Editors: Peitzman, Andrew B.; Rhodes, Michael; Schwab, C. William; Yealy, Donald M.; Fabian, Timothy C.Title: Trauma Manual, The: Trauma and Acute Care Surgery, 3rd EditionCopyright ?2008 Lippincott Williams & Wilkins> Table of Contents > 57 - Infections of Trauma Patients57Infections of Trauma PatientsPhilip S. BarieSoumitra R. EachempatiI. EpidemiologyA.Incidence. The incidence of infection following injury approaches 25%. Although most trauma-related deaths occur within the first 24 hours after injury, from exsanguination or massive injury to the central nervous system, the leading cause of posttraumatic death after the initial 24 hours is infection, usually manifesting as the multiple organ dysfunction syndrome (MODS). The high risk of infection is due to the host immune response to injury and stress; inadequate attention to the principles of infection control under emergency conditions; direct inoculation of wounds by clothing, dirt, or debris; blood transfusions; and poor glycemic control. Appropriate antibiotic prophylaxis reduces the risk, but inappropriate prophylaxis may increase the risk of infection.B.Patterns of injury. Infections following injury occur in the injured tissue, the surgical site (incision), or as a health care-associated (nosocomial) infection (HAI) such as pneumonia or catheter-related bloodstream infection (CR-BSI) (Table 57-1). Considered together, HAIs are as common as infections of the injured tissues. The likelihood of infection is higher with increasing injury severity score (ISS), increasing number of abdominal organs injured, traumatic brain injury, colon injury, shock, number of blood transfusions, and creation of an ostomy. Traumatic wounds are characterized by devitalized, ischemic tissue, with increased risk of infection if contaminated by enteric contents (e.g., penetrating abdominal trauma), fragments of clothing fabric (e.g., gunshot wounds), dirt or gravel (e.g., motor vehicle or farm injuries), or vegetation (e.g., fall from P.597

height into a tree). More wound contamination increases the risk of infection of injured tissue.TABLE 57-1 Rates of Health Care-Associated Pneumonia and Catheter-Related Bacteremia Among Various ICU Types

ICU typeCVC use* infection rate mean/medianTT use? infection rate n/median

Medical0.525.0/3.90.464.9/3.7

Pediatric0.466.6/5.20.392.9/2.3

Surgical0.614.6/3.40.449.3/8.3

Cardiovascular0.792.7/1.80.437.2/6.3

Neurosurgical0.484.6/3.10.3911.2/6.2

Trauma0.617.4/5.20.5615.2/11.4

* Number of days of catheter placement/1,000 patient-days in ICU.

?Number of days of indwelling endotracheal tube or tracheostomy/1,000 patient-days in ICU.

Infection rates are indexed per 1,000 patient-days.

(Based on the National Nosocomial Infection Surveillance System, U.S.

Centers for Disease Control and Prevention. From Bercker S, Weber-Carstens S, Deja M, et al. Critical illness polyneuropathy and myopathy in patients with acute respiratory distress syndrome. Crit Care Med 2005;33:711715.)

C.Comparison with critically ill surgical patients (nontrauma). The epidemiology of HAI is changing among critically ill patients, with higher incidences of pneumonia and CR-BSI, and stable or fewer urinary tract infections and surgical site infections. The epidemiology of infection following trauma appears to differ from other critically ill surgical patients. Trauma patients are both more likely to become infected (Table 57-1) and develop infection earlier postinjury. Pneumonia is the most common HAI following injury. The timing of onset of infection influences the choice of antimicrobial therapy.II. Risk FactorsThe host is put at risk of invasion by microbial pathogens whenever a natural epithelial barrier (e.g., skin, respiratory tract mucosa, gastrointestinal mucosa) is breached. Colonization of the epithelial barriers occurs even in healthy hosts. However, invasion does not occur unless injury or some other mechanism of inoculation occurs. Injury, catheterization, or incision breach an epithelial barrier and create a portal for tissue invasion by pathogens. Potential pathogens are ubiquitous in the environment. Innate immunity provides continuous surveillance against invasion by foreign antigens, and stimulates a repair response (inflammation), which may result in counterproductive augmentation of the inflammatory response that is destructive to the host. Prolonged or severe inflammation (e.g., the systemic inflammatory response syndrome, SIRS) (Table 57-2) is associated with the multiple organ dysfunction syndrome (MODS).A.Injury severity. Severity of injury is directly related to the risk of infection. Shock and higher Injury Severity Score (ISS) increase the risk of infection globally. Thoracoabdominal penetrating injury is associated with a higher risk of infection than either abdominal or thoracic injury alone. The risk of intraabdominal infection is higher with increasing numbers of abdominal organs injured. Several local injuries induce systemic immune, inflammatory, and coagulation responses, including pulmonary contusion and traumatic brain injury, the latter being the injury most associated with infection, especially pneumonia.TABLE 57-2 Immune Dysfunction after Trauma

Specific Immunity Lymphopenia Helper: Suppressor T-cell ratio 38C or 90 bpm

Respiratory rate >20 breaths/min or PaCO2 12.0 109/L or 200 mg/dL) was associated with an increased incidence of surgical site infection following cardiac or major general surgery. Despite these observations, little priority was assigned to prevention of hyperglycemia until the publication in 2001 by van den Berghe et al. of a prospective trial of tight glucose control (80110 mg/dL) in critically ill surgical patients (mostly cardiac surgery) by continuous infusion of insulin. Mortality was reduced by 40%. Bloodstream infections and several manifestations of MODS were reduced. Meta-analysis of recent trials confirmed that tight glucose control reduces the risk of death of critically ill surgical patients by more than 40%. The effect appears to be related to control of serum glucose concentration directly, not to any anabolic effects of insulin administration. The benefit is equivalent for diabetic and nondiabetic patients. Administration of subcutaneous insulin for glucose control does not have similar benefit. It is unknown whether lesser degrees of glucose control (e.g., 140150 mg/dL) will provide similar benefit. Glucose dyshomeostasis has several manifestations during stress (Table 57-7). Peripheral glucose uptake and utilization are increased. Glycogenolysis is depressed after initial, short-term mobilization of hepatic glycogen stores. Increased gluconeogenesis. Peripheral insulin resistance. Importantly, hyperglycemia impairs immune cell function. Neutrophils may activate spontaneously, with increased generation of adhesion molecules, impairing microcirculatory flow. Insulin-stimulated chemokinesis is decreased. Phagocytes manifest decreased respiratory burst and thus impaired microbial killing.TABLE 57-7 Glucose Dyshomeostasis During Stress and Effects on Cellular Immunity

