InternalMed_Harrison

InternalMed_Harrison. Trichinella spiralis (trichinosis); Fasciola hepatica (liver fluke), Echinococcus cysts; Schistosoma sp. The former may produce a lymphocytic pleocytosis whereas the latter two may produce an eosinophilic response in CSF associated with cerebral cysts (Echinococcus) or granulomatous lesions of brain or spinal cord Abbreviations: AFB, acid-fast bacillus; CMV, cytomegalovirus; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; FTA, fluorescent treponemal antibody absorption test; HSV, herpes simplex virus; MHA-TP, microhemagglutination assay–T. pallidum; MRI, magnetic resonance imaging; PAS, periodic acid–Schiff; PCR, polymerase chain reaction; RPR, rapid plasma reagin test; TB, tuberculosis; VDRL, Venereal Disease Research Laboratories test.


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InternalMed_Harrison. Malignancy Mononuclear cells, elevated Repeated cytologic examination of Metastatic cancer of breast, lung, stomach, or pancreas; mela protein, low glucose large volumes of CSF; CSF exam by noma, lymphoma, leukemia; meningeal gliomatosis; meninpolarizing microscopy; clonal lympho-geal sarcoma; cerebral dysgerminoma; meningeal melanoma cyte markers; deposits on nerve roots or B cell lymphoma or meninges seen on myelogram or contrast-enhanced MRI; meningeal biopsy


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InternalMed_Harrison. Chemical Mononuclear or PMNs, low Contrast-enhanced CT scan or MRI; History of recent injection into the subarachnoid space; his-compounds (may glucose, elevated protein; xan-cerebral angiogram to detect tory of sudden onset of headache; recent resection of acouscause recurrent thochromia from subarachnoid aneurysm tic neuroma or craniopharyngioma; epidermoid tumor of meningitis) hemorrhage in week prior to brain or spine, sometimes with dermoid sinus tract; pituitary presentation with “meningitis” apoplexy Primary inflammation CNS sarcoidosis Mononuclear cells; elevated Serum and CSF angiotensin-CN palsy, especially of CN VII; hypothalamic dysfunction, protein; often low glucose converting enzyme levels; biopsy of especially diabetes insipidus; abnormal chest radiograph; extraneural affected tissues or brain peripheral neuropathy or myopathy lesion/meningeal biopsy


InternalMed_Harrison

InternalMed_Harrison. Recurrent meningoencephalitis with uveitis, retinal detach-Harada syndrome ment, alopecia, lightening of eyebrows and lashes, dysacou(recurrent meningitis) sia, cataracts, glaucoma Isolated granuloma-Mononuclear cells, elevated Angiography or meningeal biopsy Subacute dementia; multiple cerebral infarctions; recent tous angiitis of the protein nervous system Systemic lupus Mononuclear or PMNs Anti-DNA antibody, antinuclear Encephalopathy; seizures; stroke; transverse myelopathy; rash; erythematosus antibodies arthritis Behçet’s syndrome Mononuclear or PMNs, elevated hemorrhages; pathergic lesions at site of skin puncture Chronic benign lym-Mononuclear cells


InternalMed_Harrison

InternalMed_Harrison. Recovery in 2–6 months, diagnosis by exclusion phocytic meningitis Mollaret’s meningitis Large endothelial cells and PCR for herpes; MRI/CT to rule out Recurrent meningitis; exclude HSV-2; rare cases due to HSV-1; (recurrent meningitis) PMNs in first hours, followed by epidermoid tumor or dural cyst occasional case associated with dural cyst mononuclear cells Drug hypersensitivity PMNs; occasionally mononu-Complete blood count (eosinophilia) Exposure to nonsteroidal anti-inflammatory agents, sulfonclear cells or eosinophils amides, isoniazid, tolmetin, ciprofloxacin, penicillin, carbamazepine, lamotrigine, IV immunoglobulin, OKT3 antibodies, phenazopyridine; improvement after discontinuation of drug; recurrence with repeat exposure


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InternalMed_Harrison. Granulomatosis Mononuclear cells Chest and sinus radiographs; urinaly-Associated sinus, pulmonary, or renal lesions; CN palsies; skin with polyangiitis sis; ANCA antibodies in serum lesions; peripheral neuropathy (Wegener’s) Other: multiple sclerosis, Sjögren’s syndrome, monogenic autoinflammatory disorders, and rarer forms of vasculitis (e.g., Cogan’s syndrome) Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; CN, cranial nerve; CSF, cerebrospinal fluid; CT, computed tomography; HSV, herpes simplex virus; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; PMNs, polymorphonuclear cells.


InternalMed_Harrison

InternalMed_Harrison. parameningeal infection; identification of a potential source of outflow (obstructive hydrocephalus), then lumbar puncture carries infection (chronic draining ear, sinusitis, right-to-left cardiac or the potential risk of brain herniation. Obstructive hydrocephalus pulmonary shunt, chronic pleuropulmonary infection) supports this usually requires direct ventricular drainage. In patients with open diagnosis. In some cases, diagnosis may be established by recogni-CSF flow pathways, elevated ICP can still occur due to impaired tion and biopsy of unusual skin lesions (Behçet’s syndrome, SLE, resorption of CSF by arachnoid villi. In such patients, lumbar punccryptococcosis, blastomycosis, Lyme disease, sporotrichosis, trypano-ture is usually safe, but repetitive or continuous lumbar drainage may somiasis, IV drug use) or enlarged lymph nodes (lymphoma, sarcoid, be necessary to prevent abrupt deterioration and death from raised tuberculosis, HIV, secondary syphilis, or Whipple’s disease). A


InternalMed_Harrison

InternalMed_Harrison. somiasis, IV drug use) or enlarged lymph nodes (lymphoma, sarcoid, be necessary to prevent abrupt deterioration and death from raised tuberculosis, HIV, secondary syphilis, or Whipple’s disease). A careful ICP. In some patients, especially those with cryptococcal meningiophthalmologic examination may reveal uveitis (Vogt-Koyanagi-tis, fatal levels of raised ICP can occur without enlarged ventricles. Harada syndrome, sarcoid, or central nervous system [CNS] lym-Contrast-enhanced MRI or CT studies of the brain and spinal phoma), keratoconjunctivitis sicca (Sjögren’s syndrome), or iridocy-cord can identify meningeal enhancement, parameningeal infecclitis (Behçet’s syndrome) and is essential to assess visual loss from tions (including brain abscess), encasement of the spinal cord papilledema. Aphthous oral lesions, genital ulcers, and hypopyon (malignancy, inflammation or infection), or nodular deposits on the suggest Behçet’s syndrome. Hepatosplenomegaly suggests lymphoma, meninges or


InternalMed_Harrison

InternalMed_Harrison. Aphthous oral lesions, genital ulcers, and hypopyon (malignancy, inflammation or infection), or nodular deposits on the suggest Behçet’s syndrome. Hepatosplenomegaly suggests lymphoma, meninges or nerve roots (malignancy or sarcoidosis) (Fig. 165-1). sarcoid, tuberculosis, or brucellosis. Herpetic lesions in the genital Imaging studies are also useful to localize areas of meningeal dis-area or on the thighs suggest HSV-2 infection. A breast nodule, a sus-ease prior to meningeal biopsy. picious pigmented skin lesion, focal bone pain, or an abdominal mass Angiographic studies can identify evidence of cerebral arteritis directs attention to possible carcinomatous meningitis. in patients with chronic meningitis and stroke.


InternalMed_Harrison

InternalMed_Harrison. Once the clinical syndrome is recognized as a potential manifesta-The CSF pressure should be measured and samples sent for bactetion of chronic meningitis, proper analysis of the CSF is essential. rial, fungal, and tuberculous culture; Venereal Disease Research However, if the possibility of raised ICP exists, a brain imaging study Laboratories (VDRL) test; cell count and differential; Gram’s should be performed before lumbar puncture. If ICP is elevated stain; and measurement of glucose and protein. Wet mount for because of a mass lesion, brain swelling, or a block in ventricular CSF fungus and parasites, india ink preparation and culture, culture


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InternalMed_Harrison. FIGURE 165-1 Primary central nervous system lymphoma. A 24-year-old man, immunosuppressed due to intestinal lymphangiectasia, developed multiple cranial neuropathies. CSF findings consisted of 100 lymphocytes/μL and a protein of 2.5 g/L (250 mg/dL); cytology and cultures were negative. Gadolinium-enhanced T1 MRI revealed diffuse, multifocal meningeal enhancement surrounding the brain-stem (A), spinal cord, and cauda equina (B).


InternalMed_Harrison

InternalMed_Harrison. for fastidious bacteria and fungi, assays for cryptococcal antigen and oligoclonal immunoglobulin bands, and cytology should be performed. Other specific CSF tests (Tables 165-2 and 165-3) or blood tests and cultures should be ordered as indicated on the basis of the history, physical examination, or preliminary CSF results (i.e., eosinophilic, mononuclear, or polymorphonuclear meningitis). Rapid diagnosis may be facilitated by serologic tests and polymerase chain reaction (PCR) testing to identify DNA sequences in the CSF that are specific for the suspected pathogen. In patients with suspected fungal infections, when other tests are negative, assays for beta-glucans may be a useful adjunct in establishing the diagnosis.


InternalMed_Harrison

InternalMed_Harrison. In most categories of chronic (not recurrent) meningitis, mononuclear cells predominate in the CSF. When neutrophils predominate after 3 weeks of illness, the principal etiologic considerations are Nocardia asteroides, Actinomyces israelii, Brucella, Mycobacterium tuberculosis (5–10% of early cases only), various fungi (Blastomyces dermatitidis, Candida albicans, Histoplasma capsulatum, Aspergillus spp., Pseudallescheria boydii, Cladophialophora bantiana), and noninfectious causes (SLE, exogenous chemical meningitis). When eosinophils predominate or are present in limited numbers in a primarily mononuclear cell response in the CSF, the differential diagnosis includes parasitic diseases (A. cantonensis, G. spinigerum, B. procyonis, or Toxocara canis infection, cysticercosis, schistosomiasis, echinococcal disease, T. gondii infection), fungal infections (6–20% eosinophils along with a predominantly lymphocyte pleocytosis, particularly with coccidioidal meningitis), neoplastic disease


InternalMed_Harrison

InternalMed_Harrison. echinococcal disease, T. gondii infection), fungal infections (6–20% eosinophils along with a predominantly lymphocyte pleocytosis, particularly with coccidioidal meningitis), neoplastic disease (lymphoma, leukemia, metastatic carcinoma), or other inflammatory processes (sarcoidosis, hypereosinophilic syndrome).


