Infection is the process of microbial invasion which results in tissue damage at the site of the infection or, in the worst-case scenario, the death of the host. Unlike colonisation, infection manifests itself both physically and physiologically. These signs may be either localised or systemic.
There are several stages in the pathogenesis of infection:
Attachment: The organism needs to attach itself to the tissues so that it can penetrate them.
Adherence often occurs at a mucosal surface, enabling the bacteria to establish itself either on or in the host, colonising the site of entry and attachment, and occurs because of interactions between adhesins (molecules which mediate adherence of bacteria to the host) and receptors on the host cell wall (Petri et al., 2009). Hair-like protrusions known as pili (see Chapter 5) enable bacteria to adhere to these receptors.
Entry of the organism: As seen in the chain of infection, there are a number of ways in which the organism can enter the host.
Multiplication, invasion and spread: Once attached, and providing that the environmental conditions required for the organism’s growth and survival are right, it will begin to multiply. It can do this locally at the site of attachment, or it may invade the bloodstream and be carried to other body sites. Clinical signs of infection then become apparent.
Evasion of host defences: The organism will try to avoid the effects of the host’s immune system.
The mechanisms that organisms employ in order to do this are discussed in Chapter 5.
Damage to tissues or the host: In some cases, the damage resulting from the infection may be so severe that it leads to the death of the host. Much of this damage is a result of bacterial toxins produced by Gram-positive and Gram-negative bacteria (Chapter 5).
When the body suffers a traumatic injury, or is invaded by microorganisms, it generates an inflammatory response, which is designed to localise the infection and limit its spread. The success of the inflammatory response, however, depends on the strength of the host’s immune system and the pathogenicity, virulence and toxigenicity of the organism involved. The physiological events that subsequently take place give rise to the cardinal signs of infection, or inflammation:
•
Redness or erythema (rubour)•
Heat (calour)•
Swelling (tumour)•
Pain (dolour)•
Loss of function.Vasodilation (widening of the blood vessels) occurs at the site of ‘injury’, caused by the release of histamines and prostaglandins from damaged cells. This results in an increased blood flow,
125
which contains plasma proteins, neutrophils and phagocytes, to the affected site. The temperature of the skin rises as a result of the increased blood supply and an increase in the metabolic activities in the cells of the tissues at the damaged site.
The capillaries that line the epithelial cells dilate, releasing plasma which causes swelling;
depending on the site involved and the severity of the swelling, this may lead to loss of function.
The process of phagocytosis begins with the release of chemokines, which attract the phagocytes to the area where they are needed. The phagocyte then attaches itself to the bacteria, surrounds it and ingests it. Some pathogens are able to evade phagocytosis, either by producing a toxin (leukocidin) which destroys the phagocyte, or because the pathogen has the ability to survive within it and multiply, yet remain in a dormant state, resulting in disease months or even years later.
An inflammatory exudate forms at the site of inflammation, consisting of fluid, cells and cellular debris. Purulent discharge or pus, often seen in wound infections or at infected intravascular cannula sites, contains living and dead organisms, phagocytes and cell debris. With some organisms such as staphylococci and streptococci, the inflammatory exudate may be excessive.
Once the invading bacteria have been dealt with, the damaged tissues and cells begin the process of repair. However, if the immune response has been weak and/or the infection overwhelming, the host may die.
Fact Box 8.9 Inflammatory markers
Inflammatory markers detect acute inflammation that may indicate infection or disease, and also measure the effectiveness of treatment or resolution of infection. They are measured by blood tests.
C-reactive protein (CRP): CRP is an ‘acute phase’ protein found in the blood in very low levels (5–10 mg/l). It binds to a molecule called phosphocoline, which is found on the surface of dead or dying cells, including some bacteria, and plays a role in activating the complement system, enhancing phagocytosis. Where there is tissue damage, CRP levels start to increase 4–6 hours after an inflammatory response is generated, generally peaking at 35–50 hours.
