crossmark LETTER TO THE EDITOR
Antimicrobial Susceptibility of Neisseria gonorrhoeae in Bangladesh (2014 Update) Rasheda Khanam,a,b Dilruba Ahmed,a Tasnim Azima
Mustafizur Rahman,a M. S. Alam,a Mausumi Amin,c Sharful Islam Khan,a Kenneth H. Mayer,d
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesha; International Center for Maternal and Newborn Health, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAb; Save the Children, Dhaka, Bangladeshc; Fenway Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USAd
D
ocumentation of Neisseria gonorrhoeae resistance to multiple antibiotics globally has given rise to major concerns regarding a future of untreatable gonorrhea (1, 2). In Bangladesh, N. gonorrhoeae antimicrobial susceptibility was last examined between 1997 to 2006 in female sex workers (FSWs), males having sex with males (MSMs), patients with sexually transmitted infections (STIs), and truckers, and resistance to ciprofloxacin, penicillin, and tetracycline with reduced susceptibility to cefixime as well as multidrug resistance were reported (3–5). The present analysis was conducted to update these data so as to inform guidelines on syndromic management of sexually transmitted infections (STIs) developed in 2006 (6) that are currently being used in Bangladesh and to enhance global surveillance by the World Health Organization. The current report presents data on antimicrobial resistance of N. gonorrhoeae from a cross-sectional bio-behavioral survey of STIs conducted among key populations (KPs) at risk of HIV in Dhaka, Bangladesh, between August and November 2014. The KPs included FSWs (n ⫽ 700), females who injected drugs (FWIDs; n ⫽ 177), male sex workers (MSWs; n ⫽ 227), and transgender women known as Hijras (n ⫽ 169). All were adults (ⱖ18 years) and were enrolled on a first-come, first-served basis from drop in centers (DICs) under the Global Fund Program for HIV, which provides STI prevention services to enlisted KPs. Individuals were enrolled only if they provided written informed consent for their participation in the study. The study was approved by the Research and Ethical Review Committees of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Study physicians conducted physical examinations and collected cervical swabs under speculum examination (FSWs and FWIDs) and anorectal swabs (MSWs and Hijras) using aseptic techniques. All swabs were transported to icddr,b in Amies charcoal transport medium within 6 to 8 h of collection. Swabs were cultured for identification of N. gonorrhoeae, and antibiotic susceptibility testing was carried out for positive isolates. Anorectal swabs were directly inoculated onto modified Thayer-Martin (MTM) agar containing vancomycin, colistin, nystatin, and trimethoprim. Cervical swabs were inoculated onto MTM agar, blood agar, and chocolate agar media. After inoculation, all plates were incubated under microaerophilic conditions (5% O2) at 35°C for at least 48 h. The identity of N. gonorrhoeae was confirmed by Gram stain, oxidase test, and Neisseria sugar test (carbohydrate degradation test). Antimicrobial susceptibility testing (AST) was performed by the Kirby-Bauer method (disc diffusion), breakpoints of sensitive, intermediate, and resistant were interpreted following Clinical and Laboratory Standards Institute (CLSI)
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guidelines (7), and N. gonorrhoeae reference strain ATCC 49226 was used as a standard. Of the 1,273 samples, 21 (5 anorectal and 16 cervical) tested positive for N. gonorrhoeae by culture. This low isolation rate (1.6%) can be explained by the fact that antibiotics were frequently given to our study participants through the HIV/STI prevention program that might have caused a reduction in the bacterial load such that it was undetectable in culture. All N. gonorrhoea cultures were tested for AST, and the results are shown in Table 1. Ceftriaxone and spectinomycin were the antibiotics to which all isolates were susceptible. The next most sensitive antibiotic was azithromycin (90.5%), followed by cefixime (85.7%). None of the isolates were sensitive to ciprofloxacin, to which resistance was found in 95.2% and intermediate resistance in 4.8% of isolates. More than 90% of the isolates were resistant to doxycycline. Multidrug resistance (against three or more antibacterial agents) was identified in 48% of isolates. Antibiotic resistance data obtained from this study are comparable to data from an earlier study (5). In this study, all participants diagnosed with STIs were provided treatment using the national STI management guidelines. The possibility of treatment failure remains given the antimicrobial resistance profile. Extrapolation of these study findings to all of Bangladesh is not possible as the study was conducted only among those KPs who were receiving STI services from DICs. Approximately half of the study participants were diagnosed with STIs previously (data not shown), using the syndromic approach, and many had received antimicrobial therapy, which could be the reason for the low recovery of N. gonorrhoeae strains. This is of relevance as the national syndromic guidelines for STI management in Bangladesh recommend treating gonorrhea and chlamydia with cefixime and azithromycin (6). However, with emerging resistance of N. gonorrhoeae to cefixime and ceftriaxone (8, 9), gonorrhea management guidelines are under scrutiny globally (10, 11). These current data from Bangladesh add to the global antimicrobial resistance data on N. gonorrhoeae and highlight the need to update the national guidelines for STI management in Bangladesh.
