INCREASING AZITHROMYCIN RESISTANCE IN SALMONELLA TYPHI: ARE WE HEADING TOWARDS A CATASTROPHE
Main Article Content
Keywords
Salmonella typhi, antimicrobial resistance pattern, Azithromycin resistance, North India.
Abstract
Background: Typhoid fever continues to remain a major public health problem in low to middle income countries (LMIC) where increasing resistance to antibiotics, our primary defense against typhoid fever, is posing a serious challenge in its management. We aimed this study to assess the latest antimicrobial resistance (AMR) pattern of salmonella typhi and paratyphi isolated from pediatric typhoid fever cases between 2019-2023.
Methods: This retrospective cross sectional observational study included assessing antibiotic sensitivity and resistance pattern of salmonella isolates from pediatric enteric fever cases against 10 antibiotics, tested by quality control disc diffusion method.
Results: Salmonella typhi was the predominant isolate 98.9% (91/92). These isolates showed persistently high resistance to conventional first line antibiotics (ampicillin 53.8% , cotrimoxazole 53.8% and chloramphenicol 50.5%) and ciprofloxacin (65.9%). Azithromycin resistance (AziR) was observed in 48.3%. The isolates showed 100% sensitivity to ceftriaxone, cefotaxime and meropenem.
Conclusion: Salmonella typhi continues to show high rates of resistance to conventional first line antibiotics and ciprofloxacin. A high percentage of isolates were azithromycin resistance in our study and this may pose a serious challenge in the out-patient treatment of uncomplicated enteric fever cases. There is strong need for continuous surveillance of AMR of salmonella species.
References
1. GRAM Typhoid Collaborators. Estimating the subnational prevalence of antimicrobial resistant Salmonella enterica serovars Typhi and Paratyphi A infections in 75 endemic countries, 1990-2019: a modelling study. Lancet Glob Health. 2024 Mar;12(3):e406-e418. doi: 10.1016/S2214-109X(23)00585-5. PMID: 38365414; PMCID: PMC10882211.
2. Senjuti Saha, Mohammad Saiful Islam Sajib, Denise Garrett, Farah N Qamar. Antimicrobial Resistance in Typhoidal Salmonella: Around the World in 3 Days. Clinical Infectious Diseases.2020 Aug 15; Vol 71(Issue Supplement 2): 91–95.
3. Yousafzai MT, Qamar FN, Shakoor S, Saleem K, Lohana H, Karim S, et al. Ceftriaxone-resistant Salmonella Typhi outbreak in Hyderabad City of Sindh, Pakistan: High time for the introduction of typhoid conjugate vaccine. Clin Infect Dis 2019; 68:16-21.
4. CDC. Antibiotic Resistance Threats in the United States, 2013 | Antibiotic/ Antimicrobial Resistance | CDC. 2014 [cited 2017 Feb 3]. Available from: https://www.cdc.gov/drugresistance/threat-report-2013/
5. World Health Organisation. Vaccines and Biologicals. Background Document: The Diagnosis, Treatment and Prevention of Typhoid Fever. Geneva. 2003. Available online: https://www.glowm.com/pdf/WHO-diagnosis%20treatment%2 0prevention%20of%20typhoid%20fever-2003-CustomLicense.pdf (accessed on 18 April 2019).
6. Clinical and Laboratory standards Institute. Performance Standards for Antimicrobial Susceptiblity Testing: 29th Information Supplement. CLSI document M100-S29. Wayne, PA; Clinical and Laboratory Standards Institute; 2019.
7. Leclercq R, Cantón R, Brown DF, Giske CG, Heisig P, MacGowan AP, et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin Microbiol Infect. 2013 Feb;19(2):141-60. doi: 10.1111/j.1469-0691.2011.03703.x. Epub 2011 Nov 25. PMID: 22117544.
8. Manchanda, V.; Bhalla, P.; Sethi, M.; Sharma, P.K. Treatment of enteric fever in children on the basis of current trends of antimicrobial susc
9. Kumar, S.; Rizvi, M.; Berry, N. Rising prevalence of enteric fever due to multidrug-resistant Salmonella: An epidemiological study. J. Med. Microbiol. 2008, 57, 1247–1250.
10. Kapil A, Sood S, Reddaiah VP, Das B, Seth P. Paratyphoid fever due to Salmonella enterica serotype Paratyphi A. Emerg Infect Dis 1997; 3: 407
11. Woods CW, Murdoch DR, Zimmerman MD, Glover WA, Basnyat B, Belbase RH, et al. Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal. Trans R Soc Trop Med Hyg 2006; 100: 1063-7.