InternalMed_Harrison

InternalMed_Harrison. It is often necessary to broaden the number of diagnostic tests if the initial workup does not reveal the cause. In addition, repeated samples of large volumes of CSF may be required to diagnose certain infectious and malignant causes of chronic meningitis. Flow cytometry for malignant cells may be useful in patients with suspected carcinomatous meningitis. Lymphomatous or carcinomatous meningitis may be diagnosed by examination of sections cut from a cell block formed by spinning down the sediment from a large volume of CSF. The diagnosis of fungal meningitis may require large volumes of CSF for culture of sediment. If standard lumbar puncture is unrewarding, a cervical cisternal tap to sample CSF near to the basal meninges may be fruitful.


InternalMed_Harrison

InternalMed_Harrison. In addition to the CSF examination, an attempt should be made to uncover pertinent underlying illnesses. Tuberculin skin test, chest radiograph, urine analysis and culture, blood count and differential, renal and liver function tests, alkaline phosphatase, sedimentation rate, antinuclear antibody, anti-Ro antibody, anti-La antibody, and serum angiotensin-converting enzyme level are often indicated. In some cases, a thorough search for a systemic site of infection is indicated. Pulmonary foci of infection may be present, particularly with fungal or tuberculous disease. Hence a CT or MRI of the chest and a sputum examination may be helpful. Abnormalities can be pursued by bronchoscopy or transthoracic needle biopsy. A tuberculin skin test is often placed, although the test has limited specificity and sensitivity for diagnosis of active disease. Liver or bone marrow biopsy may be diagnostic in some cases of miliary tuberculosis, disseminated fungal infection, sarcoidosis, or metastatic


InternalMed_Harrison

InternalMed_Harrison. and sensitivity for diagnosis of active disease. Liver or bone marrow biopsy may be diagnostic in some cases of miliary tuberculosis, disseminated fungal infection, sarcoidosis, or metastatic malignancy. Positron emission tomography with fluorodeoxyglucose may be useful in identifying a systemic site for biopsy in patients with suspected carcinomatous meningitis or sarcoidosis when other tests are unrevealing. Genetic testing can identify mutations that cause rare monogenic autoinflammatory disorders.


InternalMed_Harrison

InternalMed_Harrison. If CSF is not diagnostic then a meningeal biopsy should be strongly considered in patients who are severely disabled, who need chronic ventricular decompression, or whose illness is progressing rapidly. The activities of the surgeon, pathologist, microbiologist, and cytologist should be coordinated so that a large enough sample is obtained and the appropriate cultures and histologic and molecular studies, including electron-microscopic and PCR studies, are performed. The diagnostic yield of meningeal biopsy can be increased by targeting regions that enhance with contrast on MRI or CT. With current microsurgical techniques, most areas of the basal meninges can be accessed for biopsy via a limited craniotomy. In a series from the Mayo Clinic reported by TM Cheng et al. (Neurosurgery 34:590, 1994), MRI demonstrated meningeal enhancement in 47% of patients undergoing meningeal biopsy. Biopsy of an enhancing region was diagnostic in 80% of cases; biopsy of nonenhancing regions was


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InternalMed_Harrison. 34:590, 1994), MRI demonstrated meningeal enhancement in 47% of patients undergoing meningeal biopsy. Biopsy of an enhancing region was diagnostic in 80% of cases; biopsy of nonenhancing regions was diagnostic in only 9%; sarcoid (31%) and metastatic adenocarcinoma (25%) were the most common conditions identified. Tuberculosis is the most common condition identified in many reports from outside the United States.


InternalMed_Harrison

InternalMed_Harrison. In approximately one-third of cases, the diagnosis is not known despite careful evaluation of CSF and potential extraneural sites of disease. A number of the organisms that cause chronic meningitis may take weeks to be identified by cultures. In enigmatic cases, several options are available, determined by the extent of the clinical deficits and rate of progression. It is prudent to wait until cultures are finalized if the patient is asymptomatic or symptoms are mild and not progressive. Unfortunately, in many cases progressive neurologic deterioration occurs, and rapid treatment is required. Ventricular-peritoneal shunts may be placed to relieve hydrocephalus, but the risk of disseminating the undiagnosed inflammatory process into the abdomen must be considered.


InternalMed_Harrison

InternalMed_Harrison. Empirical Treatment Diagnosis of the causative agent is essential because effective therapies exist for many etiologies of chronic meningitis, but if the condition is left untreated, progressive damage to the CNS and cranial nerves and roots is likely to occur. Occasionally, empirical therapy must be initiated when all attempts at diagnosis fail. In general, empirical therapy in the United States consists of antimycobacterial agents, amphotericin for fungal infection, or glucocorticoids for noninfectious inflammatory causes. It is important to direct empirical therapy of lymphocytic meningitis at tuberculosis, particularly if the condition is associated with low CSF glucose and sixth and other CN palsies, since untreated disease can be devastating within weeks. Patients on prolonged anti–tumor necrosis factor therapy who develop chronic meningitis also should be treated empirically with antituberculous therapy if the etiology is uncertain. In the Mayo Clinic series, the most useful


InternalMed_Harrison

InternalMed_Harrison. necrosis factor therapy who develop chronic meningitis also should be treated empirically with antituberculous therapy if the etiology is uncertain. In the Mayo Clinic series, the most useful empirical therapy was administration of glucocorticoids rather than antituberculous therapy. Carcinomatous or lymphomatous meningitis may be difficult to diagnose initially, but the diagnosis becomes evident with time.


InternalMed_Harrison

InternalMed_Harrison. Chronic meningitis is not uncommon in the course of HIV infection. Pleocytosis and mild meningeal signs often occur at the onset of HIV infection, and occasionally low-grade meningitis persists. Toxoplasmosis commonly presents as intracranial abscesses and also may be associated with meningitis. Other important causes of chronic meningitis in AIDS include infection with Cryptococcus, Nocardia, Candida, or other fungi; syphilis; and lymphoma (Fig. 165-1). Toxoplasmosis, cryptococcosis, nocardiosis, and other fungal infections are important etiologic considerations in individuals with immunodeficiency states other than AIDS, including those due to immunosuppressive medications. Because of the increased risk of chronic meningitis and the attenuation of clinical signs of meningeal irritation in immunosuppressed individuals, CSF examination should be performed for any persistent headache or unexplained change in mental state.


InternalMed_Harrison

InternalMed_Harrison. Morton N. Swartz contributed to earlier editions of this chapter. Infectious Complications of Burns Lawrence C. Madoff, Florencia Pereyra The skin is an essential component of immunity, protecting the host from potential pathogens in the environment. Breaches in this 166e protective barrier thus represent a form of immunocompromise that predisposes the patient to infection. Thermal burns may cause massive destruction of the integument as well as derangements in humoral and cellular immunity, permitting the development of infection caused by environmental opportunists and components of the host’s skin flora.


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InternalMed_Harrison. Over the past decade, the estimated incidence of burn injuries in the United States has steadily declined; still, however, >1 million burn injuries are brought to medical attention each year. While many burn injuries are minor and require little or no intervention, 183,000 cases were reported between 2002 and 2011 to the National Burn Repository from specialized burn care facilities; of the 45,000 persons hospitalized for these injuries, 60% required intensive care and 20,000 had major burns involving at least 25% of the total body surface area. The majority of burn patients are men. Children under the age of 5 account for ~20% of all reported cases. Scalds, structural fires, and flammable liquids and gases are the major causes of burns, but electrical, chemical, and smoking-related sources also are important. Burns predispose to infection by damaging the protective barrier function of the skin, thus facilitating the entry of pathogenic microorganisms, and by inducing systemic


InternalMed_Harrison

InternalMed_Harrison. sources also are important. Burns predispose to infection by damaging the protective barrier function of the skin, thus facilitating the entry of pathogenic microorganisms, and by inducing systemic immunosuppression. It is therefore not surprising that multiorgan failure and infectious complications are the major causes of morbidity and death in serious burn injury. More than 3000 patients in the United States die of burn-related infections each year, and 6 of the top 10 complications recently identified by the American Burn Association’s 10-year review are infectious: pneumonia (4.6%), septicemia (2.7%), cellulitis/traumatic injury (2.6%), respiratory failure (2.5%), wound infection (2.2%), another infection (2.0%), renal failure (1.5%), line infection (1.4%), acute respiratory distress syndrome (1.2%), and arrhythmia (1.0%).


InternalMed_Harrison

InternalMed_Harrison. Loss of the cutaneous barrier facilitates entry of the patient’s own flora and of organisms from the hospital environment into the burn wound. Initially, the wound is colonized with gram-positive bacteria from the surrounding tissue, but the number of bacteria grows rapidly beneath the burn eschar, reaching ~8.4 × 103 cfu/g on day 4 after the burn. The avascularity of the eschar, along with the impairment of local immune responses, favors further bacterial colonization and proliferation. By day 7, the wound is colonized with other microbes, including gram-positive bacteria, gram-negative bacteria, and yeasts derived from the gastrointestinal and upper respiratory flora. Invasive infection—localized and/or systemic—occurs when these bacteria penetrate viable tissue. In addition, a role for biofilms has been recognized in experimental animal models of burn-wound infection. (Biofilms are surface-associated communities of bacteria, often embedded in a matrix, that allow the microbes to


InternalMed_Harrison

InternalMed_Harrison. biofilms has been recognized in experimental animal models of burn-wound infection. (Biofilms are surface-associated communities of bacteria, often embedded in a matrix, that allow the microbes to persist and to resist the effects of host immunity and antimicrobial agents.)


InternalMed_Harrison

InternalMed_Harrison. Streptococci and staphylococci were the predominant causes of burn-wound infection in the preantibiotic era and remain important pathogens at present. With the advent of antimicrobial agents, Pseudomonas aeruginosa became a major problem in burn-wound management. In animal models of cutaneous thermal injury and wound infection with Pseudomonas, there is an early, steady increase of neutrophils in the skin and bacterial dissemination to lungs and spleen within 72 h. Less common anaerobic bacteria are typically found in infections of electrical burns or when open wound dressings are used. The widespread use of topical and more effective antimicrobial agents has resulted in a decline in bacterial wound infections and the emergence of fungi (particularly Candida albicans, Aspergillus 166e-1 species, and the agents of mucormycosis) as increasingly important pathogens in burn-wound patients. Herpes simplex virus also has been found in burn wounds, especially those on the neck and face and


InternalMed_Harrison

InternalMed_Harrison. species, and the agents of mucormycosis) as increasingly important pathogens in burn-wound patients. Herpes simplex virus also has been found in burn wounds, especially those on the neck and face and those associated with inhalation injury. Cytomegalovirus viremia has been described in up to 71% of seropositive burn patients in prospective studies, and high levels (>1000 copies/mL) have been associated with increased duration of mechanical ventilation and longer stay in the intensive care unit (ICU).


