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The physician treating the acutely ill febrile patient must be able to recognize infections that require emergent attention. If such infections are not adequately evaluated and treated at initial presentation, the opportunity to alter an adverse outcome may be lost. In this chapter, the clinical presentations of and approach to patients with relatively common infectious disease emergencies are discussed.These infectious processes and their treatments are discussed in detail in other chapters. Noninfectious causes of fever are not covered in this chapter; information on the approach to fever of unknown origin, including that eventually shown to be of noninfectious etiology, is presented in Chap. 9. Approach to the Patient:


ACUTE FEBRILE ILLNESS

A physician must have a consistent approach to acutely ill patients. Even before the history is elicited and a physical examination performed, an immediate assessment of the patient’s general appearance yields valuable information.The perceptive physician’s subjective sense that a patient is septic or toxic often proves accurate. Visible agitation or anxiety in a febrile patient can be a harbinger of critical illness.


HISTORY

Presenting symptoms are frequently nonspecific. Detailed questions should be asked about the onset and duration of symptoms and about changes in severity or rate of progression over time. Host factors and comorbid conditions may enhance the risk of infection with certain organisms or of a more fulminant course than is usually seen. Lack of splenic function, alcoholism with significant liver disease, intravenous drug use, HIV infection, diabetes, malignancy, and chemotherapy all predispose to specific infections and frequently to increased severity. The patient should be questioned about factors that might help identify a nidus for invasive infection, such as recent upper respiratory tract infections, influenza, or varicella; prior trauma; disruption of cutaneous barriers due to lacerations, burns, surgery, or decubiti; and the presence of foreign bodies, such as nasal packing after rhinoplasty, barrier contraceptives, tampons, arteriovenous fistulas, or prosthetic joints.Travel, contact with pets or other animals, or activities that might result in tick exposure can lead to diagnoses that would not otherwise be considered. Recent dietary intake, medication use, social or occupational contact with ill individuals, vaccination history, recent sexual contacts, and menstrual history may be relevant. A review of systems should focus on any neurologic signs or sensorium alterations, rashes or skin lesions, and focal pain or tenderness and should also include a general review of respiratory, gastrointestinal, or genitourinary symptoms.


PHYSICAL EXAMINATION

A complete physical examination should be performed, with special attention to several areas that are sometimes given short shrift in routine examinations. Assessment of the patient’s general appearance and vital signs, skin and soft tissue examination, and the neurologic evaluation are of particular importance. The patient may appear either anxious and agitated or lethargic and apathetic. Fever is usually present, although elderly patients and compromised hosts [e.g., patients who are uremic or cirrhotic and those who are taking glucocorticoids or nonsteroidal antiinflammatory drugs (NSAIDs)] may be afebrile despite serious underlying infection. Measurement of blood pressure, heart rate, and respiratory rate helps determine the degree of hemodynamic and metabolic compromise. The patient’s airway must be evaluated to rule out the risk of obstruction from an invasive oropharyngeal infection. The etiologic diagnosis may become evident in the context of a thorough skin examination (Chap. 8). Petechial rashes are typically seen with meningococcemia or Rocky Mountain spotted fever (RMSF); erythroderma is associated with toxic shock syndrome (TSS) and drug fever. The soft tissue and muscle examination is critical. Areas of erythema or duskiness, edema, and tenderness may indicate underlying necrotizing fasciitis, myositis, or myonecrosis. The neurologic examination must include a careful assessment of mental status for signs of early encephalopathy. Evidence of nuchal rigidity or focal neurologic findings should be sought.


