Title:  Title: Correlation of neutrophil CD64, PCT and CRP with clinical profile in patients with sepsis/septic shock

Summary of the project:

Sepsis is a life threatening condition that arises when host responds to an infection and damages its organs. It is a major determinant of mortality in intensive care unit. Difficulty in distinguishing between bacteria and nonbacterial etiology is a major cause of misuse of antibiotics. Delay in identification and initiation of antibiotic therapy largely determines the outcome in such patients. Inappropriate and prolonged use leads to emergence of antibiotic resistance bacteria. Blood culture is gold standard but it takes time. Biomarkers have emerging role in identification of sepsis. More than 170 biomarkers have been evaluated, out of theses 34 biomarkers have been evaluated in sepsis. No single biomarker in sepsis has been proven as gold standard. Biomarkers can be used to identify or ruing out sepsis, identify patients who may benefit from specific therapies, access response to therapy and for prognostication. CRP and PCT are most widely studied biomarkers for suspected sepsis. CRP have been used since long for diagnosis of sepsis, but it’s very nonspecific and may rise with nonsepsis conditions. PCT is widely used and a promising biomarker for sepsis. It may elevate in nonsepsis conditions. Though PCT has an established role as a biomarker, diagnostic accuracy of routine PCT measurements have been questioned due to inconsistent and variable results depending on severity of illness and infection. CD64 is a neutrophilic receptor which has a high sensitivity and specificity to diagnose sepsis. It is constitutively expressed on macrophages, monocytes and eosinophils and also on resting neutrophils, to a very low extent (approximately 1000 molecules per cell). However, CD64 expression on neutrophils increases once these become activated by proinflammatory cytokines produced in response to infection and may increase within 4-6 hours upto more than 10 times than the resting levels, allowing good discrimination between resting and activated neutrophil. Several studies have indicated that nCD64 is a highly sensitive and specific marker for sepsis or bacterial infection in adults, neonates and children. Studies have shown that serial CD64 measurement can help in identifying appropriate antibiotic therapy as well as the clinical course and prognosis. Studies have shown that C64 is better than PCT in differentiating sepsis from nonsepsis conditions. Studies have suggested combination of biomarkers can be used and has promising role in sepsis. Various combinations have used with CD64 for better diagnostic value in sepsis.

Our aim is to establish this finding in our settings where patient populations are mostly from sepsis and appropriate antibiotics are to determine their mortality. We will collect data from all patients admitted in our ICU. We will measure levels of the biomarkers PCT, CD64, CRP on admission day of ICU. Blood culture will be sent on day of admission. Then serially measure the biomarkers on day 4 and day 8 of ICU admission. Again when the clinical condition of the patient deteriotes during the ICU stay, at the start of or escalation of antibiotics, blood culture and the levels of these biomarkers will be sent. Again serial levels of these biomarkers will be repeated on day 4 and 8 followed by that day. Primary objective will be to follow the serial trend of these biomarkers with clinical course of ICU patients. Diagnostic accuracy of these biomarkers and their combinations for diagnosis of sepsis and their correlation with blood culture which is the gold standard for diagnosis of sepsis will be noted. Along with prognostic value of these biomarkers alone and in combination during course of ICU stay will be noted. biomarker trends will be noted serially and its kinetics will be noted in patients with sepsis and septic shock, correlation with disease severity and culture and clinical parameters will be noted.

Levels of these biomarkers will also be noted in the control group of patients. These patients will be nonseptic patients in our ICU, who are off antibiotics, haemodynamically stable and about to discharge. Levels of these biomarkers in these nonsepic patients will be compared with those septic patients. We will note CRP, PCT for all patients and correlation of it with CD64 level. CD64 is an evolving biomarker. it along with PCT and CRP have important diagnostic and prognostic implications in ICU patients. Till now there is no literature from Indian ICU setting about kinetics and implications of these biomarkers in critically ill ICU patients. this study will be of immense help to the clinicians.

Key Words: Biomarkers, sepsis/septic shock, CD64, PCT, CRP