Accepted manuscript posted online 16 May 2016 Citation Khanam R, Ahmed D, Rahman M, Alam MS, Amin M, Khan SI, Mayer KH, Azim T. 2016. Antimicrobial susceptibility of Neisseria gonorrhoeae in Bangladesh (2014 update). Antimicrob Agents Chemother 60:4418 – 4419. doi:10.1128/AAC.00223-16. Address correspondence to Mustafizur Rahman, [email protected]. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Antimicrobial Agents and Chemotherapy
July 2016 Volume 60 Number 7
Letter to the Editor
TABLE 1 Antimicrobial susceptibility to N. gonorrhoeaea % (n) of samples with sensitivity or resistance Drug
Sensitive
Intermediate
Resistant
Cefixime Azithromycin Ceftriaxone Ciprofloxacin Doxycycline Penicillin G Spectinomycin
85.7 (18) 90.5 (19) 100 (21) 0 (0) 4.8 (1) 4.8 (1) 100 (21)
0 (0) 0 (0) 0 (0) 4.8 (1) 4.8 (1) 61.9 (13) 0 (0)
14.3 (3) 9.5 (2) 0 (0) 95.2 (20) 90.5 (19) 33.3 (7) 0 (0)
a
n ⫽ 21.
ACKNOWLEDGMENTS T.A., R.K., D.A., M.R., S.I.K., and K.H.R. designed the study and wrote the protocol. R.K., M.S.A., M.A., and D.A. were in charge of staff training, field supervision, and laboratory testing. T.A., R.K., M.R., S.I.K., M.S.A., D.A., and K.H.M. wrote the manuscript. All authors have contributed to, read, and approved the final manuscript. We thank Masud Reza, Senior Manager, Infectious Diseases Division, for his help in data analysis. Icddr,b acknowledges with gratitude the commitment of The Global Fund to Fight AIDS, Tuberculosis and Malaria to its research efforts. Icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the United Kingdom for providing core/unrestricted support.
FUNDING INFORMATION This work was funded by Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) (BAN-202-G13-H-00). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
REFERENCES 1. Tapsall JW, Ndowa F, Lewis DA, Unemo M. 2009. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther 7:821– 834. http://dx.doi.org/10 .1586/eri.09.63.
