WO2021236840A1 - Indice rapide pour test de cinétique de mortalité sab (« risk ») - Google Patents

Indice rapide pour test de cinétique de mortalité sab (« risk ») Download PDF

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WO2021236840A1
WO2021236840A1 PCT/US2021/033258 US2021033258W WO2021236840A1 WO 2021236840 A1 WO2021236840 A1 WO 2021236840A1 US 2021033258 W US2021033258 W US 2021033258W WO 2021236840 A1 WO2021236840 A1 WO 2021236840A1
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metabolite
protein
alpha
insulin
growth factor
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PCT/US2021/033258
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David J. GONZALEZ
Jacob WOZNIAK
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The Regents Of The University Of California
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56911—Bacteria
    • G01N33/56938—Staphylococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6848—Methods of protein analysis involving mass spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2440/00—Post-translational modifications [PTMs] in chemical analysis of biological material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/26—Infectious diseases, e.g. generalised sepsis

Definitions

  • Staphylococcus aureus bacteremia causes significant disease in humans, carrying mortality rates of 20 - 30%.
  • the biomarkers as disclosed herein exceed the predictive capabilities of those previously reported, particularly when used in combination.
  • a method for treating Staphylococcus aureus bacteremia comprises, or alternatively consists essentially of, or yet further consists of administering to the subject a therapy selective for the SaB, thereby treating the subject.
  • SaB Staphylococcus aureus bacteremia
  • a method for detecting Staphylococcus aureus bacteremia (SaB) or SaB infection in a subject suspect of having Staphylococcus aureus bacteremia comprises, or alternatively consists essentially of, or yet further consists of detecting level(s) of one or more of the following in a biological sample isolated for the subject: a protein as identified in any of Figure 2A and Tables 1-3, a metabolite as identified in any of Figure 2D and Tables 2 and 4, a post-translational modification (PTM) as identified in any of Tables 1-2 and 5, IL6, TNF, IL10, or CXCL8.
  • PTM post-translational modification
  • a method for treating one or more of: Staphylococcus aureus bacteremia (SaB), high-risk SaB, or low-risk SaB in a subject in a subject.
  • the subject being treated has an altered level of one or more of the following in a biological sample isolated from the subject:
  • albumin AB
  • carbamylation of albumin AB, PTM - carbamylation
  • serotransferrin TF
  • carbamylation of serotransferrin TF
  • glycosylation of 2-HS glycoprotein AHSG, PTM - glycosylation
  • glycosylation of fibronectin FN1, PTM - glycosylation
  • acyl-carnitines thyroxine
  • a metabolite having a mass-to-charge ratio (m/z) of 540.322 and a retention time (RT) of 6.57 or an equivalent thereof or a metabolite having a mass-to-to
  • Metabolite ID 349 having an m/z of 540.3225 and an RT of 6.571318
  • Metabolite ID 228 having an m/z of 548.3625 and an RT of 6.571958
  • Metabolite ID 1963 having an m/z of 1091.705 and an RT of 6.572453
  • Metabolite ID 971 having an m/z of 547.3593 and an RT of 6.571625
  • Metabolite ID 13 having an m/z of 546.3556 and an RT of 6.57188
  • Metabolite ID 4146 having an m/z of 540.8244 and an RT of 6.573601
  • Metabolite ID 4046 having an m/z of 1036.159 and an RT of 6.569577
  • Metabolite ID 854 having an m/z of 289.2171 and an RT of 4.12084
  • Metabolite ID 4046 having an m/z of 1036.159 and an RT of 6.569577
  • FIG. 10N provides K means clustered heatmap of all significantly altered, protein-normalized, modified peptides (ANOVA p ⁇ 0.05) across the four primary groups (Control groups: NN - Non-hospital, Non-infected, HN - Hospital, Non-infected; Infection groups: HS -Hospital, Survival, HM - Hospital, Mortality).
  • FIG. 10O shows serotransferrin mortality-associated PTM plot depicting modified peptide abundance (left) and modified peptide abundance normalized to total protein levels (right).
  • FIG. 12A - 12F provide extended analysis of metabolomic SaB disease modules, related to FIG. 4.
  • Non-limiting exemplary sequences of a protein as disclosed herein, or the underlying genes, or suitable antibodies for detection of the protein can be found on www.genecards.org/ or www.uniprot.org/, each of which is incorporated by reference herein in its entirety (last accessed on May 18, 2021).
  • an antibody recognizing and specifically binding to a target can be generated, for example by immunolizing an animal with an antigen of the target, harvesting the B cells from the animal’s spleen, fusing the B cells with myeoloma cells, and selecting suitable antibodies produced by the fused B cells. See, for example, Edward A. Greenfield, Antibodies: A Laboratory Manual, published by Cold Spring Harbor Laboratory, 2014.