Effects of stress response on carbohydrate metabolism Enhanced peripheral glucose uptake/utilization Hyperlactatemia Increased gluconeogenesis Depressed glycogenolysis Peripheral insulin resistance Effects of hyperglycemia on immune cell function Decreased respiratory burst of alveolar macrophages Decreased insulin-stimulated chemokinesis-Glucose-induced protein kinase C activation Increased adherence-Increased adhesion molecule generation Spontaneous activation of neutrophils

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Given that the stress response is stereotypical and pervasive among critically ill and injured surgical patients, it is reasonable to expect that tight glucose control is as important for trauma patients as it is for surgical patients, but limited data are available.III. Prevention of InfectionA.Principles. Infection is morbid, costly, and potentially a lethal complication in trauma patients. Infection can be prevented in part. However, no single method of prophylaxis is universally effective, and each patient presents a unique challenge; all available modalities must be utilized for every case. Infection control is paramount, but often underemphasized. Traumatic wounds must be cleansed thoroughly and debrided to remove devitalized tissue. Surgical incisions must be handled gently, inspected daily, and dressed if necessary using aseptic technique. Drains and catheters must be avoided if possible, and if utilized, removed as soon as possible. Antibiotics should be used sparingly so as to minimize antibiotic selection pressure on the emergence of antibiotic-resistant pathogens.B.Infection control Infection control is an individual responsibility as well as a responsibility of the trauma team and trauma unit. Hand hygiene is the single most effective means to reduce the spread of infection. Yet, if adherence to handwashing is studied, it is invariably found to be lacking. To be effective, hand cleansing with soap and water requires a minimum of 30 to 45 seconds. Alcohol gel hand cleansers are equally effective as soap and water, and compliance is higher. Universal precautions (i.e., cap, mask, gown, gloves, and protective eyewear) must be observed whenever there is a risk of splashing of body fluids (at all times in the trauma bay, and commonly in the ICU). The source of the bacteria causing infection are the patients' endogenous flora, and skin surfaces, airways, gut lumen, wounds, catheters, and inanimate surfaces within the patient's room (e.g., bed rails, and computer terminals do become colonized). Any break in natural epithelial barriers (e.g., incisions, percutaneous catheters, airway or urinary catheters) provides a portal of entry for invasion of the host by pathogenic organisms. Whether infection develops is determined primarily by the response of host defenses, as many organisms that cause infection following injury are inherently avirulent (e.g., Candida, Enterococcus, Pseudomonas). The fecal-oral route is the most common manner by which autoinfection develops, but health care workers can hasten the transmission of pathogens around a unit. Contact isolation is an important part of infection control, and should be used selectively to prevent the spread of pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, or multi-drug-resistant gram-negative bacilli. However, contact isolation may decrease the amount of time that caregivers have direct patient contact, because donning protective garb is time-consuming. By guarding against this phenomenon, an appropriate balance can be struck between attention and protection.C.Appropriate catheter care includes: Avoidance of insertion when nonessential. Appropriate skin cleansing and barrier protection during insertion. Selection of the proper catheter. Proper dressings while catheters are indwelling. Removal as soon as possible when no longer needed, or if inserted under less than ideal circumstances. The benefit of the information gained by catheterization must always be weighed against the risk of infection. Any indwelling catheter carries a risk of infection, but nontunnelled central venous catheters (and pulmonary artery catheters) pose the highest risk, including local site infections and bloodstream infections (Table 57-1). Other catheters that have a significant risk of infection include: Thoracostomy catheters (particularly if inserted as an emergency procedure). Ventriculostomy catheters for monitoring of intracranial pressure.P.602

