Investigation of In Vitro Synergistic Effect of Niclosamide with Mupirocin in Staphylococcus aureus Strains by Screening Test

Abstract

Increasing resistance to antibiotics used in Staphylococcus aureus carriers has brought up the search for alternative treatment. With this research it was aimed to examine whether niclosamide has an in vitro synergistic effect with mupirocin in S. aureus isolates. 25 methicillin-susceptible S. aureus (MSSA) and 25 methicillin-resistant S. aureus (MRSA) isolates were collected from the samples sent to our laboratory in 2021. In vitro synergistic effect between niclosamide and mupirocin was investigated by applying double disc synergy method in isolates. No synergy was detected between the two antimicrobial drugs in the isolates tested in the study. Mupirocin resistance was observed in only two of the isolates in the MRSA group, and all other isolates were found to be susceptible to mupirocin. No in vitro synergistic effect of niclosamide with mupirocin was observed in S. aureus isolates.

Keywords

• mupirocin
• niclosamide
• Staphylococcus aureus

STAPHYLOCOCCUS AUREUS SUŞLARINDA NİKLOZAMİDİN MUPİROSİN İLE IN VİTRO SİNERJİSTİK ETKİSİNİN TARAMA TESTİ İLE ARAŞTIRILMASI

Abstract

Staphylococcus aureus taşıyıcılarında kullanılan antibiyotiklere direncin artması alternatif tedavi arayışını gündeme getirmiştir. Bu araştırma ile S. aureus izolatlarında niklozamidin mupirosin ile in vitro sinerjistik etkisinin olup olmadığının incelenmesi hedeflenmiştir. 2021 yılında laboratuvarımıza gönderilen örneklerden 25 metisiline duyarlı S. aureus (MSSA) ve 25 metisiline dirençli S. aureus (MRSA) izolatı toplanmıştır. İzolatlarda çift disk sinerji yöntemi uygulanarak niklozamid ile mupirosin arasında in vitro sinerjistik etki olup olmadığı incelenmiştir. Çalışmada test edilen izolatlarda iki antimikrobiyal ilaç arasında herhangi bir sinerji saptanmamıştır. İzolatların sadece MRSA grubundaki iki tanesinde mupirosine direnç gözlenmiş olup, diğer izolatların tümünün mupirosine duyarlı olduğu bulunmuştur. S. aureus izolatlarında niklozamidin mupirosin ile in vitro sinerjistik etkisinin olmadığı gözlenmiştir.

Keywords

• mupirosin
• niklozamid
• Staphylococcus aureus

References

1. Benfield T, Espersen F, Frimodt-Moller N et al. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin Microbiol Infect. 2007;13(3):257-63.
2. Blanchard C, Brooks L, Beckley A, Colquhoun J, Dewhurst S, Dunman PM. Neomycin sulfate improves the antimicrobial activity of mupirocin-based antibacterial ointments. Antimicrob Agents Chemother. 2016;60(2):862-72.
3. Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2008;46(Suppl 5):S344-9.
4. Chowdhury AHMSK, Nandi S, Rahman M, et al. Comparison between phenotypic confirmatory test & double disc synergy test in detection of extended spectrum b-lactamases producers among gram-negative bacilli. CMOSHMC Journal. 2017;15(2):3-8.
5. Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH. Practical disk diffusion method for detection of inducible clindamycin resistance in Staphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol. 2003;41(10):4740-4744.
6. Ghiselli R, Giacometti A, Goffi L et al. Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin-soaked, collagen-sealed dacron. J Surg Res. 2001;99(2):316-20.
7. Giriyapur RS, Nandihal NW, Krishna BV, Patil AB, Chandrasekhar MR. Comparison of disc diffusion methods for the detection of extended-spectrum beta lactamase-producing enterobacteriaceae. J Lab Physicians. 2011;3(1):33-6.
8. Gottlieb GS, Fowler VG Jr, Kong LK et al. Staphylococcus aureus bacteremia in the surgical patient: a prospective analysis of 73 postoperative patients who developed Staphylococcus aureus bacteremia at a tertiary care facility. J Am Coll Surg. 2000;190(1):50-7.

