APPROACH TO THE PATIENT Infectious Disease Emergencies
• Acutely ill febrile pts require emergent attention and must be appropriately evaluated and treated at presentation to improve outcome. A quick assessment of general appearance provides a subjective sense of whether the pt is septic or toxic.
• History: Although presenting symptoms are frequently nonspecific, the physician should elicit the following elements of a directed history to help identify risk factors for particular infections:
– Onset and duration of symptoms, changes in severity or rate of progression over time
– Host factors (e.g., alcoholism, IV drug use) and comorbid conditions (e.g., asplenia, diabetes, HIV infection)
– Potential nidus for invasive infection (e.g., recent URI or influenza, trauma, burn, surgery, foreign body)
– Exposure history (e.g., travel, pets, diet, medication use, vaccination history, sick contacts, menstruation history, sexual contacts)
• Physical examination: A complete physical examination should be performed, with particular attention to general appearance, vital signs, skin and soft tissue exam, and neurologic evaluation (including mental status).
• Diagnostic workup: should be initiated rapidly, preferably before antibiotics are given
– Bloodwork: cultures, CBC with differential, electrolytes, BUN, creatinine, LFTs, blood smear examination (for parasitic or tick-borne diseases), buffy coat
– CSF cultures if meningitis is possible. If focal neurologic signs, papilledema, or abnormal mental status is noted, administer antibiotics after blood culture samples are obtained, perform brain imaging, and then consider LP.
– CT or MRI to evaluate focal abscesses; cultures of wounds or scraping of skin lesions as indicated
– No diagnostic procedure should delay treatment for more than minutes.
• Treatment: Empirical antibiotic therapy (Table 26-1) is critical.
TABLE 26-1 COMMON INFECTIOUS DISEASE EMERGENCIES
– Adjunctive therapy (e.g., glucocorticoids or IV immunoglobulin) may reduce morbidity and mortality rates for specific conditions. Dexamethasone for bacterial meningitis must be given before or with the first dose of antibiotic.
SPECIFIC PRESENTATIONS (TABLE 26-1)
Sepsis without an Obvious Focus of Primary Infection
1. Septic shock: A primary site of infection may not be evident initially.
2. Overwhelming infection in asplenic pts
a. Most infections occur within 2 years after splenectomy, with ~50% mortality.
b. Encapsulated organisms cause the majority of infections; Streptococcus pneumoniae is the most common isolate.
3. Babesiosis: A history of recent travel to endemic areas raises the possibility of this diagnosis.
a. Nonspecific symptoms occur 1–4 weeks after a tick bite and can progress to renal failure, acute respiratory failure, and DIC.
b. Asplenia, age >60 years, underlying immunosuppressive conditions, infection with the European strain Babesia divergens, and co-infection with Borrelia burgdorferi (Lyme disease) or Anaplasma phagocytophilum are risk factors for severe disease.
4. Tularemia and plague can produce typhoidal or septic syndromes with mortality rates ~30% and should be considered in the appropriate epidemiologic setting.
5. Viral hemorrhagic fevers: zoonotic viral illness from animal reservoirs or arthropod vectors (e.g., Lassa fever in Africa, hantavirus hemorrhagic fever with renal syndrome in Asia, Ebola and Marburg virus infections in Africa, and yellow fever in Africa and South America). Dengue is the most common arboviral disease worldwide; dengue hemorrhagic fever is the more severe form, with a triad of hemorrhagic manifestations, plasma leakage, and platelet counts <100,000/μL. Mortality is 10–20% but approaches 40% if dengue shock syndrome develops. Supportive care and volume replacement therapy are life-saving.