Urinary bladder catheters. Each day of endotracheal intubation and mechanical ventilation increases the risk of pneumonia. It is controversial whether tracheostomy with facilitation of pulmonary toilet decreases the risk. In terms of preventing infection, abdominal drains are the most superfluous. Whenever possible, skin preparation should be with chlorhexidine solution, which is viricidal and fungicidal as well as bactericidal. Extensive evidence-based guidelines exist for prevention of catheter-related infection. Chlorhexidine is superior to povidone-iodine solution for skin preparation prior to central venous catheter insertion. When povidone-iodine solution is used, it must be allowed to dry; it is not bactericidal when wet. Full barrier precautions (i.e., cap, mask, sterile gown, sterile gloves, eye protection, and a large field drape) are mandatory for all bedside catheter-ization procedures except arterial and urinary bladder catheterization, for which sterile gloves and a sterile field suffice. Anytime a deep catheter is inserted under less than ideal conditions as described (e.g., a central venous catheter placed hastily during a trauma or cardiac resuscitation) it must be removed (and replaced at a different site if still needed) as soon as permitted by the patient's hemodynamic status, but no longer than 24 hours after insertion. A single dose but no more of a first-generation cephalosporin (e.g., cefazolin) may prevent some infections following emergency tube thoracostomy or all ventriculostomy placements, but is not indicated for vascular or bladder catheterizations. Topical antiseptics placed postprocedure at the insertion site are of no benefit. The choice of catheter may play a role in decreasing the risk of infection with endotracheal tubes, central venous catheters, and urinary catheters. An endotracheal tube with an extra lumen that opens to the airway just above the balloon, to facilitate the aspiration of secretions that accumulate in an area that cannot be reached by routine suctioning, below the vocal cords but above the balloon on the endotracheal tube (subglottic secretions), can decrease the incidence of ventilator-associated pneumonia by one half. Antibiotic- (e.g., minocycline/rifampin) or antiseptic-coated central venous catheters (e.g., chlorhexidine/silver sulfadiazine) are effective in reducing the incidence of catheter-related bloodstream infection; the catheter coated with minocycline/rifampin appears to be most effective. Urinary bladder catheters coated with ionic silver reduce the incidence of catheter-related bacterial cystitis. Dressings must be maintained clean, dry, and intact. Maintaining an intact dressing may be difficult when the patient is agitated or the body surface is irregular (e.g., the neck [internal jugular vein catheterization] as opposed to the chest wall [subclavian vein catheterization]), but its importance must be emphasized. A simple gauze dressing is best. Occlusive transparent dressings can accumulate moisture beneath that is a usable growth medium for residual skin flora, which recolonize the skin anyway within a few hours. Mark the dressing clearly with the date and time of each change. Dressing carts or similar apparatus should not be brought from patient to patient; rather, sufficient supplies should be kept in each patient's room. Be cognizant of the possibility for inanimate objects (e.g., stethoscopes, scissors) to be transmission vectors if not cleansed thoroughly after contact with each patient. Every indwelling catheter must be evaluated daily for its continued utility; catheters must be removed as soon as possible. Protocolized ventilator weaning facilitated by daily sedation holidays and spontaneous breathing trials allow earlier endotracheal extubation and decrease the risk of pneumonia. An even better strategy may be avoidance P.603

of catheterization (intubation) entirely. Some episodes of respiratory failure can be managed with noninvasive positive-pressure ventilation delivered by mask (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP]). Improved resuscitation techniques and noninvasive monitoring techniques have decreased the utilization of pulmonary artery flotation catheters (which pose an especially high risk of infection). Most abdominal drains do not decrease the risk of infection. On the contrary, the risk is probably increased because the catheters hold open a portal for invasion by bacteria and soon become a two-way street. Other than for hepatic or pancreatic injuries, abdominal drains are seldom useful. Closed suction drains should not be left in proximity to intestinal suture lines; the negative pressures generated, particularly when such drains are stripped, may cause disruption.D. Antibiotic prophylaxis Pharmacokinetics. Shock, hypoperfusion, and hemorrhage complicate the pharmacokinetics of prophylactic antibiotic administration immediately following trauma. Shock, hypovolemia, and hypoperfusion may also increase the risk of organ dysfunction caused by antibiotics (e.g., aminogly-cosides and renal injury). Young injured patients also have higher glomerular filtration rates than older patients, which will result in more rapid clearance of antibiotics excreted in the urine. Historic recommendations, based paradoxically on the administration of aminoglycosides after trauma, recommended higher doses for prophylaxis that are given conventionally for therapy. Tissue edema associated with resuscitation will change volume of distribution of drugs, and hypoalbuminemia associated with hemodilution, plasma loss, and down-regulation of albumin synthesis (negative acute-phase reactant) can affect tissue antibiotic concentrations. However, there is little documented correlation between measured tissue concentrations and efficacy of prophylaxis. Aminoglycosides are no longer used in this indication for the most part. It may be reasonable to increase the dose of drug administered to patients in shock. However, with modern beta-lactam antibiotics, what is necessary is for the drug to be in the tissues in a concentration above the minimum inhibitory concentration (MIC) for the likely pathogens that may cause surgical site infection (e.g., S. aureus, Escherichia coli). Conventional prophylactic doses (e.g., cefazolin 1 g, cefoxitin 12 g) probably suffice unless the patient is morbidly obese or bleeding briskly.IV. DurationA.It is important that antibiotics with short elimination half-lives (e.g., cefazolin and cefoxitin) are redosed intraoperatively to ensure that tissue concentrations remain adequate during the vulnerable period when the incision is open. Surgical site infection and only surgical site infection is prevented by antibiotic prophylaxis. Antibiotic prophylaxis more than 24 hours beyond injury increases the risk of nosocomial infection. Thus, antibiotic prophylaxis in trauma must not extend beyond 24 hours except perhaps for grade III open fractures.B.Numerous randomized prospective trials have shown that 12 to 24 hours of antibiotic prophylaxis for penetrating abdominal trauma is equivalent to 5 days of prophylaxis, even when a colon injury is present, provided surgery is performed within 12 hours of injury. Penetrating abdominal trauma with no intestinal injury probably requires only a single dose of antibiotic prophylaxis.C.Catheter insertion procedures require only a single dose of prophylactic antibiotics, except perhaps for emergency tube thoracostomy. Indwelling catheters otherwise should never receive prolonged antibiotic prophylaxis. There is no benefit, and the risk is that, should infection develop, it is more likely to because of multi-drug-resistant pathogen.P.604