DIAGNOSTIC WORKUP

After a quick clinical assessment, diagnostic material should be obtained rapidly and antibiotic and supportive treatment begun. Blood (for cultures; baseline complete blood count with differential; measurement of serum electrolytes, blood urea nitrogen, serum creatinine, and serum glucose; and liver function tests) can be obtained at the time an intravenous line is placed and before antibiotics are administered. Three sets of blood cultures should be performed for patients with possible acute endocarditis. Asplenic patients should have a blood smear examined to confirm the presence of Howell-Jolly bodies (indicating the absence of splenic function) and a buffy coat examined for bacteria; these patients can have >106 organisms per milliliter of blood (compared with 104/mL in patients with an intact spleen). Blood smears from patients at risk for severe parasitic disease, such as malaria or babesiosis,must be examined for the diagnosis and quantitation of parasitemia. Blood smears may also be diagnostic in ehrlichiosis. Patients with possible meningitis should have cerebrospinal fluid (CSF) obtained before the initiation of antibiotic therapy. Focal findings, depressed mental status, or papilledema should be evaluated by brain imaging before lumbar puncture, which, in this setting, could initiate herniation. Antibiotics should be administered before imaging but after blood for cultures has been drawn. If CSF cultures are negative, blood cultures will provide the diagnosis in 50–70% of cases. Focal abscesses necessitate immediate CT or MRI as part of an evaluation for surgical intervention. Other diagnostic procedures, such as cultures of wounds or scraping of skin lesions, should not delay the initiation of treatment for more than minutes. Once emergent evaluation, diagnostic procedures, and (if appropriate) surgical consultation (see below) have been completed, other laboratory tests can be conducted. Appropriate radiography, computed axial tomography,MRI, urinaly- sis, erythrocyte sedimentation rate (ESR) determination, and transthoracic or transesophageal echocardiography may all prove important. 


THE ACUTELY ILL PATIENT

In the acutely ill patient, empirical antibiotic therapy is critical and should be administered without undue delay. Increased prevalence of antibiotic resistance in community-acquired bacteria must be considered when antibiotics are selected. Table 14-1 lists first-line treatments for infections considered in this chapter. In addition to the rapid initiation of antibiotic therapy, several of these infections require urgent surgical attention. Neurosurgical evaluation for subdural empyema or spinal epidural abscess, otolaryngologic surgery for possible mucormycosis, and cardiothoracic surgery for critically ill patients with acute endocarditis are as important as antibiotic therapy. For infections such as necrotizing fasciitis and clostridial myonecrosis, rapid surgical intervention supersedes other diagnostic or therapeutic maneuvers. Adjunctive treatments may reduce morbidity and mortality and include dexamethasone for bacterial meningitis; intravenous immunoglobulin (IVIg) for TSS and necrotizing fasciitis caused by group A Streptococcus; low-dose hydrocortisone and fludrocortisone for septic shock; and drotrecogin alfa (activated), also known as recombinant human activated protein C, for meningococcemia and severe sepsis. Adjunctive therapies should usually be initiated within the first hours of treatment; however, dexamethasone for bacterial meningitis must be given before or at the time of the first dose of antibiotic.


SPECIFIC PRESENTATIONS

The infections considered below according to common clinical presentation can have rapidly catastrophic outcomes, and their immediate recognition and treatment can be life-saving. Recommended empirical therapeutic regimens are presented in Table 14-1.


SEPSIS WITHOUT AN OBVIOUS FOCUS OF PRIMARY INFECTION

These patients initially have a brief prodrome of nonspecific symptoms and signs that progresses quickly to hemodynamic instability with hypotension, tachycardia, tachypnea, respiratory distress, and altered mental status. Disseminated intravascular coagulation (DIC) with clinical evidence of a hemorrhagic diathesis is a poor prognostic sign. Septic Shock (See also Chap. 15) Patients with bacteremia leading to septic shock may have a primary site of infection (e.g., pneumonia, pyelonephritis, or cholangitis) that is not evident initially. Elderly patients with comorbid conditions, hosts compromised by malignancy and neutropenia, and patients who have recently undergone a surgical procedure or hospitalization are at increased risk for an adverse outcome. Gram-negative bacteremia with organisms such as Pseudomonas aeruginosa or Escherichia coli and gram-positive infection with organisms such as Staphylococcus aureus or group A streptococci can present as intractable hypotension and multiorgan failure. Treatment can usually be initiated empirically on the basis of the presentation (Table 15-3). Adjunctive therapy with either drotrecogin alfa (activated) or glucocorticoids should be considered for patients with severe sepsis. Overwhelming Infection in Asplenic Patients (See also Chap. 15) Patients without splenic function are at risk for overwhelming bacterial sepsis. Asplenic adult patients succumb to sepsis at 58 times the rate of the general population; 50–70% of cases occur within the first 2 years after splenectomy, with a mortality rate of up to 80%, but the increased risk persists throughout life. In asplenia, encapsulated bacteria cause the majority of infections.