12. Shlim DR, Schwartz E, Eaton M. Clinical importance of Salmonella paratyphi A infection to enteric fever in Nepal. J Travel Med 1995; 2: 165-8.
13. Carey ME, Jain R, Yousuf M, Maes M, Dyson ZA, Thu TNH, et al. Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India. Clin Infect Dis. 2021 Mar 1;72(5):120-127.
14. Veeraraghavan B, Pragasam AK, Ray P, Kapil A, Nagaraj S, Perumal SPB, et al. Evaluation of Antimicrobial Susceptibility Profile in Salmonella Typhi and Salmonella Paratyphi A: Presenting the Current Scenario in India and Strategy for Future Management. J Infect Dis. 2021 Nov 23;224(Supple 5):502-516.
15. Wattal C, Goel N. Pediatric Blood Cultures and Antibiotic Resistance: An Overview. Indian J Pediatr. 2020 Feb;87(2):125-131. doi: 10.1007/s12098-019-03123-y. Epub 2019 Dec 21. Erratum in: Indian J Pediatr. 2020 Jun;87(6):486.
16. Iyer RN, Jangam RR, Jacinth A, Venkatalakshmi A, Nahdi FB. Prevalence and trends in the antimicrobial susceptibility pattern of Salmonella enterica serovars Typhi and Paratyphi A among children in a pediatric tertiary care hospital in South India over a period of ten years:a retrospective study. Eur J Clin Microbiol Infect Dis. 2017;36(12):2399–04.
17. Shrestha KL, Pant ND, Bhandari R, Khatri S, Shrestha B, Lekhak B: Re-emergence of the susceptibility of the Salmonella spp. isolated from blood samples to conventional first line antibiotics. Antimicrob Resist Infect Control. 2016, 5:22.
18. Saha SK, Talukder SY, Islam M, Saha S. A highly ceftriaxone-resistant Salmonella Typhi in Bangladesh. Pediatr Infect Dis J 1999; 18:387.
19. Kokare RS, Bari AK, Pereira JV, Patel K, Poojary A. Minimum inhibitory concentration (MIC) of Ceftriaxone and Azithromycin for blood culture isolates of Salmonella enterica spp. J Infect Dev Ctries. 2021 Apr 30;15(4):538-543.
20. Manoharan A, Dey D, Putlibai S, Ramaiah S, Anbarasu A, Balasubramanian S. Epidemiology of Multidrug Resistance among Salmonella enterica serovars typhi and paratyphi A at a Tertiary Pediatric Hospital in India Over a Decade; In-silico Approach to Elucidate the Molecular Mechanism of Quinolone Resistance. Int J Infect Dis. 2022 Jun;119:146-149.
21. Ali Shah SA, Nadeem M, Syed SA, Fatima Abidi ST, Khan N, Bano N. Antimicrobial Sensitivity Pattern of Salmonella Typhi: Emergence of Resistant Strains. Cureus. 2020 Nov 29;12(11): e11778.
22. Sharma P, Kumari B, Dahiya S, Kulsum U, Kumar S, Manral N, Pandey S, Kaur P, Sood S, Das BK, Kapil A. Azithromycin resistance mechanisms in typhoidal salmonellae in India: A 25 years analysis. Indian J Med Res. 2019 Mar;149(3):404-411.
23. Hooda Y, Sajib MSI, Rahman H, Luby SP, Bondy-Denomy J, Santosham M, Andrews JR, Saha SK, Saha S. Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance. PLoS Negl Trop Dis. 2019 Nov 15;13(11):e0007868. doi: 10.1371/journal.pntd.0007868. PMID: 31730615; PMCID: PMC6881056.
24. Iqbal J, Dehraj IF, Carey ME, Dyson ZA, Garrett D, Seidman JC, Kabir F, Saha S, Baker S, Qamar FN. A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan. mSphere. 2020 Jul 22;5(4):e00215-20. doi: 10.1128/mSphere.00215-20. PMID: 32699118; PMCID: PMC7376502.