V. Specific InjuriesA.Abdominal injury The data are unequivocal that prophylaxis of no more than 24 hours of a second-generation cephalosporin (e.g., cefoxitin) is equivalent to a longer course (e.g., 5 days) for penetrating abdominal trauma with injury to a hollow viscus, provided the surgery is performed within 12 hours of injury. Penetrating trauma that does not injure a hollow viscus needs only a single dose of antibiotics given prior to operation. Although not as well studied, the principle is similar for blunt abdominal trauma; if managed nonoperatively no antibiotics are required. If surgery is performed, the duration of prophylaxis (a single dose or 24 hours of prophylaxis) is determined by the pattern of injury. The abdomen may be left open temporarily as part of damage control or to prevent or manage the abdominal compartment syndrome. There is no evidence that the open abdomen requires prolonged antibiotic prophylaxis, even if a prosthesis is employed as part of the temporary closure. Another dose of prophylactic antibiotic aimed against skin flora (e.g., gram-positive cocci) is appropriate when the abdominal wall is closed or reconstructed. Neither is there evidence that prophylactic antibiotics are required if the liver and spleen are embolized as part of the nonoperative management of blunt trauma to those organs. Although suppuration of devitalized tissue is a risk following therapeutic interventional radiology for liver or spleen injury, there are no data regarding antibiotic prophylaxis. The infection risk associated with the late postsplenectomy period (bacteremia from encapsulated gram-positive cocci, for the most part, or postsplenectomy sepsis), is genuine for children but low for adults. Expert opinion often recommends prophylaxis with oral penicillin until age 18 years for splenec-tomized children. Adults do not require long-term antibiotic prophylaxis. All individuals who undergo splenectomy should receive the polyvalent pneumococcal vaccine, with booster doses at 5-year intervals. We coadmin-ister vaccines against Haemophilus influenzae and Neisseria meningitidis; timing of booster doses, if any, is unknown. Also unknown is whether patients who have undergone splenic embolization or the increasingly rare splenorraphy procedure should be vaccinated against postsplenectomy sepsis. Splenocyte immune function cannot be assessed in vivo, and the degree of devitalization of the spleen varies from patient to patient. Vaccination of the embolized patient following splenic injury is our practice, especially for children.B.Chest injuries. Little data exist to guide antibiotic prophylaxis of chest trauma. For blunt chest trauma, no antibiotic prophylaxis is indicated, even in the presence of pulmonary contusion. For suspected aspiration of gastric contents, clinical judgment must be exercised. Two thirds of patients who aspirate do not develop pneumonia, so withholding of antibiotics (technically empiric therapy, not prophylaxis in this case) is reasonable until objective evidence of pneumonia is obtained. If antibiotics are started they should be discontinued within 48 hours if the development of pneumonia is unproved (Section VII.A). Penetrating trauma to the chest should be governed by the decision of whether to administer antibiotic prophylaxis for trauma chest tubes (next point). With a thoracoabdominal injury (and corresponding increased incidence of empyema thoracis), the principles governing antibiotic prophylaxis for penetrating abdominal trauma should govern the situation. Prophylaxis of chest tubes is controversial. The guidelines of the Eastern Association for the Surgery of Trauma recommend 24 hours of prophylaxis of emergency trauma chest tubes only as a Level III recommendation (based on expert opinion).C.Fractures. Prolonged antibiotic prophylaxis of open fractures is popular among orthopedic surgeons despite the fact that current practices are supported only by P.605

retrospective data from the 1970s. A meta-analysis of 22 studies including more than 8,000 patients with closed long bone fractures showed that the incidence of infection (superficial or deep incisional surgical site infection, urinary tract infection, respiratory tract infection) was reduced by 60% by a single dose of antibiotic prophylaxis. Multidose prophylaxis did not protect against urinary or respiratory infections in that study. One recent trial of single-dose versus 5 days of prophylaxis of grade I to II open tibial fractures with a fluoroquinolone showed equivalence for single-dose prophylaxis. The guidelines of the Eastern Association for the Surgery of Trauma recommend 24 hours of prophylaxis of grade I to II open long bone fractures with an agent active against gram-positive cocci. For grade III open fractures, the addition of an agent active against gram-negative bacilli is recommended, but for 72 hours.D.Skin and soft-tissue injuries. Few studies have examined the antibiotic management of infected traumatic wounds specifically, but inclusion of small numbers of such wounds in larger trials of therapy for complicated skin and skin structure infections (cSSSI) suggests that the principles of management are similar. Infected traumatic wounds may comprise as many as 13% of all infections after injury. The likelihood of infection is influenced foremost by the degree of contamination of the wound, ranging from approximately 3% for clean wounds to about 25% for wounds that are grossly contaminated. Wounds must be inspected carefully for the removal of foreign material (e.g., clothing, gravel, vegetable matter, wadding from shotgun shells), irrigation with physiologic saline, and debridement of devitalized tissue. Risk factors for infection of traumatic lacerations repaired in the emergency department include diabetes mellitus, age (increased risk per year), foreign body, and the width of the incision. Lacerations of the head/neck region are less likely to become infected. Despite a high risk of infection posed by some wounds, there is scant evidence that traumatic injuries should receive antibiotic prophylaxis; administration is generally not recommended. The most common pathogens of infected traumatic wounds are aerobic gram-positive cocci (e.g., S. aureus), with aerobic gram-negative bacilli (e.g., E. coli, P. aeruginosa) being less common; antibiotic therapy when indicated (for overt infection) should be directed against likely pathogens. Numerous antibiotics of several classes are approved for therapy of cSSSI. Animal and human bites should be presumed to be infected because of the large bacterial inoculum that is deposited in deep tissues and the resulting challenges inherent in local wound care. The pathogens differ in bite wounds, with dog and cat bites showing a predilection for Eikenella corrodens and Pasturella multocida, respectively. A meta-analysis of eight randomized, placebo-controlled clinical trials of penicillin or macrolide prophylaxis of dog bite wounds revealed that the rate of infection was reduced by more than 40% from the control infection rate of 16%, and to an even greater degree for bites of the hand. However, the duration of prophylaxis was not defined. Human bites are likely to cause infection with oral anaerobes (e.g., anaerobic streptococci, rarely Bacteroides fragilis).E.Nutrition (Chapter 43). There is still much debate as to the ideal formula, route, and rate of feeding for injured patients. However, the effect of early enteral feeding to reduce the risk of infection following trauma or burn injury is well established.VI. MicrobiologyA.Principles of resistance. Bacteria use four different mechanisms to develop resistance to antibiotics. Cell wall permeability to antibiotics is decreased by changes in porin channels (especially important for gram-negative bacteria with complex cell walls, affecting aminoglycosides, -lactam drugs, chloramphenicol, sulfonamides, tetracyclines, and possibly quinolones).P.606