CRP levels may decrease without intervention due to the effectiveness of the immune response. If they continue to increase, particularly after antibiotic therapy has been initiated, they indicate a worsening infection or treatment failure.
Erythrocyte sedimentation rate (ESR): The ESR is a non-specific marker of infection and inflammation. It is a blood test that measures the rate at which red blood cells separate and fall to the bottom of a test tube of anticoagulated blood in an hour. A raised ESR indicates a ‘problem’.
White blood cells (WBCs): The number of white blood cells increases in bacterial infections and inflammation. The normal range is 4 to 11 × 109/L (4000–11 000 per cubic millimetre of blood) and consists of:
•
Neutrophils (2–7.5 × 109/L)•
Lymphocytes (1.3–3.5 × 109/L)•
Eosinophils (0.04–0.44 × 109/L)•
Monocytes (0.2–0.8 × 109/L)•
Basophils (up to 0.01 × 109/L)126
•
In order to destroy invading pathogens and protect the host from infection, the immune system has to be able to differentiate between what is foreign to the body and what is not.•
The immune system consists of two branches, or arms: innate (or natural) immunity and adaptive (or acquired) immunity. They work both independently of each other and together.•
Innate or natural immunity is the body’s first line of defence. Its actions are directed against any pathogen the first time the pathogen is encountered, but they do not confer life-long protection. The innate immune system consists of physical barriers, internal and external surface secretions and cells, all of which are present in the individual from birth.•
The actions of the adaptive or acquired immune response are targeted against specific antigens, which are molecules capable of inducing an immune response and reacting with antibodies and/or T lymphocytes, such as bacterial toxins or bacterial cells. The first encounter with the antigen generates a primary response, and following this initial exposure, a more powerful and rapid response is generated on encountering the antigen or pathogen a second time.•
Repeated exposure to a particular antigen or allergen can stimulate the adaptive immune response to initiate an intense reaction each time the antigen or allergen is encountered.•
Overstimulation of the immune system can result in damage to the host, and possibly death.•
The isolation of an organism from a body site is not necessarily clinically significant unless infection manifests itself both physically and physiologically. These signs may be either localised or systemic. There are five significant stages in the pathogenesis of infection.•
When the body suffers a traumatic injury, or is invaded by microorganisms, it generates an inflammatory response, which is designed to localise the infection and limit its spread. The success of this depends on the strength of the host’s immune system and the ability of the organism to cause severe infection or disease.•
The uncontrolled spread of bacteria or their toxins in the bloodstream results in septicae- mia and septic shock, which may overwhelm the immune response.Chapter summary: key points
127
Further resources are available for this book, including interactive multiple choice questions. Visit the companion website at:
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Contents
Fundamentals of Infection Prevention and Control: Theory and Practice, Second Edition. Debbie Weston.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd. Companion Website: www.wiley.com/go/fundamentalsofinfectionprevention
Sepsis
9
Sepsis and septicaemia 131
The pathogenesis of septic shock 133 The management of sepsis and
septic shock 133
Neutropenic sepsis 135
Clinical considerations 137
Clinical practice points: infection
control precautions 137
Chapter summary: key points 138
References 139
131
Fact Box 9.1 Sepsis and septicaemia
Sepsis is the ‘umbrella’ word frequently used to describe systemic infection; 18 million people die from sepsis worldwide each year (Slade et al., 2003). In the United Kingdom, mortality ranges from 37 000 to 64 000 deaths per year (www.uksepsis.org; and see Daniels, 2011).
Septicaemia is the systemic illness which arises as a result of the uncontrolled spread of bacteria or their toxins through the bloodstream, and is the leading cause of death in intensive care units (Robson and Newell, 2005; Wheeler, 2009).
Introduction
At some point, healthcare staff working in community settings such as nursing homes, or healthcare staff working on a general surgical or medical ward, will be involved in the care of a ‘septic’ patient.
This brief chapter aims to provide an overview of the pathogenesis of sepsis and its infection control management, along with the infection control management of neutropenic sepsis.
Learning outcomes
After reading this chapter, the reader will be able to: