Michael A. West and Daniel Dante Yeh
Death after traumatic injury has been described in terms of a trimodal distribution. Immediate and acute (<24 hours) deaths usually result from uncontrolled hemorrhage, but infections and multiple organ dysfunction syndrome, which often arise from infection, are responsible for a significant proportion of late deaths. Indeed, infection is responsible for most deaths in patients who survive longer than 48 hours after trauma.1 Trauma-related infections are generally divided into those that result directly from the injury (e.g., due to contamination that occurs in conjunction with the traumatic injury) and nosocomial infections that arise in the health care setting, secondary to treatment of the injury. The pathogens involved can be exogenous or endogenous bacteria, depending on the mechanism of injury and/or the iatrogenic cause. Most post-traumatic infections are polymicrobial and involve a mixture of aerobic and anaerobic organisms.2 In one series, 37–45% of all trauma patients experienced infectious complications during their initial hospitalization. Furthermore, in the same study, 80% of trauma patients staying at least 7 days in the intensive care unit met systemic inflammatory response syndrome (SIRS) criteria.3 Therefore, it is important that all caregivers understand the principles of surgical infections in the context of trauma patients. This chapter discusses the following: factors that normally prevent infection, how trauma disrupts or overwhelms normal host defenses, how to recognize and treat the most common infectious complications after traumatic injury, principles that can be employed to prevent infection, and how those principles can be applied chronologically during the treatment of trauma patients.
PATHOGENESIS OF INFECTION
Humans have evolved mechanisms to avoid infection despite the ubiquitous presence of bacteria in our environment and throughout our bodies. Under normal circumstances there is a balance between bacteria, intact environmental barriers, and host defenses (see Fig. 18-1). With surgery in general, and trauma in particular, there is a disruption in this balance that significantly increases the probability of developing an infection (Fig. 18-2). Bacteria are abundant on the surface of the skin, within the oral cavity, and present in increasing numbers down the length of the gastrointestinal tract. Bacterial numbers differ at various locations, and the pathogenic species and their respective numbers at different anatomic sites are summarized in Table 18-1. Trauma disrupts the environmental barriers that prevent bacteria from gaining access to normally sterile regions of the body. When inoculation of bacteria into normally sterile sites occurs, infection will ensue if bacteria can proliferate faster than the host defense mechanisms can eradicate them. Furthermore, there is potential for much greater disruption of normal barriers with trauma than occurs with elective surgery as there is often concomitant hypoperfusion (shock), devitalized tissue, and retained foreign bodies.
FIGURE 18-1 Under normal circumstances the determinants of infection, microbial factors, environmental factors, and host defenses interact such that there is no infection. (Adapted with permission from Meakins JL, et al. Host defenses. In: Howard RJ, Simmons RL, eds. Surgical Infectious Diseases. 2nd ed. Norwalk, CT: Appleton & Lange; 1988. Copyright © The McGraw-Hill Companies, Inc.)
FIGURE 18-2 (A) Under circumstances in which there is excessive microbial contamination, (B) serious disruption of environmental barrier, (C) impaired host defenses, or (D) all factors that ensure there will be an increased likelihood of developing infection (shaded intersection of determinants of infection).
TABLE 18-1 Pathogenic Microorganisms Present at Various Anatomic Sites
Normally, entry of microbes is limited by the integrity of environmental barriers. These environmental barriers include intact skin, respiratory, gastrointestinal, and genitourinary tracts.4 The importance of intact skin is clearly evident when one considers the potential for microbial infection seen in burn patients or in patients with toxic epidermal necrolysis.2 Many traumatic injuries are associated with an alteration in the integrity of the skin. Even minor lacerations and abrasions have the potential to disrupt crucial environmental barriers. Interventions that are made in the process of caring for trauma patients, such as insertion of intravenous or urinary catheters, tube thoracostomy, etc., disrupt the integument and may provide skin bacteria access to sterile sites. Furthermore, the quantitative number of microbes required to produce clinical infection is significantly decreased in the presence of foreign bodies, blood, or devitalized tissue.2
The bacteria that are responsible for clinical infections in surgery or trauma patients constitute a minority of the skin or gastrointestinal flora and they generally possess one or more virulence factors that facilitate infection and increase their pathogenicity. In contrast, the vast majority of endogenous and environmental bacteria are relatively nonpathogenic. For example, more than 99% of the colonic flora is nonpathogenic anaerobes that never cause clinical infections. Similarly, most skin bacteria are lactobacilli, which do not cause clinical infection either. In contrast, Staphylococcus aureus, the most common pathogen associated with surgical site infections (SSI), has numerous virulence factors that facilitate invasion and thwart host defenses. In the abdominal cavity, Escherichia coli and Bacteroides fragilis are the prototypical organisms associated with intra-abdominal infection, yet they account for only 0.01% and 1% of colonic bacteria, respectively. Indeed, to some extent the normal presence of overwhelming numbers of nonpathogenic bacteria constitutes a defense against infection. That is, infection is proportionately less likely if 99% of the inoculum is incapable of producing infection. This concept of adherent resident bacteria preventing invasion has been termed colonization resistance.4 This is an important point as skin and gastrointestinal flora changes considerably when trauma patients are hospitalized, both in terms of number and proportion of virulent bacteria and in terms of susceptibility to antibiotics, should an infection develop.
Skin flora is relatively homogeneous, although bacterial numbers are higher in the axilla and groin areas. The endogenous skin bacteria are predominately gram-positive aerobic Staphylococcus and Streptococcus species, along with Corynebacterium and Propionibacterium.4 As noted above, S. aureus is the most common pathogen present on the skin. Most recently an increasing number of S. aureusisolates from trauma patients and other community-acquired infections have been methicillin resistant (MRSA).5,6 This fact, along with knowledge of the local incidence of MRSA, needs to be taken into account in terms of appropriate empiric or prophylactic antibiotic selection for these patients.6 The oral and nasopharynx harbor large numbers of bacteria, with streptococcal species being most frequently present. Much smaller numbers of bacteria, typically 102–103 CFU/mL, are present in the normal stomach, because the normally acid pH of the stomach inhibits bacterial growth. Gastric bacterial numbers increase in the absence of gastric acid as in patients on proton pump inhibitors. Bacterial numbers are much higher in the small intestine, and the density of bacteria increases further as chyme progresses from the duodenum to the terminal ileum. Bacterial counts in the proximal gastrointestinal tract are in the range of 104–105 CFU/mL, whereas numbers in the terminal ileum are close to colonic densities (108–1010CFU/mL). Bacterial numbers in the colon are even higher, with approximately 1011–1012 CFU/mL of stool, although many of these colonic bacteria are nonpathogenic. These large numbers are also associated with very low oxygen tension, and 99.9% of bacteria present are anaerobes. The urogenital, biliary, pancreatic ductal, and distal respiratory tracts do not possess resident microflora in healthy individuals.4
Host Defense Mechanisms
Host defense refers to endogenous factors that counteract microbial invasion. In addition to the environmental factors and colonization resistance described above, humoral and cellular host defense mechanisms that are crucial to eliminate bacteria within a sterile space exist. Initially, several primitive and relatively nonspecific host defenses including proteins such as lactoferrin, fibrinogen, and complement begin to act against invading microbes. Lactoferrin sequesters the critical microbial growth factor iron, thereby limiting microbial growth. Fibrinogen within the inflammatory fluid has the ability to trap large numbers of microbes during the process in which it polymerizes into fibrin.4Complement is activated on contact with bacteria and viruses, from tissue damage, or when IgG/IgM antibodies recognize microbial agents. Activation of complement releases C3a and C5a, which are potent chemotaxins that result in recruitment of neutrophils and macrophages. These components enhance endothelial adhesiveness and increase vascular permeability. Complement activation can directly destroy microbial agents via formation of a membrane attack complex (composed of complement proteins C5–C9) and enhance microbial phagocytosis by way of C1q and C3bi subunits. In vitro studies have shown that 50–70% of a moderate inoculum is eliminated prior to the influx of phagocytic host cells.
Many different tissues also contain resident innate immune cells. These include macrophages, dendritic cells, Kupffer cells, glial cells, mesangial cells, and alveolar macrophages.7 These innate immune cells express a wide variety of pathogen-associated molecular pattern (PAMP) receptors on their surface.8–10 The best known examples of PAMPs are the toll-like receptors (TLRs) of which there are now more than 10 well-described receptor molecules.10 TLRs bind to ligands on bacteria (or damaged host tissue), and TLR binding results in activation of these cells. Activated macrophages secrete a wide array of substances in response leading to amplification and regulation of the acute proinflammatory response (Fig. 18-3). Sequential release of protein cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8, and interferon-gamma (INF-γ), follows. These mediators produce the signs and symptoms (fever, tachycardia, tachypnea, leukocytosis, etc.) that we associate with infection. IL-8 is a very potent chemoattractant for neutrophils, which are primarily responsible for ongoing microbial phagocytosis and intracellular microbial killing. Unfortunately, the same process that recruits neutrophils and stimulates phagocytosis and oxidative killing may also be responsible for damage to host tissues. Simultaneous with the innate immune proinflammatory response there is production of anti-inflammatory mediators, such as IL-10, also.11 Some of these mediators may contribute to the immune hyporesponsiveness of trauma over the ensuing days (Table 18-2).
TABLE 18-2 Immunologic Defects Associated with Traumatic Injuries
FIGURE 18-3 Schematic depiction of how acute injury simultaneously initiates the proinflammatory systemic inflammatory response syndrome (SIRS) and the anti-inflammatory compensatory anti-inflammatory response syndrome (CARS). Under normal circumstances there is a defined temporal period in which these initial responses surge and resolve. When a second or subsequent insult (“hit”) is imposed on this response, it may lead to multiple organ dysfunction syndrome (MODS) and death in a significant subset of patients. (Reproduced with permission from Ni Choileain N, Redmond HP: Cell response to surgery. Arch Surg. 2006;141(11):1132–1140. Copyright © 2006 American Medical Association. All rights reserved.)
Particular anatomic locations have additional unique factors that defend against infection.13 For example, the peritoneal cavity has lymphatic channels on the undersurface of the diaphragm that facilitate removal of bacteria.14 The subdiaphragmatic surface is a lower-pressure area, due to the effect of respiratory excursion, and this serves to move free fluid within the peritoneal cavity to this location. Movement of the diaphragm “pumps” this fluid into the thoracic duct and from there it gains rapid access to the systemic circulation. Experimental studies show that labeled bacteria inoculated into the peritoneal cavity appear in the thoracic duct within 6 minutes and in the bloodstream within 12 minutes.13 The respiratory tract has unique host defenses that help to ensure the sterility of the lung parenchyma as well. Goblet cells within the respiratory mucosa secrete mucin that helps to traps bacteria. Ciliated respiratory epithelial cells move the mucus centrally where it, and the bacteria trapped within it, can be expectorated by coughing. The presence of endotracheal tubes, smoking, inhaled toxins, and some anesthetic agents interfere with mucociliary clearance mechanisms, and this may predispose to pneumonia. Bacteria or other microbes that gain access to the alveoli are normally phagocytosed by alveolar macrophages, although the macrophage activation that may accompany this process has been proposed as one possible pathogenetic mechanism for acute lung injury (ALI) or adult respiratory distress syndrome (ARDS).15–17
To a very large extent the microbial agents responsible for infections or infectious complications after trauma are the same agents that cause most other surgical or ICU-associated infections. Table 18-1 shows the most common infectious agents that cause trauma-associated infections at various anatomic sites. Generally, Staphylococcus spp. and Streptococcus spp. are the most common pathogens responsible for infections in which the traumatic injury or operative intervention needed to treat the injury did not transgress a mucosal surface. For traumatic injuries that involve the aerodigestive tract the most common isolates are E. coli (43.4%), S. aureus (18.9%), Klebsiella pneumoniae(14.4%), and Entercoccus faecalis (5.6%).1 Hospitalized trauma patients develop nosocomial bacterial infections from the usual ICU-associated pathogens (Table 18-3). There are a few important infectious agents that can be associated with trauma, that are seldom encountered in other settings including rabies virus, Clostridium tetani, and Vibrio spp.
TABLE 18-3 ICU Pathogens Isolated from Patients with Ventilator-Associated Pneumonia
Rabies is a rare, but potentially fatal, clinical disease caused by the rabies virus. It is an RNA virus that is present in the saliva of mammals and transmission to humans generally occurs following a bite from a rabid animal. Prior to the development of a vaccine by Louis Pasteur, bites from a rabid animal were uniformly fatal. In North America, raccoons, skunks, bats, foxes, coyotes, and bobcats are the primary reservoirs. Most human rabies cases have no documented exposure to a rabid animal and the majority of these cases are associated with bat bites. Many victims underestimate the importance of a bat bite and a substantial portion do not even recall being bitten. Bats (Carnivora and Chiroptera) represent the ultimate zoonotic reservoir for the virus, as well. The rabies virus is highly labile and can be inactivated readily by ultraviolet radiation, heat, desiccation, and other environmental factors.
The word “rabies” derives from the Latin rabere meaning “to rage” and refers to the clinical manifestations of the disease that include hyperactivity, disorientation, hallucinations, and bizarre behavior. The rabies virus is neurotropic and causes an acute encephalitis. Other hallmarks of the disease include hydrophobia and aerophobia, as these stimuli tend to cause intense laryngeal and pharyngeal spasm. Once the patient begins manifesting symptoms, death is nearly certain. With increased vaccination and postexposure prophylaxis (PEP) over the past 50 years, the clinical disease is becoming increasingly uncommon, with only 32 cases of human rabies reported in the United States between 1980 and 1998. That said, it is important for the practitioner of emergency medicine/surgery to be knowledgeable about rabies since animal bites are encountered frequently in clinical practice.
Humans are not routinely vaccinated against rabies. Rather, domestic animals receive routine rabies vaccinations. If a human is bitten by a rabid animal, rabies can be prevented by PEP before the virus enters the central nervous system during the incubation period. The diagnosis of rabies can be made rapidly by identification of rabies virus in the brain of a potentially infected animal. This procedure can be performed in a timely manner, but requires euthanizing the suspected animal. The incidence of positive rabies tests ranges from as high as 6–10% in wild animals down to levels of ˜1% in domestic pets. If the rabies test is negative, then no postexposure vaccination or prophylaxis is needed. An acceptable alternative approach, if the suspected source is a domestic pet (dog, cat, ferret, etc.), is that the offending animal be quarantined and observed for 10 days. If the animal exhibits signs of rabies, the exposed person should begin PEP immediately and the animal should be euthanized and its brain tissue tested for rabies. If the animal is confirmed to have rabies, PEP should be completed. When the test results are negative, PEP can cease.
Immediate measures that should be taken to decrease the risk of rabies transmission include thorough washing of bite and scratch wounds with soap and water, followed by application of povidone–iodine or alcohol. Human rabies immune globulin (HRIG) and rabies vaccine should be given in all cases except in persons who have been immunized previously.19 Immune globulin should never be delivered in the same syringe as the vaccine, as this will cause precipitation. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics recommend a single dose (20 IU/kg) of HRIG be given to provide protection for the first 2 weeks until the vaccine elicits an antibody response. Detailed and up-to-date information for rabies exposure is available on the CDC’s Web site (http://www.cdc.gov/RABIES/), and this site should be consulted for the latest information. The ACIP recommends a regimen of human diploid cell vaccine (Imovax®) for PEP on days 0, 3, 7, 14, and 28 along with a single dose of HRIG on day 0. Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic reactions to the vaccine.
Tetanus is a rare, life-threatening condition that is caused by toxins produced by C. tetani, a spore-forming, gram-positive bacillus.20 Clostridial spores can survive indefinitely, and they are ubiquitous in soil and feces. Under anaerobic conditions the spores can germinate into mature bacilli, which elaborate the neurotoxins tetanospasmin and tetanolysin. Tetanospasmin is the toxin that produces most clinical symptoms by interfering with motor neuron release of the inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine. This loss of inhibition results in muscle spasm (usually spasm of the masseter muscle) and severe autonomic overactivity manifested by high fever, tachycardia, and hypertension. Historically, tetanus was highly fatal, but intensive medical therapy with neuromuscular blockade, mechanical ventilation, and ICU monitoring has lowered the case fatality rate to 11–28%. Since the mid-1970s there have been <100 tetanus cases reported annually in the United States. Even so, clinicians and trauma surgeons must remain alert for the potential of clostridial contamination and provide tetanus prophylaxis.20
The diagnosis of tetanus is made on clinical grounds alone, as there are no laboratory tests that can diagnose the condition or rule it out. Tetanus immunization is accomplished as a component of standard early childhood immunizations (diphtheria–pertussis–tetanus [DPT]), with administration of tetanus toxoid (TT) every 5–10 years to maintain immune memory. There have been no deaths reported in individuals who have been fully immunized. The CDC recommendations for tetanus prophylaxis depend on the wound characteristics and the prior immunization status of the patient. A wound with extensive contamination, one that is poorly vascularized, or with extensive soft tissue trauma is considered to be a tetanus-prone wound. A tetanus booster should be administered to patients who have received primary immunization, but who have not received TT during the past 10 years, or the past 5 years for tetanus-prone wounds.19 In patients who have never undergone primary immunization, human tetanus immune globulin (HTIG) should be administered along with TT at a different site. Antitetanus antibody binds to exotoxins and neutralizes their toxicity. High-risk groups such as the elderly, human immunodeficiency virus (HIV)–infected individuals, and intravenous drug users (IVDU) who had received primary vaccination may not have tetanus antibodies and more liberal use of HTIG should be considered in these groups.19
Infections Associated with Marine Trauma
Vibrio vulnificus is a gram-negative rod present in seawater that can result in atypical, necrotizing soft tissue infections when traumatic injuries occur in the ocean.21–23 V. vulnificus is common in warm seawater and thrives in water temperatures greater than 68°F (20°C). The organism is not associated with pollution or fecal waste. Approximately 25% of V. vulnificus infections are caused by direct exposure of an open wound to warm seawater containing the organism. Exposure typically occurs when the patient is participating in water activities such as boating, fishing, or swimming. Infections are occasionally attributed to contact with raw seafood or marine wildlife. The risk of developing Vibrio infection is much higher in immunocompromised patients or patients with preexisting hepatic disease or diabetes mellitus.22 Established infection with V. vulnificus can be highly invasive with mortality rates of 30–40% and a mortality greater than 50% in immunocompromised patients. A recent published report documented a 37% mortality rate even after implementation of a specific treatment guideline for necrotizing Vibrio infections.21
Patients with wound infections caused by V. vulnificus develop painful cellulitis that progresses rapidly.22–24 Physical examination will often reveal marked swelling and painful, hemorrhagic bullae surrounding traumatic wounds. In some cases, there can be rapid progression and associated systemic symptoms. Marked local tissue swelling with hemorrhagic bullae is characteristic. Systemic symptoms include fever and chills, and bacteria are present in the bloodstream in more than 50% of patients. Hypotension or septic shock may be an early symptom and alterations in mental status occur in approximately one third of patients. Table 18-4 summarizes clinical symptoms present in patients with Vibrio infection. It is important for trauma surgeons to be aware of the potential for Vibrio infections in the appropriate clinical setting, because antibiotic treatment is distinctly different from the agents typically employed for trauma patients. Aggressive surgical debridement, incision and drainage of purulent collections, and even amputation may be crucial adjuncts for management of occasionally severe soft tissue infections.22 A recent experience in 30 patients found that fasciotomy was needed in all patients, and 17% required amputation.21 Recommended antibiotics include doxycycline (100 mg iv/po bid), ceftazidime (2 g q 8 hours), cefotaxime (2 g q 8 hours), or ciprofloxacin (750 mg po bid or 400 mg iv q 12 hours).22,25
TABLE 18-4 Clinical Characteristics Associated with Vibrio vulnificus Wound Infections
Traumatic injuries that occur in freshwater conditions may develop infections from Aeromonas hydrophila.24 A. hydrophila is a gram-negative anaerobic rod that is a common pathogen of fish and amphibians. Cutaneous inoculation of the organism can result in cellulitis, abscesses, and, occasionally, necrotizing soft tissue infections. Like the situation with Vibrio infections, patients with hepatic disease and immunocompromised patients have a greater risk of developing generalized disease. A. hydrophila can be recovered from the bloodstream in a significant proportion of patients and this fact, along with a history of injury in fresh water, will aid in alerting clinicians to the correct diagnosis. Antibiotic agents active against A. hydrophila include third-generation cephalosporins, fluoroquinolones, doxycycline, or trimethoprim–sulfamethoxazole.24
PREVENTION OF INFECTIONS
As in all other aspects of surgical care, it is preferable to try to prevent infections wherever possible. A number of interventions and practices have been demonstrated to be highly effective in preventing infections after elective operations, and many of those techniques have specific application in the care of injured patients. In this section, the current evidence-based interventions to prevent infection that are applicable to trauma patients are discussed.