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InternalMed_Harrison. Autopsy reports from patients with severe thermal burns over the last decade have identified P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus in association with mortality, independent of the percentage of total body surface area burned, the percentage of full-thickness burn, inhalation injury, and day of death after the burn. Indeed, burn trauma patients who acquire secondary P. aeruginosa infection have a fourfold greater mortality rate than those without P. aeruginosa. Historically, mortality rates among burn patients infected with P. aeruginosa have been as high as 77% over a 25-year period. In addition, Acinetobacter calcoaceticus-baumannii is among the top pathogens in some burn centers.


InternalMed_Harrison

InternalMed_Harrison. The cascade of events that follow a severe burn injury and that lead to multiorgan system failure and death is thought to represent a two-step process. The burn injury itself, with ensuing hypovolemia and tissue hypoxia, is followed by invasive infection arising from large amounts of devitalized tissue. The frequency of infection parallels the extent and severity of the burn injury. Severe burn injuries cause a state of immunosuppression that affects innate and adaptive immune responses. The substantial impact of immunocompromise on infection is due to effects on both the cellular and the humoral arms of the immune system. For example, decreases in the number and activity of circulating helper T cells, increases in suppressor T cells, decreases in production and release of monocytes and macrophages, and diminution in levels of immunoglobulin follow major burns. Neutrophil and complement functions also are impaired after burns. The increased levels of multiple cytokines detected in


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InternalMed_Harrison. macrophages, and diminution in levels of immunoglobulin follow major burns. Neutrophil and complement functions also are impaired after burns. The increased levels of multiple cytokines detected in burn patients are compatible with the widely held belief that the inflammatory response becomes dysregulated in these individuals; bacterial cell products play a potent role in inducing proinflammatory mediators that contribute to this uncontrolled systemic inflammatory response. Increased permeability of the gut wall to bacteria and their components (e.g., endotoxin) also contributes to immune dysregulation and sepsis. Thus, the burn patient is predisposed to infection at remote sites (see below) as well as at the sites of burn injury. Another contributor to secondary immunosuppression after burn injuries is the endocrine system; increasing levels of vasopressin, aldosterone, cortisol, glucagon, growth hormone, catecholamines, and other hormones that directly affect lymphocyte


InternalMed_Harrison

InternalMed_Harrison. after burn injuries is the endocrine system; increasing levels of vasopressin, aldosterone, cortisol, glucagon, growth hormone, catecholamines, and other hormones that directly affect lymphocyte proliferation, secretion of proinflammatory cytokines, natural killer cell activity, and suppressive T cells are seen.


InternalMed_Harrison

InternalMed_Harrison. Since clinical indications of wound infection are difficult to interpret, wounds must be monitored carefully for changes that may reflect infection. A margin of erythema frequently surrounds the sites of burns and by itself is not usually indicative of infection. Signs of infection include the conversion of a partial-thickness to a full-thickness burn, color changes (e.g., the appearance of a dark brown or black discoloration of the wound), the new appearance of erythema or violaceous edema in normal tissue at the wound margins, the sudden separation of the eschar from subcutaneous tissues, and the degeneration of the wound with the appearance of a new eschar.


InternalMed_Harrison

InternalMed_Harrison. Early surgical excision of devitalized tissue is now widely used, and burn-wound infections can be classified in relation to the excision site as (1) burn-wound impetigo (infection characterized by loss of epithelium from a previously re-epithelialized surface, as seen in a partial-thickness burn that is allowed to close by secondary intention, a grafted burn, or a healed skin donor site); (2) burn-related surgical-wound infection (purulent infection of excised burn and donor sites that have not yet epithelialized, accompanied by positive CHAPTER 166e Infectious Complications of Burns FIGurE 166e-1 Cellulitis complicating a burn wound of the arm, with extension of the infection to adjacent healthy tissue.


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InternalMed_Harrison. CHAPTER 166e Infectious Complications of Burns FIGurE 166e-1 Cellulitis complicating a burn wound of the arm, with extension of the infection to adjacent healthy tissue. (Courtesy of Dr. Robert L. Sheridan, Massachusetts General Hospital, Boston; with permission.) cultures); (3) burn-wound cellulitis (extension of infection to surrounding healthy tissue; Fig. 166e-1); and (4) invasive infection in unexcised burn wounds (infection that is secondary to a partialor full-thickness burn wound and is manifested by separation of the eschar or by violaceous, dark brown, or black discoloration of the eschar; Fig. 166e-2). The appearance of a green discoloration of the wound or subcutaneous fat (Fig. 166e-3) or the development of ecthyma gangrenosum (see Fig. 25e-35) at a remote site points to a diagnosis of invasive P. aeruginosa infection.


InternalMed_Harrison

InternalMed_Harrison. Changes in body temperature, hypotension, tachycardia, altered mentation, neutropenia or neutrophilia, thrombocytopenia, and renal failure may result from invasive burn wounds and sepsis. However, because profound alterations in homeostasis occur as a consequence of burns per se and because inflammation without infection is a normal component of these injuries, the assessment of these changes is complicated. Alterations in body temperature, for example, are attributable to thermoregulatory dysfunction; tachycardia and hyperventilation accompany the metabolic changes induced by extensive burn injury and are not necessarily indicative of bacterial sepsis. Given the difficulty of evaluating burn wounds solely on the basis of clinical observation and laboratory data, wound biopsies are necessary FIGurE 166e-2 A severe upper-extremity burn infected with Pseudomonas aeruginosa. The wound requires additional debride-ment. Note the dark brown to black discoloration of the eschar.


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InternalMed_Harrison. FIGurE 166e-2 A severe upper-extremity burn infected with Pseudomonas aeruginosa. The wound requires additional debride-ment. Note the dark brown to black discoloration of the eschar. (Courtesy of Dr. Robert L. Sheridan, Massachusetts General Hospital, Boston; with permission.)


InternalMed_Harrison

InternalMed_Harrison. FIGurE 166e-3 A burn wound infected with Pseudomonas aeruginosa, with liquefaction of tissue. Note the green discoloration at the wound margins, which is suggestive of Pseudomonas infection. (Courtesy of Dr. Robert L. Sheridan, Massachusetts General Hospital, Boston; with permission.) for definitive diagnosis of infection. The timing of these biopsies can be guided by clinical changes, but in some centers burn wounds are routinely biopsied at regular intervals. The biopsy specimen is examined for histologic evidence of bacterial invasion, and quantitative microbiologic cultures are performed. The presence of >105 viable bacteria per gram of tissue is highly suggestive of invasive infection and of a dramatically increased risk of sepsis. Histopathologic evidence of the invasion of viable tissue and the presence of microorganisms in unburned blood vessels and lymphatics is a more definitive indicator of infection. A blood culture positive for the same organism seen in large quantities


InternalMed_Harrison

InternalMed_Harrison. tissue and the presence of microorganisms in unburned blood vessels and lymphatics is a more definitive indicator of infection. A blood culture positive for the same organism seen in large quantities in biopsied tissue is a reliable indicator of burn sepsis. Surface cultures may provide some indication of the microorganisms present in the hospital environment but are not indicative of the etiology of infection. This noninvasive technique may be of use in determining the flora present in excised burn areas or in areas where the skin is too thin for biopsy (e.g., over the ears, eyes, or digits). Rapid identification of organisms and institution of appropriate therapy are critical to the survival of patients with severe burn injury; polymerase chain reaction (PCR) is now being used for rapid identification of specific pathogens, sometimes in <6 h, to allow earlier treatment interventions.


InternalMed_Harrison

InternalMed_Harrison. In addition to infection of the burn wound itself, a number of other infections due to the immunosuppression caused by extensive burns and the manipulations necessary for clinical care put burn patients at risk. Pneumonia, now the most common infectious complication among hospitalized burn patients, is most often acquired nosocomially via the respiratory route. The incidence of ventilator-associated pneumonia among burn patients is 22–30 cases per 1000 ventilator-days—more than double that among surgical or medical ICU cohorts; this infection usually results from colonization of the lower respiratory tract and parenchyma because of sustained microaspiration. Among the risk factors associated with secondary pneumonia are inhalation injury, intubation, full-thickness chest wall burns, cutaneous thermal injuries, immobility, blood transfusions, and uncontrolled wound sepsis with hematogenous spread. Septic pulmonary emboli also may occur. Suppurative thrombophlebitis may complicate the


InternalMed_Harrison

InternalMed_Harrison. thermal injuries, immobility, blood transfusions, and uncontrolled wound sepsis with hematogenous spread. Septic pulmonary emboli also may occur. Suppurative thrombophlebitis may complicate the vascular catheterization necessary for fluid and nutritional support in burns. Endocarditis, urinary tract infection, bacterial chondritis (particularly in patients with burned ears), and intraabdominal infection also complicate serious burn injury. Staphylococcal scalded skin syndrome due to burn-wound infection with S. aureus has been described as a rare complication. Finally, burn surgical-wound infections contribute to morbidity and have been found in up to 39% of patients; these infections often result in repeat skin grafting and prolonged hospitalization.