July 2016 Volume 60 Number 7
2. Lewis DA. 2014. Global resistance of Neisseria gonorrhoeae: when theory becomes reality. Curr Opin Infect Dis 27:62– 67. http://dx.doi.org/10 .1097/QCO.0000000000000025. 3. Rahman M, Alam A, Nessa K, Nahar S, Dutta DK, Yasmin L, Monira S, Sultan Z, Khan SA, Albert MJ. 2001. Treatment failure with the use of ciprofloxacin for gonorrhea correlates with the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in Bangladesh. Clin Infect Dis 32:884 – 889. http://dx.doi.org/10.1086/319345. 4. Rahman M, Sultan Z, Monira S, Alam A, Nessa K, Islam S, Nahar S, Shama AW, Alam Khan S, Bogaerts J, Islam N, Albert J. 2002. Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Bangladesh (1997 to 1999): rapid shift to fluoroquinolone resistance. J Clin Microbiol 40:2037–2040. http://dx.doi.org/10.1128/JCM.40.6.2037-2040.2002. 5. Ahmed MU, Chawdhury FA, Hossain M, Sultan SZ, Alam M, Salahuddin G, Alam A, Nessa K, Nahar S, Shama-A-Waris, Alam A, Rahman M. 2010. Monitoring antimicrobial susceptibility of Neisseria gonorrhoeae isolated from Bangladesh during 1997-2006: emergence and pattern of drug-resistant isolates. J Health Popul Nutr 28:443– 449. 6. Government of Bangladesh. 2006. National guidelines for management of sexually transmitted infections. National AIDS/STD Programme, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of Bangladesh, Dhaka, Bangladesh. 7. Clinical and Laboratory Standards Institute. 2014. Performance standards for antimicrobial susceptibility testing; 24th informational supplement. CLSI document M100-S24. Clinical and Laboratory Standards Institute, Wayne, PA. 8. Kovari H, de Melo Oliveira MDG, Hauser P, Lauchli S, Meyer J, Weber R, Zbinden R. 2013. Decreased susceptibility of Neisseria gonorrhoeae isolates from Switzerland to cefixime and ceftriaxone: antimicrobial susceptibility data from 1990 and 2000 to 2012. BMC Infect Dis 13:603. http: //dx.doi.org/10.1186/1471-2334-13-603. 9. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. 2012. High-level cefixime-and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 56:1273– 1280. http://dx.doi.org/10.1128/AAC.05760-11. 10. Kidd S, Workowski KA. 2015. Management of gonorrhea in adolescents and adults in the United States. Clin Infect Dis 61:S785–S801. http://dx .doi.org/10.1093/cid/civ731. 11. Bignell C, FitzGerald M, Guideline Development Group; British Association for Sexual Health and HIV UK. 2011. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS 22:541– 547. http://dx.doi.org/10.1258/ijsa.2011.011267.
Antimicrobial Agents and Chemotherapy
aac.asm.org
4419
Antimicrobial Susceptibility of Neisseria gonorrhoeae in Bangladesh (2014 Update) Rasheda Khanam,a,b Dilruba Ahmed,a Tasnim Azima
Mustafizur Rahman,a M. S. Alam,a Mausumi Amin,c Sharful Islam Khan,a Kenneth H. Mayer,d
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesha; International Center for Maternal and Newborn Health, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USAb; Save the Children, Dhaka, Bangladeshc; Fenway Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USAd
D
ocumentation of Neisseria gonorrhoeae resistance to multiple antibiotics globally has given rise to major concerns regarding a future of untreatable gonorrhea (1, 2). In Bangladesh, N. gonorrhoeae antimicrobial susceptibility was last examined between 1997 to 2006 in female sex workers (FSWs), males having sex with males (MSMs), patients with sexually transmitted infections (STIs), and truckers, and resistance to ciprofloxacin, penicillin, and tetracycline with reduced susceptibility to cefixime as well as multidrug resistance were reported (3–5). The present analysis was conducted to update these data so as to inform guidelines on syndromic management of sexually transmitted infections (STIs) developed in 2006 (6) that are currently being used in Bangladesh and to enhance global surveillance by the World Health Organization. The current report presents data on antimicrobial resistance of N. gonorrhoeae from a cross-sectional bio-behavioral survey of STIs conducted among key populations (KPs) at risk of HIV in Dhaka, Bangladesh, between August and November 2014. The KPs included FSWs (n ⫽ 700), females who injected drugs (FWIDs; n ⫽ 177), male sex workers (MSWs; n ⫽ 227), and transgender women known as Hijras (n ⫽ 169). All were adults (ⱖ18 years) and were enrolled on a first-come, first-served basis from drop in centers (DICs) under the Global Fund Program for HIV, which provides STI prevention services to enlisted KPs. Individuals were enrolled