Prophylactic antibiotics are intended to prevent development of infection. The concept of prophylaxis presupposes that infection is not present at the time. The decision to use prophylactic antibiotics and the choice of agents are based on the risk of developing SSI. There are very good data regarding SSI rates for elective surgery and the incidence of SSI by wound class for elective operations is shown in Table 18-5. Traditionally, Class I or clean wounds are those that do not violate the respiratory, alimentary, or genitourinary tracts. The wound infection rate is approximately 2%. Class II, or clean-contaminated wounds, refers to elective operations on potentially contaminated organs, such as the gastrointestinal tract, genitourinary tract, and respiratory tree (the procedure will violate a mucosal surface, which can never be completely sterile). The usual incidence of infection for these types of wounds is 5–10%. Contaminated wounds (Class III) differ from Class II wounds by the degree of spillage, with an incidence of infection of 15–30%. Finally, Class IV or dirty-infected wounds are characterized by frank pus or extensive and prolonged contamination. These wounds are characterized by an infection rate of >30% if primary closure is attempted.27 Emergent operative interventions increase the wound class by one step, so it is clear that higher wound infection rates will be encountered in dealing with patients who have acute traumatic injuries that require operative intervention.
TABLE 18-5 Classification of Surgical Woundsa
In trauma surgery, the majority of wounds encountered will be Class III or IV, and the luxury of a preinoculation dose of antibiotics, as recommended by the Surgical Care Improvement Project (SCIP), is usually unavailable.28 With this in mind, it is prudent to administer a single dose of an agent with activity against community-acquired aerobic and anaerobic pathogens as soon as possible for all patients requiring operation in the thorax or abdomen. Evidence-based guidelines for antibiotic prophylaxis of other surgical interventions or different anatomic sites are summarized in Table 18-6.
TABLE 18-6 Evidence-Based Recommendations for Antibiotic Prophylaxis for Specific Interventions or Injuries
The issue of postoperative continuation of prophylactic antibiotics in penetrating abdominal trauma has been investigated extensively. The Eastern Association for the Surgery of Trauma (EAST) has published guidelines derived from an evidence-based review.40 A single preoperative dose of prophylactic antibiotics with broad-spectrum aerobic and anaerobic coverage is recommended for trauma patients sustaining penetrating abdominal wounds. Absence of a hollow viscus injury requires no further administration. If, however, a hollow viscus injury is present, there are sufficient Class I and Class II data to recommend continuation of prophylactic antibiotics for only 24 hours. Timely discontinuation of prophylactic antibiotics is important because the practice of prolonged administration of a prophylactic antibiotic has been linked to increased rates of subsequent nosocomial infections with resistant organisms.41To maintain adequate tissue and serum levels of antibiotics in the face of ongoing hemorrhage and vasoconstriction, the administered dose may be increased 2- or 3-fold and repeated after every 10th unit of blood product transfusion, although there is not strong evidence to support this practice.
Until recently, povidone–iodine scrub has been the standard disinfectant used for surgical prep and scrub. This supremacy has been challenged by several well-designed studies performed in elective surgery showing significantly lower SSI rates with the use of chlorhexidine–alcohol compared with iodine (9.5% vs. 16.1%).42 The fact that chlorhexidine–alcohol begins bacterial killing immediately on contact and does not require drying for antimicrobial effectiveness makes it potentially attractive for use in emergent surgery. One caveat regarding use of alcohol-based disinfectants is that it is imperative that the solutions be dry if electrocautery is used during surgical procedures to avoid intraoperative fires.
Glove perforation is an underappreciated phenomenon that may adversely impact the sterility of an operative procedure. Microperforation rates as high as 16% have been reported.43 When two pairs of gloves are used, inner glove perforation rate is substantially lower. In addition to patient outcome, the surgeon must consider personal safety. Epidemiologic studies report that the prevalence of HIV or hepatitis C is as high as 20–65% and 10–45%, respectively, in an urban university hospital population for patients undergoing lymph node biopsy or drainage of a soft tissue infection.44 More recently, Brady et al.45reported that the seroprevalence of undiagnosed hepatitis C virus (HCV) infection was 7.9% with another 7.8% of the population having preexisting HCV infection.
Hypothermia has been shown to be a strong prognostic indicator of poor outcome when considered in the context of the “triad of death” (hypothermia, acidosis, coagulopathy).46 In addition to inducing an acquired coagulopathy, hypothermia has profound adverse effects on SSI rates. In elective colorectal surgery a prospective, randomized study compared a group in whom intraoperative normothermia (36.6°C) was maintained to a control group with mild hypothermia (34.7°C). The normothermic group had a significantly lower rate of SSI (6% vs. 19%) and a 20% shorter hospital stay.47 The precise mechanism for the beneficial effects of normothermia remains unclear, but may relate to tissue perfusion and improved host defense. Therefore, every reasonable effort should be made to maintain normothermia.
The role of oxygen in development of SSI was examined in another prospective randomized study in patients undergoing elective colorectal operations. The authors observed a significantly lower SSI rate when 80% versus 30% inspired oxygen was delivered during the operation.48 It is noteworthy that other studies have failed to replicate these results49 and that this intervention has never been studied in a trauma population; however, an alternative interpretation of this study in elective patients is that it is best to avoid lower intraoperative FiO2.
There has recently been an extensive marketing effort advocating the use of antibiotic-coated sutures to decrease SSI. Several anecdotal reports describe impressive decreases in the incidence of wound infections (4.9% down from 10.8%) when the authors switched to antibiotic-coated suture.50 Sutures decrease the inoculum of bacteria needed to establish infection and can serve as a foreign body within potentially infected wounds. So while it is clear that studies to specifically compare the efficacy of antibiotic-coated sutures with regular sutures are needed before strong recommendations can be made, there is a sound physiologic basis for a potential benefit. An additional consideration, however, is whether this intervention, like many others, is cost-effective.
Autologous blood transfusion can be lifesaving for an exsanguinating patient, but numerous authors have reported worse infectious complications with increased blood utilization both in the immediate resuscitation51–54 and when used in a delayed fashion.55–57 Transfusion results in a multitude of immunosuppressive effects, including: (1) decreased CD3+, CD4+ and CD8+ cells; (2) overall reduced T-cell proliferation to mitogenic stimuli; (3) decreased natural killer cell activity; (4) defective antigen presentation; and (5) impaired cell-mediated immunity.58 The increased risk of infection associated with blood transfusion appears to be dose dependent57,59 and logistic regression analyses report that the risk of infection increases 13% per unit transfused.60 Taylor et al.61 report that for each unit of packed red blood cells (PRBCs) transfused, the odds of developing a nosocomial infection were increased by a factor of 1.5. The age of the transfused blood is an additional risk factor for infectious complications.62–64 As blood ages in the blood bank, it undergoes predictable changes that affect its ability to deliver oxygen. This “storage lesion” includes the following: (1) an increased affinity of hemoglobin for oxygen and reduced oxygen release to tissues; (2) depletion of 2,3-diphosphoglyerate (2,3-DPG) with resultant inadequacy of oxygen transport by red blood cells; (3) reduction in deformability, altered adhesiveness, and aggregability; and (4) accumulation of bioactive compounds with proinflammatory effects. In trauma patients, Offner and coworkers64 estimated that each transfused unit of RBC older than 14 days increased the risk of major infection by 13%.
