Use of Procalcitonin for Optimizing Antimicrobial Therapy in Long Term ICU Patients

Most of the studies are conducted to evaluate the role of procalcitonin in the diagnosis and management of sepsis at the time of admission or in a defined set of patients [Respiratory infection, surgical sepsis, neonatal sepsis, emergency department, burn patients etc]. The aim of the study was to determine the role of serial monitoring of PCT-serum level with the clinical assessment of the patients and guiding the antimicrobial therapy. The study was conducted for two months and all patients admitted to ICU with suspected sepsis, were included in the study. Patient’s demography, SOFA score, APACHE II score and other laboratory parameters were recorded. The blood sample was collected on the day of admission and on alternate days till ten days of admission or discharge from ICU whichever comes earlier. The sera were separated and quantitative estimation of PCT was done by ELISA based technique. In total seven patients were included in the study. The median baseline level of PCT was 135.45 ng/ml higher than the other studies. The baseline level had no correlation with the severity of illness. Two of the patients admitted with septic shock succumbed to infection. There was 30% increase in PCT from baseline in these patients. All patients, who improved clinically and transfer out of the ICU and survived showed >10% decrease in PCT. The percent change in PCT started increasing a day before clinical deterioration in one of the patient. Hence percent change in PCT level may be used as a supportive marker while escalating/ de-escalating/ continuing same antimicrobial therapy. Key-words: Procalcitonin, Sepsis, Serial monitoring, Intensive care unit (ICU), Antimicrobial Therapy INTRODUCTION Systemic inflammation is a common problem in Intensive care unit (ICU) and fever is one of the most common symptoms seen in such patients. The etiology of fever could be infectious or non-infectious . The infectious causes require early diagnosis and immediate treatment with appropriate antibiotics, as failing to do so could result in significant morbidity and mortality associated with sepsis . How to cite this article Kumar S, Sachdeva K, Rajan S, Matlani M. Use of Procalcitonin for Optimizing Antimicrobial Therapy in Long Term ICU Patients. Int. J. Life Sci. Scienti. Res., 2018; 4(3): 1766-1773 Access this article online www.ijlssr.com In other cases where non-infectious insults are responsible for systemic inflammatory response syndrome (SIRS), the diagnosis remains difficult and results in over use of antibiotics . Moreover, most of the patients in ICU with the slowly evolving disease are often colonized with bacteria at multiple sites and hence some degree of inflammation is always there . Hence clinicians are often in dilemma to decide whether there is persisting inflammation or a new infection, whether to start a new course of antibiotics or wait and observe with the existing antibiotics. The available diagnostic tools to differentiate between infectious and non-infectious SIRS are of little help. Microbiological examinations confirmed bacteremia in only about 30% of patients with sepsis [5] and the result takes several hours to days. Systemic inflammatory markers, such as C reactive protein (CRP) and Research Article Copyright © 2015 2018| IJLS R by Society for Scientific Research under a C BY-NC 4.0 International License Volume 04 | Is ue 03 | Page 176 Int. J. Life Sci. Scienti. Res. eISSN: 2455-1716 Kumar et al., 2018 DOI:10.21276/ijlssr.2018.4.3.5 Copyright © 2015 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 03 | Page 1767 erythrocyte sedimentation rate (ESR), have poor sensitivity and specificity in diagnosing bacterial infections . Hence, a biomarker to rapidly and accurately identify sepsis is warranted for use in the clinical setting. Currently, procalcitonin (PCT) has emerged as a promising biomarker for bacterial infections. PCT is a precursor protein of calcitonin. Unlike calcitonin, which is only produced in the C-cells of the thyroid gland, PCT can be produced ubiquitously throughout the human body. The production of PCT is up-regulated by pro-inflammatory cytokines, bacterial endotoxins, and lipopolysaccharide. Interferon gamma, a cytokine associated with viral infections, reduces the up-regulation of PCT. It has been shown that PCT levels in non-infectious febrile conditions, such as autoimmune diseases or fever caused by malignant disorders stay low. Furthermore, an increase in PCT levels can be monitored within 4 to 6 h after the start of infection . Many studies are conducted to evaluate the role of procalcitonin in diagnosis and management of sepsis at the time of admission in the emergency department . Most of these patients often utilize emergency department as the first point of healthcare contact . The clinical need to differentiate infectious from non-infectious SIRS is particularly important in such set up as diagnosing