METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI  İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI

Oglou, Moumperra; Şimşek Yavuz, Serap; Günel, Gülşen; Aktaş, Zerrin; Nurtop, Elif; Can, Füsun; Eraksoy, Ömer

doi:https://dx.doi.org/10.26650/IUITFD.1671981

Araştırma Makalesi

DOI :10.26650/IUITFD.1671981 IUP :10.26650/IUITFD.1671981 Tam Metin (PDF)

METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI

Moumperra Chral Oglou, Serap Şimşek Yavuz, Gülşen Günel, Zerrin Aktaş, Elif Nurtop, Füsun Can, Ömer Haluk Eraksoy

Amaç: Bazı stafilokoksik β-laktamazlar, özellikle daha yüksek inokulum varlığında, sefazolin (Cz) ve ampisilin-sulbaktam (SAM) dahil olmak üzere penisilin dışındaki β-laktamları parçayalabilir ki buna inokulum etkisi (InE) denir. Bu çalışmada bakteriyemik hastalardan izole edilen S.aureus(MSSA) suşlarında farklı β-laktamlara karşı InE'nin insidansı ve klinik etkileri araştırılmıştır.

Gereç ve Yöntemler: Çalışmaya MSSA bakteriyemisi olan hastalar dahil edildi. MSSA suşları, standart ve yüksek inokulumda disk difüzyon ve sıvı mikrodilüsyon yöntemi ile test edildi. β-laktama zların varlığı ve tipi PCR artı DNA dizilemesi ile doğrulandı. InE, yüksek inokulumda minimal inhibtör konsantrasyon (MİK) değerlerinde 4 kat veya daha fazla artış olarak tanımlandı. Hasta verileri retrospektif olarak elde edildi.

Bulgular: 52 MSSA suşunun %85'i Tip A β-laktamaz pozitifti. Suşların %25'i, %38,5'i ve %3,8'i sırasıyla Cz, SAM ve seftriaksona karşı InE gösterdi. SAMInE gösteren MSSA suşlarıyla infekte olmuş ve SAM ile tedavi edilen hastalardaki ölüm oranı, SAM ile tedavi edilmeyenlere göre önemli ölçüde daha yüksekti (p=0,044, OR 7,8).

Sonuç: MSSA suşlarının tip A β-laktamazı tarafından en çok etkile nen β-laktamın SAM olduğu, bunu Cz’nin takip ettiği ve bu etkinin daha yüksek inokulumla daha belirgin hale geldiği görülmüştür. SAMInE gösteren MSSA suşlarıyla infekte olmuş bakteriyemili hastaların SAM’la tedavisi ölüm oranını artırabilir.

Anahtar Kelimeler: Ampisilin-sulbaktam, bakteriyemi, sefazolin, inokulum etkisi, MSSA, Staphylococcus aureus

DOI :10.26650/IUITFD.1671981 IUP :10.26650/IUITFD.1671981 Tam Metin (PDF)

CONSEQUENCES OF THE INOCULUM EFFECT AGAINST Β-LACTAMS IN METHICILLIN-SUSCEPTIBLE STAPHYLOCOCCUS AUREUS (MSSA) STRAINS

Moumperra Chral Oglou, Serap Şimşek Yavuz, Gülşen Günel, Zerrin Aktaş, Elif Nurtop, Füsun Can, Ömer Haluk Eraksoy

Objective: Some staphylococcal β-lactamases could destroy β lactams other than penicillin, including cefazolin (Cz) and ampi cillin-sulbactam (SAM), especially in the presence of higher inocu lum, which is called the inoculum effect (InE). We investigated the incidence and clinical implications of InE against different β-lac tams including in S.aureus (MSSA) strains isolated from bacteremic patients.

Material and Methods: Patients with MSSA bacteraemia were included. MSSA strains were tested with the disk diffusion and broth microdilution method at standard and high inoculum. The presence and type of β-lactamases were confirmed by PCR plus DNA sequencing. InE was defined as a 4-fold or greater increase in minimal inhibitor concentration (MIC) values at high inoculum. Patient data were obtained retrospectively.