To minimize infectious risk, one should limit blood transfusion in nonbleeding patients. A large multicenter randomized study reported the safety of a restrictive transfusion strategy (trigger of 7.0 g/dL hemoglobin) compared to a liberal strategy with a trigger of 10.0 g/dL. In fact, patients who were younger and less sick had over double mortality rates when liberally transfused. When the subgroup of trauma patients was reviewed in a secondary analysis, McIntyre et al.65 confirmed the safety of the restrictive strategy. Additionally, practices to be avoided include transfusing multiple units of blood in stable nonbleeding patients, using blood as a volume expander, and transfusing blood preemptively in anticipation of future operative blood loss. Advanced age should not be used as a sole criterion to transfuse a patient. Several recent guidelines describe transfusion of autologous RBCs in trauma patients in the postresuscitation period.66,67
The timing, adequacy, and route of administration of nutrition to trauma patients have definite implications for infectious complications. Adequate nutrition is essential for patient recovery and healing of traumatic wounds. This is because trauma causes increased metabolism and protein turnover, and this results in a catabolic state characterized by skeletal muscle breakdown, impaired healing, and immunosuppression. After resuscitation is complete nutritional support should be instituted and the enteral route is preferred. Numerous trials have compared enteral nutrition (EN) with parenteral nutrition (PN). Advantages of the enteral route include lower cost, maintenance of function of the gut mucosal barrier, and more physiologic delivery of nutrients while the advantages of PN are primarily related to the consistency of adequate calorie provision. Based on the available high-quality studies, the evidence strongly favors the use of EN over PN in regards to infectious complications.68–70 Traditional markers of nutrition (albumin, transferrin, and retinal-binding protein) are restored better using EN.69 An additional factor that has been implicated in infectious complications is the issue of glycemic control. Current recommendations relating to glycemic control71 are in flux, but it appears clear that results are improved when high levels of glucose are avoided. Enthusiasm for “very tight” glucose control has waned after several studies showed no benefit and increased complications with attempts to maintain blood glucose <110 mg/dL.72–74
Although several studies comparing early and late tracheostomy have been performed, there is still no consensus regarding whether earlier tracheostomy impacts development of ventilator-associated pneumonia (VAP).75–77 The current EAST recommendations (Level 3) are that early tracheostomy be considered in trauma patients anticipated to require mechanical ventilation of >7 days.78 The decision to perform tracheostomy is often institution and surgeon specific. A recent meta-analysis identified high-risk groups that were likely to benefit from early (≤72 hours) tracheostomy.75
Diagnosis of Infection
Almost by definition, infectious problems are never the presenting complaint of a patient who has sustained an acute traumatic injury; however, recognition of an infection in a patient recovering from traumatic injuries is a common, and sometimes challenging, clinical problem. Several of the signs and symptoms that we commonly associate with infections are frequently present in trauma patients. The immediate physiologic and immunologic response to tissue injury is initiation of the inflammatory response. Acute traumatic injuries cause the cardinal signs of inflammation including pain (dolor), edema (turgor), heat (calor), redness (rubor), and loss of function (functio laesa). Furthermore, trauma victims will often have several of the SIRS criteria (e.g., tachycardia, elevated temperature, elevated WBC) in the setting of a clinical context in which they are at increased risk for infection.79
Diagnosis of infection requires a high clinical suspicion, tempered by knowledge of the most likely infectious complications at various time points after injury. Finally, this is filtered by experience with caring for patients with similar injuries. As discussed in the earlier section on “Prevention of Infections,” the preferred management of infections is to prevent their occurrence. When prevention measures have been ineffective, the diagnosis of infection is based on clinical, laboratory, and radiologic methods. Most trauma patients, especially those requiring operative interventions, those with open fractures, or those who have sustained penetrating trauma, will be treated with a course of empiric antibiotics (Table 18-7). The choice of specific antimicrobial agents is determined by the endogenous pathogens or likely exogenous contamination (e.g., exposure to Vibrio spp. with marine trauma, exposure to Clostridium sp. with farm injury) that would be present at the anatomic site of injury.
TABLE 18-7 Recommendations for Antibiotic Choice and Duration for Different Anatomic Regions and Mechanisms of Injury
Hospitalized patients are at risk for development of nosocomial infections and diagnosis is made on the basis of a high suspicion with laboratory and/or radiologic confirmation. In most cases, bacterial culture constitutes the “gold standard” for diagnosis of infection, although at times it can be impractical or impossible to obtain adequate samples. The most specific culture information, if available, is obtained with quantitative or semiquantitative methods (e.g., burn wound biopsy, bronchoscopic alveolar lavage [BAL], or non-BAL). In cases where cultures cannot be obtained, empiric treatment is initiated based on the most likely pathogenic organisms and adjusted based on clinical response. Evidence-based recommendations have been developed for diagnosis and antimicrobial treatment of most hospital-acquired infections,81–86 albeit not specifically addressing trauma patients. The trauma glue grant (www.gluegrant.org) has proposed a standard operating procedure (SOP) to go about identifying the source of infection in critically ill trauma patients (Fig. 18-4).88 This SOP emphasizes and prioritizes the most likely infections and suggests acceptable antimicrobial agents that are otherwise consistent with evidence-based guidelines from infectious disease specialty societies for a wide range of different infections. Diagnostic imaging, particularly cross-sectional imaging, and/or ultrasound, can be helpful to identify and access potentially infected fluid collections in deep locations. Percutaneous aspiration and/or drainage has largely replaced the need for operative management of deep infections and abscesses.89,90
FIGURE 18-4 Diagnostic approach to identify and treat postinjury infections in critically ill trauma patients. (Figure from West et al.88 Used with permission.)
Intra-abdominal infections, particularly an abscess, represent relatively common infectious complications of both blunt and penetrating abdominal trauma. The presence of very high numbers of bacteria within the gut coupled with the impaired perfusion present in shock states and the immune alterations associated with trauma results in a 10–25% incidence of intra-abdominal infection. Appropriate resuscitation and empiric antibiotics, along with sound intraoperative decision making, minimize the risk for infectious complications. Primary control of the source (see section on Operating Room) is crucial to limit the likelihood for postoperative infections. Primary infection is relatively rare, but may be the presenting complaint in patients in whom a hollow viscus injury has not been recognized. Clinical examination may provide sufficient information to warrant abdominal exploration, and the presence of peritoneal signs or other signs of an acute abdomen should not be ignored in trauma patients. Peritonitis and acute abdominal signs may develop if bacterial contamination has been present for >12 hours. More often, even acutely, diagnostic studies such as an abdominal CT scan will suggest the diagnosis (e.g., unexplained free fluid or free intraabdominal air is highly suspicious for injury to a hollow viscus). Diagnostic imaging is much more important to identify postoperative abdominal infections, since physical examination may be equivocal in awake patients and it may be impossible to adequately examine sedated trauma victims in the ICU.
Intra-abdominal infections that are identified later in the hospital course are much more likely to be caused by hospital-associated, rather than community-associated, organisms. This is because most patients will have received one or several doses of antibiotics (frequently relatively broad-spectrum antibiotics) that will have altered the remaining bacterial flora.88 Late intra-abdominal infections may grow Pseudomonas spp., Serratia spp., or Candida spp. Percutaneous aspiration and/or drainage has become the mainstay for treatment of late intra-abdominal abscesses and fluid collections. Whenever possible, material from intra-abdominal collections should be sent for Gram stain, culture, and sensitivity determination because of the high incidence of resistant bacteria that are encountered in recent series.91 The Surgical Infection Society and the Infectious Disease Society of American recently published updated evidence-based guidelines to inform antibiotic choices for abdominal infection.92 These guidelines differentiate between community- and hospital-acquired infections (Tables 18-8 and 18-9). As a general rule, antimicrobial coverage directed against community abdominal pathogens may be given within the first 3 days after injury, whereas antibiotic choices ≥4 days after injury should anticipate hospital organisms.
