Susceptibility patterns of Streptococcus pyogenes isolated in the Italian Hospital of Desio: a 20-year (2000-2019) retrospective study

Background: Streptococcus pyogenes is a Gram-positive bacterium responsible for different infections, some of them serious and life-threatening. Increasing antimicrobial resistance trends have been observed in S. pyogenes isolates worldwide. In the present study, data of susceptibility patterns of S. pyogenes isolates were retrieved from 2000 to 2019 with the aim to observe the emergence of resistance and to guide clinicians in prescription appropriateness.

Materials and Methods: we collected a total of 4,958 unique S. pyogenes strains from positive samples, out of them 4,597 (93%) were from throat swabs, followed by vaginal swabs, skin swabs, blood cultures, and ear swabs. The median age of patients was 10 years (range 0-94 years).

Results: the analysis was performed on the data collected from throat samples and blood cultures. In the isolates from throat specimens, except β-lactams and glycopeptides (vancomycin) which presented 100% of susceptibility, and tetracycline which presented an average resistance rate of 26%, all the other antibiotics tested showed significant increasing resistance trends: clindamycin 13-23%, erythromycin 29-35%, and levofloxacin 5-12% (p<0.01). About susceptibilities of isolates from blood cultures, although the low number of isolates, we observed 98-100% of susceptibility.

Conclusions: although this work is single-center, national and regional active surveillance projects are needed to monitor antimicrobial resistance trends of S. pyogenes, and to help physicians in antibiotic prescription in subjects affected by acute or recurrent sore throats.

1. Abraham T, Sistla S. Trends in antimicrobial resistance patterns of Group A streptococci, molecular basis and implications. Indian J Med Microbiol 2018;36:186-91.

2. Alcolea-Medina A, Snell LB, Alder C, et al. The on-going Streptococcus pyogenes (Group A Streptococcus) outbreak in London, United Kingdom, in December 2022: a molecular epidemiology study. Clin Microbiol Infect 2023;29:887-90.

3. Alves-Barroco C, Rivas-García L, Fernandes AR, Baptista PV. Tackling multidrug resistance in Streptococci - from novel biotherapeutic strategies to nanomedicines. Front Microbiol 2020;11:579916.

4. Barnett T, Indraratna A, Sanderson-Smith M. Secreted virulence factors of Streptococcus pyogenes. In: Ferretti JJ, Stevens DL, Fischetti VA (eds.), Streptococcus pyogenes: basic biology to clinical manifestations. 2nd edition. University of Oklahoma Health Sciences Center; Oklahoma City, USA; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587095/

5. Barros RR. Antimicrobial resistance among beta-hemolytic Streptococcus in Brazil: an overview. Antibiotics (Basel) 2021;10:973.

6. Bowen AC, Lilliebridge RA, Tong SY, et al. Is Streptococcus pyogenes resistant or susceptible to trimethoprim-sulfamethoxazole? J Clin Microbiol 2012;50:4067-72.

7. Brouwer S, Rivera-Hernandez T, Curren BF, et al. Pathogenesis, epidemiology and control of Group A Streptococcus infection. Nat Rev Microbiol 2023;21:431-47.

8. Calvo C, Saavedra Lozano J. Current epidemiological situation of Streptococcus pyogenes infections. An Pediatr (Engl Ed) 2024;100:161-3.

9. Centers for Disease Control and Prevention (CDCP). Increase in pediatric invasive group A Streptococcal infections 2022. Available from: https://emergency.cdc.gov/han/2022/han00484.asp

10. Clinical Laboratory and Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. 31st edition. CLSI supplement M100. 2021.

11. Creti R, Imperi M, Baldassarri L, et al. Types, virulence factors, and antibiotic resistance of invasive Streptococcus pyogenes isolates from Italy: what has changed in 11 years? J Clin Microbiol 2007;45:2249-56.

12. European Centre for Disease Prevention and Control (ECDC). Surveillance and disease data for antimicrobial resistance. ECDC; Stockholm, Sweden; 2022. Available from: https://www.ecdc.europa.eu/en/antimicrobial-resistance/surveillance-and-disease-data

13. The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0 2021. Available from: http://www.eucast.org.

14. Fay K, Onukwube J, Chochua S, et al. Patterns of antibiotic nonsusceptibility among invasive group A Streptococcus infections - United States, 2006-2017. Clin Infect Dis 2021;73:1957-64.

15. Ferretti JJ, Stevens DL, Fischetti VA (eds). Streptococcus pyogenes: basic biology to clinical manifestations. 2nd edition. University of Oklahoma Health Sciences Center; Oklahoma City, USA; 2022.

16. Friães A, Lopes JP, Melo-Cristino J, et al. Changes in Streptococcus pyogenes causing invasive disease in Portugal: evidence for superantigen gene loss and acquisition. Int J Med Microbiol 2013;303:505-13.

17. Gajdács M, Ábrók M, Lázár A, Burián K. Beta-haemolytic group A, C and G streptococcal infections in Southern Hungary: a 10-year population-based retrospective survey (2008-2017) and a review of the literature. Infect Drug Resist 2020;13:4739-49.

18. Gergova R, Boyanov V, Muhtarova A, Alexandrova A. A Review of the impact of streptococcal infections and antimicrobial resistance on human health. Antibiotics (Basel) 2024;13:360.

19. Hakenbeck R, Brückner R, Denapaite D, Maurer P. Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae. Future Microbiol. 2012 Mar;7(3):395-410.