or excluding infection can alter treatment care of patient e.g. starting antibiotics, admit vs discharge. It has been found that the PCT may offer a more tailor made treatment to the individual patient with fever in the emergency department. Other studies are conducted in a defined set of patients (Respiratory infection, surgical sepsis, neonatal sepsis, burn patients etc.). For patients with community acquired pneumonia, the serum PCT concentration is able to differentiate bacterial from viral causes. Postcardiotomy patients, who are at particularly high risk for postoperative infections and frequently develop postoperative SIRS and circulatory failure that can mimic severe bacterial infection, have been the focus of particular interest. However, the accuracy of PCT to distinguish infected from non-infected patients in this setting is poor . The present study was conducted in ICU (Medical surgical) of a large public sector tertiary care hospital. The patients admitted here are often referred from other private or small healthcare facilities. Majority of the patients suspected to have sepsis have already been receiving antibiotics. This makes the clinical decision even more difficult e.g. whether to continue the same antibiotic or escalates/ de-escalates the antibiotics. As this set up is usually not the first point of healthcare contact of patients, the baseline level of procalcitonin will not reflect the level in the initial days of illness or before starting the antibiotic. Hence single point measurement of PCT has limited role here. Therefore the aim was to address the role of serial PCT-serum monitoring in ICU patients to predict mortality and treatment failure in sepsis and guiding antimicrobial therapy. MATERIALS AND METHODS The ethical approval of this study was taken from the Institute Ethics Committee before starting the study. Written informed consent was obtained from all patients or their relatives before enrollment. Study designProspective observational study. Study siteThe study was conducted at Intensive Care Unit [Medical and Surgical] of a tertiary care Hospital, Delhi, India. The hospital is a 1531 bedded, tertiary care, government hospital. The daily average out-patient department visits were 9538 and in-patient admission were 434. The ICU (Medical and Surgical) is eight bedded and admits patients with medical or surgical complications and hence caters mixed population. The hospital provides diagnostic laboratory support for multiple disciplines like hematology, pathology, histopathology, biochemistry etc. The hospital has also clinical microbiology laboratory that performs microscopy, serology, culture, identification, and sensitivity of various micro-organism by conventional and/or molecular techniques as per standard microbiological protocol . The laboratory participates in internal and external quality assurance program. Study DurationThe study was conducted for 2 months in August to September, 2017. Inclusion criteriaAll patients staying for more than 24 hours in the ICU suspected to have sepsis were consecutively enrolled in the study. The study subjects were grouped into severe sepsis and septic shock based on American College of Chest Physicians/Society of Int. J. Life Sci. Scienti. Res. eISSN: 2455-1716 Kumar et al., 2018 DOI:10.21276/ijlssr.2018.4.3.5 Copyright © 2015 2018| IJLSSR by Society for Scientific Research under a CC BY-NC 4.0 International License Volume 04 | Issue 03 | Page 1767 Critical Care Medicine (ACCP/SCCM) Consensus guidelines . Exclusion criteriaPatients were excluded from the study if anticipated duration of stay was under 24 hours, severe immuno-compromised, autoimmune disease, on chemotherapy or on chronic steroid therapy. Follow up periodAll patients included in the study were contacted telephonically within 28 days of ICU admission to find out 28 days mortality, if any. Data collectionAt admission, the patient’s age, sex, height, and weight was recorded. Daily record of the clinical status of the patients was maintained. These data included the following: clinical status (severe sepsis or septic shock); Acute Physiology and Chronic Health Evaluation (APACHE)-II score; SOFA score, temperature; heart rate; respiratory rate; blood pressure; central venous pressure; laboratory analysis and arterial blood gas analysis. The daily course of the treatment and antimicrobials therapy was also recorded. The final determination of the patient’s status was done retrospectively, on the basis of the complete patient charts, results of microbiological cultures and other investigations requested by attending physician. Estimation of Human procalcitoninQuantitative estimation of serum PCT was measured by using QAYEEBIO manufactured by Qayee Biotechnology Co., Ltd. Shanghai [Lot No. 08/2016 (96T), Cat No QY-E02848] as per manufacturer instruction. The blood sample was collected from eligible patients on alternate days till 10 days of admission in ICU. Blood samples were centrifuged at 300