Adults, who are more likely to have antibody to these organisms, are at lower risk than children. Streptococcus pneumoniae is the most common isolate, causing 50–70% of cases, but the risk of infection with Haemophilus influenzae or Neisseria meningitidis is also high. Severe clinical manifestations of infections due to E. coli, S. aureus, group B streptococci, P. aeruginosa, Capnocytophaga, Babesia, and Plasmodium have been described. Babesiosis (See also Chap. 117) A history of recent travel to endemic areas raises the possibility of infection with Babesia. Between 1 and 4 weeks after a tick bite, the patient experiences chills, fatigue, anorexia, myalgia, arthralgia, shortness of breath, nausea, and headache; ecchymosis and/or petechiae are occasionally seen. The tick that most commonly transmits Babesia, Ixodes scapularis, also transmits Borrelia burgdorferi (the agent of Lyme disease) and Ehrlichia; co-infection can occur, resulting in more severe disease. Infection with the European species Babesia divergens is more frequently fulminant than that due to the U.S. species Babesia microti. B. divergens causes a febrile syndrome with hemolysis, jaundice, hemoglobinemia, and renal failure and is associated with a mortality rate of >50%. Severe babesiosis is especially common in asplenic hosts but does occur in hosts with normal splenic function, particularly at >60 years of age. Complications include renal failure, acute respiratory failure, and DIC.


Other Sepsis Syndromes Tularemia (Chap. 59) is seen throughout the United States but occurs primarily in Arkansas, Oklahoma, and Missouri.This disease is associated with wild rabbit, tick, and tabanid fly contact.The uncommon typhoidal form can be associated with gram-negative septic shock and a mortality rate of >30%. In the United States, plague (Chap. 60) occurs primarily in New Mexico,Arizona, and Colorado after contact with ground squirrels, prairie dogs, or chipmunks. Plague can occur with greater frequency outside the United States, especially in developing countries in Africa and Asia. The septic form is particularly rare and is associated with shock, multiorgan failure, and a 30% mortality rate.These rare infections should be considered in the appropriate epidemiologic setting.The Centers for Disease Control and Prevention lists tularemia and plague, along with anthrax, as important agents that might be used for bioterrorism (Chap. 6).


SEPSIS WITH SKIN MANIFESTATIONS 

Maculopapular rashes may reflect early meningococcal or rickettsial disease but are usually associated with nonemergent infections. Exanthems are usually viral. Primary HIV infection commonly presents with a rash that is typically maculopapular and involves the upper part of the body but can spread to the palms and soles. The patient is usually febrile and can have lymphadenopathy, severe headache, dysphagia, diarrhea, myalgias, and arthralgias. Recognition of this syndrome provides an opportunity to prevent transmission and to institute treatment and monitoring early on. Petechial rashes caused by viruses are seldom associated with hypotension or a toxic appearance, although severe measles can be an exception. In other settings, petechial rashes require more urgent attention.


Meningococcemia (See also Chap. 44) Almost three-quarters of patients with bacteremic N. meningitidis infection have a rash. Meningococcemia most often affects young children (i.e., those 6 months to 5 years old). In Sub-Saharan Africa, the high prevalence of serogroup A meningococcal disease has been a threat to public health for more than a century. In addition, epidemic outbreaks occur every 8–12 years. In the United States, sporadic cases and outbreaks occur in day-care centers, schools (grade school through college), and army barracks. Household members of index cases are at 400–800 times greater risk of disease than the general population. Patients may exhibit fever, headache, nausea, vomiting, myalgias, changes in mental status, and meningismus. However, the rapidly progressive form of disease is not usually associated with meningitis.


The rash is initially pink, blanching, and maculopapular, appearing on the trunk and extremities, but then becomes hemorrhagic, forming petechiae. Petechiae are first seen at the ankles, wrists, axillae, mucosal surfaces, and palpebral and bulbar conjunctiva, with subsequent spread to the lower extremities and trunk. A cluster of petechiae may be seen at pressure points—e.g., where a blood pressure cuff has been inflated. In rapidly progressive meningococcemia (10–20% of cases), the petechial rash quickly becomes purpuric and patients develop DIC, multiorgan failure, and shock. Of these patients, 50–60% die, and survivors often require extensive debridement or amputation of gangrenous extremities. Hypotension with petechiae for <12 h is associated with significant mortality. The mortality rate can exceed 90% among patients without meningitis who have rash, hypotension, and a normal or low white blood cell (WBC) count and ESR. Cyanosis, coma, oliguria, metabolic acidosis, and elevated partial thromboplastin time are also associated with a fatal outcome.