  • the gene name is used to represent the protein or a fragment thereof as used herein.
  • the peptide, protein, biological complex or other active compound is purified to represent greater than 90%, often greater than 95% of all macromolecular species present in a purified preparation prior to admixture with other formulation ingredients.
  • the purified preparation may be essentially homogeneous, wherein other macromolecular species are not detectable by conventional techniques.
  • MS mass spectrometry
  • MS refers to an analytical technique to identify compounds by their mass.
  • MS refers to methods of filtering, detecting, and measuring ions based on their mass-to-charge ratio, or "m/z”.
  • MS technology generally includes (1) ionizing the compounds to form charged compounds; and (2) detecting the molecular weight of the charged compounds and calculating a mass-to-charge ratio. The compounds maybe ionized and detected by any suitable means.
  • a “mass spectrometer” generally includes an ionizer and an ion detector.
  • post-translational modification refers to modifications that occur on a peptide after its translation by ribosomes is complete.
  • PTM refers to any modification of a natural or non-natural amino acid which occurs after such: an amino acid has been translationally incorporated into a polypeptide chain.
  • a post-translational modification may be a covalent chemical modification or enzymatic modification.
  • a biological sample is obtained from a subject.
  • samples include, but are not limited to, cell sample, tissue sample, tumor biopsy, liquid samples such as blood and other liquid samples of biological origin (including, but not limited to, ocular fluids (aqueous and vitreous humor), peripheral blood, sera, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, prostatic fluid, cowper’s fluid or pre-ejaculatory fluid, female ejaculate, sweat, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, ascites, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions/flushing, synovial fluid, mucosal
  • lactic acidosis and acute kidney injury are associated with increased SaB mortality, and are potential markers of mitochondrial dysfunction, reflecting profound effects on host metabolism (Mikkelsen et ah, 2009, Mikkelsen; Ralto and Parikh, 2016, Semin Nephrol 36, 8-16; Singer, 2014, Virulence 5, 66-72).
  • a comprehensive and unbiased assessment of host factors altered in response to SaB may elucidate additional key features that can help predict patient outcomes and guide development of novel therapeutics.
  • critical host responses modulated by interaction with an invading pathogen must be elucidated, not only as single entities, but how they function as a dynamic, concerted network.
  • glycosylated fetuin A or a fragment or derivative thereof carbamylation of albumin, carbamylation of serum transferrin (serotransferrin), glycosylated fetuin A atN156, AHSGN156 HexNAc(4)Hex(5)NeuAc(2), modified EEF2 peptides, modified GLOl peptides, modified MAT2B peptides, decreased level of modified ILK peptides, increased of modified SPSB4 peptides (oxidation at W104), and decreased level of modified serotrasferrin peptides; and
  • the therapy is administered to the subject within 48 hours of clinical presentation. In a further embodiment, the therapy is administered to the subject within 24 hours of clinical presentation. In yet a further embodiment, the therapy is administered to the subject within 6 hours of clinical presentation.
  • Plasma serine protease inhibitor (SERPINA5), Insulin-like growth factor binding protein 1 (IGFBP1), Insulin-like growth factor-binding protein 2 (IGFBP2), Insulin like growth factor-binding protein 4 (IGFBP4), Insulin-like growth factor-binding protein 7 (IGFBP7), Insulin-like growth factor-binding protein 6 (IGFBP6), Insulin-like growth factor binding protein 3 (IGFBP3), Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS), Apolipoprotein, apolipoprotein D, apolipoprotein B, apolipoprotein M, apolipoprotein Al, apolipoprotein A2, apolipoprotein LI, apolipoprotein Cl, apolipoprotein A4, Insulin-like growth factor 1 (IGF-I), Insulin-like growth factor 2 (IGF -II), Thyroxine binding globulin (SERPINA7), Alpha- 1 -anti