Production of specific antibiotic inactivating-enzymes by either plasmid-mediated or chromosomally mediated mechanisms affects aminoglycosides, -lactam drugs, chloramphenicol, and macrolides. Alteration of the target for antibiotic binding in the cell wall affects -lactam drugs and vancomycin, whereas alteration of target enzymes can affect -lactam drugs, sulfonamides, quinolones, and rifampin. Drugs that bind to the bacterial ribosome (aminoglycosides, chloramphenicol, macrolides, lincosamides, streptogramins, and tetracyclines) are also susceptible to alteration of the receptor on the ribosome. Antibiotics may be extruded actively once entry to the cell is achieved in the case of macrolides, lincosamines, streptogramins, quinolones, and tetracyclines.B.Gram-positive cocci. Gram-positive cocci are collectively the most common causes of infection following injury. Infections most likely caused by gram-positive cocci include infections following neurosurgery (e.g., ventriculitis following invasive monitoring of intracranial pressure), sinusitis, CR-BSI, device/implant-associated infections, and cSSSI. Respiratory tract and urinary tract infections may also be caused by gram-positive cocci. S. aureus is the most important pathogen among the gram-positive cocci. Sixty percent of hospital-acquired isolates of S. aureus are resistant to methicillin (MRSA), whereas 25% of community-acquired strains are now resistant (CA-MRSA). Staphylococcal resistance to vancomycin is reported but remains rare and is induced only after prolonged exposure to vancomycin among debilitated patients (e.g., dialysis patients). S. aureus is a major pathogen in sinusitis, CR-BSI, cSSSI, and pneumonia. S. epidermidis is almost invariably resistant to methicillin (MRSE, 85%), and is the major pathogen in CR-BSI and device/implant-associated infections. Enterococcus spp. can cause cSSSI, CR-BSI, and infections of the urinary tract. About 30% of enterococci are resistant to vancomycin (VRE), but the pattern is species specific. Whereas 70% of E. faecium isolated are VRE, the same is true for only 3% of E. faecalis isolates. The incidence of VRE may be reaching a plateau, but VRE poses a threat only to debilitated patients after prolonged hospitalization. Colonization of the feces with VRE usually precedes invasive infection, and cannot be eradicated pharmacologically. Risk factors for the acquisition of VRE include prolonged hospitalization, readmission to the ICU, and therapy with vancomycin or third-generation cephalosporins. Because of the high prevalence of MRSA, vancomycin remains the most-prescribed antibiotic for resistant gram-positive cocci despite poor tissue penetration and the risk of toxicity. Alternatives for therapy include linezolid, tigecycline, daptomycin (but not for pneumonia) and quinupristin/dalfopristin (used seldom because of multiple toxicities). Some retrospective analyses suggest that outcomes for pneumonia and soft tissue infection may be improved when linezolid is used compared to vancomycin, but prospective corroboration is required.C.Gram-negative bacilli. Gram-negative bacilli are less common as pathogens than gram-positive cocci, but are important in the pathogenesis of skin/skin structure infection (particularly after inoculation of a wound), lower respiratory tract infection, and intraabdominal infection. Although Enterobacteriaceae such as E. coli or Klebsiella spp. predominate in intraabdominal infection, P. aeruginosa is the second most common ICU pathogen overall and the bacterium most closely associated with death from HAI. P. aeruginosa can infect virtually any tissue, including synovium and vitreous humor. P. aeruginosa bacteremia can cause or complicate pneumonia, and other metastatic infections can follow. Antimicrobial resistance is a major problem with P. aeruginosa, Acinetobacter sp., and Klebsiella sp., and increasing among Enterobacteriaceae other than Klebsiella. Cephalosporin resistance among gram-negative bacilli can be the result of induction of chromosomal -lactamases after prolonged or repeated exposure to the antibiotic. The extended-spectrum cephalosporins are rendered ineffective when P.607

bacteria such as enteric gram-negative bacilli mutate to produce constitutively a -lactamase that is normally an inducible enzyme. Although resistance to cephalosporins can occur by several mechanisms, the appearance of chromoso-mally mediated -lactamases has been identified as a consequence of the use of third-generation cephalosporins. Resistance rates decline when use is restricted. The mutant bacteria develop resistance rapidly to both cephalosporins and entire other classes of -lactam antibiotics. It is justifiable therefore to restrict the use of ceftazidime, especially in institutions grappling with an ESBL-producing bacterium. The carbapenems and aminoglycosides generally retain useful microbicidal activity against ESBL-producing strains, but ESBL-producing strains can cause fatal infections because of delayed recognition and consequent delayed empiric antimicrobial therapy. Unfortunately, routine antimicrobial susceptibility testing does not detect ESBL-producing strains. Therefore, heightened clinical suspicion must be followed by confirmatory laboratory testing of the suspicious organism. The resistance problem in gram-negative bacteria is not limited to cephalosporin resistance. Metalloproteinases and carbapenemases threaten the utility of carbapenems to treat infections caused by Pseudomonas and Acinetobacter. The fastest-growing resistance problem for gram-negative bacilli in the United States is quinolone resistance, particularly against Pseudomonas. Quinolone resistance is chromosomally mediated for the most part, primarily by changes in the target sites (DNA gyrase or topoisomerase IV) for the antibiotic. Changes in permeability or efflux may cause resistance to quinolones as well. Quinolone resistance is easy to induce if a less-than-maximally effective drug or dose is chosen for initial therapy. Resistance to one quinolone may also increase the MIC for other quinolones against the organism, so a highly active agent given in adequate dosage is essential for empiric therapy with quinolones.D.Fungi and yeast Most fungi and yeast are avirulent opportunistic pathogens that do not threaten healthy patients. However, such infections should also be unusual in the typical critically ill or injured patient. Unless occurring in a profoundly immunosuppressed patient (i.e., cancer chemotherapy with neutropenia, bone marrow transplant or nonrenal solid organ transplant) fungal infections are usually the result of antibiotic overuse. Prolonged broad-spectrum antibiotic therapy suppresses host flora, and creates the opportunity for overgrowth of commensal flora. The most common health care-acquired fungal infections are caused by Candida spp., which are part of gut flora in approximately one quarter of patients. Some experts believe that high-risk patients (including those who require intensive antibiotic therapy) should be treated prophylactically with an azole anti-fungal agent (e.g., fluconazole) to prevent invasive infection, which can be lethal. Although colonization with Candida does precede invasive infection, the utility of antifungal prophylaxis requires confirmation. However, most surgical patients do not manifest fungemia. Widespread prescribing of fluconazole has led to emergence of resistance among Candida sp. that are normally susceptible to fluconazole (e.g., C. albicans, C. tropicalis). Empiric therapy of suspected invasive fungal infections is probably not necessary in most centers that have a low incidence of such infections, but must address the possibility of resistant Candida if administered. Therefore, fluconazole should not be used until an organism that is likely to be susceptible to fluconazole is identified (most centers do not perform fungal susceptibility testing). Empiric therapy choices include conventional amphotericin B, lipid formulations of amphotericin B, or the echinocandins, caspofungin or mica-fungin. Conventional amphotericin B is seldom used currently because of substantial toxicity (e.g., febrile reactions, hypokelemia, renal insufficiency). The lipid formulations mitigate the toxicity, but at high cost. Caspofungin is P.608