Correction of protein C deficiency may improve outcome. Antibiotics given in the office by the primary care provider before hospital evaluation and admission may improve prognosis; this observation suggests that early initiation of treatment may be life-saving. Rocky Mountain Spotted Fever (See also Chap. 75) RMSF is a tickborne disease caused by Rickettsia rickettsii that occurs throughout North and South America. A history of known tick bite is common; however, if such a history is lacking, a history of travel or outdoor activity (e.g., camping in tick-infested areas) can be ascertained. For the first 3 days, headache, fever, malaise, myalgias, nausea, vomiting, and anorexia are present. By day 3, half of patients have skin findings. Blanching macules develop initially on the wrists and ankles and then spread over the legs and trunk. The lesions become hemorrhagic and are frequently petechial. The rash spreads to palms and soles later in the course. The centripetal spread is a classic feature of RMSF.However, 10–15% of patients with RMSF never develop a rash. The patient can be hypotensive and develop noncardiogenic pulmonary edema, confusion, lethargy, and encephalitis progressing to coma. The CSF contains 10–100 cells/ìL, usually with a predominance of mononuclear cells.The CSF glucose level is often normal; the protein concentration may be slightly elevated. Renal and hepatic injury and bleeding secondary to vascular damage are noted. Untreated infection has a mortality rate of 30%. Although RMSF is the most severe rickettsial disease, other rickettsial diseases cause significant morbidity and mortality worldwide. Mediterranean spotted fever caused by Rickettsia conorii is found in Africa, southwestern and south-central Asia, and southern Europe. Patients have fever, flulike symptoms, and an inoculation eschar at the site of the tick bite. A maculopapular rash develops within 1–7 days, involving the palms and soles but sparing the face.


Elderly patients or those with diabetes, alcoholism, uremia, or congestive heart failure are at risk for severe disease characterized by neurologic involvement, respiratory distress, and gangrene of the digits. Mortality rates associated with this severe form of disease approach 50%. Epidemic typhus, caused by Rickettsia prowazekii, is transmitted in louse-infested environments and emerges in conditions of extreme poverty, war, and natural disaster. Patients experience a sudden onset of high fevers, severe headache, cough, myalgias, and abdominal pain. A maculopapular rash develops (primarily on the trunk) in more than half of patients and can progress to petechiae and purpura. Serious signs include delirium, coma, seizures, noncardiogenic pulmonary edema, skin necrosis, and peripheral gangrene. Mortality rates approached 60% in the preantibiotic era 159 and continue to exceed 10–15% in contemporary outbreaks. Scrub typhus, caused by Orientia tsutsugamushi—a separate genus in the family Rickettsiaceae—is transmitted by larval mites or chiggers and is one of the most common infections in southeastern Asia and the western Pacific. The organism is found in areas of heavy scrub vegetation (e.g., along riverbanks). Patients present with fever and lymphadenopathy, may have an inoculation eschar, and may develop a maculopapular rash. Severe cases progress to pneumonia, meningoencephalitis, DIC, and renal failure. Mortality rates range from 1% to 35%. If recognized in a timely fashion, rickettsial disease is very responsive to treatment. Doxycycline (100 mg twice daily for 3–14 days) is the treatment of choice for both adults and children.The newer macrolides and chloramphenicol may be suitable alternatives. Purpura Fulminans (See also Chaps. 15 and 44) Purpura fulminans is the cutaneous manifestation of DIC and presents as large ecchymotic areas and hemorrhagic bullae. Progression of petechiae to purpura, ecchymoses, and gangrene is associated with congestive heart failure, septic shock, acute renal failure, acidosis, hypoxia, hypotension, and death. Purpura fulminans has been associated primarily with N. meningitidis but, in splenectomized patients, may be associated with S. pneumoniae and H. influenzae. Several small studies have suggested that correction of the protein C deficiency evident in meningococcal purpura fulminans with drotrecogin alfa (activated) may dramatically improve outcome.