9. Gwisai T, Hollingsworth NR, Cowles S et al. Repurposing niclosamide as a versatile antimicrobial surface coating against device-associated, hospital-acquired bacterial infections. Biomed Mater. 2017;12(4):045010.
10. Hu Y, Coates AR. Enhancement by novel anti-methicillin-resistant Staphylococcus aureus compound HT61 of the activity of neomycin, gentamicin, mupirocin and chlorhexidine: in vitro and in vivo studies. J Antimicrob Chemother. 2013;68(2):374-84.
11. Huang SS, Singh R, McKinnell JA et al. Decolonization to reduce postdischarge infection risk among MRSA carriers. N Engl J Med. 2019;380(7):638-50.
12. Jones RN. Global epidemiology of antimicrobial resistance among community-acquired and nosocomial pathogens: a five-year summary from the SENTRY Antimicrobial Surveillance Program (1997-2001). Semin Respir Crit Care Med. 2003;24(1):121-34.
13. Khoshnood S, Heidary M, Asadi A et al. A review on mechanism of action, resistance, synergism, and clinical implications of mupirocin against Staphylococcus aureus. Biomed Pharmacother. 2019;109:1809-18.
14. Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997;10(3):505-20.
15. Laishram S, Pragasam AK, Bakthavatchalam YD, Veeraraghavan B. An update on technical, interpretative and clinical relevance of antimicrobial synergy testing methodologies. Indian J Med Microbiol. 2017;35(4):445-68.
16. LaPlante KL. In vitro activity of lysostaphin, mupirocin, and tea tree oil against clinical methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis. 2007;57(4):413-8.
17. Levy PY, Ollivier M, Drancourt M, Raoult D, Argenson JN. Relation between nasal carriage of Staphylococcus aureus and surgical site infection in orthopedic surgery: the role of nasal contamination. A systematic literature review and meta-analysis. Orthop Traumatol Surg Res. 2013;99(6):645-51.
18. Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520-32.
19. medchemexpress. Niclosamide, https://www.medchemexpress.com/Niclosamide.html Erişim tarihi:01.12.2021
20. Miller MA, Dascal A, Portnoy J, Mendelson J. Development of mupirocin resistance among methicillin-resistant Staphylococcus aureus after widespread use of nasal mupirocin ointment. Infect Control Hosp Epidemiol. 1996;17(12):811-3.
21. Parenti MA, Hatfield SM, Leyden JJ. Mupirocin: a topical antibiotic with a unique structure and mechanism of action. Clin Pharm. 1987;6(10):761-70.
22. Poovelikunnel T, Gethin G, Humphreys H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother. 2015;70(10):2681-92.
23. Rajamuthiah R, Fuchs BB, Conery AL et al. Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus. PLoS One. 2015;10(4):e0124595.
24. Sakr A, Bregeon F, Rolain JM, Blin O. Staphylococcus aureus nasal decolonization strategies: a review. Expert Rev Anti Infect Ther. 2019;17(5):327-40.
25. Sareyyupoglu B, Ozyurt M, Haznedaroglu T, Ardic N. Detection of methicillin and mupirocin resistance in staphylococcal hospital isolates with a touchdown multiplex polymerase chain reaction. Folia Microbiol (Praha). 2008;53(4):363-7.
26. Schweizer M, Perencevich E, McDanel J et al. Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis. BMJ. 2013;346:f2743.
27. Testing TECoAS. Breakpoint tables for interpretation of MICs and zone diameters 2021, https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf Erişim tarihi: 30.11.2021
28. Turnidge JD and Bell JM. Antimicrobial Susceptibility on Solid Media, “Amsterdam D (eds): Antibiotics in Laboratory Medicine, 6.baskı” kitabında s. 44-88, Wolters Kluwer Health (2015).
29. van Rijen MM, Bonten M, Wenzel RP, Kluytmans JA. Intranasal mupirocin for reduction of Staphylococcus aureus infections in surgical patients with nasal carriage: a systematic review. J Antimicrob Chemother. 2008;61(2):254-61.
30. Yazgi H, Ertek M, Ozbek A, Kadanali A. [Nasal carriage of Staphylococcus aureus in hospital personnel and the normal population and antibiotic resistance of the isolates]. Mikrobiyol Bul. 2003;37(2-3):137-42.