  • Metabolite ID 349 having an m/z of 540.3225 and an RT of 6.571318, , Metabolite ID 228 having an m/z of 548.3625 and an RT of 6.571958, Metabolite ID 1963 having an m/z of 1091.705 and an RT of 6.572453, Metabolite ID 971 having an m/z of 547.3593 and an RT of 6.571625, Metabolite ID 13 having an m/z of 546.3556 and an RT of 6.57188, Metabolite ID 4146 having an m/z of 540.8244 and an RT of 6.573601, Metabolite ID 4046 having an m/z of 1036.159 and an RT of 6.569577, Metabolite ID 1374 having an m/z of 787.9906 and an RT of 6.571293, Metabolite ID 2304 having an m/z of 788.9945 and an RT of 6.571611, Metabolite ID 3933 having an m/
  • EGF and pentraxin domain-containing protein 1 SVEP1
  • Cystatin-B CSTB
  • Pulmonary surfactant-associated protein B SFTPB
  • IGFBP2 Insulin like growth factor-binding protein 2
  • MT1G Metallothionein-IG
  • TEMPI Metalloproteinase inhibitor 1
  • EFEMP1 EGF-containing fibulin-like extracellular matrix protein 1
  • LAMA2 Laminin subunit alpha-2
  • DSC2 Desmocollin-2
  • NEOl Neogenin
  • CFB Complement factor B
  • Collagen alpha-3(VI) chain COL6A3
  • Metabolite ID 349 having an m/z of 540.3225 and an RT of 6.571318
  • Metabolite ID 228 having an m/z of 548.3625 and an RT of 6.571958
  • Metabolite ID 320 having an m/z 227.0790367 of and an RT of 0.86769725
  • Metabolite ID 971 having an m/z of 547.3593 and an RT of 6.571625
  • Metabolite ID 670 having an m/z 595.493461 of and an RT of 8.8597215
  • Metabolite ID 13 having an m/z of 546.3556 and an RT of 6.57188
  • Metabolite ID 1379 having an m/z 299.6719585 of and an RT of 7.241768583
  • Metabolite ID 2385 having an m/z 482.3238254 of and an RT of 6.245950417
  • Metabolite ID 4146 having an m/z of 540.8244 and an
  • albumin AB
  • carbamylation of albumin AB, PTM - carbamylation
  • serotransferrin TF
  • carbamylation of serotransferrin TF
  • glycosylation of 2-HS glycoprotein AHSG, PTM - glycosylation
  • glycosylation of fibronectin FN1, PTM - glycosylation
  • acyl-carnitines thyroxine
  • a metabolite having a mass-to-charge ratio (m/z) of 540.322 and a retention time (RT) of 6.57 or an equivalent thereof or a metabolite having a mass-to-to
  • Fetuin B Fetuin B
  • SERPINDl Heparin cofactor 2
  • CNDP1 Torsin-3A
  • CBP complement factor B
  • IGFALS Insulin-like growth factor-binding protein complex acid labile subunit
  • IGFBP2 Insulin-like growth factor-binding protein 2
  • CSH Complement factor H
  • PON3 Serum paraoxonase/lactonase 3
  • AHSG Haptoglobin
  • Coagulation factor X F10), Hyaluronan-binding protein 2 (HABP2), Fibrinogen alpha chain (FGA), Immunoglobulin heavy variable 4-28 (IGHV4-28), Fibronectin (FN1), Adiponectin (ADIPOQ),
  • an altered level compared to a control indicates a positive detection of SaB or high-risk SaB or low-risk SaB.
  • the control is the level of a healthy subject or a subject free of SaB or high-risk SaB or low-risk SaB, or an average thereof.
  • interleukin 10 interleukin 10
  • IL6 interleukin 6
  • IL8 interleukin 8
  • ALB carbamylation of albumin
  • TF carbamylation of serotransferrin
  • acyl-carnitines a metabolite having a mass-to- charge ratio (m/z) of 509.272 and a retention time (RT) of 3.94 or an equivalent thereof, or a metabolite having a mass-to-charge ratio (m/z) of 289.217 and a retention time (RT) of 4.12 or an equivalent thereof;
  • the following in the biological sample isolated from the subject indicates a positive detection of SaB or high-risk SaB:
  • SPSB4 SPRY domain-containing SOCS box protein 4
  • the level of a PTM is normalized to the total amount of the modified protein and the unmodified protein. In some embodiments, the level of a PTM is normalized to the total amount of all proteins.
  • a method of treating a subject having or suspect of having or diagnosed of having Staphylococcus aureus bacteremia comprises, or alternatively consists essentially of, or yet further consists of administering one or both of an agent which stimulates the thyroid signaling or an agent which stimulates the adiponectin signal to the subject.
  • the agnet that stimulating the thyroid signaling comprises, or consists essentially of, or yet further consists of a thyroid hormone, or thyroxine (T4).
  • Glycosylation has been used as biomarkers for various diseases, including cancer (Silsirivanit, 2019, Adv Clin Chem 89, 189-213), Alzheimer’s disease (Regan et al., 2019, Medicines (Basel) 6) and chronic inflammatory conditions (Gornik and Lauc, 2008,
  • the top unmodified biomarker was fetuin B and the top modified biomarker was glycosylation of fetuin A.