Ecthyma Gangrenosum Septic shock caused by P. aeruginosa or Aeromonas hydrophila can be associated with ecthyma gangrenosum (see Fig. 53-1): hemorrhagic vesicles surrounded by a rim of erythema with central necrosis and ulceration.These gram-negative bacteremias are most common among patients with neutropenia, extensive burns, and hypogammaglobulinemia. Other Emergent Infections Associated with Rash Vibrio vulnificus and other noncholera Vibrio bacteremic infections (Chap. 57) can cause focal skin lesions and overwhelming sepsis in hosts with liver disease. After ingestion of contaminated shellfish, there is a sudden onset of malaise, chills, fever, and hypotension.The patient develops bullous or hemorrhagic skin lesions, usually on the lower extremities, and 75% of patients have leg pain.The mortality rate can be as high as 50–60%. Capnocytophaga canimorsus can cause septic shock in asplenic patients. Infection with this fastidious gram-negative rod typically presents after a dog bite as fever, chills, myalgia, vomiting, diarrhea, dyspnea, confusion, and headache. Findings can include an exanthem or erythema multiforme, cyanotic mottling or peripheral cyanosis, petechiae, and ecchymosis. About 30% of patients with this fulminant form die of overwhelming sepsis and DIC, and survivors may require amputation because of gangrene.


Erythroderma TSS (Chaps. 35 and 36) is usually associated with erythroderma. The patient presents with fever, malaise,myalgias, nausea, vomiting, diarrhea, and confusion.There is a sunburn-type rash that may be subtle and patchy but is usually diffuse and is found on the face, trunk, and extremities. Erythroderma, which desquamates after 1–2 weeks, is more common in Staphylococcus-associated than in Streptococcus-associated TSS.Hypotension develops rapidly— often within hours—after the onset of symptoms. Multiorgan failure is seen. Early renal failure may precede hypotension and distinguishes this syndrome from other septic shock syndromes. Commonly there is no indication of a primary focal infection, although possible cutaneous or mucosal portals of entry for the organism can be ascertained when a careful history is taken. Colonization rather than overt infection of the vagina or a postoperative wound, for example, is typical with staphylococcal TSS, and the mucosal areas appear hyperemic but not infected. The diagnosis of TSS is defined by the clinical criteria of fever, rash, hypotension, and multiorgan involvement. The mortality rate is 5% for menstruation-associated TSS, 10–15% for nonmenstrual TSS, and 30–70% for streptococcal TSS. Viral Hemorrhagic Fevers Viral hemorrhagic fevers (Chaps. 99 and 100) are zoonotic illnesses caused by viruses that reside in either animal reservoirs or arthropod vectors.


These diseases occur worldwide and are restricted to areas where the host species live. They are caused by four major groups of viruses: Arenaviridae (e.g., Lassa fever in Africa), Bunyaviridae (e.g., Rift Valley fever in Africa or hantavirus hemorrhagic fever with renal syndrome in Asia), Filoviridae (e.g., Ebola and Marburg virus infections in Africa), and Flaviviridae (e.g., yellow fever in Africa and South America and dengue in Asia, Africa, and the Americas). Lassa fever as well as Ebola and Marburg virus infections are also transmitted from person to person. The vectors for most viral fevers are found in rural areas; dengue and yellow fever are important exceptions. After a prodrome of fever, myalgias, and malaise, patients develop evidence of vascular damage, petechiae, and local hemorrhage. Shock, multifocal hemorrhaging, and neurologic signs (e.g., seizures or coma) predict a poor prognosis. Although supportive care to maintain blood pressure and intravascular volume is key, ribavirin may be useful against Arenaviridae and Bunyaviridae. Dengue (Chap. 99) is the most common arboviral disease worldwide. More than a quarter of a million cases of dengue hemorrhagic fever occur each year, with 25,000 deaths. Patients have a triad of symptoms: hemorrhagic manifestations, evidence of plasma leakage, and platelet counts <100,000/ìL. Mortality rates are 10–20%. If dengue shock syndrome develops, mortality can reach 40%. Immediate supportive care and volumereplacement therapy are life-saving.  