broadly active against yeast and fungi including Candida spp. and Aspergillus sp., and a logical, if expensive, choice for empiric therapy, but data are scant, particularly in surgical patients. Comparative studies suggest that the triazole voriconazole may be more effective than amphotericin B for invasive aspergillosis.VII. Nosocomial InfectionsAmong the nosocomial infections, pleuropulmonary infections (pneumonia, empyema) are more common than bacteremia, which in turn is more common than urinary tract infection. This section examines the factors that contribute to the increased risk of infection after trauma, considers what can be done to reduce the risk of infection, and determines how best to accomplish the risk reduction.A.Pneumonia. The most common health care-associated infection following critical illness or injury is pneumonia (HAP). Trauma patients may be at specific risk for development of pneumonia (or empyema, which complicates 5% of cases of posttraumatic pneumonia) for several reasons. Chest wall injury (e.g., rib fractures) decreases thoracic compliance and impair pulmonary toilet. Direct (e.g., penetrating injury, pulmonary contusion) or indirect (e.g., acute respiratory distress syndrome, ARDS) pulmonary injury may depress local pulmonary host defenses directly. Traumatic brain injury may produce obtundation or coma and impair airway reflexes, leading to an increased risk of aspiration of gastric contents. Iatrogenic risk factors include prolonged bed rest, supine positioning, tracheal or nasogastric intubation, narcotic analgesics and sedatives, and prolonged mechanical ventilation. Even a single day of mechanical ventilation increases the risk of ventilator-associated pneumonia (VAP) demonstrably. Pneumonia can be prevented by careful adherence to the principles of infection control. Positioning the head of the bed up 30 degrees at all times Daily sedation holidays and assessment for liberation from mechanical ventilation Prophylaxis of stress-related gastric mucosal hemorrhage and venous thromboembolic disease Some authors describe HAP or VAP as early-onset or late-onset, with onset more than 5 days after admission or intubation, respectively, being the defining time. Whether this distinction is important is unclear. The microbiology of early-onset HAP/VAP differs, in that it is more likely to be caused by relatively antibiotic-susceptible bacteria such as S. pneumoniae, H. influenzae, or methicillin-sensitive S. aureus (MSSA). Late-onset HAP and especially VAP tend to be caused by methicillin-resistant S. aureus (MRSA), P. aeruginosa, Acinetobacter spp., and the Enterobacteriaceae (although E. coli pneumonia is relatively uncommon). The diagnosis of VAP in particular is controversial. The pharynx becomes colonized soon after hospitalization with potential pathogens. Similarly, artificial airways (e.g., endotracheal or tracheostomy tubes) become coated with a gly-cocalyx biofilm that can sequester pathogens (especially P. aeruginosa) from the actions of antibiotics. Routine sputum collection for culture and susceptibility testing by standard endotracheal suctioning can contaminate the specimen with these upper airway colonists, thereby leading to the overdiagnosis and consequent overtreatment of VAP. To reduce this risk, quantitative microbiology testing of sputum obtained by a technique that minimizes the possibility of contamination has been advocated. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) or the use of a protected-specimen brush (PSB) catheter can reduce the risk of contamination of the specimen and increase the accuracy by increasing the specificity of the diagnosis, and make antibiotic administration more accurate. The P.609

