NEUROLOGIC INFECTIONS WITH OR WITHOUT SEPTIC SHOCK
Bacterial Meningitis Bacterial meningitis is one of the most common infectious emergencies involving the central nervous system. Although hosts with cell-mediated immune deficiency, including transplant recipients, diabetic patients, the elderly, and cancer patients treated with certain chemotherapeutic agents, are at particular risk for Listeria monocytogenes meningitis, most cases in adults are due to S. pneumoniae (30 to 50%) and N. meningitidis (10 to 35%). An early presentation of headache, meningismus, and fever is classic but is seen in only half 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. The presentation is fulminant, with sepsis and brain edema, 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 to 20% of cases; 50 to 60% of patients have bacteremia. A poor neurologic outcome is associated with coma at any time during the course or with a CSF glucose level of <0.6 mmol/L (<10 mg/dL). Mortality is associated with coma, respiratory distress, shock, a CSF protein level of >2.5 g/L, a peripheral white blood cell count of <5000/uL, and a serum sodium level of <135 mmol/L.
Suppurative Intracranial Infections Other rare intracranial lesions that present with sepsis and hemodynamic instability are subdural empyema, septic cavernous sinus thrombosis, and septic superior sagittal sinus thrombosis. Rapid recognition of the toxic patient with central neurologic signs is crucial to improvement of the dismal prognosis of these entities.
Subdural Empyema This infection arises from the paranasal sinus in 60 to 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 to 20% die.
Septic Cavernous Sinus Thrombosis This condition follows a facial or sphenoid sinus infection; 70% of cases are due to staphylococci and the remainder 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
Brain Abscess 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% 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 unrecognized endocarditis. The infection progresses over several days from cerebritis to an abscess with a mature capsule. 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 to 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 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 with advanced disease. Unrecognized infection results in a 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; 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, and staphylococci are the most common etiologic agents; in HIV-infected intravenous drug users, therapy must cover gram-negative rods and methicillin-resistant S. aureus. If a patient gives a history of antecedent back pain and has new neurologic symptoms, this diagnosis must immediately be considered. 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. Rapid recognition and treatment, including immediate drainage, can prevent or minimize permanent neurologic sequelae.
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. Death occurs secondary to septic shock or toxin production with hemodynamic instability and multiorgan failure. 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 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 an inexorable invasive course with high mortality.
Acute Bacterial Endocarditis 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 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, change 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. Rapid intervention is crucial for a successful outcome.
DIAGNOSTIC WORKUP OF THE ACUTELY ILL PATIENT
After a quick clinical assessment, diagnostic material should be obtained rapidly and antibiotic and supportive treatment begun. In the sepsis syndromes, 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. For patients with possible acute endocarditis, three sets of blood cultures should be performed. 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 to 104/mL in patients with an intact spleen). Blood smears from patients with possible cerebral malaria or babesiosis must be examined for the diagnosis and quantitation of parasitemia. Blood smears may also be diagnostic in ehrlichiosis.
Patients with meningitis should have CSF obtained before the initiation of antibiotic therapy. If focal neurologic signs, abnormal mental status, or papilledema mandates brain imaging before a lumbar puncture, antibiotics should be administered prior to imaging but after blood for cultures has been drawn. If CSF cultures are negative, laboratory examination of CSF by latex agglutination or immunoprecipitation can be attempted to make an etiologic diagnosis. However, blood cultures will provide the diagnosis in 50 to 70% of cases.
Focal abscesses necessitate immediate computed tomography or magnetic resonance imaging 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, magnetic resonance imaging, urinalysis, erythrocyte sedimentation rate determination, and transthoracic or transesophageal echocardiography may all prove important.
TREATMENT
lists first-line treatments for the infections considered in this chapter. (For a more detailed discussion of treatment, see specific chapters.) In addition to the initiation of parenteral antibiotic therapy, several of these infections require urgent surgical attention. General surgery for possible necrotizing fasciitis or myonecrosis, 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 the rapid commencement of antibiotic therapy. For infections such as necrotizing fasciitis and clostridial myonecrosis, rapid surgical intervention supercedes other diagnostic or therapeutic maneuvers.
Acutely ill febrile patients require close observation, aggressive supportive measures, and¾in most cases¾admission to intensive care units. Adjunctive treatments, such as intravenous immunoglobulin administration for TSS, can be considered after initial stabilization. The most important task of the physician is to recognize the acute infectious emergency and proceed with appropriate urgency.
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