SEPSIS WITH A SOFT TISSUE/MUSCLE PRIMARY FOCUS 

Necrotizing Fasciitis This infection may arise at a site of minimal trauma or postoperative incision and may also be associated with recent varicella, childbirth, or muscle strain. The most common causes of necrotizing fasciitis are group A streptococci alone (Chap. 36) and a mixed facultative and anaerobic flora (Chap. 21). Diabetes mellitus, peripheral vascular disease, and intravenous drug use are associated risk factors. Use of NSAIDs has been reported to allow progression of skin or soft tissue infections; however, prospective studies have not shown that NSAIDs increase the risk of disease or exacerbate established infection.The patient may have bacteremia and hypotension without other organ-system failure. Physical findings are minimal compared with the severity of pain and the degree of fever.The examination is often unremarkable except for soft tissue edema and erythema.The infected area is red, hot, shiny, swollen, and exquisitely tender. In untreated infection, the overlying skin develops blue-gray patches after 36 h, and cutaneous bullae and necrosis develop after 3–5 days. Necrotizing fasciitis due to a mixed flora, but not that due to group A streptococci, can be associated with gas production. Without treatment, pain decreases because of thrombosis of the small blood vessels and destruction of the peripheral nerves—an ominous sign.


The mortality rate is 25–30% overall, >70% in association with TSS, and nearly 100% without surgical intervention. Life-threatening necrotizing fasciitis may also be due to Clostridium perfringens (Chap. 42); in this condition, the patient is extremely toxic and the mortality rate is high.Within 48 h, rapid tissue invasion and systemic toxicity associated with hemolysis and death ensue. The distinction between this entity and clostridial myonecrosis is made by muscle biopsy. Necrotizing fasciitis caused by community-acquired methicillin-resistant S. aureus (MRSA) was recently described. The MRSA-infected patients required extensive surgical debridement, but there were no deaths. Clostridial Myonecrosis (See also Chap. 42) Myonecrosis is often associated with trauma or surgery but can be spontaneous. The incubation period is usually 12–24 h long, and massive necrotizing gangrene develops within hours of onset. Systemic toxicity, shock, and death can occur within 12 h. The patient’s pain and toxic appearance are out of proportion to physical findings. On examination, the patient is febrile, apathetic, tachycardic, and tachypneic and may express a feeling of impending doom.


Hypotension and renal failure develop later, and hyperalertness is evident preterminally. The skin over the affected area is bronzebrown, mottled, and edematous. Bullous lesions with serosanguineous drainage and a mousy or sweet odor can be present. Crepitus can occur secondary to gas production in muscle tissue.The mortality rate is >65% with spontaneous myonecrosis, which is often associated with Clostridium septicum and underlying malignancy. The mortality rates associated with trunk and limb infection are 63% and 12%, respectively, and any delay in surgical treatment increases the risk of death.


NEUROLOGIC INFECTIONS WITH OR WITHOUT SEPTIC SHOCK

Bacterial Meningitis (See also Chap. 29) Bacterial meningitis is one of the most common infectious disease emergencies involving the central nervous system. Although hosts with cell-mediated immune deficiency (including transplant recipients, diabetic patients, elderly patients, and cancer patients receiving certain chemotherapeutic agents) are at particular risk for Listeria monocytogenes meningitis, most cases in adults are due to S. pneumoniae (30–50%) and N. meningitidis (10–35%). The classic presentation of headache, meningismus, and fever is seen in only one-half to twothirds of patients. The elderly can present without fever or meningeal signs despite lethargy and confusion. Cerebral dysfunction is evidenced by confusion, delirium, and lethargy that can progress to coma. A fulminant presentation with sepsis and brain edema occurs in some cases; papilledema at presentation is unusual and suggests another diagnosis (e.g., an intracranial lesion). Focal signs, including cranial nerve palsies (IV, VI, VII), can be seen in 10–20% of cases; 50–70% of patients have bacteremia. A poor outcome is associated with coma, hypotension, meningitis due to S. pneumoniae, respiratory distress, a CSF glucose level of <0.6 mmol/L (<10 mg/dL), a CSF protein level of >2.5 g/L, a peripheral WBC count of <5000/ìL, and a serum sodium level of <135 mmol/L.


