Gram-Negative Bacterial Mediated Sepsis - Case Study Example

Gram-negative Bacterial Mediated Sepsis Name Institutional Affiliation Date Abstract Sepsis is a common condition and represents an important factor in the morbidity and mortality of patients. The economic burden of disease is one of the highest. Sepsis occurs when the body triggers a systemic inflammatory response against infection. The aim of this research is to understand gram-negative mediated sepsis by discussing the definition of sepsis, its significance, systemic effects and treatment. Data to inform the study was gathered from 13 e-journals published in PubMed, BMC, Medline and other validated medical databases. The articles were selected on the basis of their relevance to the topic and their newness in publication dates between 2009 and 2015. The synthesized data reveals sepsis clinical understanding has developed slowly over time. As a result of slow detection and diagnosis, sepsis is significant in the morbidity and mortality rates of populations. Systemic effects of sepsis include inflammatory cascades responsible for triggering most of the pathologies associated with sepsis including coagulation, leuococytosis, leukopenia, hyperthermia, hypothermia, tachycardia, tachypnoea, multiple organ failure in severe sepsis, and sepsis shock. Treatment for sepsis entails antibiotic therapy targeting site infection and common pathogens involved –Haemophilus, Enterobacter, and Pseudomonas, fluid resuscitation, ventilation, vasopressor therapy, glycemic control and treatment with activated protein C. Introduction The medical concept of sepsis has been around for many years (Martin 2013). The term sepsis was introduced by Hippocrates in the 4th Century B.C in reference to the process of organic matter decay (Funk, Parrillo & Kumar 2009). In the 11th Century, the philosopher Avicenna used the term ‘blood rot’ for conditions linked to severe purulent processes (Funk, Parrillo & Kumar 2009). The observation of the severe systemic toxicity process increased and in the 19th century that the term sepsis was officially associated with the process (Funk, Parrillo & Kumar 2009). The scientist Pfeiffer coined the tern endotoxin in the beginning of the 20th century. The understanding that endotoxins expressed by Gram-negative bacteria were responsible for fever and shock during an infection increased (Manji, Wood & Kumar 2009). Further research continued in the 20th century to determine the biochemical nature of endotoxins and the associated pathophysiology in infection. This paper gives the current definition of sepsis, its significance, systemic effects and treatment. a. A referenced definition of sepsis Various definitions have developed in the attempt to clinically understand sepsis and the most accepted definition of sepsis is: a clinical syndrome characterized by the presence of both infection and a systemic inflammatory response (Martin 2013). Sepsis is a clinical illness caused by microbial invasion of sterile tissues or cavities of the body (McPherson et al. 2013). b. Significance of sepsis on Patient morbidity and mortality Sepsis significantly contributes to the morbidity and mortality of populations with severe sepsis claiming between 36,000 and 64,000 lives in the U.K annually (Daniels 2011). In the U.S, at least 750,000 cases of severe sepsis are diagnosed every year (Shapiro et al. 2015). In the European Union, the incidence of severe sepsis is 90.4 cases per a population of 100,000 people (Daniels 2011). Worldwide, the documented incidence of sepsis is at 1.8 million cases per year, but considering that the figure can be unreliable due to low recognition and diagnosis rates (Daniels 2011). Patient mortality from sepsis has also risen by over 35% from 1,400 deaths per day reported in 1992 to 20,000 deaths per day reported in 2010s worldwide (Daniels 2011). Many critically ill patients dying of infectious diseases usually die of sepsis and sepsis-related organ dysfunction (McPherson et al. 2013). Sepsis is more frequent in children and the elderly due to weak or underdeveloped immune system. People with HIV, cancer, diabetes or any other conditions that weaken or alter the immune system are also at high risk for sepsis (Daniels 2011). Medical costs Sepsis has significant impact on healthcare resources as it is one