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

Abstract

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.

Keywords

• Ampicillin-sulbactam
• bacteraemia
• cefazolin
• inoculum effect
• MSSA
• Staphylococcus aureus

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

Abstract

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.

Keywords

• Ampisilin-sulbaktam
• bakteriyemi
• sefazolin
• inokulum etkisi
• MSSA
• Staphylococcus aureus

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