20. Huang YC, Lai JF, Wu CJ, et al. High-level levofloxacin-resistant emm12 group A Streptococcus, 2012-2018: a multicenter study in Taiwan. J Microbiol Immunol Infect 2023;56:8759.

21. Iacchini S, Boros S, Pezzotti P, et al. AR-ISS: sorveglianza nazionale dell’Antibiotico-Resistenza. Rapporti ISS Sorveglianza RIS-4/2023. Istituto Superiore di Sanità; Rome, Italy; 2023.

22. Ikebe T, Hirasawa K, Suzuki R, et al. Antimicrobial susceptibility survey of Streptococcus pyogenes isolated in Japan from patients with severe invasive group A streptococcal infections. Antimicrob Agents Chemother 2005;49:788-90.

23. Johnson AF, LaRock CN. Antibiotic Treatment, Mechanisms for Failure, and Adjunctive Therapies for Infections by Group A Streptococcus. Front Microbiol 2021;12:760255.

24. Kassim A, Omuse G, Premji Z, Revathi G. Comparison of Clinical Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines for the interpretation of antibiotic susceptibility at a University teaching hospital in Nairobi, Kenya: a cross-sectional study. Ann Clin Microbiol Antimicrob 2016;15:21.

25. Kebede D, Admas A, Mekonnen D. Prevalence and antibiotics susceptibility profiles of Streptococcus pyogenes among pediatric patients with acute pharyngitis at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia. BMC Microbiol 2021;21:135.

26. Khademi F, Vaez H, Sahebkar A, Taheri RA. Group A Streptococcus antibiotic resistance in Iranian Children: a meta-analysis. Oman Med J 2021;36:e222.

27. Kimura K, Nagano N, Arakawa Y. Classification of group B streptococci with reduced β-lactam susceptibility (GBS-RBS) based on the amino acid substitutions in PBPs. J Antimicrob Chemother 2015;70:1601-3.

28. Lamagni TL, Guy R, Chand MA, et al. Resurgence of invasive group A streptococcal infections in England, 2022. Lancet Infect Dis 2023;23:e15-21.

29. Luiken REC, Van Gompel L, Munk P, et al. Associations between antimicrobial use and the faecal resistome on broiler farms from nine European countries. J Antimicrob Chemother 2019;74:2596-604.

30. Massese M, La Sorda M, De Maio F, et al. Epidemiology of group A streptococcal infection: are we ready for a new scenario? Lancet Microbe 2024;5:620-1.

31. Meisal R, Høiby EA, Caugant DA, Musser JM. Molecular characteristics of pharyngeal and invasive emm3 Streptococcus pyogenes strains from Norway, 1988-2003. Eur J Clin Microbiol Infect Dis 2010;29:31-43.

32. Meletis G, Soulopoulos Ketikidis AL, Floropoulou N, et al. Antimicrobial resistance rates of Streptococcus pyogenes in a Greek tertiary care hospital: 6-year data and literature review. New Microbiol 2023;46:37-42.

33. Miller KM, Tanz RR, Shulman ST, et al. Standardization of Epidemiological Surveillance of Group A Streptococcal Pharyngitis. Open Forum Infect Dis 2022;9:S5-14.

34. Miller KM, Van Beneden C, McDonald M, et al. Standardization of epidemiological surveillance of acute poststreptococcal glomerulonephritis. Open Forum Infect Dis 2022;9:S57-64.

35. Patel A, Guzman-Cottrill J, Fleming-Dutra K, et al. Increased Prevalence of Group A Streptococcus (GAS) High Level Macrolide Resistance During the COVID-19 Pandemic. Open Forum Infectious Diseases. Oxford University Press; Ocford, UK; 2022.

36. Reijtman V, García ME, Mastroianni A, et al. Evaluation of a rapid diagnostic test for the detection of Streptococcus pyogenes in invasive infections. Rev Argent Microbiol 2020;52:261-5.

37. Sabharwal KA, Simon MW. Are clinicians overdiagnosing strep throat and overprescribing antibiotics? Front Pediatr 2023;11:1248903.

38. Silva-Costa C, Ramirez M, Melo-Cristino J, Portuguese Group for Study of Streptococcal Infections. Declining macrolide resistance in Streptococcus pyogenes in Portugal (2007-13) was accompanied by continuous clonal changes. J Antimicrob Chemother 2015;70:2729-33.

39. StataCorp. Stata Statistical Software: Release 16. StataCorp LLC; College Station, TX; 2019.

40. Van Heirstraeten L, Leten G, Lammens C, et al. Increase in fluoroquinolone non-susceptibility among clinical Streptococcus pyogenes in Belgium during 2007-10. J Antimicrob Chemother 2012;67:2602-5.

41. Vannice KS, Ricaldi J, Nanduri S, et al. Streptococcus pyogenes pbp2x Mutation Confers Reduced Susceptibility to β-Lactam Antibiotics. Clin In-fect Dis 2020;71:201-4.

42. Villalón P, Bárcena M, Medina-Pascual MJ, et al. National surveillance of tetracycline, erythromycin, and clindamycin resistance in invasive Streptococcus pyogenes: a retrospective study of the situation in Spain, 2007-2020. Antibiotics (Basel) 2023;12:99.

43. World Health Organization (WHO). Antimicrobial resistance. 2022. Available at: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

44. World Health Organization (WHO). Disease outbreak news; increased incidence of scarlet fever and invasive group A Streptococcus infection - multi-country. 2022. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON429

45. Yu D, Zheng Y, Yang Y. Is there emergence of β-lactam antibiotic-resistant Streptococcus pyogenes in China? Infect Drug Resist 2020;13:2323-7.