of the most expensive conditions to treat (Torio & Andrews 2013). By the time a sepsis diagnosis is made, the patient will have gone through extensive diagnosis and differential protocols which increase costs though lengthier hospital stays (McPherson et al. 2013). Using a nation-wide sample of the United States, Lagu et al. (2012) found that the total hospital costs for all patients with severe sepsis increased from USD 15.4 billion in 2003 to $24.3 billion in 2007, which is a 57percent increase. In 2011, sepsis resulted in aggregate healthcare costs of $20.3 billion and was the most expensive condition billed to Medicare (Torio & Andrews 2013). Patients in the high-risk group are also at risk of developing nosocomial sepsis because of their frequent interaction with the healthcare system and this increases their medical costs (Martin 2012). The early identification and treatment of sepsis can help to reduce the economic burden of the disease and save lives (Silva & Araujo 2009). c. Systemic effects of sepsis including Sepsis cascades A patient’s immune system responds to a critical illness of infectious or non-infectious cause through systemic inflammatory response (SIRS); Sepsis is diagnosed if the SIRS is due to an infection (McPherson et al. 2013). SIRS shows two or more of the following symptoms: hyperthermia above 38°C or hypothermia below 36°C, tachycardia with over 90 beats per minute, respiratory rate of over 20 breaths per minute or partial pressure of carbon dioxide (PaCO2) at less than 4.3 kilopascal leading to elevated concentration of bicarbonate in the blood, leuococytosis or sometimes leucopenia (Shapiro et al. 2010). Inflammatory cascades in pathophysiology of sepsis entail production of inflammatory cytokines, adhesion molecules, reactive oxygen species and vasoactive mediators (Kendra et al. 2013). The response is usually to an infection caused by the endotoxin lipopolysaccharide from the cell wall of Gram negative bacteria. Severe sepsis occurs when the sepsis occurs with organ hypoperfusion, characterized by hypoxoemia, lactic acidosis, oliguria and altered cerebral function (Shapiro et al. 2010). Multiple organ failure may occur due to abnormal organ perfusion and oxygenation (McPherson et al. 2013). Potential for shock The potential for shock in sepsis is certain if the patient has developed severe sepsis with hypotension, the systolic blood pressure at less than 90mmHg (Kendra et al. 2013). The symptom is present despite adequate fluid resuscitation and vasopressor therapy. Coagulopathy Sepsis is often associated with coagulopathy, presented with bleeding and microvascular thrombi, mechanisms of multiple organ failure (Shapiro et al. 2010). Coagulopathy is triggered by a cytokine-mediated activation of tissue factor dependent extrinsic pathway with the inflammatory cytokines IL-1 and TNF-α acting on the endothelial surface (Kendra et al. 2013). Tissue factor leads to production of thrombin, a proinflammatory substance which results in clots in the microvasculature (Kendra et al. 2013). Other pathologies Other pathologies triggered by the systemic effects of sepsis include respiratory dysfunction manifesting as tachypnoea, hypoxaemia and respiratory alkalosis and may progress to acute lung injury and acute respiratory distress syndrome (Manji, Wood & Kumar 2009). Cardiovascular dysfunction also presents with tachycardia and stroke. Renal dysfunction presents with symptoms of low urine output as the kidney is susceptible to leukocyte mediated tissue injury with neutrophil aggregation (Manji, Wood & Kumar 2009). Metabolic disturbances are common in sepsis due changes in the haemodynamic regulation (Kendra et al. 2013). d. Treatment of sepsis Antimicrobial therapy with empirical antibiotics is started immediately even if the causative pathogen is yet to be isolated (Tamma, Cosgrove & Maragakis 2012). Appropriate empirical antimicrobial therapy must be guided by the knowledge of the most common sites of infection, for example, lungs, abdomen and urinary tract, and their most common infecting microorganisms (Tamma, Cosgrove & Maragakis 2012). Gram-negative bacteria common in sepsis include Haemophilus influenzae, Klebsiella spp., Legionella pneumophilia, Pseudomonas aeruginosa, Escherichia coli, and Enteroccocus spp (Tamma, Cosgrove & Maragakis 2012). Some