Use of interleukin-27 as a diagnostic biomarker for bacterial infection in critically ill patients
Embodiments of the invention are directed to methods of diagnosing bacterial infection in a critically ill patient. The methods include obtaining a sample from the patient and determining the patient's level of IL-27 expression. Embodiments of the invention are also directed to methods that include determining both the patient's levels of IL-27 expression and PCT expression and using the combined result to provide a diagnosis of bacterial infection in a critically ill patient.
1. A method for diagnosing and treating sepsis in a critically ill patient presenting with fever and other signs of a systemic inflammatory response syndrome (SIRS) comprising:
obtaining a serum sample from the patient, wherein the serum sample is obtained from the patient within the first 24 hours of the patient meeting the clinical criterial for SIRS or sepsis;
measuring serum interleukin 27 (IL-27) protein concentration in said sample;
diagnosing the patient with sepsis when the serum IL-27 protein concentration is 5 ng/ml or higher, and
administering one or more antibiotics to the diagnosed patient.
2. The method of claim 1 , wherein the IL-27 protein concentration of 5 ng/ml or higher provides a diagnosis of bacterial infection in a critically ill patient with greater than 80% specificity and/or greater than 80% positive predictive value.
3. The method of claim 1 , wherein the IL-27 protein concentration of 5 ng/ml or higher provides a diagnosis of bacterial infection in a critically ill patient with greater than 90% specificity and/or greater than 90% positive predictive value.
4. The method of claim 1 , wherein procalcitonin (PCT) concentration is also measured, and wherein said IL-27 and said PCT protein concentration results are used in combination to differentiate sterile inflammation and bacterial infection in said patient.
5. A method for treating a critically ill patient presenting with fever and other signs of a systemic inflammatory response syndrome (SIRS) or sepsis comprising:
obtaining a serum sample from the patient;
measuring serum IL-27 protein concentration and procalcitonin (PCT) in said sample;
diagnosing the patient with sepsis when the serum IL-27 protein concentration is 5 ng/ml or higher, and administering one or more antibiotics to the patient diagnosed with sepsis;
diagnosing the patient with SIRS when the serum IL-27 protein concentration is less than 5 ng/ml and the PCT concentration is less than 3 ng/ml; and
treating the patient diagnosed with SIRS with an SIRS therapy selected from one or more of intubation, supplemental oxygen, assisted ventilation, fluid and electrolyte resuscitation, surgical procedures, kidney dialysis, and blood pressure medication.
6. The method of claim 5 , wherein IL-27 protein concentration of 5 ng/ml or higher provides a diagnosis of bacterial infection in a critically ill patient with greater than 80% specificity and/or greater than 80% positive predictive value.
7. The method of claim 5 , wherein IL-27 protein concentration of 5 ng/ml or higher provides a diagnosis of bacterial infection in a critically ill patient with greater than 90% specificity and/or greater than 90% positive predictive value.
8. The method of claim 5 , wherein PCT concentration of less than 3 ng/ml provides a diagnosis of sterile inflammation in a critically ill patient with greater than 80% specificity and/or greater than 80% positive predictive value.
9. A method for diagnosing and treating a bacterial infection in a human patient in need thereof, the method comprising determining the amount of IL-27 protein in a serum sample from the patient, diagnosing the patient with a bacterial infection when the serum IL-27 protein concentration is 5 ng/ml or higher, and administering one or more antibiotics to the diagnosed patient.
10. The method of claim 9 , wherein the patient displays clinical signs of a systemic inflammatory response (SIRS) or sepsis.
11. The method of claim 10 , wherein the serum sample is obtained from the patient within the first 24 hours of the patient meeting the clinical criterial for SIRS or sepsis.
12. The method of claim 11 , wherein the amount of IL-27 protein in the serum sample is determined using flow cytometry.
13. The method of claim 12 , further comprising determining the amount of procalcitonin in the serum sample.
14. The method of claim 1 , wherein the one or more antibiotics is selected from the group consisting of cefotaxime, ticarcillin-clavulanate, piperacillin-tazobactam, imipenem-cilastatin, meropenem, clindamycin, metronidazole, ceftriaxone, ciprofloxacin, cefepime, levofloxacin, and vanomycin.
15. The method of claim 5 , wherein the one or more antibiotics is selected from the group consisting of cefotaxime, ticarcillin-clavulanate, piperacillin-tazobactam, imipenem-cilastatin, meropenem, clindamycin, metronidazole, ceftriaxone, ciprofloxacin, cefepime, levofloxacin, and vanomycin.