25. Duy PT, Dongol S, Giri A, Nguyen To NT, Dan Thanh HN, Nhu Quynh NP, Duc Trung P, Thwaites GE, Basnyat B, Baker S, Rabaa MA, Karkey A. The emergence of azithromycin-resistant Salmonella Typhi in Nepal. JAC Antimicrob Resist. 2020 Dec 21;2(4):dlaa109. doi: 10.1093/jacamr/dlaa109. PMID: 34223059; PMCID: PMC8210228
26. Biswas M, Biswas S, Gupta B, Mascellino MT, Rakshit A, Chakraborty B. Changing Paradigms in Antibiotic Resistance in Salmonella Species with Focus on Fluoroquinolone Resistance: A 5-Year Retrospective Study of Enteric Fever in a Tertiary Care Hospital in Kolkata, India. Antibiotics (Basel). 2022 Sep 26;11(10):1308.
27. Britto CD, Dyson ZA, Duchene S, Carter MJ, Gurung M, Kelly DF, Murdoch DR, Ansari I, Thorson S, Shrestha S, Adhikari N, Dougan G, Holt KE, Pollard AJ. Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy. PLoS Negl Trop Dis. 2018 Apr 23;12(4):e0006408
28. Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet 2015; 47 : 632-9
29. International Typhoid Consortium, Wong VK, Holt KE, Okoro C, Baker S, Pickard DJ, Marks F,et al. Molecular surveillance identifies multiple transmissions of typhoid in west Africa. PLoS Negl Trop Dis 2016; 10 : e0004781.
30. Britto CD, John J, Verghese VP, Pollard AJ. A systematic review of antimicrobial resistance of typhoidal Salmonella in India. Indian J Med Res. 2019 Feb;149(2):151-163.
31. Devanga Ragupathi NK, Muthuirulandi Sethuvel DP, Shankar BA, Munusamy E, Anandan S, Veeraraghavan B. Draft genome sequence of blaTEM-1-mediated cephalosporin-resistant Salmonella enterica serovar Typhi from bloodstream infection. J Glob Antimicrob Resist 2016; 7 : 11-2.
32. Rodrigues C, Kapil A, Sharma A, Devanga Ragupathi NK, Inbanathan FY, Veeraraghavan B, et al. Whole-Genome Shotgun Sequencing of cephalosporin-resistant Salmonella enterica serovar Typhi. Genome Announc 2017; 5: e01639-16.
33. Klemm EJ, Shakoor S, Page AJ, Qamar FN, Judge K, saeed DK, et al. Emergence of an extensively drug-resistant Salmonella enterica serovar typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third generation cephalosporins.
2. Senjuti Saha, Mohammad Saiful Islam Sajib, Denise Garrett, Farah N Qamar. Antimicrobial Resistance in Typhoidal Salmonella: Around the World in 3 Days. Clinical Infectious Diseases.2020 Aug 15; Vol 71(Issue Supplement 2): 91–95.
3. Yousafzai MT, Qamar FN, Shakoor S, Saleem K, Lohana H, Karim S, et al. Ceftriaxone-resistant Salmonella Typhi outbreak in Hyderabad City of Sindh, Pakistan: High time for the introduction of typhoid conjugate vaccine. Clin Infect Dis 2019; 68:16-21.
4. CDC. Antibiotic Resistance Threats in the United States, 2013 | Antibiotic/ Antimicrobial Resistance | CDC. 2014 [cited 2017 Feb 3]. Available from: https://www.cdc.gov/drugresistance/threat-report-2013/
5. World Health Organisation. Vaccines and Biologicals. Background Document: The Diagnosis, Treatment and Prevention of Typhoid Fever. Geneva. 2003. Available online: https://www.glowm.com/pdf/WHO-diagnosis%20treatment%2 0prevention%20of%20typhoid%20fever-2003-CustomLicense.pdf (accessed on 18 April 2019).
6. Clinical and Laboratory standards Institute. Performance Standards for Antimicrobial Susceptiblity Testing: 29th Information Supplement. CLSI document M100-S29. Wayne, PA; Clinical and Laboratory Standards Institute; 2019.
7. Leclercq R, Cantón R, Brown DF, Giske CG, Heisig P, MacGowan AP, et al. EUCAST expert rules in antimicrobial susceptibility testing. Clin Microbiol Infect. 2013 Feb;19(2):141-60. doi: 10.1111/j.1469-0691.2011.03703.x. Epub 2011 Nov 25. PMID: 22117544.
8. Manchanda, V.; Bhalla, P.; Sethi, M.; Sharma, P.K. Treatment of enteric fever in children on the basis of current trends of antimicrobial susc
9. Kumar, S.; Rizvi, M.; Berry, N. Rising prevalence of enteric fever due to multidrug-resistant Salmonella: An epidemiological study. J. Med. Microbiol. 2008, 57, 1247–1250.