Sepsis with Skin Manifestations
1. Maculopapular rashes: usually not emergent but can occur in early meningococcemia or rickettsial disease
2. Petechiae: warrant urgent attention when accompanied by hypotension or a toxic appearance
a. Meningococcemia: Young children and their household contacts are at greatest risk; outbreaks occur in schools, day-care centers, and military barracks.
i. Petechiae begin at ankles, wrists, axillae, and mucosal surfaces and progress to purpura and DIC.
ii. Other symptoms include headache, nausea, myalgias, altered mental status, and meningismus.
iii. Mortality rates are 50–60%; early treatment initiation may be life-saving.
b. Rocky Mountain spotted fever: A history of a tick bite and/or travel or outdoor activity can often be ascertained.
i. Rash appears by day 3 (but never develops in 10–15% of pts). Blanching macules become hemorrhagic, starting at wrists and ankles and spreading to legs and trunk (centripetal spread), then palms and soles.
ii. Other symptoms include headache, malaise, myalgias, nausea, vomiting, and anorexia. In severe cases, hypotension, encephalitis, and coma can ensue.
c. Other rickettsial diseases: Mediterranean spotted fever (Africa, southwestern and south-central Asia, southern Europe) is characterized by an inoculation eschar at the site of the tick bite and has a mortality rate of ~50%. Epidemic typhus occurs in louse-infested areas, usually in a setting of poverty, war, or natural disaster; mortality rates are 10–15%. In scrub typhus (southeastern Asia and western Pacific), the etiologic organism is found in areas of heavy scrub vegetation (e.g., riverbanks); 1–35% of pts die.
3 Purpura fulminans: cutaneous manifestation of DIC with large ecchymotic areas and hemorrhagic bullae. It is associated primarily with Neisseria meningitidis but can also be associated with S. pneumoniaeand Haemophilus influenzae in asplenic pts.
4. Ecthyma gangrenosum: hemorrhagic vesicles with central necrosis and ulceration and a rim of erythema seen in pts with septic shock due to Pseudomonas aeruginosa or Aeromonas hydrophila
5. Bullous or hemorrhagic lesions: can be caused by Escherichia coli and organisms in the genus Vibrio (V. vulnificus and other noncholera vibrios from seawater or contaminated raw shellfish), Aeromonas, and Klebsiella, particularly in pts with liver disease
6. Erythroderma: diffuse sunburn-like rash, often associated with toxic shock syndrome (TSS, defined by clinical criteria of hypotension, multi-organ failure, fever, and rash) in acutely ill pts; more common in staphylococcal TSS than streptococcal TSS
Sepsis with a Soft Tissue/Muscle Primary Focus
1. Necrotizing fasciitis: characterized by extensive necrosis of the SC tissue and fascia; typically caused by group A streptococci
a. Exam is notable for high fever and pain out of proportion to physical findings; the infected area is red, hot, shiny, and exquisitely tender. Lessening of pain in the absence of treatment is an ominous sign that represents destruction of peripheral nerves.
b. Risk factors: trauma, varicella, childbirth, and comorbid conditions (e.g., diabetes, peripheral vascular disease, IV drug use)
c. Mortality rates are ~100% without surgery, >70% in the setting of TSS, and 15–34% overall.
2. Clostridial myonecrosis: often associated with trauma or surgery, with massive necrotizing gangrene developing within hours of onset
a. Spontaneous cases are associated with Clostridium septicum infection and underlying malignancy.
b. Pain and toxic appearance are out of proportion to physical findings. Pts are apathetic and may have a sense of impending doom.
c. Skin overlying the affected area is mottled, bronze-brown in color, and edematous. Crepitus may be present. Bullous lesions may drain serosanguineous fluid with a mousy or sweet odor.
d. Mortality rates are 12% for myonecrosis of extremities, 63% for myonecrosis of the trunk, and >65% for spontaneous myonecrosis.
