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42 INFECTIOUS DISEASE EMERGENCIES

42 INFECTIOUS DISEASE EMERGENCIES
Harrison’s Manual of Medicine

42

INFECTIOUS DISEASE EMERGENCIES

General Considerations
Sepsis without an Obvious Focus of Primary Infection
Sepsis with Skin Manifestations
Sepsis with a Soft Tissue/Muscle Primary Focus
Neurologic Infections with or without Septic Shock
Focal Syndromes with a Fulminant Course
Diagnostic Workup of the Acutely Ill Patient
Bibliography

It is important to recognize potentially catastrophic infections that require emergent attention and empirical therapy. In many cases, appropriate therapy at presentation will decrease the likelihood of a fatal outcome in the acutely ill infected febrile patient.
General Considerations
A febrile patient who appears agitated or anxious should raise suspicion of impending decompensation. Information on symptom chronology, focal symptoms, travel, contact with animals (including insects), recent activities, and recent infections should be obtained, as should a vaccination history and a full review of systems. Comorbid conditions, such as lack of splenic function, alcoholism, liver disease, IV drug use, HIV infection, diabetes, presence of prosthetic material, malignancy, steroid use, and chemotherapy, may all predispose to increased severity of specific infections. Vital signs should be carefully measured, with the caveat that elderly, uremic, and cirrhotic individuals and patients taking steroids or NSAIDs may be afebrile despite serious underlying infection. A complete physical examination should be performed, with special attention to skin, soft tissue, and neurologic examination.
Sepsis without an Obvious Focus of Primary Infection
These pts have a brief prodrome of nonspecific Sx that progresses quickly to hemodynamic instability with hypotension, tachycardia, tachypnea, respiratory distress, or altered mental status. Septic shock is often due to gram-negative bacilli such as Pseudomonas aeruginosa, Escherichia coli, or Aeromonas hydrophila or to gram-positive organisms such as Staphylococcus aureus or group A streptococci. Treatment can usually be initiated empirically on the basis of the presentation (Table 42-1). Sepsis in asplenic pts is 600 times more common than sepsis in the general population, usually occurs within 2 years of loss of splenic function, and carries a mortality rate of 80%. Encapsulated bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, are common etiologic agents; overwhelming infections with E. coli, S. aureus, group B streptococci, P. aeruginosa, Capnocytophaga spp., Babesia spp., and Plasmodium spp. have also been reported. Babesiosis manifests 1 to 4 weeks after the pt is bitten by the tick Ixodes scapularis, presenting with chills, fatigue, anorexia, nausea, myalgia, arthralgia, and headache; severe cases can include hemolysis and renal failure. Severe babesiosis is common in asplenic pts, those coinfected with Borrelia burgdorferi (the agent of Lyme disease) and/or Ehrlichia spp., and those infected with the European species Babesia divergens. In the appropriate epidemiologic circumstances, tularemia should be considered in the setting of wild rabbit, tick, or tabanid fly contact. Plague should be considered after contact with ground squirrels, prairie dogs, or chipmunks in the Southwest and Colorado.