10. Kapil A, Sood S, Reddaiah VP, Das B, Seth P. Paratyphoid fever due to Salmonella enterica serotype Paratyphi A. Emerg Infect Dis 1997; 3: 407
11. Woods CW, Murdoch DR, Zimmerman MD, Glover WA, Basnyat B, Belbase RH, et al. Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal. Trans R Soc Trop Med Hyg 2006; 100: 1063-7.
12. Shlim DR, Schwartz E, Eaton M. Clinical importance of Salmonella paratyphi A infection to enteric fever in Nepal. J Travel Med 1995; 2: 165-8.
13. Carey ME, Jain R, Yousuf M, Maes M, Dyson ZA, Thu TNH, et al. Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India. Clin Infect Dis. 2021 Mar 1;72(5):120-127.
14. Veeraraghavan B, Pragasam AK, Ray P, Kapil A, Nagaraj S, Perumal SPB, et al. Evaluation of Antimicrobial Susceptibility Profile in Salmonella Typhi and Salmonella Paratyphi A: Presenting the Current Scenario in India and Strategy for Future Management. J Infect Dis. 2021 Nov 23;224(Supple 5):502-516.
15. Wattal C, Goel N. Pediatric Blood Cultures and Antibiotic Resistance: An Overview. Indian J Pediatr. 2020 Feb;87(2):125-131. doi: 10.1007/s12098-019-03123-y. Epub 2019 Dec 21. Erratum in: Indian J Pediatr. 2020 Jun;87(6):486.
16. Iyer RN, Jangam RR, Jacinth A, Venkatalakshmi A, Nahdi FB. Prevalence and trends in the antimicrobial susceptibility pattern of Salmonella enterica serovars Typhi and Paratyphi A among children in a pediatric tertiary care hospital in South India over a period of ten years:a retrospective study. Eur J Clin Microbiol Infect Dis. 2017;36(12):2399–04.
17. Shrestha KL, Pant ND, Bhandari R, Khatri S, Shrestha B, Lekhak B: Re-emergence of the susceptibility of the Salmonella spp. isolated from blood samples to conventional first line antibiotics. Antimicrob Resist Infect Control. 2016, 5:22.
18. Saha SK, Talukder SY, Islam M, Saha S. A highly ceftriaxone-resistant Salmonella Typhi in Bangladesh. Pediatr Infect Dis J 1999; 18:387.
19. Kokare RS, Bari AK, Pereira JV, Patel K, Poojary A. Minimum inhibitory concentration (MIC) of Ceftriaxone and Azithromycin for blood culture isolates of Salmonella enterica spp. J Infect Dev Ctries. 2021 Apr 30;15(4):538-543.
20. Manoharan A, Dey D, Putlibai S, Ramaiah S, Anbarasu A, Balasubramanian S. Epidemiology of Multidrug Resistance among Salmonella enterica serovars typhi and paratyphi A at a Tertiary Pediatric Hospital in India Over a Decade; In-silico Approach to Elucidate the Molecular Mechanism of Quinolone Resistance. Int J Infect Dis. 2022 Jun;119:146-149.
21. Ali Shah SA, Nadeem M, Syed SA, Fatima Abidi ST, Khan N, Bano N. Antimicrobial Sensitivity Pattern of Salmonella Typhi: Emergence of Resistant Strains. Cureus. 2020 Nov 29;12(11): e11778.
22. Sharma P, Kumari B, Dahiya S, Kulsum U, Kumar S, Manral N, Pandey S, Kaur P, Sood S, Das BK, Kapil A. Azithromycin resistance mechanisms in typhoidal salmonellae in India: A 25 years analysis. Indian J Med Res. 2019 Mar;149(3):404-411.
23. Hooda Y, Sajib MSI, Rahman H, Luby SP, Bondy-Denomy J, Santosham M, Andrews JR, Saha SK, Saha S. Molecular mechanism of azithromycin resistance among typhoidal Salmonella strains in Bangladesh identified through passive pediatric surveillance. PLoS Negl Trop Dis. 2019 Nov 15;13(11):e0007868. doi: 10.1371/journal.pntd.0007868. PMID: 31730615; PMCID: PMC6881056.
24. Iqbal J, Dehraj IF, Carey ME, Dyson ZA, Garrett D, Seidman JC, Kabir F, Saha S, Baker S, Qamar FN. A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan. mSphere. 2020 Jul 22;5(4):e00215-20. doi: 10.1128/mSphere.00215-20. PMID: 32699118; PMCID: PMC7376502.