Neurologic Infections with or without Septic Shock
1. Bacterial meningitis: Most cases in adults are caused by S. pneumoniae (30–50%) or N. meningitidis (10–35%).
a. Classic triad of headache, meningismus, and fever in only one-half to two-thirds of pts
b. Blood cultures positive in 50–70% of pts
c. Predictors of a poor outcome include meningitis due to S. pneumoniae, coma, respiratory distress, hypotension, CSF protein >2.5 g/L, CSF glucose <10 mg/dL, peripheral WBC count <5000/μL, and serum Na+ <135 mmol/L.
2. Brain abscess: often present without systemic signs. Presentations are more consistent with a space-occupying lesion in the brain.
a. 70% of pts have headache and/or altered mental status, 50% have focal neurologic signs, and 25% have papilledema.
b. Lesions arise from contiguous foci (e.g., sinusitis or otitis) or hematogenous infection (e.g., endocarditis).
c. >50% of cases are polymicrobial, involving both aerobic (primarily streptococcal) and anaerobic organisms.
d. Mortality is low, but morbidity is high (30–55%).
3. Intracranial and spinal epidural abscesses (ICEAs and SEAs): ICEAs are rare in the United States, but SEAs are on the rise. Both are more common in areas with limited access to health care.
a. ICEAs are typically polymicrobial and present as fever, mental status changes, and neck pain.
b. SEAs are typically due to hematogenous seeding (with staphylococci most commonly isolated) and present as fever, localized spinal tenderness, and back pain.
4. Cerebral malaria: should be urgently considered in pts who have recently traveled to endemic areas and present with a febrile illness and neurologic signs
a. Fulminant Plasmodium falciparum infection is associated with fever >40°C, hypotension, jaundice, ARDS, and bleeding. Nuchal rigidity and photophobia are rare.
b. Unrecognized infection results in a 20–30% mortality rate.
Focal Syndromes with a Fulminant Course
1. Rhinocerebral mucormycosis: presents as low-grade fever, dull sinus pain, diplopia, impaired mental status, chemosis, proptosis, hard-palate lesions that respect the midline, and dusky or necrotic nasal turbinates; generally occurs in pts with immunocompromising conditions
2. Acute bacterial endocarditis: presents as fever, fatigue, and malaise within 2 weeks of infection and is associated with rapid valvular destruction, pulmonary edema, and myocardial abscesses
a. Etiologies include Staphylococcus aureus, S. pneumoniae, Listeria monocytogenes, Haemophilus spp., and streptococci of group A, B, or G.
b. Although Janeway lesions (hemorrhagic macules on the palms or soles) can be seen, other embolic phenomena (e.g., petechiae, Roth’s spots, splinter hemorrhages) are less common.
c. Features can include rapid valvular destruction, pulmonary edema, hypotension, myocardial abscesses, conduction abnormalities and arrhythmias, large friable vegetations, and major arterial emboli with tissue infarction.
d. Mortality rates are 10–40%.
3. Inhalational anthrax: of increasing concern, given the potential of Bacillus anthracis as a bioterrorism agent
a. Clinical symptoms are nonspecific, but chest x-rays show mediastinal widening, pulmonary infiltrates, and pleural effusions.
b. Hemorrhagic meningitis occurs in 38% of pts.
c. Urgent antimicrobial therapy is needed, ideally with a multidrug regimen in the prodromal period.
4. Avian influenza (H5N1): occurs primarily in Southeast Asia after exposure to poultry. Pts can rapidly develop bilateral pneumonia, ARDS, and multiorgan failure, culminating in death. Human-to-human transmission is rare.
5. Hantavirus pulmonary syndrome: occurs primarily following rodent exposure in rural areas of the southwestern United States, Canada, and South America.
a. A nonspecific viral prodrome can rapidly progress to pulmonary edema, respiratory failure, myocardial depression, and death.
b. In an appropriate epidemiologic setting, the early onset of thrombocytopenia may distinguish this syndrome from other febrile illnesses.
For a more detailed discussion, see Barlam TF, Kasper DL: Approach to the Acutely III Infected Febrile Patient, Chap. 121, p. 1023, in HPIM-18.