antimicrobial therapeutic choices include third generation cephalosporin, ceftriaxone, carbapenem, antipseudomonal beta-lactamase inhibitor, vamcomycin, moxifloxacin, and ampicillin which can be combined with other therapeutic choices (Tamma, Cosgrove & Maragakis 2012). Ventilation helps to optimize oxygen delivery to critical organs (Tamma, Cosgrove & Maragakis 2012). Fluid resuscitation with intravenous fluids such as albumin and crystalloid solutions may reduce mortality risks (Nasa, Juneja & Singh 2012). Vasopressor treatment with dopamine and norepinephrine help in sepsis shock (Nasa, Juneja & Singh 2012). Dopamine increases the cardiac index and systemic vascular resistance while norepinephrine is a potent vasoconstrictor which helps to reverse hypotension. Low-dose corticosteroid treatment acts as an anti-inflammatory and provides vascular tone in severe sepsis (Nasa, Juneja & Singh 2012). Activated protein C has antithrombotic, anti-inflammatory, and profibrinolytic properties and can help to reduce mortality in sepsis patients (Shiramizo et al. 2011). Glycemic control decreases the rate of infectious complications and improves patient’s outcome (Nasa, Juneja & Singh 2012). Conclusion Sepsis, a systemic inflammatory response to microbial infection encompasses a range of systemic effects whose understanding is increasing with time. Meanwhile, sepsis is still a significant cause of mortality and morbidity and high medical costs. Systemic effects caused by the inflammatory cascade in sepsis results in a myriad of symptoms including multiple organ failure and sepsis shock. Current therapies in the treatment of sepsis include antibiotics, ventilation, vasopressor therapy, fluid resuscitation, steroids, activated protein C and glycemic control. Greater understanding of the pathophysiology of the clinical features of sepsis will allows the rationale use and assessment of current therapies. References: Daniels, R 2011, ‘Surviving the first hours in sepsis: Getting the basics right: An intensivist’s perspective. Journal of Antimicrobial Chemotherapy, vol. 66, no. 2, pp. 11-23. Funk, D, Parrillo, J, & Kumar, A 2009, ‘Sepsis and septic shock: A history’, Critical Care Clinics, vol. 25, no. 1, pp. 83-101. Kendra, I, Osuchowski, M, Stearns-Kurosawa, D, Kurosawa, S, Stepien V, & Remick, D 2013, ‘Sepsis: Multiple abnormalities, heterogeneous responses, and evolving understanding’, Physiological Review, vol. 93, no. 3, pp. 1247-1288. Lagu, T, Rothberg, M, Shieh, M, Pekow, P, Steingrub, J, & Lindaneur, P 2012, ‘Hospitalizations, costs and outcomes of severe sepsis in the United States 2003 to 2007. Critical Care Medicine, vol. 40, is. 3, pp. 754-761. Manji, R, Wood, K, & Kumar, A 2009, ‘The history and evolution of circulatory shock’, Critical Care Clinics, vol. 25, no. 1, pp. 1-29. Martin, G 2012, ‘Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes’, Expert Review in Anti-Infective Therapy, vol. 10, no. 6, pp. 701-706. McPherson, D, Griffiths, C, Williams, M, Baker, A, Klodawski, E, Jacobson, B, & Donaldson, L 2013, ‘Sepsis-associated mortality in England: An analysis of multiple cause of death data from 2001 to 2010’, British Medical Journal, vol. 3, Is. 8, doi:10.1136/bmjopen-2013-002586. Nasa, P, Juneja, D, & Singh, O 2012, ‘Severe sepsis and septic shock in the elderly: An overview. World Journal of Critical Care Medicine, vol. 4, no. 1, pp. 23-30. Shapiro, N, Khankin, E, Meurs, M, Shish, S, Lu, S, Yano, M, Castro, P…2010, ‘Leptin exacerbates sepsis-mediated morbidity and mortality’, The Journal of Immunology, vol. 185, pp. 517-524. Shiramizo, S, Marra, A, Durao, M, Paes, A, Edmond, M & Santos, O 2011, ‘Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting’, PLoS One, vol. 6, no. 11, doi:  10.1371/journal.pone.0026790 Silva, E & Araujo, V 2009, ‘Economic and social burden of severe sepsis’, Yearbook of Intensive Care and Emergency Medicine, pp. 129-136, doi: 10.1007/978-3-540-92276-6_13. Tamma, P, Cosgrove, S, & Maragakis, L 2012, ‘Combination therapy for treatment of infections with Gram-negative bacteria’, Clinical Microbiology Reviews, vol. 25, no. 3, pp. 450-470. Torio, C & Andrews, R 2013, ‘National inpatient hospital costs: The most expensive conditions by payer, 2011’, Healthcare Cost and Utilization Project (HCUP) Statistical Briefs, no. 160. PMID: 24199255 Read More