Results: 85% of the 52 MSSA strains were Type A β-lactamase positive. 25%, 38.5%, and 3.8% of the strains showed InE against Cz, SAM, and ceftriaxone, respectively. The mortality rate in patients infected with MSSA strains showing SAMInE and treated with SAM was significantly higher than in those not treated with SAM (p=0.044, OR 7.8, 95).

Conclusion: SAM was the most affected β-lactam by type A β lactamase of MSSA strains, followed by Cz, and this effect became more prominent with higher inoculum. SAM treatment of the patients infected with the MSSA strains showing SAMInE may increase mortality.

Anahtar Kelimeler: Ampicillin-sulbactam, bacteraemia, cefazolin, inoculum effect, MSSA, Staphylococcus aureus

Referanslar

Lam JC, Stokes W. The Golden Grapes of Wrath - Staphylococcus aureus Bacteremia: A Clinical Review. Am J Med 2023;136(1):19-26. google scholar
Lenhard JR, Bulman ZP. Inoculum effect of β-lactam antibiotics. J Antimicrob Chemother 2019;74(10):2825-43. google scholar
Weis S, Kesselmeier M, Davis JS, Morris AM, Lee S, Scherag A, et al. Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia. Clin Microbiol Infect 2019;25(7):818-27. google scholar
European Committee on Antimicrobial Susceptibility Testing. Antimicrobial Susceptibility Testing, EUCAST Disk Diffusion Method 2024. April 14, 2025 2024, https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_ test_documents/2024_manuals/Manual_v_12.0_EUCAST_Disk_Test_2024.pdf . google scholar
Clinical and Laboratory Institute. Methods for dilution antimicrobial susceptibility tests f or bacteria that grow aerobically; Approved Standard— Ninth Edition. CLSI document M07-A9. 2012, Wayne, PA: Clinical and Laboratory Standards Institute, 1-63, ISBN 1-56238-783-9. google scholar
Nannini EC, Stryjewski ME, Singh KV, Bourgogne A, Rude TH, Corey GR, et al. Inoculum effect with cefazolin among clinical isolates of methicillin- google scholar
susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure. Antimicrob Agents Chemother 2009;53(8):3437-41. google scholar
Song KH, Jung SI, Lee S, Park S, Kim ES, Park KH, et al. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum betalactam antibiotics. Eur J Clin Microbiol Infect Dis 2019;38(1):67-74. google scholar
Saeki M, Shinagawa M, Yakuwa Y, Nirasawa S, Sato Y, Yanagihara N, Takahashi S. Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other beta-lactams. J Infect Chemother 2018;24(3):212-5. google scholar
Lo CK, Sritharan A, Zhang J, Li N, Zhang C, Wang F, et al. Clinical significance of cefazolin inoculum effect in serious MSSA infections: a systematic review. JAC Antimicrob Resist 2024;6(3):dlae069. google scholar
Bush K, Bradford PA. Epidemiology of β-Lactamase-Producing Pathogens. Clin Microbiol Rev 2020;33(2):e00047-19. google scholar
Livorsi DJ, Crispell E, Satola SW, Burd EM, Jerris R, Wang YF, Farley MM. Prevalence of blaZ gene types and the inoculum effect with cefazolin among bloodstream isolates of methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother 2012;56(8):4474-7. google scholar
Lee S, Kwon KT, Kim HI, Chang HH, Lee JM, Choe PG, et al. Clinical implications of cefazolin inoculum effect and β-lactamase type on methicillin-susceptible Staphylococcus aureus bacteremia. Microb Drug Resist 2014;20(6):568-74. google scholar
George CRR, Lahra MM, NguyenT, Gatus B. Disc Test for Detecting Staphylococcus aureus Strains producing type a and type C β-lactamases. Microbiol Spectr 2023;11(4):e0022023. google scholar
Mossman AK, Svishchuk J, Waddell BJM, Izydorczyk CS, Buckley PT, Hilliard JJ, et al. Staphylococcus aureus in non-cystic fibrosis bronchiectasis: prevalence and genomic basis of high inoculum β-lactam resistance. Ann Am Thorac Soc 2022;19(8):1285-93. google scholar