TABLE 18-8 SIS/IDSA Evidence-Based Guidelines for Antibiotic Choices for Community-Acquired Intra-Abdominal Infections
TABLE 18-9 SIS/IDSA Evidence-Based Guidelines for Initial Adult Antibiotic Dosing in Intra-Abdominal Infections
Under normal circumstances the pleural cavity has a net negative pressure and a very small (<20 mL) volume of fluid.93 The present understanding of fluid flux within the pleural cavity implicates the lymphatics in the parietal pleural as the main route through which fluid is removed.94 Pleural fluid normally turns over at a rate of ˜0.15 mL/(kg h) (10–12 mL/h for a 70-kg individual), and the maximum capacity for lymphatic drainage is estimated to be ˜700 mL per day (˜30 mL/h). If there is increased production or decreased clearance of pleural fluid, a pleural effusion will develop. Pleural effusions are frequently associated with fluid overload, but can also arise in the setting of acute inflammatory processes of the lung including pneumonia (parapnemonic effusion), ALI, or ARDS. Chest trauma, both blunt and penetrating, can induce alterations within the pleural cavity, with loss of negative pressure (traumatic pneumothorax), accumulation of blood (hemothorax), or a combination of both (hemopneumothorax). Treatment of a hemothorax or pneumothorax generally requires inserting a thoracostomy tube, and this intervention introduces the possibility of bacterial contamination of the fluid or blood present within the pleural cavity. In addition, since lymphatic stomata of the parietal pleural are the means by which blood and/or fluid is normally reabsorbed, the presence of fibrin clot obstructs this route of egress and contributes to persistence of fluid within the chest cavity. As discussed in Section “Prevention of Infections,” the presence of bacteria, blood, foreign bodies, and unexpanded lung can predispose to infection within the pleural cavity or what is recognized clinically as an empyema.
The diagnosis of empyema requires sampling of fluid or tissue from the pleural space.95 Analysis of pleural fluid will demonstrate a , glucose <40, the presence of bacteria on Gram stain, or a positive culture in the presence of empyema.96 Table 18-10 shows the most common bacterial isolates from post-traumatic empyema, although it is worth noting that some obviously purulent collections may fail to have positive cultures. It is now generally understood that post-traumatic empyema arises from exogenous contamination of the pleural cavity. This was demonstrated clearly by Hoth et al.97 who obtained simultaneous bronchoalveolar lavage and pleural cultures and noted that there was minimal correlation between pleural cultures and BAL samples. Recognition that skin flora is associated with empyema underscores the importance of using sterile technique during insertion of a thoracostomy tube. Studies examining risk factors for development of empyema have identified the duration of drainage through a chest tube and incomplete evacuation of hemothorax as two of the leading factors.98 Retained hemothorax and empyema complicate about 4% of patients with a hemothorax that was treated with a thoracostomy tube.99
TABLE 18-10 Bacteriology of Post-Traumatic Empyema
Several modalities have been employed to treat empyema.96 Complete evacuation of a hemothorax and reexpansion of the lung at the time the initial chest tube is inserted are important to prevent empyema. Chest CT scans showing pleural thickening or incomplete evacuation may be important adjuncts in managing patients with thoracic trauma. Instillation of fibrinolytic agents has been demonstrated to aid in the evacuation of a retained hemothorax; however, this may be dangerous in the presence of intrathoracic injury. There is now considerable enthusiasm for early use of video-assisted thoracoscopy (VATS), which has proven to be safe and more cost-effective than a second thoracostomy tube.99,100 Ideally, VATS should be performed within 7 days of injury, as the rates of empyema and conversion to thoracotomy are increased after 1 week.101
Trauma-related osteomyelitis and septic arthritis represent not uncommon complications of musculoskeletal injury.102 While hematogenous dissemination of bacteria is involved in most nontraumatic bone and joint infections, post-traumatic musculoskeletal infections generally arise from bacteria introduced exogenously, either at the time of injury or during operative repair. Although a variety of bacterial species have been isolated from post-traumatic osteomyelitis and septic arthritis (see Table 18-11), Staphylococcus species are far and away the most common isolates.103,104 S. aureus and S. epidermidis have a number of virulence factors that provide a particular predilection to bone tissue.104 These virulence factors are summarized in Table 18-12, but include adhesive properties and exotoxins and enzymes that facilitate invasion. Another property that has recently been recognized as being etiologically important to the development and persistence of osteomyelitis is a small colony variant (SCV) phenotype that grows more slowly and has increased resistance to aminoglycosides and decreased hemolytic activity. Clinical use of aminoglycoside beads and broader-spectrum antibiotics may select for these more resilient SCV phenotypes in vivo.
TABLE 18-11 Bacteria Isolated from Septic Joints and Osteomyelitic Bone Infections
TABLE 18-12 Selected Virulence Determinants for S. aureus Bone and Joint Infections
The presence of contaminating bacteria at the site of a bone or joint injury incites a vigorous local inflammatory response. The local source of the inflammatory cytokines TNF, IL-1, and IL-6 is not entirely clear, but osteoblasts may contribute. In any case, high local levels of proinflammatory cytokines have dramatic effects on bone turnover and new bone formation. TNF and IL-1 induce increased maturation of osteoclasts and enhance osteoclastic activity.105At the same time these mediators inhibit mesenchymal cell differentiation into osteoblasts. Similar processes contribute to cartilage and bone destruction in chronic arthritides. In such settings anti-TNF and anti-IL-1 therapies have been very successful in preventing inflammation.106 The net impact of increased osteoclast and decreased osteoblast activity is either bone destruction or inhibition of bone healing. Furthermore, contact between osteoblasts and S. aureus can induce TNF-related apoptosis-inducing ligand (TRAIL), which, in the presence of Fas-associated death domain (FADD), commits cells to apoptotic cell death.
There are several unique factors associated with bone infection that underscore the importance of evidence-based recommendations that emphasize early and continuing aggressive debridement of orthopedic injuries, particularly those associated with open or contaminated wounds. At sites of bone or joint injury local blood supply to fragments may be interrupted predisposing to bone necrosis. Lack of blood supply also precludes delivery of systemic antibiotics, host inflammatory cells, and the molecular oxygen needed for oxygen-dependent bactericidal activity of such cells. It is axiomatic that all dead bone must be removed to minimize the risk of bone infection. In addition, many orthopedic injuries require the presence of plates, rods, or other foreign bodies to stabilize fractures. Only very low levels of bacteria are needed experimentally to produce infection in the presence of a foreign body. If there is extensive local bony destruction and/or contamination, many orthopedic surgeons will utilize external fixation devices to minimize, but not eliminate, the risk of infection and nonunion.
Occupational Exposure to Environmental Pathogens
It is an unfortunate reality that health care workers in general and surgeons in particular, are exposed to blood-borne occupational hazards, including hepatitis B virus (HBV), HCV, and HIV. Body fluids considered potentially infectious include blood, cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. Conversely, exposures to nonbloody feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious as the risk for transmission of HBV, HCV, and HIV infection from these fluids is extremely low.107 Personal protective measures that have been demonstrated to be effective include double gloving, using blunt needles for fascial closure, protective eye shields, impervious surgical gowns, and routine implementation of universal precautions.
While prevention is obviously the best course of action, certain measures taken after an exposure can decrease the risk of seroconversion. The first step involves treatment of the exposure site. Wounds and skin sites should be washed with soap and water and mucous membranes flushed with water. There is no evidence to support applying antiseptics to the wound or expressing fluid to reduce the risk of transmitting a blood-borne pathogen. The CDC strongly discourages the application of caustic agents (e.g., bleach) or the injection of antiseptics or disinfectants into the wound. Second, the exposure source should be evaluated for HBV, HCV, and HIV status. If the status is unknown, the patient should be informed of the incident. The health care practitioner must be aware of applicable state and local laws regarding informed consent for serologic testing. Testing of needles or other sharp instruments involved in the exposure is not acceptable as a replacement or complement to testing the source patient. Additional up-to-date resources and recommendations are available via the National Clinician’s Postexposure Prophylaxis Hotline (PEPline, 888-448-4911 or via http://www.nccc.ucsf.edu/).
