The relationship among infection, sepsis, and the systemic inflammatory response syndrome (SIRS). (Modified from the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864.)

A mild systemic inflammatory response to an injury, infection, or other bodily insult may normally have salutatory effects. However, a marked or prolonged response, such as that associated with severe infections, is often deleterious and can result in widespread organ dysfunction. Although gram-negative organisms account for most cases of infection-related SIRS, many other infectious agents are capable of inducing the same syndrome. These organisms either elaborate toxins or stimulate release of substances that trigger this response. The most commonly recognized initiators are the lipopolysaccharides, which are released by gram-negative bacteria. Lipopolysaccharide is composed of an O polysaccharide, a core, and lipid A. The O polysaccharide distinguishes between different types of gram-negative bacteria, whereas lipid A, an endotoxin, is responsible for the compound’s toxicity. The resulting response to endotoxin involves a complex interaction between macrophages/monocytes, neutrophils, lymphocytes, platelets, and endothelial cells that can affect nearly every organ.

The central mechanism in initiating SIRS appears to be the abnormal secretion of cytokines. These low-molecular-weight peptides and glycoproteins function as intercellular mediators regulating such biological processes as local and systemic immune responses, inflammation, wound healing, and hematopoiesis. The most important cytokines released during SIRS are interleukin-6, adrenomedullin, soluble CD14, the adhesion molecule sELAM-1, macrophage inflammatory protein-1α, extracellular phospholipase A2, and C-reactive protein. The resulting inflammatory response includes release of potentially harmful phospholipids, attraction of neutrophils, and activation of the complement, kinin, and coagulation cascades.

Increased phospholipase A2 levels release arachidonic acid from cell membrane phospholipids. Cyclooxygenase converts arachidonic acid to thromboxane and prostaglandins, whereas lipoxygenase converts arachidonic acid into leukotrienes (slow-reacting substances of anaphylaxis). Increased phospholipase A2 and acetyltransferase activities result in the formation of another potent proinflammatory compound, platelet-activating factor. Attraction and activation of neutrophils releases a variety of proteases and free radical compounds that damage vascular endothelium. Activation of monocytes causes them to express increased amounts of tissue factor, which in turn can activate both the intrinsic and extrinsic coagulation cascades.

Gram-negative organisms account for most cases of infection-related SIRS.

These organisms either elaborate toxins or stimulate release of substances that trigger this response. The most commonly recognized initiators are the lipopolysaccharides, which are released by gram-negative bacteria.

Lipopolysaccharide is composed of an O polysaccharide, a core, and lipid A. The O polysaccharide distinguishes between different types of gram-negative bacteria, whereas lipid A, an endotoxin, is responsible for the compound’s toxicity. The resulting response to endotoxin involves a complex interaction between macrophages/monocytes, neutrophils, lymphocytes, platelets, and endothelial cells that can affect nearly every organ.

The central mechanism in initiating SIRS appears to be the abnormal secretion of cytokines. These low-molecular-weight peptides and glycoproteins function as intercellular mediators regulating such biological processes as local and systemic immune responses, inflammation, wound healing, and hematopoiesis. The most important cytokines released during SIRS are interleukin-6, adrenomedullin, soluble CD14, the adhesion molecule sELAM-1, macrophage inflammatory protein-1α, extracellular phospholipase A2, and C-reactive protein. The resulting inflammatory response includes release of potentially harmful phospholipids, attraction of neutrophils, and activation of the complement, kinin, and coagulation cascades.

Increased phospholipase A2 levels release arachidonic acid from cell membrane phospholipids. Cyclooxygenase converts arachidonic acid to thromboxane and prostaglandins, whereas lipoxygenase converts arachidonic acid into leukotrienes (slow-reacting substances of anaphylaxis). Increased phospholipase A2 and acetyltransferase activities result in the formation of another potent proinflammatory compound, platelet-activating factor. Attraction and activation of neutrophils releases a variety of proteases and free radical compounds that damage vascular endothelium. Activation of monocytes causes them to express increased amounts of tissue factor, which in turn can activate both the intrinsic and extrinsic coagulation cascades.

Complications of Injecting Drug Use

• Local problems—Abscess (Figures 240-2 
  

  A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of ­Richard P. Usatine, MD.)

  and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2
  • IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
  • Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
• IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
  • Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.