Suppurative Intracranial Infections (See also Chap. 29) In suppurative intracranial infections, rare intracranial lesions present along with sepsis and hemodynamic instability. Rapid recognition of the toxic patient with central neurologic signs is crucial to improvement of the dismal prognosis of these entities. Subdural empyema arises from the paranasal sinus in 60–70% of cases. Microaerophilic streptococci and staphylococci are the predominant etiologic organisms. The patient is toxic, with fever, headache, and nuchal rigidity. Of all patients, 75% have focal signs, and 6–20% die. Despite improved survival rates, 15–44% of patients are left with permanent neurologic deficits. Septic cavernous sinus thrombosis follows a facial or sphenoid sinus infection; 70% of cases are due to staphylococci, and the remainder is due primarily to aerobic or anaerobic streptococci. A unilateral or retroorbital headache progresses to a toxic appearance and fever within days. Three-quarters of patients have unilateral periorbital edema that becomes bilateral and then progresses to ptosis, proptosis, ophthalmoplegia, and papilledema. The mortality rate is as high as 30%. Septic thrombosis of the superior sagittal sinus spreads from the ethmoid or maxillary sinuses and is caused by S. pneumoniae, other streptococci, and staphylococci.


The fulminant course is characterized by headache, nausea, vomiting, rapid progression to confusion and coma, nuchal rigidity, and brainstem signs. If the sinus is totally thrombosed, the mortality rate exceeds 80%. Brain Abscess 161 (See also Chap. 29) Brain abscess often occurs without systemic signs. Almost half of patients are afebrile, and presentations are more consistent with a space-occupying lesion in the brain; 70% of patients have headache, 50% have focal neurologic signs, and 25% have papilledema. Abscesses can present as single or multiple lesions resulting from contiguous foci or hematogenous infection, such as endocarditis. The infection progresses over several days from cerebritis to an abscess with a mature capsule. More than half of infections are polymicrobial, with an etiology consisting of aerobic bacteria (primarily streptococcal species) and anaerobes. Abscesses arising hematogenously are especially apt to rupture into the ventricular space, causing a sudden and severe deterioration in clinical status and high mortality. Otherwise, mortality is low, but morbidity is high (30–55%). Patients presenting with stroke and a parameningeal infectious focus, such as sinusitis or otitis, may have a brain abscess, and physicians must maintain a high level of suspicion.


Prognosis worsens in patients with a fulminant course, delayed diagnosis, abscess rupture into the ventricles,multiple abscesses, or abnormal neurologic status at presentation. Cerebral Malaria (See also Chap. 116) This entity should be urgently considered if patients who have recently traveled to areas endemic for malaria present with a febrile illness and lethargy or other neurologic signs. Fulminant malaria is caused by Plasmodium falciparum and is associated with temperatures of >40°C (>104°F), hypotension, jaundice, adult respiratory distress syndrome, and bleeding. By definition, any patient with a change in mental status or repeated seizure in the setting of fulminant malaria has cerebral malaria. In adults, this nonspecific febrile illness progresses to coma over several days; occasionally, coma occurs within hours and death within 24 h. Nuchal rigidity and photophobia are rare. On physical examination, symmetric encephalopathy is typical, and upper motor neuron dysfunction with decorticate and decerebrate posturing can be seen in advanced disease.


Unrecognized infection results in a 20–30% mortality rate. Spinal Epidural Abscesses Patients with spinal epidural abscesses often present with back pain and develop neurologic deficits late in their course. At-risk patients include those with diabetes mellitus; intravenous drug use; chronic alcohol abuse; recent spinal trauma, surgery, or epidural anesthesia; and other comorbid conditions, such as HIV infection.The thoracic or lumbar spine is the most common location; cervical spine infections are associated with worse outcomes. Staphylococci are the most common etiologic agents.This diagnosis must immediately be considered in patients with a history of antecedent back pain and new neurologic symptoms. Almost 60% of patients have fever, and almost 90% have back pain. Paresthesia, bowel and bladder dysfunction, radicular pain, and weakness are frequent neurologic complaints, and examination of the patient may reveal abnormal reflexes and motor and sensory deficits. The ESR and leukocyte counts are usually elevated. Rapid recognition and treatment, which may include surgical drainage, can prevent or minimize permanent neurologic sequelae.