only if they provided written informed consent for their participation in the study. The study was approved by the Research and Ethical Review Committees of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Study physicians conducted physical examinations and collected cervical swabs under speculum examination (FSWs and FWIDs) and anorectal swabs (MSWs and Hijras) using aseptic techniques. All swabs were transported to icddr,b in Amies charcoal transport medium within 6 to 8 h of collection. Swabs were cultured for identification of N. gonorrhoeae, and antibiotic susceptibility testing was carried out for positive isolates. Anorectal swabs were directly inoculated onto modified Thayer-Martin (MTM) agar containing vancomycin, colistin, nystatin, and trimethoprim. Cervical swabs were inoculated onto MTM agar, blood agar, and chocolate agar media. After inoculation, all plates were incubated under microaerophilic conditions (5% O2) at 35°C for at least 48 h. The identity of N. gonorrhoeae was confirmed by Gram stain, oxidase test, and Neisseria sugar test (carbohydrate degradation test). Antimicrobial susceptibility testing (AST) was performed by the Kirby-Bauer method (disc diffusion), breakpoints of sensitive, intermediate, and resistant were interpreted following Clinical and Laboratory Standards Institute (CLSI)
4418
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guidelines (7), and N. gonorrhoeae reference strain ATCC 49226 was used as a standard. Of the 1,273 samples, 21 (5 anorectal and 16 cervical) tested positive for N. gonorrhoeae by culture. This low isolation rate (1.6%) can be explained by the fact that antibiotics were frequently given to our study participants through the HIV/STI prevention program that might have caused a reduction in the bacterial load such that it was undetectable in culture. All N. gonorrhoea cultures were tested for AST, and the results are shown in Table 1. Ceftriaxone and spectinomycin were the antibiotics to which all isolates were susceptible. The next most sensitive antibiotic was azithromycin (90.5%), followed by cefixime (85.7%). None of the isolates were sensitive to ciprofloxacin, to which resistance was found in 95.2% and intermediate resistance in 4.8% of isolates. More than 90% of the isolates were resistant to doxycycline. Multidrug resistance (against three or more antibacterial agents) was identified in 48% of isolates. Antibiotic resistance data obtained from this study are comparable to data from an earlier study (5). In this study, all participants diagnosed with STIs were provided treatment using the national STI management guidelines. The possibility of treatment failure remains given the antimicrobial resistance profile. Extrapolation of these study findings to all of Bangladesh is not possible as the study was conducted only among those KPs who were receiving STI services from DICs. Approximately half of the study participants were diagnosed with STIs previously (data not shown), using the syndromic approach, and many had received antimicrobial therapy, which could be the reason for the low recovery of N. gonorrhoeae strains. This is of relevance as the national syndromic guidelines for STI management in Bangladesh recommend treating gonorrhea and chlamydia with cefixime and azithromycin (6). However, with emerging resistance of N. gonorrhoeae to cefixime and ceftriaxone (8, 9), gonorrhea management guidelines are under scrutiny globally (10, 11). These current data from Bangladesh add to the global antimicrobial resistance data on N. gonorrhoeae and highlight the need to update the national guidelines for STI management in Bangladesh.
Accepted manuscript posted online 16 May 2016 Citation Khanam R, Ahmed D, Rahman M, Alam MS, Amin M, Khan SI, Mayer KH, Azim T. 2016. Antimicrobial susceptibility of Neisseria gonorrhoeae in Bangladesh (2014 update). Antimicrob Agents Chemother 60:4418 – 4419. doi:10.1128/AAC.00223-16. Address correspondence to Mustafizur Rahman, [email protected]. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Antimicrobial Agents and Chemotherapy
July 2016 Volume 60 Number 7
Letter to the Editor
TABLE 1 Antimicrobial susceptibility to N. gonorrhoeaea % (n) of samples with sensitivity or resistance Drug
Sensitive
Intermediate
Resistant
Cefixime Azithromycin Ceftriaxone Ciprofloxacin Doxycycline Penicillin G Spectinomycin
85.7 (18) 90.5 (19) 100 (21) 0 (0) 4.8 (1) 4.8 (1) 100 (21)
0 (0) 0 (0) 0 (0) 4.8 (1) 4.8 (1) 61.9 (13) 0 (0)
14.3 (3) 9.5 (2) 0 (0) 95.2 (20) 90.5 (19) 33.3 (7) 0 (0)
a
n ⫽ 21.