threshold for the diagnosis of VAP is 104 colony-forming units (cfu)/mL (some authors argue that the threshold should be 105 cfu/mL for trauma patients) of a single organism, and 103 cfu/mL for the PSB technique. Techniques for both BAL and PSB specimen collection without bron-choscopy have been developed, so quantitative microbiology may be more important than bronchoscopy. The most common causative organisms for VAP are MRSA and P. aeruginosa; effective empiric antibiotic therapy must account for both. Misdirected (against resistant pathogens) or delayed antibiotic therapy of VAP are major causes of therapeutic failure and death. Recent data suggest that the duration of therapy for VAP should be as brief as eight days for most cases of VAP, with the possible exception of cases caused by non-fermenting gram-negative bacilli (e.g., P. aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia), which may require up to 2 weeks of therapy. The mortality rate of pneumonia complicating trauma is approximately 20%, whereas it is approximately 35% for VAP in critically ill surgical patients. Whether this difference relates to the timing of onset, microbiology, or underlying host factors such as age or severity of illness/injury is conjectural. Management based on quantitative microbiology may be associated with lower mortality. It is clear, however, that reliance on quantitative microbiology can increase clinician confidence that pneumonia is not present when testing is non-revealing, allowing the withholding or truncation of antibiotic therapy, which is unquestionably beneficial for those who are not infected and who do not need antibiotics.B.Catheter-related bloodstream infection Trauma and hemodynamically unstable nontrauma ICU patients often require reliable large-bore intravenous access. Placed typically into central veins (e.g., femoral, internal jugular, or subclavian vein), these catheters are prone to local infection and bloodstream infection. Prevention by strict adherence to infection control and proper insertion technique is crucial because trauma patients are at particularly high risk for infection of central venous catheters (Table 57-1). When placed under elective (controlled) circumstances, proper insertion technique mandates that the operator prepare the operative field with chlorhexidine (not povidone-iodine solution), drape the entire bed into a sterile field, and don a cap, mask, and sterile gown and gloves. When sterile procedure or technique is breached, the risk of infection increases exponentially, and the catheter should be removed and replaced (if still needed) at a different site using strict sterile technique as soon as the patient's condition permits (ideally within 24 hours). Infection risk for femoral vein catheters is highest, and lowest for catheters placed via the subclavian route. Peripheral vein catheters, peripherally placed central catheters (PICC), and tunneled central venous catheters (e.g., Hickman, Broviac), pose less risk of infection than percutaneous central venous catheters. Information campaigns, educational initiatives, and strict adherence to insertion protocols are all effective to decrease the risk of CR-BSI. Antibiotic- and antiseptic-coated catheters are controversial, but may decrease the risk of infection. Catheter infection is diagnosed by isolation of >15 cfu from a segment of catheter by the semi-quantitative roll-plate technique. The diagnosis of CR-BSI is confirmed when the isolates from blood and the cultured catheter are identical. The pathogens of CR-BSI are predominantly gram-positive cocci, most commonly MRSE, MRSA, and enterococci. Unfortunately MRSE is not only the most common cause of CR-BSI, but also the most common cause of false-positive blood cultures because of contamination during the collection process. Isolation of MRSE from a single blood culture is likely a contaminant (do not treat), especially if the P.610

patient has no indwelling hardware that might become infected secondarily (e.g., prosthetic joint or heart valve). Gram-negative bacillary pathogens are less common, and fungal CR-BSI are unusual in trauma patients. Treatment is by removal of the catheter (for peripheral or percutaneous central venous catheters) with parenteral antibiotics, at least initially. Catheter-related bloodstream infections caused by MRSA require at least 2 weeks of therapy; some authorities argue for a longer course because of the risk of metastatic infection. Vancomycin or linezolid may be chosen for MRSA CR-BSI (or MRSE when treatment is indicated), with daptomycin as an alternative. Therapy for enterococcal or gram-negative CR-BSI is dictated by bacterial susceptibility, without clear consensus as to duration of therapy. Beyond removal of the catheter, treatment of fungal CR-BSI is controversial. Some authorities recommend removal of the catheter as sole therapy; others recommend at least 2 weeks of systemic antifungal therapy.C.Peritonitis The peritonitis associated commonly with perforated viscus is referred to as secondary peritonitis. In the trauma setting, secondary peritonitis may occur after penetrating injury to the intestine that is not treated promptly (>12 hours delay). Other causes include dehiscence of a bowel anastomosis with leakage of succus entericus, or development of an intraabdominal abscess. Secondary peritonitis is polymicrobial, with anaerobic gram-negative bacilli (e.g., B. fragilis) predominating, and E. coli and Klebsiella spp. isolated commonly. Any of a number of antibiotic regimens of appropriate spectrum may be appropriate. Enterococci, Pseudomonas, and other bacteria may be isolated, but do not require specific therapy if the patient is otherwise healthy (e.g., not immunocompromised) and responding to therapy as prescribed. When secondary peritonitis develops in a hospitalized patient as a complication of disease or therapy, the flora are likely to reflect those encountered in the hospital. For example, enterococci, Enterobacter, and Pseudomonas are more prevalent, whereas E. coli and Klebsiella are less common. Antibiotic therapy must be adjusted accordingly, and surgical source control must be achieved. Failure of two source control procedures with persistent intraabdominal collections is referred to as tertiary peritonitis. Tertiary peritonitis represents complete failure of intraabdominal host defenses. Therefore, it is controversial whether tertiary peritonitis is a true invasive infection, or rather colonization of the peritoneal cavity with incompetent local host defenses. The latter view is supported by the observation that the commonly isolated bacteria in tertiary peritonitis are avirulent opportunists such as MRSE, enterococci, Pseudomonas, and C. albicans. Some authorities recommend that these patients be managed with an open-abdomen technique, so that manual peritoneal toilet can be provided under sedation or anesthesia, possibly at the bedside. At times, there is no alternative to open-abdomen management if the infection extends to involve the abdominal wall, and extensive debridement is required.D.Clostridium difficile-associated disease Clostridium difficile-associated disease (CDAD) (formerly pseudomembra-nous colitis) develops because antibiotic therapy disrupts the balance of colonic flora, allowing the selection and overgrowth of C. difficile, present in the fecal flora of 3 % of normal hosts. Any antibiotic can induce this selection pressure, even when given appropriately as single-dose surgical prophylaxis, although clindamycin, third-generation cephalosporins, and fluoroquinolones have a predilection. Even antibiotics used to treat CDAD (e.g., metronizazole) have been associated with CDAD. Clostridium difficile-associated disease is unquestionably a nosocomial infection. Spores can persist on inanimate surfaces for prolonged periods, and pathogens can be transmitted from patient-to-patient by contaminated equipment (e.g., P.611