Mairi A, Pantel A, Sotto A, Touati A. OXA-48-like carbapenemases producing Enterobacteriaceae in different niches. Eur J Clin Microbiol Infect Dis 2018;37(4):587-604. google scholar
Jafari A, Falahatkar S, Delpasand K, Sabati H, Sedigh Ebrahim-Saraie H. Emergence of Escherichia coli ST131 Causing Urinary Tract Infection in Western Asia: A Systematic Review and Meta-Analysis. Microb Drug Resist 2020;26(11):1357-64. google scholar
Carvajal LP, Rincon S, Echeverri AM, Porras J, Rios R, Ordoñez KM, et al. Novel Insights into the Classification of Staphylococcal β-Lactamases in Relation to the Cefazolin Inoculum Effect. Antimicrob Agents Chemother 2020;64(5):e02511-9. google scholar
Lee SH, Park WB, Lee S, Park S, Kim SW, Lee JM, et al. Association between Type A blaZ Gene polymorphism and cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother 2016;60(11):6928-32. google scholar
Payne DJ, Cramp R, Winstanley DJ, Konowles DJ. Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important betalactamases. Antimicrob Agents Chemother 1994;38(4):767-72. google scholar
Paul M, Zemer-Wassercug N, Talker O, Lishtzinsky Y, Lev B, Samra Z, et al. Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia? Clin Microbiol Infect 2011;17(10):1581-6. google scholar
Başaran S, Şimşek-Yavuz S, Çopur B, Yir A, Çağatay A, Öncül O, et al. Analysis of risk factors for mortality in methicillin-sensitive Staphylococcus aureus bacteremia: Cefazolin is associated with better ourcome. J Ist Faculty Med 2019;82(3):131-8. google scholar
Uda A, Onuma K, Shigemura K, Kitagawa K, Yan Y, Osawa K, et al. Impact of Cefazolin Shortage on Clinical Outcomes of Adult Patients with Bacteremia Caused by Methicillin-Susceptible Staphylococcus aureus in a Tertiary Care University Hospital. Antibiotics (Basel) 2021;10(10):1247. google scholar
Beganovic M, Cusumano JA, Lopes V, LaPlante KL, Caffrey AR. Comparative effectiveness of exclusive exposure to nafcillin or oxacillin, cefazolin, piperacillin/tazobactam, and fluoroquinolones among a national cohort of veterans with methicillin-susceptible Staphylococcus aureus bloodstream infection. Open Forum Infect Dis 2019;6(7):ofz270. google scholar
Hirai J, Asai N, Hagihara M, Kishino T, Kato H, Sakanashi D, et al. Comparative effectiveness of ampicillin/sulbactam versus cefazolin as targeted therapy google scholar
for bacteremia caused by beta-lactamase-producing methicillin-sensitive Staphylococcus aureus: a single-center retrospective study. Antibiotics 2022;11(11):1505. google scholar
Nannini EC, Stryjewski ME, Singh KV, Rude TH, Corey GR, Fowler VG Jr, et al. Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother 2010;54(5):2206-8. google scholar
Skov R, Frimodt-Moller N, Espersen F. In vitro susceptibility of Staphylococcus aureus towards amoxycillin-clavulanic acid, penicillin-clavulanic acid, dicloxacillin and cefuroxime. APMIS 2002;110(7-8):559-64. google scholar
Buis DTP, van der Vaart TW, Prins JM, van der Meer JTM, Bonten MJM, Sieswerda E, et al. Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study. J Antimicrob Chemother 2023;78(7):1175-81. google scholar
Alexander JAN, Worrall LJ, Hu J, Vuckovic M, Satishkumar N, Poon R, et al. Structural basis of broad-spectrum β-lactam resistance in Staphylococcus aureus. Nature 2023;613(7943):375-82. google scholar

Atıflar

Biçimlendirilmiş bir atıfı kopyalayıp yapıştırın veya seçtiğiniz biçimde dışa aktarmak için seçeneklerden birini kullanın

DIŞA AKTAR

APA

Oglou, M.C., Şimşek Yavuz, S., Günel, G., Aktaş, Z., Nurtop, E., Can, F., & Eraksoy, Ö.H. (2025). METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI. İstanbul Tıp Fakültesi Dergisi, 88(3), 216-226. https://doi.org/10.26650/IUITFD.1671981

