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Updated: Nov 4, 2025
Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
Published on: February 9, 2011
Matrix metalloproteinase MMP-8, TIMP-1 and MMP-8/TIMP-1 ratio in plasma in methicillin-sensitive Staphylococcus
Erik Forsblom1,2, Taina Tervahartiala3, Eeva Ruotsalainen1
1Division of Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Background:
Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear.
Methods:
MMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined.
Results:
Altogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (p<0.01). Higher day 3 and 5 MMP-8 levels were associated to mortality at day 14 and 28 (p<0.01) and day 90 (p<0.05). Day 3 MMP-8 cut-off value of 203 ng/ml predicted death within 14 days with an area under the curve (AUC) of 0.70 (95% CI 0.57-0.82) (p<0.01). Day 5 MMP-8 cut-off value of 239 ng/ml predicted death within 14 days with an AUC of 0.76 (95% CI 0.65-0.87) (p<0.001). The results for MMP-8/TIMP-1 resembled that of MMP-8. TIMP-1 had no prognostic impact. In Cox regression analysis day 3 or 5 MMP-8 or day 3 MMP-8/TIMP-1 had no prognostic impact whereas day 5 MMP-8/TIMP-1 predicted mortality within 14 days (HR, 4.71; CI, 95% 1.67-13.3; p<0.01).
Conclusion:
MMP-8 and MMP-8/TIMP-1 ratio were high 3-5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.
Insights
Matrix metalloproteinase-8 (MMP-8) levels, but not tissue inhibitor of metalloproteinases-1 (TIMP-1), predict mortality in Staphylococcus aureus bacteremia (SAB). Elevated MMP-8 and MMP-8/TIMP-1 ratios early in infection indicate severe disease and poor prognosis.
Area of Science:
- Biochemistry
- Infectious Diseases
- Clinical Medicine
Background:
- Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) are known sepsis prognostic markers.
- Their role and prognostic value in Staphylococcus aureus bacteremia (SAB) remain unevaluated.
- Understanding these markers in SAB is crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate MMP-8 and TIMP-1 levels in methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB).
- To determine the association of MMP-8, TIMP-1, and their ratio with disease severity and early mortality in MS-SAB.
- To explore the potential role of matrix metalloproteinase activation in SAB pathogenesis.
Main Methods:
- MMP-8, TIMP-1, and MMP-8/TIMP-1 molar ratio were measured at days 3, 5, and 28 post-positive blood culture in 395 SAB patients.
- Correlation with disease severity (severe sepsis, infection focus) and mortality (days 14, 28, 90) was analyzed.
- Receiver operating characteristic (ROC) analysis and Cox regression were used to assess prognostic values.
Main Results:
- Higher MMP-8 levels at days 3 and 5 were observed in patients with severe sepsis or infection focus (p<0.01).
- Elevated day 3 and 5 MMP-8 levels predicted mortality at 14, 28 (p<0.01), and 90 days (p<0.05).
- Specific MMP-8 cut-off values at day 3 (203 ng/ml) and day 5 (239 ng/ml) predicted 14-day mortality with high AUC (0.70-0.76). TIMP-1 alone had no prognostic impact.
Conclusions:
- Elevated MMP-8 and MMP-8/TIMP-1 ratios 3-5 days post-diagnosis are associated with severe MS-SAB, infection focus, and 14-day mortality.
- These findings suggest that matrix metalloproteinase activation may contribute to the pathogenesis of severe SAB.
- MMP-8 and the MMP-8/TIMP-1 ratio show potential as early biomarkers for severe SAB outcomes.
