor Jackie A Cassell

  • Collaborators Members of the WHO GASP SEAR Network are: Bhutan: Dorji Dorji, Tshokey, Jigme Dorji Wangchuk National Referral Hospital (JDW/NRH), Thimpu; Indonesia: Anis Karuniawati, Medical Faculty, University of Indonesia, Dr Cipto Mangunkusumo Hospital, Jakarta; India: Arun Risbud, Sangeeta Kulkarni, National AIDS Research Institute, Pune; VG Ramachandran, Shukla Rudra, Rumpa Saha, University College of Medical Sciences and GTB Hospital, Delhi; N Thilakavathi, Mangala Adisesh, Institute of Venereology, Chennai; Preena Bhalla, Deepti Rawat, Maulana Azad Medical College, Delhi; G Sasi Kala, Osmania General Hospital, Hyderabad; Ishita Ghosh, Gopi Thawani, Institute of Serology Kolkata; Supriya Tankhiwale, VR Shegokar, Government Medical College, Nagpur; Tanuja Javadekar, Baroda Medical College, Vadodra; Myanmar: Eh Htoo Pe, National Health Laboratory, Yangon; Sri Lanka: Sujatha Mananwatte, National STD/AIDS Control Programme, Colombo, Lilani Karunanayake, Medical Research Institute, Colombo; Thailand: Busaba Thaipitakpong, Piyanoot Noja, Malai Khamhaeng, Prisana Buasakul, Bureau of AIDS, TB and STIs, Department of Disease Control, Ministry of Public Health, Bangkok.

  • Contributors MB was the surveillance and microbiology lead for WHO GASP in SEAR countries, involved in creation and expansion of the GASP network, designed the study, coordinated the work, collected the data, carried out analysis of data and preparation of the manuscript. MK participated in data analysis and preparation of the manuscript. VS, SS and VR collaborated in the writing of the manuscript. All authors of the WHO GASP SEAR Network contributed to data analysis from their centres. Guarantor of the article: MB.

  • Funding Financial support for this study was provided by the World Health Organization (S16-APW-028, SEA-2012-A20-APW-011), National AIDS Control Organization, India (F.9(58)DSACS/STI(AD)/NACP-III/2009-10) and Indian Council of Medical Research (ID No. 2006-0685).

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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