When an exposure to HBV occurs, the risk of seroconversion is dependent on the degree of contact (i.e., size of the inoculum) and the hepatitis B e-antigen (HBeAg) status of the source. For example, if the patient is HBeAg positive, the risk of developing HBV infection is about 50%, compared to 25% if the patient is HBeAg negative. PEP includes hepatitis B immune globulin (HBIG) and, possibly, the hepatitis B vaccination series, depending on the hepatitis B antigen status of the patient and the antibody status of the at-risk health care worker. If indicated, HBIG should be given as soon as possible, since early administration after exposure to hepatitis B surface antigen–positive blood can provide an estimated 75% protection from HB infection.107
In contrast to HBV, HCV is not efficiently transmitted via occupational exposure. It is estimated that HCV seroconversion after accidental percutaneous exposure from an HCV-positive source occurs 1.8% of the time, and some have suggested that transmission occurs only from puncture by hollow-bore needles. Transmission has never been reported after intact or nonintact skin exposure to blood and only rarely occurs after exposure of mucous membranes to blood. Currently, intravenous immune globulin (IVIG) is not recommended after occupational HCV exposure. The rationale is based on several clinical observations including the following: (1) HCV infection does not incite a protective antibody response; (2) studies of IVIG use for PEP in HAV and HBV cannot be extrapolated to HCV; and (3) HCV IVIG use in chimpanzees has failed to prevent HCV seroconversion after exposure.107 There is no evidence that the administration of INF-α or antiviral agents prevents HCV infection after occupational exposure and their use is not currently recommended. The exposed health care worker should be tested for baseline HCV viral status and continue close follow-up for 12 months for the purpose of early identification should seroconversion occur. Additionally, the health care worker should contact the CDC Hepatitis Information Line (888) 443-7232 or http://www.cdc.gov/hepatitis.107
Like HCV, transmission of HIV occurs rarely after occupational exposure. The CDC estimates that the risk of seroconversion is approximately 0.3% following a percutaneous exposure to HIV-infected blood and 0.09% after exposure of a mucous membrane. For exposure to fluids or tissues other than HIV-infected blood, the risk of transmission has not been quantified, but is probably much lower. The U.S. Public Health Service (PHS) guidelines recommend a combination of zidovudine (ZDV) and lamivudine (3TC) as the first choice for PEP regimens. To maximize the possibility of protection, PEP should be initiated as soon as possible and the health care worker exposed to HIV should be evaluated within hours. A baseline HIV test should be performed and HIV antibody testing should be performed for at least 6 months postexposure (at 6 weeks, 12 weeks, and 6 months). Currently, a 4-week regimen is advised for most HIV exposures and an expanded regimen including a third drug may be added for exposures that pose an increased risk for HIV transmission. If the source person’s virus is known to be resistant to the routine PEP regimen, selection of an alternate regimen is highly recommended.107
CHRONOLOGIC APPROACH TO PREVENTION, RECOGNITION, AND TREATMENT OF INFECTIONS IN TRAUMA PATIENTS
Efforts to minimize infection must be initiated as soon as the patient arrives in the trauma bay. Although the initial focus will appropriately center on control of hemorrhage and initiation of resuscitation, these efforts will have beneficial impacts on reducing the risk of infection, as well. Restoration of adequate blood flow and oxygen delivery is the first step in reducing the incidence of infection. It has been clearly shown that the incidence of infection from invasive procedures in the ICU such as insertion of a central venous line or chest tube can be dramatically decreased by employing full-barrier precautions.108 Full-barrier precautions may not always be practical in severely injured victims, but suspension of proven infection control measures and sterile technique for invasive procedures should be the rare exception, rather than the rule. Maintenance of normothermia likewise represents optimal treatment for the trauma patient and has the additional benefit that it will decrease the likelihood for development of infectious complications.47 Contaminated wounds should be cleaned and/or formally debrided in an urgent time frame, although more recent reviews of experience in high-energy orthopedic injuries have downplayed the importance of time to debridement as an important factor in development of osteomyelitis.109 TT booster should be administered to all patients, unless it is known that they have received a booster dose within 5 years.
Prophylactic or empiric antibiotics should be initiated in the trauma bay, if they are indicated. Antibiotics should be started in all patients with penetrating injuries, with open fractures, and in any patient in whom there is a high likelihood of injury to a hollow viscus. Due to the hostile environment in which military injuries occur, current recommendations are that injured soldiers start oral or parenteral antibiotics as soon as possible if there is trauma involving any break in the skin. Patients with blunt mechanisms who require operative interventions should receive perioperative antibiotic prophylaxis according to the established, evidence-based guidelines. Antibiotic choices for different anatomic regions are compiled in Table 18-7.
The conduct of operative interventions, if needed, can also significantly impact the likelihood for postoperative infectious complications. The primary factor(s) determining the risk for infection is the nature and magnitude of the traumatic injury requiring surgical intervention. Furthermore, it is crucial that the operating surgeon keep in mind that the highest priority during an exploratory laparotomy for hemorrhagic shock is control of bleeding. For example, if a patient sustained abdominal gunshot wounds with multiple enterotomies and an injury to the inferior vena cava and right renal hilum, it is highly likely that the surgeon would encounter blood and massive intestinal contamination on entering the abdomen. The initial focus must be on controlling hemorrhage, and this may require resisting the usual surgical impulse to stop enteric leakage. The analogy is similar to the principle applied to prioritization of exsanguinating abdominal hemorrhage, in a patient with a severe traumatic brain injury. The best way to save the brain (or to minimize infection) is to control the hemorrhage!
Once hemorrhage is controlled, it is appropriate to stop ongoing leakage from the bowel and to try to remove most gross contamination. In addition to the bacterial contamination arising from enteric leakage, disruption of gastrointestinal integrity also releases foreign bodies (e.g., undigested food particles), mucin, and bile. Any or all of these so-called adjuvant substances have been shown to significantly decrease the inoculum of bacteria needed to establish infection. Adjuvant substances enhance bacterial infectivity via two mechanisms. First, some adjuvant substances augment bacterial growth or stimulate bacteria to express virulence factors.110 The second mechanism involves interference with host defense mechanisms such as the function of innate immune cells.14 For example, bile’s detergent activity can result in lysis of polymorphonuclear leukocytes and macrophages. Blood and devitalized tissue are two additional adjuvant factors that are frequently present. Blood (specifically hemoglobin) can be metabolized into a leukotoxin by some species of enteric bacteria.111 Fibrin clots sequester bacteria and make them inaccessible to host phagocytes, and this action may predispose to late development of intra-abdominal abscesses.112,113 Devitalized, ischemic, or necrotic tissue is a potent source of damage/danger signals that can activate host immune cells and exacerbate acute inflammation, while at the same time interfere with phagocytosis and oxidative killing mechanisms of the host defense cells.8,114 Thus, it is desirable to remove most blood and blood clot from the peritoneal cavity to the extent possible. This can be accomplished by irrigating the peritoneal cavity with a goal of removing the obvious contamination, foreign material, and blood. It is worth noting that a prospective randomized study showed no benefit to formal meticulous debridement to remove fibrinous debris from the peritoneal cavity in established peritonitis.115 While it is a popular aphorism that “the solution to pollution is dilution,” there is scant evidence to back up this bias. Experimentally, the best approach involves the least amount of irrigation that will remove gross contamination and adjuvant material.
Evidence-based guidelines for antimicrobial prophylaxis of trauma recommend broad-spectrum agents with activity against the anticipated pathogens that are likely to be encountered at the anatomic area of injury.116 The guidelines are predicated on the principle that it is always the best course to anticipate the worst case scenario. In terms of infectious risk for blunt or penetrating abdominal injury, this requires coverage against colonic bacterial flora. Therefore, agents with activity against aerobic and anaerobic bacteria are recommended in the case of abdominal trauma.116–118 With injuries to the extremities the most likely pathogens will be aerobic gram-positive bacteria, particularly Staphylococcus species. Injury to maxillofacial structures requires antibiotic prophylaxis with activity against normal oral flora, and neurosurgical procedures most often employ agents similar to those used for the extremities.
Little is known about the pharmacology of antibiotics in the acute resuscitative phase of trauma. Most of the available data are derived from healthy individuals and, therefore, cannot be applied to injured patients. Buijk et al.119described a cohort of 89 critically ill patients who received aminoglycosides. In these septic patients, the volume of distribution was significantly higher than in those without septic shock, and the maximum concentration of antibiotic achieved was significantly lower. In a study of patients who required significant resuscitation with fluids and blood during a laparotomy, the volume of distribution was significantly expanded and correlated with the degree of fluid resuscitation. Additionally, antibiotic elimination was more rapid in these injured patients when compared with normal estimates.120
With massive blood loss antibiotic prophylaxis will require frequent redosing to maintain plasma and tissue levels above the mean inhibitory concentration (MIC). Animal models of experimental infection after hemorrhagic shock report better prophylaxis with increasing doses of appropriate intraoperative antibiotics.121 Large volume resuscitation and altered endothelial permeability with trauma or burns result in an expanded volume of distribution. Renal dysfunction from hypovolemia, myoglobinuria, or radiologic contrast often accompanies severe injury, but the potential risk of nephropathy has no impact on acute antibiotic dosing. The greatest risk for subsequent infectious complications arises from underdosing rather than overdosing in acute trauma.
The conduct of the operation itself significantly impacts the chances for survival and the risk of infection. Abundant data from elective surgery underscore the importance of maintaining normothermia, avoiding shock, and minimizing use of blood transfusion.47,55,57,122 Damage control surgery, with an emphasis on acute management of immediate life-threatening injuries, has the collateral benefit of positively impacting the incidence of postoperative infectious complications.123 In most cases with a damage control approach, vascular reconstruction and bowel anastomoses, if needed, will be delayed until the patient is warm, adequately resuscitated, and hemodynamically stable. While the emphasis is not on infection control, but rather on acute management of life-threatening injuries, this approach has been shown to decrease the incidence of intra-abdominal complications. Most surgeons continue empiric prophylactic antibiotics while the wound is temporarily closed, although this approach has not been formally evaluated for efficacy. There is insufficient evidence to recommend for or against the use of prophylactic antibiotics in the management of an open abdomen.
If the patient is hemodynamically stable, euvolemic, and normothermic, then there is no adverse impact to definitively managing abdominal, vascular, neurosurgical, or orthopedic injuries during the first operation. In a grossly contaminated wound, primary closure is associated with an unacceptably high wound infection rate. Delayed primary closure (DPC), a practice dating back to Ambrose Pare, was advocated by surgical pioneer John Hunter in the 1700s and popularized during World War I.124 It is based on the normal development of fine granulations within the wound prior to definitive closure. Thus, DPC combines the infective resistance of healing by secondary intention with the cosmesis and patient satisfaction of primary closure. Randomized prospective trials have reported significantly lower rates of wound infections when compared with primary closure in the management of grossly contaminated wounds.125–127
The management of penetrating wounds to the colon has evolved since World War II, when the diverting ostomy reduced mortality rates to about 30% in the preantibiotic era. With improvements in trauma resuscitation and accumulating experience with antibiotics, investigators began to question whether fecal diversion was necessary after colonic repair. Initially, Stone and Fabian128 published the first prospective randomized trial of colostomy versus primary repair. They excluded patients with “high-risk” criteria such as shock, hemorrhage, greater than two organs injured, gross contamination, operative delay greater than 8 hours, injury requiring resection, and loss of the abdominal wall. Subsequent investigations have reported that primary colon repair, even in the face of “high-risk” criteria, is associated with a decreased incidence of infectious complications when compared with diverting ostomy.129–131.