ACKNOWLEDGMENTS T.A., R.K., D.A., M.R., S.I.K., and K.H.R. designed the study and wrote the protocol. R.K., M.S.A., M.A., and D.A. were in charge of staff training, field supervision, and laboratory testing. T.A., R.K., M.R., S.I.K., M.S.A., D.A., and K.H.M. wrote the manuscript. All authors have contributed to, read, and approved the final manuscript. We thank Masud Reza, Senior Manager, Infectious Diseases Division, for his help in data analysis. Icddr,b acknowledges with gratitude the commitment of The Global Fund to Fight AIDS, Tuberculosis and Malaria to its research efforts. Icddr,b is also grateful to the Governments of Bangladesh, Canada, Sweden and the United Kingdom for providing core/unrestricted support.
FUNDING INFORMATION This work was funded by Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) (BAN-202-G13-H-00). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
REFERENCES 1. Tapsall JW, Ndowa F, Lewis DA, Unemo M. 2009. Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther 7:821– 834. http://dx.doi.org/10 .1586/eri.09.63.
July 2016 Volume 60 Number 7
2. Lewis DA. 2014. Global resistance of Neisseria gonorrhoeae: when theory becomes reality. Curr Opin Infect Dis 27:62– 67. http://dx.doi.org/10 .1097/QCO.0000000000000025. 3. Rahman M, Alam A, Nessa K, Nahar S, Dutta DK, Yasmin L, Monira S, Sultan Z, Khan SA, Albert MJ. 2001. Treatment failure with the use of ciprofloxacin for gonorrhea correlates with the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in Bangladesh. Clin Infect Dis 32:884 – 889. http://dx.doi.org/10.1086/319345. 4. Rahman M, Sultan Z, Monira S, Alam A, Nessa K, Islam S, Nahar S, Shama AW, Alam Khan S, Bogaerts J, Islam N, Albert J. 2002. Antimicrobial susceptibility of Neisseria gonorrhoeae isolated in Bangladesh (1997 to 1999): rapid shift to fluoroquinolone resistance. J Clin Microbiol 40:2037–2040. http://dx.doi.org/10.1128/JCM.40.6.2037-2040.2002. 5. Ahmed MU, Chawdhury FA, Hossain M, Sultan SZ, Alam M, Salahuddin G, Alam A, Nessa K, Nahar S, Shama-A-Waris, Alam A, Rahman M. 2010. Monitoring antimicrobial susceptibility of Neisseria gonorrhoeae isolated from Bangladesh during 1997-2006: emergence and pattern of drug-resistant isolates. J Health Popul Nutr 28:443– 449. 6. Government of Bangladesh. 2006. National guidelines for management of sexually transmitted infections. National AIDS/STD Programme, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of Bangladesh, Dhaka, Bangladesh. 7. Clinical and Laboratory Standards Institute. 2014. Performance standards for antimicrobial susceptibility testing; 24th informational supplement. CLSI document M100-S24. Clinical and Laboratory Standards Institute, Wayne, PA. 8. Kovari H, de Melo Oliveira MDG, Hauser P, Lauchli S, Meyer J, Weber R, Zbinden R. 2013. Decreased susceptibility of Neisseria gonorrhoeae isolates from Switzerland to cefixime and ceftriaxone: antimicrobial susceptibility data from 1990 and 2000 to 2012. BMC Infect Dis 13:603. http: //dx.doi.org/10.1186/1471-2334-13-603. 9. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P. 2012. High-level cefixime-and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 56:1273– 1280. http://dx.doi.org/10.1128/AAC.05760-11. 10. Kidd S, Workowski KA. 2015. Management of gonorrhea in adolescents and adults in the United States. Clin Infect Dis 61:S785–S801. http://dx .doi.org/10.1093/cid/civ731. 11. Bignell C, FitzGerald M, Guideline Development Group; British Association for Sexual Health and HIV UK. 2011. UK national guideline for the management of gonorrhoea in adults, 2011. Int J STD AIDS 22:541– 547. http://dx.doi.org/10.1258/ijsa.2011.011267.
Antimicrobial Agents and Chemotherapy
aac.asm.org
4419
