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Corticosteroids, rifampicin and LMWH impact plasma aMMP-8 and TIMP-1 and aMMP-8/TIMP-1 molar ratio in
E Forsblom1, A Järvinen1, M Kivelä-Rajamäki1
1Division of Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Meilahti Triangle Hospital, Haartmaninkatu 4, Helsinki, P.O. Box 372, FIN-00029 HUS, Helsinki, Finland.
Objectives:
Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) predict outcomes in Staphylococcus aureus bacteremia (SAB). However, the impact of medications on MMPs and their prognostic capability in SAB lacks evaluation.
Methods:
Prospective study with aMMP-8, TIMP-1, and aMMP-8/TIMP-1 determined in methicillin-sensitive SAB (MS-SAB). We evaluated the effect of the medications on MMPs.
Results:
Overall, 395 patients with MS-SAB received 21 different medications. Most medications did not affect MMPs. Prehospital corticosteroids elevated day 3 aMMP-8 and aMMP-8/TIMP-1 (P <0.01). In-hospital corticosteroids is associated with higher day 3 and 28 (P <0.01) aMMP-8 levels and higher day 3, 5, and 28 (P <0.01) aMMP-8/TIMP-1. Rifampicin elevated day 3, 5, and 28 aMMP-8 (P <0.01) and aMMP-8/TIMP-1 (P <0.05). Low-weight molecular heparin (LMWH) elevated day 3, 5, and 28 aMMP-8 and TIMP-1 (P <0.01) and day 5 and 28 aMMP-8/TIMP-1 (P < 0.05). A prognostic survival value of aMMP-8/TIMP-1 in Cox Regression was observed for patients treated with corticosteroids, rifampicin, or LMWH.
Conclusions:
Corticosteroids, rifampicin, and LMWH may elevate aMMP-8 and aMMP-8/TIMP-1 levels in MS-SAB; however, the prognostic value of aMMP-8/TIMP-1 is not disrupted. Clinicians should consider the presence of corticosteroids, rifampicin, and LMWH when applying MMPs as biomarkers for risk stratification in patients with MS-SAB.
Insights
Certain medications like corticosteroids, rifampicin, and LMWH can increase matrix metalloproteinase-8 (MMP-8) and MMP-8/TIMP-1 levels in Staphylococcus aureus bacteremia (SAB). However, the prognostic value of MMP-8/TIMP-1 remains reliable for risk stratification.
Area of Science:
- Biochemistry
- Clinical Medicine
- Pharmacology
Background:
- Matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) are established prognostic biomarkers in Staphylococcus aureus bacteremia (SAB).
- The influence of common medications on MMP-8 and TIMP-1 levels and their predictive accuracy in SAB is not well understood.
Purpose of the Study:
- To investigate the impact of various medications on MMP-8 and TIMP-1 levels in patients with methicillin-sensitive SAB (MS-SAB).
- To evaluate whether medication-induced changes affect the prognostic capability of MMP-8/TIMP-1 ratios in MS-SAB outcomes.
Main Methods:
- Prospective study involving 395 patients with MS-SAB.
- Measurement of active MMP-8 (aMMP-8), TIMP-1, and the aMMP-8/TIMP-1 ratio at multiple time points.
- Analysis of the effects of 21 different medications on MMP levels and their association with patient outcomes.
Main Results:
- Most medications did not significantly alter aMMP-8, TIMP-1, or aMMP-8/TIMP-1 levels.
- Corticosteroids, rifampicin, and low-molecular-weight heparin (LMWH) were associated with elevated aMMP-8 and aMMP-8/TIMP-1 levels.
- The prognostic survival value of the aMMP-8/TIMP-1 ratio in Cox regression remained significant for patients treated with these specific medications.
Conclusions:
- Corticosteroids, rifampicin, and LMWH can increase aMMP-8 and aMMP-8/TIMP-1 levels in MS-SAB patients.
- Despite these elevations, the prognostic utility of the aMMP-8/TIMP-1 ratio for risk stratification is preserved.
- Clinicians should consider concurrent medication use when interpreting MMP-based biomarkers for risk assessment in MS-SAB.