OTHER FOCAL SYNDROMES WITH A FULMINANT COURSE

Infection at virtually any primary focus (e.g., osteomyelitis, pneumonia, pyelonephritis, or cholangitis) can result in bacteremia and sepsis.TSS has been associated with focal infections such as septic arthritis, peritonitis, sinusitis, and wound infection. Rapid clinical deterioration and death can be associated with destruction of the primary site of infection, as is seen in endocarditis and in necrotizing infections of the oropharynx (in which edema suddenly compromises the airway). Rhinocerebral Mucormycosis (See also Chap. 109) Patients with diabetes or malignancy are at risk for invasive rhinocerebral mucormycosis. Patients present with low-grade fever, dull sinus pain, diplopia, decreased mental status, decreased ocular motion, chemosis, proptosis, dusky or necrotic nasal turbinates, and necrotic hard-palate lesions that respect the midline.Without rapid recognition and intervention, the process continues on an inexorable invasive course, with high mortality. Acute Bacterial Endocarditis (See also Chap. 19) This entity presents with a much more aggressive course than subacute endocarditis. Bacteria such as S. aureus, S. pneumoniae, L. monocytogenes, Haemophilus spp., and streptococci of groups A, B, and G attack native valves. Mortality rates range from 10% to 40%.The host may have comorbid conditions such as underlying malignancy, diabetes mellitus, intravenous drug use, or alcoholism.


The patient presents with fever, fatigue, and malaise <2 weeks after onset of infection. On physical examination, a changing murmur and congestive heart failure may be noted. Hemorrhagic macules on palms or soles ( Janeway’s lesions) sometimes develop. Petechiae, Roth’s spots, splinter hemorrhages, and splenomegaly are unusual. Rapid valvular destruction, particularly of the aortic valve, results in pulmonary edema and hypotension. Myocardial abscesses can form, eroding through the septum or into the conduction system and causing life-threatening arrhythmias or high-degree conduction block. Large friable vegetations can result in major arterial emboli, metastatic infection, or tissue infarction. Emboli can lead to stroke, changes in mental status, visual disturbances, aphasia, ataxia, headache, meningismus, brain abscess, cerebritis, spinal cord infarct with paraplegia, arthralgia, osteomyelitis, splenic abscess, septic arthritis, and hematuria. Older patients with S. aureus endocarditis are especially likely to present with nonspecific symptoms—a circumstance that delays diagnosis and worsens prognosis. Rapid intervention is crucial for a successful outcome.


Inhalational Anthrax (See also Chap. 6) Inhalational anthrax, the most severe form of disease caused by Bacillus anthracis, had not been reported in the United States for more than 25 years until the recent use of this organism as an agent of bioterrorism (Chap. 6). Patients presented with malaise, fever, cough, nausea, drenching sweats, shortness of breath, and headache. Rhinorrhea was unusual. All patients had abnormal chest roentgenograms at presentation. Pulmonary infiltrates, mediastinal widening, and pleural effusions were the most common findings. Hemorrhagic meningitis was seen in 38% of these patients. Survival was more likely when antibiotics were given during the prodromal period and if multidrug regimens were used. In the absence of urgent intervention with antimicrobial agents and supportive care, inhalational anthrax progresses rapidly to hypotension, cyanosis, and death. Avian Influenza (H5N1) Infection (See also Chap. 88) Human cases of avian influenza were first reported in Hong Kong. Recent cases have occurred primarily in Southeast Asia, particularlyVietnam. However, evidence of a rapidly expanding geographic distribution of the virus throughout the world is of grave concern. Avian influenza should be considered in patients with severe respiratory tract illness, particularly if they have been exposed to poultry.To date, human- to-human transmission is rare. Patients present with high fever, an influenza-like illness, and lower respiratory tract symptoms.Watery diarrhea may develop and may precede respiratory symptoms.


Dyspnea develops a median of 5 days after the onset of symptoms and can progress to respiratory distress syndrome, multiorgan failure, and death within 9–10 days after the onset of illness. Early antiviral treatment with neuraminidase inhibitors should be initiated along with aggressive supportive measures. Hantavirus Pulmonary Syndrome (See also Chap. 99) Hantavirus pulmonary syndrome (HPS) has been documented in the United States (primarily the southwestern states), Canada, and South America. Most cases occur in rural areas and are associated with exposure to rodents. Patients present with a nonspecific viral prodrome of fever, malaise, myalgias, nausea, vomiting, and dizziness that may progress to pulmonary edema and respiratory failure. HPS causes myocardial depression and increased pulmonary vascular permeability; therefore, careful fluid resuscitation and use of pressor agents are crucial. Aggressive cardiopulmonary support during the first few hours of illness can be life-saving.