The purpose of this assessment is to evaluate the clinical and cost effectiveness of using procalcitonin testing with standard clinical practice to guide antibiotic treatment in the following populations:
Adults and children with confirmed or highly suspected sepsis in intensive care settings.
Adults and children with suspected bacterial infection presenting to the emergency department.
Infections, such as pneumonia, may be caused by bacteria or viruses. Bacterial infections can be treated with antibiotics, but antibiotic treatment is inappropriate for viral infections. Many people, especially children, are often treated with antibiotics without the causative agent being known. Common side effects of antibiotics include mild stomach upset and diarrhoea. Less commonly, people may have an allergic reaction to an antibiotic. Furthermore, overuse of broad‑spectrum antibiotics contributes to the development and spread of antimicrobial resistance. Therefore, rapid and accurate determination of the presence or absence of bacterial infection is important to reduce unnecessary exposure to antibiotics.
Sepsis is a common and serious problem among patients being treated in intensive care units. Bacteria are the most common cause of sepsis, but systemic viral and fungal infections can also occur. Symptoms of sepsis include fever or a very low body temperature, rapid breathing and altered mental status, such as reduced alertness or confusion. These symptoms also occur with systemic inflammatory response syndrome, a life‑threatening condition that can be caused by the body's overreaction to an infection or a non‑infectious event such as trauma or burns. Clinicians must be able to rapidly distinguish between infectious and non‑infectious causes of systemic inflammatory response syndrome, as well as between different agents of infection, to guide appropriate therapy.
Severe sepsis is one of the most common reasons for admission to an intensive care unit. In its most severe form, septic shock, it has a mortality rate of 40% to 60%, which is thought to increase substantially for every hour of delay in starting appropriate antibiotic treatment. Therefore, broad‑spectrum, high‑potency antibiotics are widely used in intensive care units. It is important for clinicians to be able to monitor the progression of sepsis and the response to antibiotic treatment so that broad‑spectrum antibiotic treatment can be narrowed or reduced (de‑escalated) as soon as possible.
The Department of Health and Social Care's UK 5 Year Antimicrobial Resistance Strategy 2013 to 2018 sets out actions to slow the development and spread of antimicrobial resistance. One aim of the strategy is to conserve and steward the effectiveness of existing antimicrobials by ensuring antibiotics are used responsibly and less often. Rapid and accurate determination of the presence or absence of bacterial infection is important to guide appropriate antibiotic therapy and to reduce unnecessary exposure to antibiotics.
The most common type of bacterial infection in people attending the emergency department is respiratory tract infection. Lower respiratory tract infection includes: acute bronchitis; acute exacerbations of chronic obstructive pulmonary disease or asthma; and pneumonia. It is a major cause of sepsis in children and adults. In addition to the lungs, the most common sites of bacterial infection leading to sepsis are the urinary tract, abdomen and pelvis. Sepsis can also result from skin infections (such as cellulitis), post‑surgical infections and infections of the nervous system (such as meningitis or encephalitis).
Sepsis is the presence of systemic inflammatory response syndrome in addition to a documented or presumed infection. Untreated sepsis can progress to severe sepsis, resulting in sepsis‑induced organ dysfunction. That is, when the body's response to infection interferes with the functioning of vital organs, such as the heart, kidneys, lungs or liver. Severe sepsis can progress to multiple organ failure causing septic shock.
Septic shock is defined as sepsis‑induced hypotension (low blood pressure) that continues despite adequate fluid resuscitation. Septic shock prevents organs from getting enough oxygenated blood. Complications of septic shock can include respiratory failure, heart failure, kidney injury or failure, abnormal blood clotting and death.
A diagnosis of sepsis, according to the Surviving Sepsis Campaign's guidelines (2012) should be based on infection, documented or suspected, plus some of the following criteria:
General variables: temperature above 38.3°C or below 36°C; heart rate greater than 90 beats per minute; rapid breathing; altered mental status; significant oedema; and high blood sugar in the absence of diabetes.
Inflammatory variables: low or high white blood cell count or more than 10% immature forms; raised plasma C‑reactive protein; and raised plasma procalcitonin.
Haemodynamic and tissue perfusion variables: low blood pressure; and raised blood lactate (a concentration of equal to or greater than 4 mmol/litre suggests tissue hypoperfusion).
Organ dysfunction variables: low arterial blood oxygen; reduced urine output; increased creatinine levels (indicating impaired kidney function); coagulation abnormalities; absent bowel sounds; reduced platelet count; and raised plasma bilirubin levels.
The Surviving Sepsis Campaign's guidelines (2012) make the following additional recommendations for diagnosing sepsis:
Collect at least 2 sets of blood cultures (aerobic and anaerobic) before antimicrobial treatment if such cultures do not cause significant delay (more than 45 minutes) in starting antimicrobial treatment.
Collect cultures from other sites that may be the source of infection, such as wounds, urine, cerebrospinal fluid, respiratory secretions or other body fluids, before antimicrobial treatment, if doing so does not cause significant delay in starting antimicrobial treatment.
Imaging studies, such as CT or X‑ray, should be performed to confirm a potential source of infection.
The treatment of sepsis varies based on the initial infection, the organs affected and the extent of tissue damage. If sepsis is detected early enough it may be possible for patients to be treated with antibiotics in an outpatient setting. If sepsis is severe the patient is usually admitted to the intensive care unit and treated with empiric intravenous antibiotics (antibiotics are selected based on experience without specific microbial information to support the decision).
The Surviving Sepsis Campaign's guidelines (2012) make the following recommendations for managing sepsis:
Initial resuscitation: carry out quantitative resuscitation of patients with sepsis‑induced tissue hypoperfusion and meet target thresholds within the first 6 hours.
Antimicrobial therapy: administer intravenous empiric antimicrobials within the first hour of diagnosing septic shock and severe sepsis. Assess antimicrobial treatment daily for potential de‑escalation.
Source control: make a rapid diagnosis of the specific site of infection and carry out source control measures.
Other supportive therapy: may include intravenous fluid therapy, vasopressors and inotropes for prevention or correction of low blood pressure; administration of blood products; mechanical ventilation for sepsis‑induced acute respiratory distress syndrome; sedation, analgesia and neuromuscular blockade; glucose control; renal replacement therapy; deep vein thrombosis prophylaxis; stress ulcer prophylaxis; and oral or enteral feeding.