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InternalMed_Harrison. against gram-positive pathogens (e.g., oxacillin, 2 g IV every 4 h) and 166e-3 with a drug active against P. aeruginosa and other gram-negative


InternalMed_Harrison

InternalMed_Harrison. The ultimate goal of burn-wound management is closure and healing of the wound. Early surgical excision of burned tissue, with extensive debridement of necrotic tissue and grafting of skin or skin substitutes, greatly decreases mortality rates associated with severe burns. In addition, the four widely used topical antimicrobial agents—silver sulfadiazine cream, mafenide acetate cream, silver nitrate cream, and nanocrystalline silver dressings—dramatically decrease the bacterial burden of burn wounds and reduce the incidence of burn-wound infection; these agents are routinely applied to partial-and full-thickness burns. The bactericidal properties of silver are related to its effect on respiratory enzymes on bacterial cell walls; its interaction with structural proteins causes keratinocyte and fibroblast toxicity that can delay wound healing if silver-based compounds are used indiscriminately. All four agents are broadly active against many bacteria and some fungi and are useful before


InternalMed_Harrison

InternalMed_Harrison. and fibroblast toxicity that can delay wound healing if silver-based compounds are used indiscriminately. All four agents are broadly active against many bacteria and some fungi and are useful before bacterial colonization is established. Silver sulfadiazine is often used initially, but its value can be limited by bacterial resistance, poor wound penetration, or toxicity (leukopenia). Mafenide acetate has broader activity against gram-negative bacteria. The cream penetrates eschars and thus can prevent or treat infection beneath them; its use without dressings allows regular examination of the wound area. The foremost disadvantages of mafenide acetate are that it can inhibit carbonic anhydrase, resulting in metabolic acidosis, and that it elicits hypersensitivity reactions in up to 7% of patients. This agent is most often used when gram-negative bacteria invade the burn wound and when treatment with silver sulfadiazine fails. The activity of mafenide acetate against gram-positive


InternalMed_Harrison

InternalMed_Harrison. of patients. This agent is most often used when gram-negative bacteria invade the burn wound and when treatment with silver sulfadiazine fails. The activity of mafenide acetate against gram-positive bacteria is limited. Nanocrystalline silver dressings provide broader antimicrobial coverage than any other available topical preparation, exhibiting activity against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE), moderate ability to penetrate eschars, and limited toxicity. In addition, this approach provides controlled and prolonged release of nanocrystalline silver into the wound, limiting the number of dressing changes and therefore reducing the risk of nosocomial infections as well as the cost of treatment. Mupirocin, a topical antimicrobial agent used to eradicate nasal colonization with MRSA, is increasingly being used in burn units where MRSA is prevalent. The efficacy of mupirocin in reducing burn-wound bacterial counts and preventing systemic


InternalMed_Harrison

InternalMed_Harrison. to eradicate nasal colonization with MRSA, is increasingly being used in burn units where MRSA is prevalent. The efficacy of mupirocin in reducing burn-wound bacterial counts and preventing systemic infections is comparable to that of silver sulfadiazine.


InternalMed_Harrison

InternalMed_Harrison. In recent years, rates of fungal infection have increased in burn patients. When superficial fungal infection occurs, nystatin may be mixed with silver sulfadiazine or mafenide acetate as topical therapy. A small study found that nystatin powder (6 million units/g) was effective for treatment of superficial and deep burn-wound infections caused by Aspergillus or Fusarium species. In addition to these products, moisture-retention ointments with antimicrobial properties can promote rapid autolysis, debridement, and moist healing of partial-thickness wounds.


InternalMed_Harrison

InternalMed_Harrison. When invasive wound infection is diagnosed, topical therapy should be changed to mafenide acetate. Subeschar clysis (the direct instillation of an antibiotic, often piperacillin, into wound tissues under the eschar) is a useful adjunct to surgical and systemic antimicrobial therapy. Systemic treatment with antibiotics active against the pathogens present in the wound should be instituted. In the absence of culture data, treatment should be broad in spectrum, covering organisms commonly encountered in that particular burn unit. Such coverage is usually achieved with an antibiotic active rods (e.g., mezlocillin, 3 g IV every 4 h; gentamicin, 5 mg/kg IV per day). In penicillin-allergic patients, vancomycin (1 g IV every 12 h) may be substituted for oxacillin (and is efficacious against MRSA), and ciprofloxacin (400 mg IV every 12 h) may be substituted for mezlocillin. Oxazolidinone antibiotics like linezolid have demonstrated efficacy in reducing bacterial growth and toxic shock syndrome


InternalMed_Harrison

InternalMed_Harrison. and ciprofloxacin (400 mg IV every 12 h) may be substituted for mezlocillin. Oxazolidinone antibiotics like linezolid have demonstrated efficacy in reducing bacterial growth and toxic shock syndrome toxin 1 levels in animal models of MRSA burn-wound infections.


InternalMed_Harrison

InternalMed_Harrison. Patients with burn wounds frequently have alterations in metabolism and renal clearance mechanisms that mandate the monitoring of serum antibiotic levels. The levels achieved with standard doses are often subtherapeutic. Treatment of infections caused by emerging resistant pathogens remains a challenge in the care of burn patients. MRSA, resistant enterococci, multidrug-resistant gram-negative rods, and Enterobacteriaceae producing extended-spectrum β-lactamases have been associated with burn-wound infections and identified in burn-unit outbreaks. Strict infection-control practices (including microbiologic surveillance in burn units) and appropriate antimicrobial therapy remain important measures in reducing rates of infection due to resistant organisms.


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InternalMed_Harrison. In general, prophylactic systemic antibiotics have no role in the management of burn wounds and can, in fact, lead to colonization with resistant microorganisms. In some studies, antibiotic prophylaxis has been associated with increases in secondary infections of the upper and lower respiratory tract and the urinary tract as well as with prolonged hospitalization. An exception involves cases requiring burn-wound manipulation. Since procedures such as debridement, excision, or grafting frequently result in bacteremia, prophylactic systemic antibiotics are administered at the time of wound manipulation; the specific agents used should be chosen on the basis of data obtained by wound culture or data on the hospital’s resident flora.


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InternalMed_Harrison. The use of oral antibiotics for selective digestive decontamination (SDD) to decrease bacterial colonization and the risk of burn-wound infection is controversial and has not been widely adopted. In a randomized, double-blind, placebo-controlled trial in patients with burns involving >20% of the total body surface area, SDD was associated with reduced mortality rates in the burn ICU and in the hospital and also with a reduced incidence of pneumonia. The effects of SDD on the normal anaerobic bowel flora must be taken into consideration before this approach is used.


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InternalMed_Harrison. Strategies to reduce or limit systemic spread of wound infections, particularly to the lung, may be useful adjuncts to therapy. Some of these strategies are aimed at reducing neutrophilic inflammation at the site of injury, which can accelerate biofilm formation, particularly by P. aeruginosa. For example, in animal models of cutaneous burns with P. aeruginosa wound inoculation, a single dose of azithromycin administered early reduces rates of Pseudomonas infection and systemic spread to lung and spleen and appears to have effects similar to those of classic anti-Pseudomonas agents, such as tobramycin. The extent to which azithromycin can be administered early in humans to prevent dissemination remains to be studied.


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InternalMed_Harrison. All burn-injury patients should undergo tetanus booster immunization if they have completed primary immunization but have not received a booster dose in the past 5 years. Patients without prior immunization should receive tetanus immune globulin and undergo primary immunization. CHAPTER 166e Infectious Complications of Burns Infectious Complications of Bites Lawrence C. Madoff, Florencia Pereyra The skin is an essential component of nonspecific immunity, protect-ing the host from potential pathogens in the environment. Breaches in 167e this protective barrier thus represent a form of immunocompromise that predisposes the patient to infection. Bites and scratches from animals and humans allow the inoculation of microorganisms past the skin’s protective barrier into deeper, susceptible host tissues.


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InternalMed_Harrison. Each year in the United States, millions of animal-bite wounds are sustained. The vast majority are inflicted by pet dogs and cats, which number >100 million; the annual incidence of dog and cat bites has been reported as 300 bites per 100,000 population. Other bite wounds are a consequence of encounters with animals in the wild or in occupational settings. While many of these wounds require minimal or no therapy, a significant number result in infection, which may be life-threatening. The microbiology of bite-wound infections in general reflects the oropharyngeal flora of the biting animal, although organisms from the soil, the skin of the animal and the victim, and the animal’s feces may also be involved.


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InternalMed_Harrison. In the United States, dogs bite >4.7 million people each year and are responsible for 80% of all animal-bite wounds, an estimated 15–20% of which become infected. Each year, 800,000 Americans seek medical attention for dog bites; of those injured, 386,000 require treatment in an emergency department, with >1000 emergency department visits each day and about a dozen deaths per year. Most dog bites are provoked and are inflicted by the victim’s pet or by a dog known to the victim. These bites are frequently sustained during efforts to break up a dogfight. Children are more likely than adults to sustain canine bites, with the highest incidence of 6 bites/1000 population among boys 5–9 years old. Victims are more often male than female, and bites most often involve an upper extremity. Among children <4 years old, two-thirds of all these injuries involve the head or neck. Infection typically manifests 8–24 h after the bite as pain at the site of injury with cellulitis accompanied by


InternalMed_Harrison

InternalMed_Harrison. children <4 years old, two-thirds of all these injuries involve the head or neck. Infection typically manifests 8–24 h after the bite as pain at the site of injury with cellulitis accompanied by purulent, sometimes foul-smelling discharge. Septic arthritis and osteomyelitis may develop if a canine tooth penetrates synovium or bone. Systemic manifestations (e.g., fever, lymphadenopathy, and lymphangitis) also may occur. The microbiology of dog-bite wound infections is usually mixed and includes β-hemolytic streptococci, Pasteurella species, Staphylococcus species (including methicillin-resistant Staphylococcus aureus [MRSA]), Eikenella corrodens, and Capnocytophaga canimorsus. Many wounds also include anaerobic bacteria such as Actinomyces, Fusobacterium, Prevotella, and Porphyromonas species.


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InternalMed_Harrison. While most infections resulting from dog-bite injuries are localized to the area of injury, many of the microorganisms involved are capable of causing systemic infection, including bacteremia, meningitis, brain abscess, endocarditis, and chorioamnionitis. These infections are particularly likely in hosts with edema or compromised lymphatic drainage in the involved extremity (e.g., after a bite on the arm in a woman who has undergone mastectomy) and in patients who are immunocompromised by medication or disease (e.g., glucocorticoid use, systemic lupus erythematosus, acute leukemia, or hepatic cirrhosis). In addition, dog bites and scratches may result in systemic illnesses such as rabies (Chap. 232) and tetanus (Chap. 177).


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InternalMed_Harrison. Infection with C. canimorsus following dog-bite wounds may result in fulminant sepsis, disseminated intravascular coagulation, and renal failure, particularly in hosts who have impaired hepatic function, who have undergone splenectomy, or who are immunosuppressed. This thin gram-negative rod is difficult to culture on most solid media but grows in a variety of liquid media. The bacteria are occasionally seen within polymorphonuclear leukocytes on Wright-stained smears of peripheral blood from septic patients. Tularemia (Chap. 195) also has 167e-1 been reported to follow dog bites.