25. Duy PT, Dongol S, Giri A, Nguyen To NT, Dan Thanh HN, Nhu Quynh NP, Duc Trung P, Thwaites GE, Basnyat B, Baker S, Rabaa MA, Karkey A. The emergence of azithromycin-resistant Salmonella Typhi in Nepal. JAC Antimicrob Resist. 2020 Dec 21;2(4):dlaa109. doi: 10.1093/jacamr/dlaa109. PMID: 34223059; PMCID: PMC8210228
26. Biswas M, Biswas S, Gupta B, Mascellino MT, Rakshit A, Chakraborty B. Changing Paradigms in Antibiotic Resistance in Salmonella Species with Focus on Fluoroquinolone Resistance: A 5-Year Retrospective Study of Enteric Fever in a Tertiary Care Hospital in Kolkata, India. Antibiotics (Basel). 2022 Sep 26;11(10):1308.
27. Britto CD, Dyson ZA, Duchene S, Carter MJ, Gurung M, Kelly DF, Murdoch DR, Ansari I, Thorson S, Shrestha S, Adhikari N, Dougan G, Holt KE, Pollard AJ. Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy. PLoS Negl Trop Dis. 2018 Apr 23;12(4):e0006408
28. Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet 2015; 47 : 632-9
29. International Typhoid Consortium, Wong VK, Holt KE, Okoro C, Baker S, Pickard DJ, Marks F,et al. Molecular surveillance identifies multiple transmissions of typhoid in west Africa. PLoS Negl Trop Dis 2016; 10 : e0004781.
30. Britto CD, John J, Verghese VP, Pollard AJ. A systematic review of antimicrobial resistance of typhoidal Salmonella in India. Indian J Med Res. 2019 Feb;149(2):151-163.
31. Devanga Ragupathi NK, Muthuirulandi Sethuvel DP, Shankar BA, Munusamy E, Anandan S, Veeraraghavan B. Draft genome sequence of blaTEM-1-mediated cephalosporin-resistant Salmonella enterica serovar Typhi from bloodstream infection. J Glob Antimicrob Resist 2016; 7 : 11-2.
32. Rodrigues C, Kapil A, Sharma A, Devanga Ragupathi NK, Inbanathan FY, Veeraraghavan B, et al. Whole-Genome Shotgun Sequencing of cephalosporin-resistant Salmonella enterica serovar Typhi. Genome Announc 2017; 5: e01639-16.
33. Klemm EJ, Shakoor S, Page AJ, Qamar FN, Judge K, saeed DK, et al. Emergence of an extensively drug-resistant Salmonella enterica serovar typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third generation cephalosporins.
Article Sidebar
Published
Dec 12, 2024
Article Details
How to Cite
Nazir A Parray, Ayaz Ahmed, Umar R Khan, Mushtaq A Wani, Zeeshan A Mir, S Saleem Yousuf, Reyaz A Malik, & Asif Ahmed. (2024). INCREASING AZITHROMYCIN RESISTANCE IN SALMONELLA TYPHI: ARE WE HEADING TOWARDS A CATASTROPHE. Journal of Population Therapeutics and Clinical Pharmacology, 31(11), 2194-2201. https://doi.org/10.53555/1586t858
Section
Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Author Biographies
Nazir A Parray
Department of Pediatrics, SKIMS Medical College Srinagar.
Ayaz Ahmed
Department of Pediatrics, SKIMS Medical College Srinagar.
Umar R Khan
Department of Microbiology, SKIMS Medical College Srinagar.
Mushtaq A Wani
Department of Pediatrics, AFSMS & RC Faridabad.
Zeeshan A Mir
Department of Pediatrics, SKIMS Medical College Srinagar.
S Saleem Yousuf
Department of Pediatrics, SKIMS Medical College Srinagar.
Reyaz A Malik
Department of Pediatrics, SKIMS Medical College Srinagar.
Asif Ahmed
Department of Pediatrics, SKIMS Medical College Srinagar.
How to Cite
Nazir A Parray, Ayaz Ahmed, Umar R Khan, Mushtaq A Wani, Zeeshan A Mir, S Saleem Yousuf, Reyaz A Malik, & Asif Ahmed. (2024). INCREASING AZITHROMYCIN RESISTANCE IN SALMONELLA TYPHI: ARE WE HEADING TOWARDS A CATASTROPHE. Journal of Population Therapeutics and Clinical Pharmacology, 31(11), 2194-2201. https://doi.org/10.53555/1586t858