AMA

Oglou M C, Şimşek Yavuz S, Günel G, Aktaş Z, Nurtop E, Can F, Eraksoy Ö H. METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI. İstanbul Tıp Fakültesi Dergisi. 2025;88(3):216-226. https://doi.org/10.26650/IUITFD.1671981

ABNT

Oglou, M.C.; Şimşek Yavuz, S.; Günel, G.; Aktaş, Z.; Nurtop, E.; Can, F.; Eraksoy, Ö.H. METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI. İstanbul Tıp Fakültesi Dergisi, [Publisher Location], v. 88, n. 3, p. 216-226, 2025.

Chicago: Author-Date Style

Oglou, Moumperra Chral, and Serap Şimşek Yavuz and Gülşen Günel and Zerrin Aktaş and Elif Nurtop and Füsun Can and Ömer Haluk Eraksoy. 2025. “METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI.” İstanbul Tıp Fakültesi Dergisi 88, no. 3: 216-226. https://doi.org/10.26650/IUITFD.1671981

Chicago: Humanities Style

Oglou, Moumperra Chral, and Serap Şimşek Yavuz and Gülşen Günel and Zerrin Aktaş and Elif Nurtop and Füsun Can and Ömer Haluk Eraksoy. “METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI.” İstanbul Tıp Fakültesi Dergisi 88, no. 3 (Sep. 2025): 216-226. https://doi.org/10.26650/IUITFD.1671981

Harvard: Australian Style

Oglou, MC & Şimşek Yavuz, S & Günel, G & Aktaş, Z & Nurtop, E & Can, F & Eraksoy, ÖH 2025, 'METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI', İstanbul Tıp Fakültesi Dergisi, vol. 88, no. 3, pp. 216-226, viewed 6 Sep. 2025, https://doi.org/10.26650/IUITFD.1671981

Harvard: Author-Date Style

Oglou, M.C. and Şimşek Yavuz, S. and Günel, G. and Aktaş, Z. and Nurtop, E. and Can, F. and Eraksoy, Ö.H. (2025) ‘METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI’, İstanbul Tıp Fakültesi Dergisi, 88(3), pp. 216-226. https://doi.org/10.26650/IUITFD.1671981 (6 Sep. 2025).

MLA

Oglou, Moumperra Chral, and Serap Şimşek Yavuz and Gülşen Günel and Zerrin Aktaş and Elif Nurtop and Füsun Can and Ömer Haluk Eraksoy. “METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI.” İstanbul Tıp Fakültesi Dergisi, vol. 88, no. 3, 2025, pp. 216-226. [Database Container], https://doi.org/10.26650/IUITFD.1671981

Vancouver

Oglou MC, Şimşek Yavuz S, Günel G, Aktaş Z, Nurtop E, Can F, Eraksoy ÖH. METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI. İstanbul Tıp Fakültesi Dergisi [Internet]. 6 Sep. 2025 [cited 6 Sep. 2025];88(3):216-226. Available from: https://doi.org/10.26650/IUITFD.1671981 doi: 10.26650/IUITFD.1671981

ISNAD

Oglou, MoumperraChral - Şimşek Yavuz, Serap - Günel, Gülşen - Aktaş, Zerrin - Nurtop, Elif - Can, Füsun - Eraksoy, ÖmerHaluk. “METİSİLİNE DUYARLI STAPHYLOCOCCUS AUREUS (MSSA) SUŞLARININ β-LAKTAMLARA KARŞI İNOKULÜM ETKİSİ GÖSTERMESİNİN SONUÇLARI”. İstanbul Tıp Fakültesi Dergisi 88/3 (Sep. 2025): 216-226. https://doi.org/10.26650/IUITFD.1671981

Cilt 88, Sayı 32025, S. 216-226

ZAMAN ÇİZELGESİ

Gönderim	16.04.2025
Kabul	20.06.2025
Çevrimiçi Yayınlanma	18.07.2025

LİSANS

Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.

İstanbul Tıp Fakültesi Dergisi