Open pelvic fractures are associated with extremely high morbidity and mortality, mostly from septic complications. Diverting colostomies are often placed in such patients, but the evidence supporting this approach is weak and is generally derived from small retrospective studies. One systematic review found no difference in the overall infection rate with or without colostomy, with the exception of a lower complication rate when colostomy was used for perineal/rectal wounds.132 More studies are required to provide definitive recommendations.
Recommendations for management of extremity fractures continue to evolve. A recent large study found that the most important factor in outcome was early transfer to a trauma center for definitive management.109 Specifically, this study called into question the benefit of early operative debridement of open fractures, inasmuch as time to operative debridement did not confer a statistically significant benefit. The concept of damage control has also been applied to orthopedic injuries.133 Recent military experiences also underscore the utility of this concept, coupled with more liberal use of external fixation devices to minimize infectious complications in this hostile environment.134 With proper debridement and acute management of the fracture, it is interesting to note that bacteria inoculated into fractures at the time of injury are rarely isolated from postoperative infections. Rather, hospital-acquired flora are almost universally responsible for infections in fractures.82
ICU and Early Postoperative Period
Infectious complications are commonly encountered in the early postoperative period and are even more likely to be seen in patients who require ongoing critical care (Table 18-13). Clinicians should have a high index of suspicion and consider potential sources of infection in the context of the injuries, the characteristics of the patient, the likely offending organisms, and the length of hospital stay. The immediate postoperative course of a severely injured patient is characterized by a vigorous SIRS response.79 Clinical signs such as mild to moderate fever and tachycardia are almost universal. Furthermore, it is now known that danger signals released from injured tissue activate innate immune responses via the same TLR pathways stimulated by bacterial infection. Leukocytosis is a common manifestation of the SIRS response and there is little utility in monitoring the white blood cell count immediately after injury. It is useful to keep the overall trajectory of the patient in mind before automatically initiating a series of expensive and low yield investigations (e.g., blood cultures, urinalysis, x-rays). Identifying infection is particularly difficult in the ICU setting.86,135 Injured patients are at increased risk for development of nosocomial infections such as pneumonia, catheter-related bloodstream infections (CRBSI), urinary tract infections (UTI), antibiotic-associated colitis, and SSI; however, critically ill trauma victims are susceptible to severe sepsis and septic shock, as well. The Surviving Sepsis Campaign has emphasized the importance of prompt recognition, aggressive resuscitation, and early institution of broad-spectrum antimicrobial agents in their recently updated evidence-based guidelines (Table 18-14).86 In the sections that follow we discuss the diagnosis and treatment of common postinjury/postoperative infections that are frequently encountered in trauma patients.
TABLE 18-13 Nosocomial Infections in the Surgical/Trauma Intensive Care Unit
TABLE 18-14 Surviving Sepsis Guidelines for Initial Resuscitation and Infection Control Priorities for Septic Shock and Severe Sepsis
In a broad sense, pneumonia can be divided into community-acquired pneumonia (CAP) and hospital- or health care–associated pneumonia (HCAP), the former being present on admission and the latter manifesting later in the hospital course. HCAP can further be divided into early (<4 days) and late (≥4 days). These distinctions are more than merely pedantic, as the most likely responsible organisms are different and require different spectrums of antibiotic coverage. All postoperative patients are at risk for pulmonary complications and, therefore, aggressive mobilization and pulmonary toilet should be employed when possible. Unfortunately, injuries such as rib fractures that interfere with coughing and deep breathing, orthopedic injuries that limit mobility, or traumatic brain injuries result in an altered mental status, and complicate pulmonary toilet. CAP should be treated in accordance with local prevalence patterns, most commonly with ceftraixone and azithromycin, as the most common microbes are Haemophilus influenzae and Streptococcus pneumoniae. Early HCAP is initially treated with vancomycin (for MRSA coverage) and ceftraixone.137
Within the broader category of HCAP an important subgroup is patients who develop pneumonia on mechanical ventilation. VAP is a leading cause of morbidity and mortality in the injured population and remains a daunting diagnostic challenge.138,139 In the intensive care unit there are abundant data focusing on the utility of measures designed to prevent VAP.140 Simple measures such as routine hand hygiene and elevation (30–45°) of the head of bed to decrease the likelihood of reflux have resulted in dramatic decreases in VAP rates. Reverse Trendelenberg positioning is an acceptable alternative in patients who must remain supine. Subglottic suctioning and chlorhexidine oral hygiene have been shown to be effective though to a lesser degree, and all of these measures have been incorporated into “ventilator bundles.”140 The duration of mechanical ventilation is the greatest risk factor for development of VAP, with an estimated incidence of 1.2–3.5% risk of developing pneumonia per day of mechanical ventilation.141 Every effort should be made to achieve liberation from the ventilator as soon as possible. Patients should be assessed daily for a trial of spontaneous breathing and extubation should occur if the patient successfully passes the trial.139,142,143
The diagnosis of pneumonia can be challenging in critically ill trauma patients because physical examination is often limited in the obtunded or sedated patient. In addition, lung contusions or atelectasis complicate interpretation of chest x-rays and bacterial colonization of the endotracheal tube and trachea is universal after a few days of mechanical ventilation. There is value in using the clinical pulmonary infection score (CPIS, see Table 18-15) initially described by Pugin to compare invasive and noninvasive pulmonary sampling techniques for VAP.145 Subsequent trials have shown that CPIS alone is not sufficiently accurate to diagnose or rule out VAP.146 In the authors’ hands the CPIS is useful in that a low initial CPIS can direct the team to search for an extrapulmonic source of infection and a day 3 improvement in an initial high CPIS may alter the duration of antibiotic therapy.
TABLE 18-15 Clinical Pulmonary Infection Score (CPIS)
Diagnostic sampling of the respiratory tract will greatly assist in differentiating tracheal colonization from true infection and in guiding antibiotic therapy. Three modalities of diagnostic sampling of the lower respiratory tree, BAL, bronchoscopic protected specimen brushing, and blind “mini-BAL,” are currently employed and the specimens are sent for quantitative or semiquantitative microbiologic culture.147Some controversy remains as to the optimal mode for sampling and the quantitative criteria differ depending on the diagnostic method of diagnosis. A positive confirmatory culture is defined as a BAL or mini-BAL culture >104 CFU/mL or protected specimen brush >103 CFU/mL. A true pneumonia will also manifest as a new radiographic infiltrate, increased oxygen requirements, and the presence of thick, copious secretions. These diagnostic criteria must be satisfied within a 48-hour period.
When pneumonia is identified, it is important to institute therapy as soon as possible. Current recommendations for antimicrobial coverage for pneumonia, and especially VAP, emphasize beginning with broad-spectrum coverage and then de-escalating or narrowing the coverage once culture results are obtained. Inadequate initial antibiotic therapy has repeatedly been shown to be associated with worse outcomes and increased mortality.86,148–150 Beyond 5 days after hospital admission, the patient is at risk for infection by resistant organisms such as Pseudomonas, Acinetobacter, and extended-spectrum beta-lactamase producers such as Klebsiella and E. coli, especially if previously exposed to antibiotics. Gram-negative coverage should include piperacillin/tazobactam, cefepime, imipenem, or meropenem. The addition of an aminoglycoside for “synergistic effect” against Pseudomonas is not supported by current guidelines. With the increasing prevalence of MRSA, vancomycin should always be included as initial empiric coverage. Once pneumonia has been diagnosed and therapy initiated, the next question is the appropriate duration of therapy. An oft-quoted study by Chastre et al.151 reported that an 8-day antibiotic course was equivalent to 15-day therapy for VAP. The foremost consideration should be the clinical status of the patient, with a good response consisting of resolution of elevated temperature, resolving leukocytosis, decreased respiratory secretions, and improved oxygenation. Radiographic resolution often lags behind clinical improvement.
Urinary Tract Infections
UTI is the most common hospital-acquired infection and is almost universally associated with an indwelling urinary catheter.152–154 Most injured patients in the ICU require urinary drainage and differentiation between urinary colonization and infection can be difficult. The diagnosis of UTI requires a quantitative urine culture with >105 CFU/mL along with at least one of the following clinical criteria: (1) temperature >38.5°C, (2) or <3K, and (3) urinary urgency, dysuria, or suprapubic tenderness. Additionally, these factors must be present within a contiguous 48-hour period. A recent study of trauma patients in an ICU setting suggested that early (within 14 days of admission) UTI were an infrequent source of sepsis and, when present, were seldom associated with fever or leukocytosis. Clinically significant urinary infections usually occur in the setting of urinary trauma and/or repair. Responsible organisms in hospitalized patients include E. coli, Pseudomonas, Proteus, Enterobacter, Serratia, and Citrobacter.155 Gram-negative coverage is indicated. Fortunately, many systemic antibiotics are excreted via the kidney and will achieve urinary levels that far exceed the MICs for most of these pathogens.