  • Fetuins belong to the cy statin superfamily of proteins (Dabrowska et al., 2015, Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 159, 352-359; Olivier et al., 2000, Biochem J 350 Pt 2, 589-597) and can transport free fatty acids in the bloodstream (Cayatte et al., 1990, J Biol Chem 265, 5883-5888).
  • fetuin A and B are commonly studied in metabolic disorders such as obesity and diabetes, but fetuin A has also been shown to exert anti-inflammatory effects (Wang and Sama, 2012, Curr Mol Med 12, 625-633). Notably, fetuin A supplementation is protective in mouse models of systemic inflammation (Cayatte et al., 1990). Thus, defining the role of fetuin B in this process and whether glycosylation of either of these proteins impacts their activity could be of significant interest to the infectious and inflammatory disease communities. Regardless, both proteins can now be classified as high quality biomarkers of SaB patient mortality.
  • Protein carbamylation is a non-enzymatic PTM (Jaisson et al., 2018, Adv Clin Chem 84, 1-38) that is related to a number of pathological processes, including chronic kidney disease (Berg et al., 2013, Sci Transl Med 5, 175ral29) and rheumatoid arthritis (Pruijn, 2015, Front Immunol 6, 192).
  • adiponectin also has anti-inflammatory, cardioprotective and vasoprotective effects (Achari and Jain, 2017) and adiponectin KO mice are more susceptible to polymicrobial sepsis (Teoh et al., 2008, Am J Physiol Endocrinol Metab 295, E658-664).
  • the data indicate a protective role for adiponectin signaling in SaB infection models.
  • RISK48 TEST A list of 11 proteins/metabolites converted to a high throughput mass spectrometry method can predict (92% predictability) patient death within 24 hours of clinical presentation. See, Table 2.
  • Table 1 provides a biomarker set for 24-hour risk test (RISK24).
  • Table 2 provides a biomarker set for 48-hour risk test (RISK48).
  • RISK -24 a method and related compositions and/or kits which allows a rapid immuno-assay test that can be completed within 24 hours (hrs). Such method is referred to herein as RISK -24.
  • the method comprising detecting levels of the proteins, metabolites and PTMs as identified in FIG. 14 and/or Table 1.
  • RISK-48 a method and related compositions and/or kits which allows a rapid immuno-assay test that can be completed within 48 hours (hrs). Such method is referred to herein as RISK-48.
  • the method comprising detecting levels of the protein, metabolites and PTMs as identified in FIG. 15 and/or Table 2.
  • composition or a kit for detecting levels of the proteins, metabolites and PTMs as disclosed herein is provided herein.
  • the composition or kit comprises, or consists essentially of, or yet further consists of antibodies, each of which recognizes and specifically binds to a protein, metabolite, or PTM as disclosed herein.
  • the composition or kit further comprises a reporting reagent (such as radioisotopes, fluorochromes, chemiluminescent compounds, dyes, and proteins, including enzymes or fluorescent proteins, optionally conjugated to an antibody recognizing and specifically binding to the antibody of the protein, metabolite or PTM).
  • a reporting reagent such as radioisotopes, fluorochromes, chemiluminescent compounds, dyes, and proteins, including enzymes or fluorescent proteins, optionally conjugated to an antibody recognizing and specifically binding to the antibody of the protein, metabolite or PTM.
  • Such reporting reagent is able to generate a detectable signal when the antibody binds to the protein, metabolite or PTM.
  • those methods, compositions and kits provide a rapid detection of SaB, SaB infection, and/or high-risk SaB, allowing a faster treatment and/or a treatment specific for the SaB, SaB infection, and/or high-risk SaB, and thus resulting in a better and more desirable prognosis.
  • kits comprising, or alternatively consisting essentially of, or yet further consisting of one or more agents for use in any method as disclosed herein, and an optional instruction.
  • the agents comprise, or alternatively consist essentially of, or yet further consist of an antibody specifically recognizes and binds to a protein, a metabolites and/or a PTM as disclosed herein.
  • the agents further comprise an agent suitable for use in an immunoassay, a mass spectrometry or another detection method as disclosed herein, such as a solvent or a standard for calibrate the instrument.
  • the agents further comprises a positive control or a negative control or both.
  • a positive control can be quantified by a method as disclosed herein under the same experimental setting of quantifying a biological sample, and shows a positive detection.
  • a negative control on the other side, can be quantified by a method as disclosed herein under the same experimental setting of quantifying the biological sample, and shows a negative detection. Accordingly, one of skill in the art can compare the biological sample with the negative or positive control and determine whether the biological sample shows a negative or positive detection.