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InternalMed_Harrison. Although less common than dog bites, cat bites and scratches result in infection in more than half of all cases. Because the cat’s narrow, sharp canine teeth penetrate deeply into tissue, cat bites are more likely than dog bites to cause septic arthritis and osteomyelitis; the development of these conditions is particularly likely when punctures are located over or near a joint, especially in the hand. Women sustain cat bites more frequently than do men. These bites most often involve the hands and arms. Both bites and scratches from cats are prone to infection from organisms in the cat’s oropharynx. Pasteurella multocida, a normal component of the feline oral flora, is a small gram-negative coccobacillus implicated in the majority of cat-bite wound infections. Like that of dog-bite wound infections, however, the microflora of cat-bite wound infections is usually mixed. Other microorganisms causing infection after cat bites are similar to those causing dog-bite wound infections.


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InternalMed_Harrison. The same risk factors for systemic infection following dog-bite wounds apply to cat-bite wounds. Pasteurella infections tend to advance rapidly, often within hours, causing severe inflammation accompanied by purulent drainage; Pasteurella may also be spread by respiratory droplets from animals, resulting in pneumonia or bacteremia. Like dog-bite wounds, cat-bite wounds may result in the transmission of rabies or in the development of tetanus. Infection with Bartonella henselae causes cat-scratch disease (Chap. 197) and is an important late consequence of cat bites and scratches. Tularemia (Chap. 195) also has been reported to follow cat bites.


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InternalMed_Harrison. Infections have been attributed to bites from many animal species. Often these bites are sustained as a consequence of occupational exposure (farmers, laboratory workers, veterinarians) or recreational exposure (hunters and trappers, wilderness campers, owners of exotic pets). Generally, the microflora of bite wounds reflects the oral flora of the biting animal. Most members of the cat family, including feral cats, harbor P. multocida. Bite wounds from aquatic animals such as alligators or piranhas may contain Aeromonas hydrophila. Venomous snakebites (Chap. 474) result in severe inflammatory responses and tissue necrosis—conditions that render these injuries prone to infection. The snake’s oral flora includes many species of aerobes and anaerobes, such as Pseudomonas aeruginosa, Serratia marcescens, Proteus species, Staphylococcus epidermidis, Bacteroides fragilis, and Clostridium species. Bites from nonhuman primates are highly susceptible to infection with pathogens similar to


InternalMed_Harrison

InternalMed_Harrison. marcescens, Proteus species, Staphylococcus epidermidis, Bacteroides fragilis, and Clostridium species. Bites from nonhuman primates are highly susceptible to infection with pathogens similar to those isolated from human bites (see below). Bites from Old World monkeys (Macaca) may also result in the transmission of B virus (Herpesvirus simiae, cercopithecine herpesvirus), a cause of serious infection of the human central nervous system. Bites of seals, walruses, and polar bears may cause a chronic suppurative infection known as seal finger, which is probably due to one or more species of Mycoplasma colonizing these animals.


InternalMed_Harrison

InternalMed_Harrison. Small rodents, including rats, mice, and gerbils, as well as ani iformis (a microaerophilic, pleomorphic gram-negative rod) or Spirillum minor (a spirochete); these organisms cause a clinical illness known as rat-bite fever. The vast majority of cases in the United States are streptobacillary, whereas Spirillum infection occurs mainly in Asia.


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InternalMed_Harrison. In the United States, the risk of rodent bites is usually greatest among laboratory workers or inhabitants of rodent-infested dwellings (particularly children). Rat-bite fever is distinguished from acute bite-wound infection by its typical manifestation after the initial wound has healed. Streptobacillary disease follows an incubation period of 3–10 days. Fever, chills, myalgias, headache, and severe migratory arthralgias are usually followed by a maculopapular rash, which characteristically involves the palms and soles and may become confluent or purpuric. Complications include endocarditis, myocarditis, meningitis, pneumonia, and abscesses in many organs. Haverhill fever is an


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InternalMed_Harrison. S. moniliformis infection acquired from contaminated milk or drinking water and has similar manifestations. Streptobacillary rat-bite fever was frequently fatal in the preantibiotic era. The differential diagnosis includes Rocky Mountain spotted fever, Lyme disease, leptospirosis, and secondary syphilis. The diagnosis is made by direct observation of the causative organisms in tissue or blood, by culture of the organisms on enriched media, or by serologic testing with specific agglutinins. Spirillum infection (referred to in Japan as sodoku) causes pain and purple swelling at the site of the initial bite, with associated lymphangitis and regional lymphadenopathy, after an incubation period of 1–4 weeks. The systemic illness includes fever, chills, and headache. The original lesion may eventually progress to an eschar. The infection is diagnosed by direct visualization of the spirochetes in blood or tissue or by animal inoculation.


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InternalMed_Harrison. Finally, NO-1 (CDC nonoxidizer group 1) is a bacterium associated with dogand cat-bite wounds. Infections in which NO-1 has been isolated have tended to manifest locally (i.e., as abscess and cellulitis). These infections have occurred in healthy persons with no underlying illness and in some instances have progressed from localized to systemic illnesses. The phenotypic characteristics of NO-1 are similar to those of asaccharolytic Acinetobacter species; i.e., NO-1 is oxidase-, indole-, and urease-negative. To date, all strains identified have been shown to be susceptible to aminoglycosides, β-lactam antibiotics, tetracyclines, quinolones, and sulfonamides.


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InternalMed_Harrison. Human bites may be self-inflicted; may be sustained by medical personnel caring for patients; or may take place during fights, domestic abuse, or sexual activity. Human-bite wounds become infected more frequently (~10–15% of the time) than do bites inflicted by other animals. These infections reflect the diverse oral microflora of humans, which includes multiple species of aerobic and anaerobic bacteria. Common aerobic isolates include viridans streptococci, S. aureus,


InternalMed_Harrison

InternalMed_Harrison. E. corrodens (which is particularly common in clenched-fist injury; see below), and Haemophilus influenzae. Anaerobic species, including Fusobacterium nucleatum and Prevotella, Porphyromonas, and Peptostreptococcus species, are isolated from 50% of wound infections due to human bites; many of these isolates produce β-lactamases. The oral flora of hospitalized and debilitated patients often includes Enterobacteriaceae in addition to the usual organisms. Hepatitis B, hepatitis C, herpes simplex virus infection, syphilis, tuberculosis, actinomycosis, and tetanus have been reported to be transmitted by human bites; it is biologically possible to transmit HIV through human bites, although this event is quite unlikely.


InternalMed_Harrison

InternalMed_Harrison. Human bites are categorized as either occlusional injuries, which are inflicted by actual biting, or clenched-fist injuries, which are sustained when the fist of one individual strikes the teeth of another, causing traumatic laceration of the hand. For several reasons, clenched-fist injuries, which are sometimes referred to as “fight bite” and which are more common than occlusional injuries, result in particularly serious infections. The deep spaces of the hand, including the bones, joints, and tendons, are frequently inoculated with organisms in the course of such injuries. The clenched position of the fist during injury, followed by extension of the hand, may further promote the introduction of bacteria as contaminated tendons retract beneath the skin’s surface. Moreover, medical attention is often sought only after frank infection develops. APPROACH TO THE PATIENT:


InternalMed_Harrison

InternalMed_Harrison. APPROACH TO THE PATIENT: A careful history should be elicited, including the type of biting animal, the type of attack (provoked or unprovoked), and the amount of time elapsed since injury. Local and regional public-health authorities should be contacted to determine whether an individual species could be rabid and/or to locate and observe the biting animal when rabies prophylaxis may be indicated (Chap. 232).


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InternalMed_Harrison. Suspicious human-bite wounds should provoke careful questioning regarding domestic or child abuse. Details on antibiotic allergies, immunosuppression, splenectomy, liver disease, mastectomy, and immunization history should be obtained. The wound should be inspected carefully for evidence of infection, including redness, exudate, and foul odor. The type of wound (puncture, laceration, or scratch); the depth of penetration; and the possible involvement of joints, tendons, nerves, and bones should be assessed. It is often useful to include a diagram or photograph of the wound in the medical record. In addition, a general physical examination should be conducted and should include an assessment of vital signs as well as an evaluation for evidence of lymphangitis, lymphadenopathy, dermatologic lesions, and functional limitations. Injuries to the hand warrant consultation with a hand surgeon for the assessment of tendon, nerve, and muscular damage. Radiographs should be obtained when bone


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InternalMed_Harrison. lesions, and functional limitations. Injuries to the hand warrant consultation with a hand surgeon for the assessment of tendon, nerve, and muscular damage. Radiographs should be obtained when bone may have been penetrated or a tooth fragment may be present. Culture and Gram’s staining of all infected wounds are essential; anaerobic cultures should be undertaken if abscesses, devitalized tissue, or foul-smelling exudate is present. A small-tipped swab may be used to culture deep punctures or small lacerations. It is also reasonable to culture samples from apparently uninfected wounds due to bites inflicted by animals other than dogs and cats, since the microorganisms causing disease are less predictable in these cases. The white blood cell count should be determined and the blood cultured if systemic infection is suspected.


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InternalMed_Harrison. Wound closure is controversial in bite injuries. Many authorities prefer not to attempt primary closure of wounds that are or may become infected, choosing instead to irrigate these wounds copiously, debride devitalized tissue, remove foreign bodies, and approximate the wound edges. Delayed primary closure may be undertaken after the risk of infection is over. Small uninfected wounds may be allowed to close by secondary intention. Puncture wounds due to cat bites should be left unsutured because of the high rate at which they become infected. Facial wounds are usually sutured after thorough cleaning and irrigation because of the importance of a good cosmetic result in this area and because anatomic factors such as an excellent blood supply and the absence of dependent edema lessen the risk of infection.