Catheter-Related Bloodstream Infection
While decreasing in incidence in recent years, CRBSI remains a source of serious morbidity, increased hospital and ICU stay, increased costs, and potential death.156,157 The decision to insert a central line should not be taken lightly. Indications for central access include poor peripheral access, administration of TPN, and administration of high-dose vasoactive medications. A large-bore introducer is commonly inserted in the acute resuscitation of an unstable patient. Often, the clinician is faced with the difficult decision to remove necessary central access or maintain the catheter in the face of potential line sepsis.
In trauma patients whose catheters were placed emergently using nonsterile technique, the lines should be removed and replaced, if needed, with aseptically inserted catheters at new sites. Femoral venous catheters are associated with unacceptably high rates of both infection and deep vein thrombosis and catheters at these sites should be removed as soon as possible. The use of peripherally inserted central catheters (PICC) is associated with a lower incidence of CRBSI. Routine guidewire exchange at predefined intervals does not decrease the rate of CRBSI and may even increase the incidence. Using an evidence-based approach Pronovost et al.158 reported a 66% sustained reduction in the incidence of CRBSI by removing unnecessary catheters, avoiding the femoral site, using full-barrier precautions during insertion, hand washing, and cleaning the skin with chlorhexidine.
When presented with a possible CRBSI, remember that this is a diagnosis of exclusion and requires the presence of bacteremia or fungemia in a patient in whom there is no alternate source of infection. Without local signs of infection (i.e., redness and purulence), a search for other infectious etiologies should always be performed first. As a caveat, infected catheters are frequently thrombogenic and the first sign of infection may be an inability to aspirate blood through the port. In addition to meeting SIRS criteria, the patient must have microbiologic evidence of catheter infection as follows: (1) positive semiquantitative culture (>15 CFU/cm catheter segment); (2) quantitative (>103CFU/cm catheter segment) culture with the same organism isolated from blood cultures; and (3) simultaneous quantitative blood cultures with CVC to blood ratio of the same bacterial species.
Surgical Site Infections
SSI are infections arising at the site of a previous surgical procedure, defined as a location in which an incision had been made or a procedure performed.159,160 Classification of SSI is based on the anatomic depth of the infection and whether the infection is present in the wound or within an organ space. Superficial and deep incisional SSI are differentiated based on whether the infection extends below the fascial layers (deep SSI). By convention, SSI are infections identified within 30 days of the initial surgical procedure.
Superficial SSI are not infrequent in trauma patients based on the wound classification, disruption of environmental barriers, bacterial inoculation at the time of injury, and dysfunction of host defenses seen with injury. Diagnosis of a superficial SSI is determined by the presence of at least one of the following clinical criteria at the site of a surgical procedure: (1) purulent drainage from the surgical incision; (2) culture of organisms from an aseptically obtained fluid or tissue sample from the incision; (3) clinical signs or symptoms of infection; or (4) clinical diagnosis of infection by the surgeon (e.g., the need to open wound). Conditions such as stitch abscesses and erythema or serous drainage at external fixator pin sites do not constitute superficial SSI. In contrast to superficial SSI, a deep SSI involves the deeper soft tissues (e.g., fascial and muscle layers) at the site of the surgical incision and ≥1 of the following: (a) purulent drainage deep to the fascia or muscle layers; (b) spontaneous fascial dehiscence; or (c) identification of a deep abscess on direct examination, during reoperation, or radiologic examination. Finally, an organ space SSI involves anatomic structures (e.g., organs or spaces) that were manipulated during the surgical procedure. In addition, diagnosis of an organ space SSI is based on at least one of the following: (1) purulent drainage from a drain placed into the organ or space (either incisional or percutaneously drained); (2) culture-positive fluid or tissue; or (3) the presence of an abscess during reoperation or radiologic evaluation.
Treatment of SSI depends on the location and depth of infection.88,92,161 Superficial SSI are treated by opening of the surgical incision followed by local wound care. There is no demonstrated benefit to systemic antibiotic treatment for superficial SSI in the absence of systemic symptoms. For deep SSI and organ space infections, it is advisable to try to obtain cultures of any purulent drainage, since prior antibiotic selection pressure and the increasing incidence of resistant strains within hospitals makes it difficult to predict antimicrobial responses.88 In the face of negative cultures, a not infrequent occurrence, clinicians should base antibiotic choices on the anticipated pathogens at the anatomic site. It is well to keep in mind that infections that arise after treatment with a longer course of antibiotics will almost certainly be resistant or, at best, only partially sensitive to the initial agent used. Thus, while awaiting culture and sensitivity results, it is wise to employ a different antibiotic agent or even class.
Clostridium difficile Diarrhea
C. difficile is a gram-positive anaerobic bacterium that is a frequent cause of infectious colitis.162,163 It is a part of the normal colonic flora in 2–5% of the healthy population and is normally nonpathogenic. The incidence in the trauma population has been reported to be 3%.164 Disruption of the colonic flora by antibiotics causes relative overgrowth of this organism. Although the occurrence has been reported with all antibiotics, the association is highest with clindamycin and third-generation cephalosporins. The organism reproduces via spore formation and should be considered highly contagious, as the spores are heat resistant and stomach acid resistant. Additionally, alcohol-based hand sanitizers are ineffective in eradicating the spores. Soap and water hand washing is mandatory after contact with a contagious patient. Since 2001, there has been a significant increase in the incidence of C. difficile infection to approximately 84 per 100,000, and this has coincided with an increased number of serious or fatal infections. The higher failure rates being reported (18.2%) with metronidazole therapy have prompted several professional societies to recommend vancomycin as a first-line agent for patients with severe infection (at a dose of 125 mg four times per day, per os). Vancomycin can also be administered per rectum by enema (500 mg four times daily). For milder infections, oral metronidazole remains the preferred treatment because of its lower cost. For both severe and mild infections, intravenous or oral metronidazole (500 mg four times daily) may be given.
After initial treatment, recurrence rates after treatment with metronidazole or vancomycin are 20% and may be a result of reinfection with a different strain of C. difficile or persistence of the initial strain. If it is the latter, the recurrent episode may be treated with the same agent used to treat the initial episode. After the first recurrence, the risk of a second recurrence is 40% and 60% after two or more recurrences. There are no standard recommendations for treatment of multiple recurrences; however, a recently completed multicenter, randomized, double-blind placebo-controlled trial of monoclonal antibodies to C. difficile toxins A and B reported significantly lower recurrence rates among the treatment arm when compared with placebo (7% vs. 25%, ).165
The optimal timing of administration of vaccines after traumatic splenectomy is unknown, but data suggest an increasing trend for elevated functional antibody activity with a delay in vaccination and improved immune antibody response to vaccination at 14 days after surgery.166 The ACIP recommends the use of the 23-valent polysaccharide pneumococcal vaccine for persons 2–64 years of age who have functional or anatomic asplenia. The CDC suggests a single booster dose for those older than 2 years of age who are at high risk for serious pneumococcal infection and those most likely to have a rapid decline in antibody titers. A single revaccination should be given at least 5 years after the first dose, with further dosing not recommended routinely. H. influenzae vaccination with ActHIB conjugate vaccine is recommended. The available meningococcal vaccine protects against serotypes A, C, Y, and W-135 of Neisseria meningitidis.19 There currently is no recommendation to revaccinate for H. influenza type b or meningococcus. Most trauma patients will be discharged from the hospital much earlier, and given that the population of trauma patients is characterized by poor follow-up, it is probably best to vaccinate the patient prior to discharge rather than wait 14 days (Table 18-16).
TABLE 18-16 Recommendations for Postsplenectomy Vaccinationsa
Late Infectious Complications
Overwhelming Postsplenectomy Infection (OPSI)
Historically, the spleen was considered expendable and the prevailing opinion was that it could be removed with relative impunity. Our current understanding is that the spleen plays an important role in the production of immune mediators that aid in the clearance of bacteria and viruses. Splenic mediators (opsonins) coat circulating bacteria and viruses and convert them into immune complexes, facilitating clearance.167,168 It is difficult to estimate the current incidence of OPSI, as most of the published data on OPSI antedate the widespread availability of the pneumococcal and H. influenzae vaccines. The time since splenectomy is an important risk factor as 50–70% of admissions to the hospital for serious infections occur within the first 2 years. In a review of articles published between 1966 and 1996, Bisharat et al.169 identified almost 20,000 patients who had undergone splenectomy with a median follow-up of 6.9 years. The overall incidence of postsplenectomy infection was 3.2%, with a 1.4% mortality rate. The incidence of infection and mortality were marginally lower (2.3% and 1.1%, respectively) in the 920 trauma patients included in the study. Interestingly, among the trauma patients the mean interval between splenectomy and infection was 49.7 months. Pneumococcal infections account for the majority of reported cases while H. influenzae type b, N. meningitides, and Group A Streptococcus account for an additional 25%.167
Surgical Site Infection after Discharge
In the modern health care environment there is increased pressure for earlier hospital discharge. While this practice is reported to be safe and clearly decreases costs, it complicates identification of SSI. In a prospective study of 268 patients, 33% of all patients with SSI were diagnosed after hospital discharge.170 Trauma caregivers should educate patients about signs and symptoms of SSI at the time of discharge and request that they be notified if infections are identified. In the future it is conceivable that shared electronic health records may aid in identification of late SSI.
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