  • the agent is a substance (such as a plate, a strip, or a bead) immobilized one or more of the antibodies.
  • Metabolomics data were interrogated for small molecules using MZmine (Olivon et ah, 2017, Anal Chem 89, 7836-7840) and Global Natural Products Social Networking Molecular Networking (GNPS) (Wang et ah, 2016, Nat Biotechnol 34, 828-837).
  • Modified proteins, including glycoproteins were identified by combining molecular networking with a PTM-tolerant database search through Byonic (Bern et ah,
  • the ensemble feature selection approach ensures that the top-ranked biomarkers are not correlated to one another and therefore could be used in combination for the enhanced prediction of SaB patient mortality (Williams, 2009, Arthritis Res Ther 11, 130).
  • Using the top two markers from both workflows significantly enhanced the predictive power relative to the individual markers alone (FIG. 2G).
  • applicant validated fetuin B (FIG. 2H) and other top biomarkers (FIG. 8F- FIG. 8G) in a subset of the samples using enzyme-linked immunosorbent assays (ELISAs) (Fetuin B AUC 0.8945).
  • ELISAs enzyme-linked immunosorbent assays
  • proteomics cluster 2 (C2) captured the host response to infection, regardless of mortality status. Within this cluster applicant found C- reactive protein and serum-amyloid proteins 1 and 2, along with other major components of the acute-phase response (FIGS. 11A-11E).
  • Other interesting clusters include clusters 4, 5 and 6, which showed increases (cluster 5) and decreases (clusters 4 and 6) in the mortality group making them prime clusters for further investigation. Clusters 1 and 3 were largely healthy control-specific and hospital control-specific, respectively, but did not demonstrate a strong association with infection or mortality.
  • the ECM adhesion proteins ICAM1 and VCAM1 have previously been shown to be elevated in SaB patients, particularly those with endocarditis (Soderquist et ah, 1999, Clin Exp Immunol 118, 408- 411), and TNF can be used as mortality biomarkers in humans (Rose et al., 2012).
  • the striking enrichment for IGFBPs in this cluster represents a novel finding in the data.
  • clusters 1 and 3 showed increased expression in the mortality group relative to other cohorts.
  • cluster 2 showed an increase in the survival group relative to mortality and cluster 4 showed a decrease in expression with infection, which went down further if the patient died.
  • Cluster 5 had a strong healthy association and clusters 6 and 7 showed increased expression in the hospitalized, non-infected group.
  • applicant renamed the most interesting clusters according to their mortality expression directions and magnitude (Cl: mMortality++, C3: mMortality+, C4: mMortality-; m signifies “metabolomics”).
  • Thyroid hormone dysfunction during non-specific sepsis also known as euthyroid sick syndrome, is well characterized (Bello et ah, 2009, Chest 135, 1448-1454; Plikat et ah, 2007, Metabolism 56, 239-244); however, it has not been previously associated specifically with SaB infections nor mortality.
  • cytokines have demonstrated strong associations with SaB mortality in previous studies (TNF and ILIO (Rose et ak, 2012; Rose et ah, 2017); IL6 and CXCL8 (Guimaraes et ah, 2019)), providing validation for this approach.
  • This analysis further indicates that CCL5 and CXCL12 may also be linked to SaB mortality and merit further study. Focusing in on the top 3 cytokines predicted from this analysis (IL6, TNF and ILIO) applicant found that the majority of the connections were to proteins in pMortality+ (FIG. 6C).
  • Embodiment 10 The method of any one of embodiments 7-9, wherein one or more of the following in a biological sample isolated from the subject indicates a positive detection:
  • Embodiment 23 The method of any one of embodiments 1-22, wherein the therapy comprises one or more of antibiotics, optionally selected from b-lactam, vancomycin, daptomycin, and/or ceftaroline.
  • Embodiment 28 The method of any one of embodiments 1-27, wherein the therapy is administered to the subject within 48 hours of clinical presentation, optionally wherein the therapy is administered to the subject within 24 hours of clinical presentation, and further optionally wherein the therapy is administered to the subject within 6 hours of clinical presentation.
  • Embodiment 29 A kit comprising one or more agents (such as an antibody or a substance immobilized the antibody) for use in a method of any one of embodiments 1-28, and an optional instruction.

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Abstract

L'invention concerne des méthodes et des compositions pour le traitement, la détection ou la détermination du pronostic de bactérémie à Staphylococcus aureus (SaB) chez un sujet.
PCT/US2021/033258 2020-05-20 2021-05-19 Indice rapide pour test de cinétique de mortalité sab (« risk ») WO2021236840A1 (fr)

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