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InternalMed_Harrison. ANTIBIOTIC THERAPY Established Infection Antibiotics should be administered for all established bite-wound infections and should be chosen in light of the most likely potential pathogens, as indicated by the biting species and by Gram’s stain and culture results (Table 167e-1). For dog and cat bites, antibiotics should be effective against S. aureus, Pasteurella species, C. canimorsus, streptococci, and oral anaerobes. For human bites, agents with activity against S. aureus,


InternalMed_Harrison

InternalMed_Harrison. H. influenzae, and β-lactamase-positive oral anaerobes should be used. The combination of an extended-spectrum penicillin with a β-lactamase inhibitor (amoxicillin/clavulanic acid, ticarcillin/ clavulanic acid, ampicillin/sulbactam) appears to offer the most reliable coverage for these pathogens. Second-generation cephalosporins (cefuroxime, cefoxitin) also offer substantial coverage. The choice of antibiotics for penicillin-allergic patients (particularly those in whom immediate-type hypersensitivity makes the use of cephalosporins hazardous) is more difficult and is based primarily on in vitro sensitivity since data on clinical efficacy are inadequate. The combination of an antibiotic active against gram-positive cocci and anaerobes (such as clindamycin) with trimethoprim-sulfamethoxazole or a fluoroquinolone, which is active against many of the other potential pathogens, would appear reasonable. In vitro data suggest that azithromycin alone provides coverage against most commonly


InternalMed_Harrison

InternalMed_Harrison. or a fluoroquinolone, which is active against many of the other potential pathogens, would appear reasonable. In vitro data suggest that azithromycin alone provides coverage against most commonly isolated bite-wound pathogens. As MRSA becomes


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InternalMed_Harrison. Rodent Streptobacillus moniliformis, Penicillin VK (500 mg PO Doxycycline (100 mg PO bid) Sometimes — Leptospira spp., P. multocida qid) aAntibiotic choices should be based on culture data when available. These suggestions for empirical therapy need to be tailored to individual circumstances and local conditions. IV regimens should be used for hospitalized patients. A single IV dose of antibiotics may be given to patients who will be discharged after initial management. bProphylactic antibiotics are suggested for severe or extensive wounds, facial wounds, and crush injuries; when bone or joint may be involved; and when comorbidity is present (see text). cMay be hazardous in patients with immediate-type hypersensitivity to penicillin. Abbreviations: DS, double-strength; TMP-SMX, trimethoprim-sulfamethoxazole.


InternalMed_Harrison

InternalMed_Harrison. Abbreviations: DS, double-strength; TMP-SMX, trimethoprim-sulfamethoxazole. more common in the community and evidence of its transmission between humans and their animal contacts increases, empirical use of agents active against MRSA should be considered in high-risk situations while culture results are awaited. Antibiotics are generally given for 10–14 days, but the response to therapy must be carefully monitored. Failure to respond should prompt a consideration of diagnostic alternatives and surgical evaluation for possible drainage or debridement. Complications such as osteomyelitis or septic arthritis mandate a longer duration of therapy. Management of C. canimorsus sepsis requires a 2-week course of IV penicillin G (2 million units IV every 4 h) and supportive measures. Alternative agents for the treatment of C. canimorsus infection include cephalosporins and fluoroquinolones. Serious infection with


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InternalMed_Harrison. P. multocida (e.g., pneumonia, sepsis, or meningitis) also should be treated with IV penicillin G. Alternative agents include secondor third-generation cephalosporins or ciprofloxacin. Bites by venomous snakes (Chap. 474) may not require antibiotic treatment. Because it is often difficult to distinguish signs of infection from tissue damage caused by the envenomation, many authorities continue to recommend treatment directed against the snake’s oral flora—i.e., the administration of broadly active agents such as ceftriaxone (1–2 g IV every 12–24 h) or ampicillin/sulbactam (1.5–3.0 g IV every 6 h). Seal finger appears to respond to doxycycline (100 mg twice daily for a duration guided by the response to therapy).


InternalMed_Harrison

InternalMed_Harrison. Presumptive or Prophylactic Therapy The use of antibiotics for patients presenting early (within 8 h) after bite injury is controversial. Although symptomatic infection frequently will not yet have manifested at this point, many early wounds will harbor pathogens, and many will become infected. Studies of antibiotic prophylaxis for wound infections are limited and have often included only small numbers of cases in which various types of wounds have been managed according to various protocols. A meta-analysis of eight randomized trials of prophylactic antibiotics in patients with dog-bite wounds demonstrated a reduction in the rate of infection by 50% with prophylaxis. However, in the absence of sound clinical trials, many clinicians base the decision to treat bite wounds with empirical antibiotics on the species of the biting animal; the location, severity, and extent of the bite wound; and the existence of comorbid conditions in the host. All humanand monkey-bite wounds should be


InternalMed_Harrison

InternalMed_Harrison. antibiotics on the species of the biting animal; the location, severity, and extent of the bite wound; and the existence of comorbid conditions in the host. All humanand monkey-bite wounds should be treated presumptively because of the high rate of infection. Most cat-bite wounds, particularly those involving the hand, should be treated. Other factors favoring treatment for bite wounds include severe injury, as in crush wounds; potential bone or joint involvement; involvement of the hands or genital region; host immunocompromise, including that due to liver disease or splenectomy; and prior mastectomy on the side of an involved upper extremity. When prophylactic antibiotics are administered, they are usually given for 3–5 days.


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InternalMed_Harrison. Rabies and Tetanus Prophylaxis Rabies prophylaxis, consisting of both passive administration of rabies immune globulin (with as much of the dose as possible infiltrated into and around the wound) and active immunization with rabies vaccine, should be given in consultation with local and regional public health authorities for some animal bites and scratches as well as for certain nonbite exposures (Chap. 232). Rabies is endemic in a variety of animals, including dogs and cats in many areas of the world. Many local health authorities require the reporting of all animal bites. A tetanus booster immunization should be given if the patient has undergone primary immunization but has not received a booster dose in the past 5 years. Patients who have not previously completed primary immunization should be immunized and should also receive tetanus immune globulin. Elevation of the site of injury is an important adjunct to antimicrobial therapy. Immobilization of the infected area, especially


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InternalMed_Harrison. should be immunized and should also receive tetanus immune globulin. Elevation of the site of injury is an important adjunct to antimicrobial therapy. Immobilization of the infected area, especially the hand, also is beneficial.


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InternalMed_Harrison. Infections Acquired in Health Care facilities Robert A. Weinstein The costs of hospital-acquired (nosocomial) and other health care– associated infections are great. These infections have affected as many 168 SEC TIon 3 as 1.7 million patients at a cost of ~$28–33 billion and 99,000 lives in


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InternalMed_Harrison. U.S. hospitals annually. Although efforts to lower infection risks have been challenged by the numbers of immunocompromised patients, antibiotic-resistant bacteria, fungal and viral superinfections, and invasive devices and procedures, a prevailing viewpoint—often termed “zero tolerance”—is that almost all health care–associated infections should be avoidable with strict application of evidence-based prevention guidelines (Table 168-1). In fact, rates of device-related infections—historically, the largest drivers of risk—have fallen steadily over the past few years. Unfortunately, at the same time, antimicrobial-resistant pathogens have risen in number and are estimated to contribute to ~23,000 deaths in and outside of hospitals annually. This chapter reviews health care–associated and device-related infections as well as basic surveillance, prevention, control, and treatment activities.


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InternalMed_Harrison. ORGANIZATION, RESPONSIBILITIES, AND INCREASING SCRUTINY OF HEALTH CARE–ASSOCIATED INFECTION PROGRAMS The standards of the Joint Commission require all accredited hospitals to have active programs for surveillance, prevention, and control of nosocomial infections. Education of physicians in infection control and health care epidemiology is required in infectious disease fellowship programs and is available in online courses. Concerns over “patient safety” have led to federal legislation that prevents U.S. hospitals from upgrading Medicare charges to pay for hospital costs resulting from at least 14 specific nosocomial events (Table 168-2) and have prompted national efforts to publicly


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InternalMed_Harrison. Abbreviations: AHRQ, Agency for Healthcare Research and Quality; APIC, Association for Professionals in Infection Control and Epidemiology; CAP, College of American Pathologists; CDC, Centers for Disease Control and Prevention; CMS, Centers for Medicare & Medicaid Services; CSTE, Council of State and Territorial Epidemiologists; DHQP, Division of Healthcare Quality Promotion; HHS, Health and Human Services; HICPAC, Healthcare Infection Control Practices Advisory Committee; HIS, Hospital Infection Society; IDSA, Infectious Diseases Society of America; IHI, Institute for Healthcare Improvement; IOM, Institute of Medicine; MedQIC, Medicare Quality Improvement Community; NIOSH, National Institute for Occupational Safety and Health; NQF, National Quality Forum; NSQIP, National Surgical Quality Improvement Program; OSHA, Occupational Safety & Health Administration; PQRI, Physician Quality Reporting Initiative; SHEA, Society for Healthcare Epidemiology of America.


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InternalMed_Harrison. report on processes of patient care (e.g., timely administration and of Health and Human Services released a major interagency Action appropriateness of perioperative antibiotic prophylaxis) and patient Plan to Prevent Healthcare-Associated Infections, including a outcomes (e.g., surgical wound infection rates). Neither the carrot list of 5-year national prevention targets that are mostly on track (pay-for-performance) nor the stick (nonpayment for preventable (Table 168-3). infections) appears to have impacted infection rates. The effect of public attention may be more positive; in 2009, the U.S. Department


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InternalMed_Harrison. Traditionally, infection preventionists have surveyed inpatients for infections acquired in hospitals (defined as those neither present nor incubating at the time of admission). Surveillance most often requires review of microbiology laboratory results, “shoe-leather” epidemiol- ogy on nursing wards, and application of standardized definitions of infection. Progressively more infection-control programs use comput-Blood incompatibilities erized hospital databases for algorithm-driven electronic surveillance Decubitus ulcers (stages III and IV) (e.g., of vascular catheter and surgical wound infections) that removes Fractures/other injuries from falls or trauma observer bias and, by so doing, provides data that are more reliable for Catheter-associated urinary tract infections interfacility comparisons. Although infection surveillance in nursing homes and some long-term acute-care hospitals (LTACHs) is still in its formative stage, the role of these facilities in the transmission of


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InternalMed_Harrison. Manifestations of poor glycemic control to infection surveillance and control. Surgical-site infection following certain orthopedic procedures Most hospitals aim surveillance at infections associated with high-Surgical-site infection following bariatric surgery for obesity level morbidity or expense. Quality-improvement activities in infecSurgical-site infection following cardiac electronic device implantation tion control have led to increased surveillance of personnel compliance Venous thromboembolism (after hip or knee replacement) with infection control policies (e.g., adherence to influenza vaccination recommendations). In the spirit of “what is measured improves,” the Iatrogenic pneumothorax with venous catheterization majority of states now require public reporting of processes for pre aBased on the U.S. Federal Deficit Reduction Act of 2005. As of October 2012, Medicare vention of health care–associated infection and/or patient outcomes.


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InternalMed_Harrison. stopped paying additional money to hospitals for these 14 health care–acquired conditions. See www.cms.gov/HospitalAcqCond/ (last accessed November 13, 2014). As a result, in some locales, the surveillance pendulum is swinging SuMMARy of PRogRESS TowARD THE nInE nATIonAL TARgETS foR ELIMInATIon of HEALTH CARE–ASSoCIATED InfECTIonS, u.S. DEPARTMEnT of HEALTH AnD HuMAn SERvICES: MIDPoInT EvALuATIon aExamples of changes: Catheter-related bloodstream infections decreased to ~1.7/1000 catheter-days; C. difficile infections increased to ~11.2 cases/10,000 discharges; catheter-related urinary tract infections decreased to ~3.1/1000 catheter-days; and hospital-onset MRSA invasive infections decreased to ~4.5/100,000 persons.