bedpans, rectal thermometers) or on the hands of health care workers. The alcohol gel that is used increasingly for hand disinfection is not active against spores of C. difficile. Therefore, handwashing with soap and water is necessary when caring for an infected patient or during outbreaks. The clinical spectrum of CD AD is wide, ranging from asymptomatic (8% of affected patients do not have diarrhea) to life-threatening transmural pan-colitis with perforation and severe sepsis or septic shock. The typical patient will have fever, abdominal distention, copious diarrhea, and leukocytosis. Bleeding from the colon is rare, and if observed should prompt strongly an alternative diagnosis. Diagnosis by assay for the enterotoxins in a fresh stool specimen has largely supplanted colonoscopy. Up to 50% of patients do not have the characteristic colonic mucosal pseudomembranes (hence, the change in nomenclature as well). Treatment of mild cases consists of withdrawal of the offending antibiotic; oral antibiotic therapy is often prescribed. More severe cases may require par-enteral metronidazole or oral or enteral vancomycin (by lavage or enema, if ileus precludes oral therapy); parenteral vancomycin is ineffective. On occasion, patients with severe disease may require total abdominal colectomy. The prevalence of severe disease has increased markedly with the emergence of a new strain of C. difficile. The new strain has undergone a mutation of a gene that suppresses toxin production, such that far more toxin is elaborated, resulting in clinically severe, systemic disease.E.Sinusitis Nosocomial sinusitis is a dangerous, closed-space infection that is increasing in incidence, but difficult to diagnose and therefore controversial as to its incidence and importance. Patients with transnasal tubes (particularly nasotracheal intubation, after 7 days of which the incidence is one third) and maxillofacial trauma are at particular risk. Purulent or foul-smelling nasal discharge is an obvious clue to the diagnosis, but not always present. So, sinusitis must be sought radiographically by CT of the facial bones to identify sinus mucosal thickening or opacifica-tion. Because the process is often occult, the more the diagnosis is sought, the more often it will be confirmed. Sinusitis should be suspected in any patient with sepsis, particularly if initial cultures (e.g., blood, sputum, urine, indwelling vascular catheters) are unre-vealing. If sinusitis is suspected, the diagnosis is confirmed by maxillary antral tap, lavage, and culture using aseptic technique. Gram-positive cocci, gram-negative bacilli (including P. aeruginosa), and fungi (incidence, 8%) are possible pathogens; initial therapy should be based on local susceptibility patterns. Most antibiotics that might be chosen achieve adequate tissue penetration. The duration of therapy should be based on the patient's clinical response. Refractory cases may require repetitive lavage of the sinus, or a formal drainage procedure. Sinusitis is a predisposing factor for VAP, and may be a source of pathogens that gain access to the lower respiratory tract. The association may be temporal; both infections are associated with prolonged endotracheal intubation. However, there is 85% concordance between sinusitis pathogens and pneumonia pathogens in patients who develop VAP subsequently, lending credence to the hypothesis that purulent drainage from infected sinuses inoculates the lower airway.F.Decubitus ulcer. Infection from decubitus ulcer may be obvious or covert. Patients are at substantially increased risk with prolonged bed rest (>7 days), which may be mitigated by specialized bedding. Vasopressor therapy and poor nutrition may be additional risk factors, but any association is unsubstantiated. Morbid obesity is a clear risk factor, given that routine turning and positioning of such patients is a formidable undertaking. Most decubitus ulcers form in the pre-sacral area, but can form anywhere unremitting pressure is placed upon tissue. For example, if the position of the endotracheal tube at the lips is not changed periodically, ulceration may occur at the corner of the mouth. Also, occipital P.612

decubitus ulceration results from ill-fitting cervical collars, when used for an obtunded patient or when clearance of the cervical spine is delayed. When evaluating a patient for occult infection, the skin must be inspected systematically for decubitus ulcers. Deep ulcers (Stage III, involving subcutaneous fat; Stage IV, involving fascia, muscle, or bone) may require debridement or systemic antibiotic therapy. In rare cases, a decubitus ulcer may transform into a life-threatening necrotizing soft-tissue infection.VIII. Multiple Organ Dysfunction SyndromeA.Epidemiology The multiple organ dysfunction syndrome (MODS) is the leading cause of death following critical illness and injury (>24 hours postinjury). Patients who develop any component of organ dysfunction are 20-fold more likely to die. The development of MODS usually follows infection and sepsis (75%) but may follow massive tissue injury (25%; e.g., multiple, trauma, burns, severe pancreatitis). The degree (number of affected organs) and magnitude (severity of dysfunction) closely correlate with the initial severity of illness and the severity and persistence of the proinflammatory state (systemic inflammatory response syndrome, SIRS) in response to illness/injury. Several scoring systems have been described to quantify MODS (Table 57-8); descriptive utility is comparable. Quantification of MODS is useful for prognostication; the magnitude of MODS is related closely to the mortality rate, which is 70% or more when MODS is manifest fully.B.Risk factors and pathogenesis The usual presentation of MODS is multifactorial and involves multiple organ systems. Only in occasional circumstances (e.g., transfusion-associated acute lung injury, TRALI) is the cause of MODS identifiable discretely or manifested by dysfunction of a single organ. Even though the inciting injury may be localized, the host response is usually systemic. Severe sepsis (by definition, sepsis with dysfunction of at least one organ) and tissue injury are the usual precipitants of MODS, but the pathogenesis is complex and usually multifactorial. Many hypotheses of the pathogenesis of MODS have complimentary or overlapping features with the pathophysiology still not elucidated.TABLE 57-8 Multiple Organ Dysfunction Score

01234

Pulmonary (PaO2:FiO2 ratio)>300226300151225761505.7

Cardiovascular (HR = HR X RAP/MAP)1010.115.015.120.020.130.0>30.0

Hepatic (serum bilirubin, mg/dL)1.21.33.53.67.07.114.0>14.0

CNS (Glasgow Coma Scale score)1513141012796

Hematologic (platelet count 103/mm3)1208112051802150