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InternalMed_Harrison. Abbreviations: EIP, CDC’s Emerging Infections Program; HCUP, Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project; MRSA, methicillin-resistant Staphylococcus aureus; NHSN, CDC’s National Healthcare Safety Network; SCIP, Surgical Care Improvement Project. Source: Adapted from www.hhs.gov/ash/initiatives/hai/nationaltargets/ (last accessed November 13, 2014).


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InternalMed_Harrison. Source: Adapted from www.hhs.gov/ash/initiatives/hai/nationaltargets/ (last accessed November 13, 2014). back to use of “house-wide” surveillance, and many states now require that hospitals use the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN) reporting system to provide uniform definitions and to facilitate transmission of data. Increasing reliance on the NHSN by states to facilitate public reporting has led to participation by more than 12,000 facilities (~4700 of the ~5700 acute-care hospitals in the United States, ~540 LTACHs, ~270 inpatient rehabilitation facilities, ~6000 outpatient dialysis facilities, ~300 ambulatory surgery centers, ~150 long-term-care facilities). This level of participation provides a nationwide view of health care– associated infections and represents a watershed in potential access to national rates of antimicrobial use and resistance.


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InternalMed_Harrison. Results of surveillance are expressed as rates. In general, for example, 5–10% of patients develop nosocomial infections. However, such broad statistics have little value unless qualified by duration of risk, by site of infection, by patient population, and by exposure to risk factors. To account for some of these variables, the CDC now uses a Standardized Infection Ratio (SIR; www.cdc.gov/hai/national-annual-sir/) as part of NHSN rate reporting. Meaningful denominators for infection rates include the number of patients exposed to a specific risk (e.g., patients using mechanical ventilators) or the number of intervention days (e.g., 1000 patient-days on a ventilator). As use of invasive devices such as indwelling bladder catheters has purposely been decreased, the denominators have become smaller, but the fact that patients who still require such devices may be those at intrinsically higher risk (potential numerators) may paradoxically increase rates when device-days account for the


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InternalMed_Harrison. smaller, but the fact that patients who still require such devices may be those at intrinsically higher risk (potential numerators) may paradoxically increase rates when device-days account for the denominator. Temporal trends in rates should be reviewed, and rates should be compared with regional and national benchmarks that incorporate the SIR. Interhospital comparisons still may be misleading because of the wide range in risk factors and severity of underlying illnesses. Process measures (e.g., adherence to hand hygiene) do not usually require risk adjustment, and outcome measures (e.g., cardiac surgery wound-infection rates) can identify hospitals with outlier infection rates (e.g., in the top deciles) for further evaluation. Moreover, temporal analysis of a hospital’s infection rates can help to determine whether control measures are succeeding and where increased efforts should be focused.


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InternalMed_Harrison. Nosocomial infections follow basic epidemiologic patterns that can help to direct prevention and control measures. Nosocomial pathogens have reservoirs, are transmitted by largely predictable routes, and require susceptible hosts. Reservoirs and sources exist in the inanimate environment (e.g., residual Clostridium difficile spores on frequently touched surfaces in patients’ rooms) and in the animate environment (e.g., infected or colonized health care workers, patients, and hospital visitors). The mode of transmission usually is either cross-infection (e.g., indirect spread of pathogens from one patient to another on the inadequately cleaned hands of hospital personnel) or autoinoculation (e.g., aspiration of oropharyngeal flora into the lungs along an endotracheal tube). Occasionally, pathogens (e.g., group A streptococci and many respiratory viruses) are spread from person to person via large infectious droplets released by coughing or sneezing. Much less common—but often


InternalMed_Harrison

InternalMed_Harrison. pathogens (e.g., group A streptococci and many respiratory viruses) are spread from person to person via large infectious droplets released by coughing or sneezing. Much less common—but often devastating in terms of epidemic risk—is true airborne spread of small or droplet nuclei (as in nosocomial chickenpox) or common-source spread (e.g., by contaminated IV fluids). Factors that increase host susceptibility include underlying conditions, abnormalities of innate defense (e.g., due to genetic polymorphisms; see Chap. 82), and medical-surgical interventions and procedures that compromise host defenses.


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InternalMed_Harrison. Hospitals’ infection-control programs must determine general and specific control measures. Given the prominence of cross-infection, hand hygiene is cited traditionally as the most important preventive measure. Health care workers’ rates of adherence to hand-hygiene recommendations are abysmally low (often <50%). Reasons cited include inconvenience, time pressures, and skin damage from frequent washing. Sinkless alcohol rubs are quick and highly effective and actually improve hand condition since they contain emollients and allow the retention of natural protective oils that would be removed with repeated rinsing. Use of alcohol hand rubs between patient contacts is recommended for all health care workers except when hands are visibly soiled or after care of a patient who is part of a health care facility outbreak of infection with C. difficile, whose spores resist killing by alcohol and require mechanical removal. In these cases, washing with soap and running water is recommended. A


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InternalMed_Harrison. care facility outbreak of infection with C. difficile, whose spores resist killing by alcohol and require mechanical removal. In these cases, washing with soap and running water is recommended. A number of innovative systems have been developed to track hand-hygiene adherence in real time and to provide feedback; although this approach is exciting, sustained improvements in rates remain to be seen.


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InternalMed_Harrison. The fact that >25–50% of nosocomial infections are due to the combined effect of the patient’s own flora and invasive devices highlights the importance of improvements in the use and design of such devices. Intensive education, “bundling” of evidence-based interventions (Table 168-4), and use of checklists to facilitate adherence have reduced infection rates (Table 168-3) through improved asepsis in handling and earlier removal of invasive devices. It is especially noteworthy that turnover or shortages of trained personnel jeopardize safe and effective patient care and have been associated with increased infection rates.


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InternalMed_Harrison. Urinary tract infections (UTIs) account for ~30–40% of nosocomial infections; up to 3% of bacteriuric patients develop bacteremia. Although UTIs contribute at most 15% to prolongation of hospital stay and may have an attributable cost in the range of only $1300, these infections are reservoirs and sources for spread of antibiotic-resistant bacteria. Most nosocomial UTIs are associated with preceding instrumentation or indwelling bladder catheters, which create a 3–7% risk of infection each day. UTIs generally are caused by pathogens that spread up the periurethral space from the patient’s perineum or gastrointestinal tract—the most common pathogenesis in women—or via intraluminal contamination of urinary catheters, usually due to cross-infection by caregivers who are irrigating catheters or emptying drainage bags. Pathogens come occasionally from Prevention of Central Venous Catheter Infections Catheter insertion bundle:


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InternalMed_Harrison. Prevention of Central Venous Catheter Infections Catheter insertion bundle: Educate personnel about catheter insertion and care. Use chlorhexidine to prepare the insertion site. Use maximal barrier precautions and asepsis during catheter insertion. Consolidate insertion supplies (e.g., in an insertion kit or cart). Use a checklist to enhance adherence to the “insertion bundle.” Empower nurses to halt insertion if asepsis is breached. Catheter maintenance bundle: Cleanse patients daily with chlorhexidine. Maintain clean, dry dressings. Enforce hand hygiene among health care workers. Ask daily: Is the catheter needed? Remove catheter if not needed or used. Prevention of Ventilator-Associated Events Elevate head of bed to 30–45 degrees. Decontaminate oropharynx regularly with chlorhexidine (controversial). Give “sedation vacation” and assess readiness to extubate daily. Use peptic ulcer disease prophylaxis. Use deep-vein thrombosis prophylaxis (unless contraindicated).


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InternalMed_Harrison. Prevention of Surgical-Site Infections Choose a surgeon wisely. Administer prophylactic antibiotics within 1 h before surgery; discontinue within 24 h. Limit any hair removal to the time of surgery; use clippers or do not remove hair at all. Prepare surgical site with chlorhexidine-alcohol. Maintain normal perioperative glucose levels (cardiac surgery patients).a Maintain perioperative normothermia (colorectal surgery patients).a Prevention of Urinary Tract Infections Place bladder catheters only when absolutely needed (e.g., to relieve obstruction), not solely for the provider’s convenience. Use aseptic technique for catheter insertion and urinary tract instrumentation. Minimize manipulation or opening of drainage systems. Ask daily: Is the bladder catheter needed? Remove catheter if not needed. Prevention of Pathogen Cross-Transmission Cleanse hands with alcohol hand rub before and after all contacts with patients or their environments.


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InternalMed_Harrison. Prevention of Pathogen Cross-Transmission Cleanse hands with alcohol hand rub before and after all contacts with patients or their environments. aThese components of care are supported by clinical trials and experimental evidence in the specified populations; they may prove valuable for other surgical patients as well. Source: Adapted from information presented at the following websites: www.cdc.gov/ hicpac/pubs.html; www.cdc.gov/HAI/prevent/prevention.html; www.ihi.org. inadequately disinfected urologic equipment and rarely from contaminated supplies.


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InternalMed_Harrison. inadequately disinfected urologic equipment and rarely from contaminated supplies. Hospitals should monitor essential performance measures for preventing nosocomial UTIs (Table 168-4). Prompts to clinicians to assess a patient’s need for continued use of an indwelling bladder catheter can improve removal rates and lessen the risk of UTI. Guidelines for managing postoperative urinary retention (e.g., with bladder scanners) also may limit the use or duration of catheterization. Other approaches to the prevention of UTIs have included the use of topical meatal antimicrobial agents, drainage bag disinfectants, and anti-infective catheters. None of the latter three measures is considered routine.


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InternalMed_Harrison. Administration of systemic antimicrobial agents for other purposes decreases the risk of UTI during the first 4 days of catheterization, after which resistant bacteria or yeasts emerge as pathogens. Prophylactic antibiotic administration at the time of catheter removal has been reported to decrease the risk of UTI. Selective decontamination of the gut also is associated with a reduced risk. Again, however, none of these approaches is routine. Irrigation of catheters, with or without antimicrobial agents, may actually increase the risk of infection. A condom catheter for men without bladder obstruction may be more acceptable than an indwelling catheter and may lessen the risk of UTI if maintained carefully. The role of suprapubic catheters in preventing infection is not well defined.


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InternalMed_Harrison. Treatment of UTIs is based on the results of quantitative urine cultures (Chap. 162). The most common pathogens are Escherichia coli, nosocomial gram-negative bacilli, enterococci, and Candida. Several caveats apply in the treatment of institutionally acquired infection. First, in patients with chronic indwelling bladder catheters, especially those in long-term-care facilities, “catheter flora”—microorganisms living on encrustations within the catheter lumen—may differ from actual urinary tract pathogens. Therefore, for suspected UTI in the setting of chronic catheterization (especially in women), it is useful to replace the bladder catheter and to obtain a freshly voided urine specimen. Second, as in all nosocomial infections, at the time treatment is initiated on the basis of a positive culture, it is useful to repeat the culture to verify the persistence of infection. Third, the frequency with which UTIs occur may lead to the erroneous assumption that the urinary tract alone is the


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InternalMed_Harrison. culture, it is useful to repeat the culture to verify the persistence of infection. Third, the frequency with which UTIs occur may lead to the erroneous assumption that the urinary tract alone is the source of infection in a febrile hospitalized patient. Fourth, recovery of Staphylococcus aureus from urine cultures may result from hematogenous seeding and may indicate an occult systemic infection. Finally, although Candida is now the most common pathogen in nosocomial UTIs among patients on intensive care units (ICUs), treatment of candiduria is often unsuccessful and is recommended only when there is upper-pole or bladder-wall invasion, obstruction, neutropenia, or immunosuppression.


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InternalMed_Harrison. Historically, pneumonia has accounted for ~10–15% of nosocomial infections; ventilator-associated pneumonia (VAP) occurred in 1 to >4 patients per 1000 ventilator-days, and these infections were reported as responsible for a mean of 10 extra hospital days and $23,000 in extra costs per episode. Most cases of bacterial nosocomial pneumonia are caused by aspiration of endogenous or hospital-acquired oropharyngeal (and occasionally gastric) flora. Nosocomial pneumonias are associated with more deaths than are infections at any other body site. However, attributable mortality rates suggest that the risk of dying from nosocomial pneumonia is affected greatly by other factors, including comorbidities, inadequate antibiotic treatment, and the involvement of specific pathogens (particularly Pseudomonas aeruginosa or Acinetobacter). Surveillance and accurate diagnosis of pneumonia have been problematic in hospitals because many patients, especially those in the ICU, have abnormal chest


InternalMed_Harrison

InternalMed_Harrison. Pseudomonas aeruginosa or Acinetobacter). Surveillance and accurate diagnosis of pneumonia have been problematic in hospitals because many patients, especially those in the ICU, have abnormal chest roentgenographs, fever, and leukocytosis potentially attributable to multiple causes. This diagnostic uncertainty has led to a refocus from VAP to “ventilatorassociated events” (VAEs), conditions, and complications, for which worsening physiologic parameters, such as oxygenation, are key metrics. Early data suggest that ~5–10% of patients using mechanical ventilators develop VAEs. Viral pneumonias, which are particularly important in pediatric and immunocompromised patients, are discussed in the virology section and in Chap. 153.


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InternalMed_Harrison. Risk factors for nosocomial pneumonia include those events that increase colonization by potential pathogens (e.g., prior antimicrobial therapy, contaminated ventilator circuits or equipment, or decreased gastric acidity); those that facilitate aspiration of oropharyngeal contents into the lower respiratory tract (e.g., intubation, decreased levels of consciousness, or presence of a nasogastric tube); and those that reduce host defense mechanisms in the lung and permit overgrowth of aspirated pathogens (e.g., chronic obstructive pulmonary disease, extremes of age, or upper abdominal surgery).


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InternalMed_Harrison. Control measures for pneumonia (Table 168-4) are aimed at frequent testing of readiness for extubation, remediation of risk factors in patient care (e.g., minimizing aspiration-prone supine positioning), and aseptic care of respirator equipment (e.g., disinfecting or sterilizing all inline reusable components such as nebulizers, replacing tubing/breathing circuits only if required because of malfunction or visible soiling—rather than on the basis of duration of use—to lessen the number of breaks in the system, and teaching aseptic technique for suctioning). Although the benefits of selective decontamination of the oropharynx and gut with nonabsorbable antimicrobial agents and/ or use of short-course postintubation systemic antibiotics have been controversial, a randomized multicenter trial demonstrated lowered ICU mortality rates among patients on mechanical ventilation who underwent oropharyngeal decontamination.


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InternalMed_Harrison. Among the logical preventive measures that require further investigation are placement of endotracheal tubes that provide channels for subglottic drainage of secretions, which has been associated with reduced infection risks during short-term postoperative use, and noninvasive mechanical ventilation whenever feasible. Use of silver-coated endotracheal tubes may lessen risk of VAP but is not considered routine. It is noteworthy that reducing the rate of VAP often has not reduced overall ICU mortality; this fact suggests that this infection is a marker for patients with an otherwise-heightened risk of death.


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InternalMed_Harrison. The most likely pathogens for nosocomial pneumonia and treatment options are discussed in Chap. 153. Several considerations regarding diagnosis and treatment are worth emphasizing. First, clinical criteria for diagnosis (e.g., fever, leukocytosis, development of purulent secretions, new or changing radiographic infiltrates, changes in oxygen requirement or ventilator settings) have high sensitivity but relatively low specificity. These criteria are most useful for selecting patients for bronchoscopic or nonbronchoscopic procedures that yield lower respiratory tract samples protected from upper-tract contamination; quantitative cultures of such specimens have diagnostic sensitivities in the range of 80%. Second, early-onset nosocomial pneumonia, which manifests within the first 4 days of hospitalization, is most often caused by community-acquired pathogens such as Streptococcus pneumoniae and Haemophilus species, although some studies have challenged this view. Late-onset pneumonias


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InternalMed_Harrison. hospitalization, is most often caused by community-acquired pathogens such as Streptococcus pneumoniae and Haemophilus species, although some studies have challenged this view. Late-onset pneumonias most commonly are due to


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InternalMed_Harrison. S. aureus, P. aeruginosa, Enterobacter species, Klebsiella pneumoniae, or Acinetobacter. When invasive techniques are used to diagnose VAP, the proportion of isolates accounted for by gram-negative bacilli decreases from 50–70% to 35–45%. Infection is polymicrobial in as many as 20–40% of cases. The role of anaerobic bacteria in VAP is not well defined. Third, one multicenter study suggested that 8 days is an appropriate duration of therapy for nosocomial pneumonia, with a longer duration (15 days in that study) when the pathogen is Acinetobacter or P. aeruginosa. Finally, in febrile patients (particularly those who have endotracheal or gastric tubes inserted through the nares), occult respiratory tract infections, especially bacterial sinusitis and otitis media, should be considered.


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InternalMed_Harrison. Wound infections occur in ~500,000 patients each year, account for ~15–20% of nosocomial infections, contribute up to 7–10 extra postoperative hospital days, and result in $3000 to $29,000 in extra costs, depending on the operative procedure and pathogen(s). The average wound infection has an incubation period of 5–7 days—longer than many postoperative stays. For this reason and because many procedures are now performed on an outpatient basis, the incidence of wound infections has become more difficult to assess. These infections usually are caused by the patient’s endogenous or hospital-acquired skin and mucosal flora and occasionally are due to airborne spread of skin squames that may be shed into the wound from members of the operating-room team. True airborne spread of infection through droplet nuclei is rare in operating rooms unless there is a “disseminator” (e.g., of group A streptococci or staphylococci) among the staff. In general, the common risks for postoperative wound


InternalMed_Harrison

InternalMed_Harrison. droplet nuclei is rare in operating rooms unless there is a “disseminator” (e.g., of group A streptococci or staphylococci) among the staff. In general, the common risks for postoperative wound infection are related to the surgeon’s technical skill, the patient’s underlying conditions (e.g., diabetes mellitus, obesity) or advanced age, and inappropriate timing of antibiotic prophylaxis. Additional risks include the presence of drains, prolonged preoperative hospital stays, shaving of operative sites by razor the day before surgery, long duration of surgery, and infection at remote sites (e.g., untreated UTI).


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InternalMed_Harrison. The substantial literature related to risk factors for surgical-site infections and the recognized morbidity and cost of these infections have led to national prevention efforts and to recommendations for “bundling” preventive measures (Table 168-4). Additional measures 915 include attention to technical surgical issues (e.g., avoiding open or prophylactic drains), operating-room asepsis, and preoperative therapy for active infection. Reporting surveillance results to surgeons has been associated with reductions in infection rates. Preoperative administration of intranasal mupirocin to patients colonized with S. aureus, preoperative antiseptic bathing, and intraand postoperative oxygen supplementation have been controversial because of conflicting study results, but evidence seems mostly to favor these interventions.


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InternalMed_Harrison. The process of diagnosing and treating wound infections begins with a careful assessment of the surgical site in the febrile postoperative patient. Diagnosis of deeper organ-space infections or subphrenic abscesses requires a high index of suspicion and the use of CT or MRI. Diagnosis of infections of prosthetic devices, such as orthopedic implants, may be particularly difficult and often requires the use of interventional radiographic techniques to obtain periprosthetic specimens for culture. Cultures of periprosthetic joint tissue obtained at surgery may miss pathogens that are cloistered in prosthesis-adherent biofilms; cultures of sonicates from explanted prosthetic joints have been more sensitive, particularly for patients who have received antimicrobial agents within 2 weeks of surgery.


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InternalMed_Harrison. The most common pathogens in postoperative wound infections are S. aureus, coagulase-negative staphylococci, and enteric and anaerobic bacteria. In rapidly progressing postoperative infections manifesting within 24–48 h of a surgical procedure, the level of suspicion regarding group A streptococcal or clostridial infection (Chaps. 173 and 179) should be high. Treatment of postoperative wound infections requires drainage or surgical excision of infected or necrotic material and antibiotic therapy aimed at the most likely or laboratory-confirmed pathogens.


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InternalMed_Harrison. Intravascular device–related bacteremias cause ~10–15% of nosocomial infections; central vascular catheters (CVCs) account for most of these bloodstream infections. Past national estimates indicated that as many as 200,000 bloodstream infections associated with CVCs occurred each year in the United States, with attributable mortality rates of 12–25%, an excess mean length of hospital stay of 12 days, and an estimated cost of $3700 to $29,000 per episode; one-third to one-half of these episodes occurred in ICUs. However, infection rates have dropped steadily (Table 168-3) since the publication of guidelines by the Healthcare Infection Control Practices Advisory Committee (HICPAC) in 2002. With increasing care of seriously ill patients in the community, vascular catheter–associated bloodstream infections acquired in outpatient settings are becoming more frequent. Broader surveillance for infections—outside ICUs and even outside hospitals—will be needed.