Table 42-1 Common Infectious Disease Emergencies

Sepsis with Skin Manifestations
Maculopapular and petechial rashes may reflect early meningococcal or rickettsial disease. Exanthems are usually viral. Meningococcemia usually affects children 6 months to 5 years old although sporadic cases occur in students of school age and residents of army barracks. N. meningitidis sepsis (Waterhouse- Friderichsen syndrome) carries a mortality rate of 50–60%. This rapidly progressive form of disease is usually not associated with meningitis, but meningitis should be ruled out in any case of suspected meningococcemia. Initially, a blanching maculopapular rash appears on the trunk and extremities; then petechiae form on the ankles, wrists, mucosal surfaces, and pressure points. Rash, hypotension, and a normal or low WBC and ESR confer 90% mortality. Initiation of early treatment can be lifesaving (Table 42-1). Rocky Mountain spotted fever (RMSF) is caused by tick-transmitted Rickettsia rickettsii and occurs throughout the United States. RMSF begins with general symptoms of fever, malaise, myalgia, and nausea. In 50% of pts, blanching macules develop over the distal extremities after 72 h and progress centripetally. The lesions become hemorrhagic, and a septic picture with ARDS, encephalitis, and multiorgan failure can develop. The CSF contains 10–100 cells/µL with a monocytic predominance. Untreated infection has a mortality of 30%. Purpura fulminans is the cutaneous manifestation of DIC and most commonly results from overwhelming infection with N. meningitidis, H. influenzae, or S. pneumoniae. Skin lesions can rapidly progress from petechial to hemorrhagic, and rapidly progressive multiorgan failure may occur. Ecthyma gangrenosum, classically developing secondary to infection with P. aeruginosa or A. hydrophila in an immunocompromised pt, presents as hemorrhagic vesicles progressing to central necrosis, with a rim of erythema. In pts with underlying liver disease, Vibrio vulnificus infection from contaminated shellfish can progress rapidly to a septic picture with bullous or hemorrhagic skin lesions and a mortality rate of 50%. Asplenic pts with Capnocytophaga canimorsus infection from a dog bite can present with a diffuse exanthem or erythema multiforme before developing a septic picture. This infection has a 30% mortality. Toxic shock syndrome (TSS) has defined diagnostic criteria that include erythroderma, fever, confusion, hypotension, and multiorgan failure. TSS is due to toxin-producing S. aureus or Streptococcus spp., with higher mortality in streptococcal TSS.
Sepsis with a Soft Tissue/Muscle Primary Focus
Necrotizing fasciitis occurs in pts predisposed by diabetes, IV drug use, and peripheral vascular disease. It is most commonly due to group A Streptococcus or mixed aerobic/anaerobic organisms at a site of minor trauma. Fever and pain out of proportion to physical findings are common. Surgical intervention is mandatory. Necrotizing fasciitis due to Clostridium perfringens is associated with rapidly progressive hemolysis and a septic picture. Clostridial myonecrosis is characterized by massive necrotizing gangrene and a septic picture developing within hours of onset. The affected area has a bronzed appearance, and bullous lesions with serosanguineous drainage and a mousy odor may be noted. Myonecrosis due to Clostridium septicum, often spontaneous, occurs in pts with underlying malignancy and is associated with high mortality (highest among pts with involvement of the trunk).
Neurologic Infections with or without Septic Shock
Rapid recognition of the septic pt with central neurologic signs is crucial to improvement of the dismal prognosis of these entities. Acute bacterial meningitis is one of the most common infectious disease emergencies affecting the CNS. Most cases are caused by S. pneumoniae (30–50%) or N. meningitidis (10–35%); pts with immunosuppression or diabetes and the elderly are at increased risk for Listeria monocytogenes meningitis. The classic triad of fever, headache, and meningismus should be sought. Papilledema is uncommon on presentation. Palsies of cranial nerves IV, VI, and VII can be seen in 10–20% of cases. Mortality is associated with coma, a septic picture, a CSF protein level of >2.5 g/L, a peripheral WBC of <5000/µL, and hyponatremia. Subdural empyema arises from the paranasal sinuses in 60–70% of cases, and microaerophilic streptococci and staphylococci are usually the microbiologic causes. Focal signs are present in 75% of cases, and mortality is 6–20%. Unilateral or retroorbital headache associated with fever should raise suspicion of septic cavernous sinus thrombosis, an unusual complication of a facial or sphenoid sinus infection. Staphylococci and aerobic and anaerobic streptococci are the usual causes. Most pts have periorbital edema progressing to ptosis, proptosis, ophthalmoplegia, and papilledema. Mortality is 30%. Ethmoid or maxillary sinusitis is rarely complicated by septic thrombosis of the superior sagittal sinus, most commonly caused by S. pneumoniae, other streptococci, and staphylococci. A fulminant course presents as headache, nausea, and vomiting progressing to coma, nuchal rigidity, and brainstem signs, with death in >80% of cases. Brain abscess often presents as headache or focal neurologic signs in an afebrile pt. Abscesses can originate from a contiguous or hematogenous source, and those arising hematogenously have a greater chance of intraventricular rupture, which carries a high mortality rate. Prognosis is poor in pts with rapid deterioration, delayed diagnosis, intraventricular rupture, multiple abscesses, and an abnormal neurologic examination on presentation. High fever and deteriorating mental status after travel to endemic areas should raise the suspicion of cerebral malaria secondary to Plasmodium falciparum infection. Nuchal rigidity is rare, and mortality is 30% if diagnosis is delayed. Spinal epidural abscess presents with fever in 60% of cases and with back pain in 90% and is most commonly seen in pts with a history of diabetes, IV drug use, recent spinal trauma or surgery, and HIV infection. S. aureus is the most common etiology, although gram-negative rods or methicillin-resistant S. aureus can be present in HIV- infected IV drug users. Neurologic deficits develop late in the course of this infection. Urgent surgical intervention can minimize permanent neurologic sequelae.
Focal Syndromes with a Fulminant Course
Rapid death from sepsis can occur in TSS due to a toxin-producing infection of a joint, a wound, a postoperative site, the peritoneum, or sinuses. Sudden airway obstruction from an oropharyngeal infection can cause rapid deterioration and death (Chap. 50). Delayed diagnosis of and surgical intervention in rhinocerebral mucormycosis are associated with high mortality (Chap. 50). Acute bacterial endocarditis is usually due to S. aureus, S. pneumoniae, L. monocytogenes, Haemophilus spp., or group A, B, or G streptococci; mortality ranges from 10 to 40%. Pts present with fever of <2 weeks’ duration, peripheral embolic stigmata are sometimes present, and a changing heart murmur or CHF may be noted. Mortality is associated with rapid valvular destruction, myocardial abscess, arterial emboli from friable valve vegetations, and metastatic infections. Rapid intervention is essential for a successful outcome.
Diagnostic Workup of the Acutely Ill Patient
Before antibiotic therapy is initiated, clinical assessment and procurement of diagnostic material should be accomplished as quickly as possible. Baseline blood exam should include blood cultures; CBC with differential; measurement of serum electrolytes, BUN, creatinine, and glucose; basic coagulation studies; and LFTs. Three sets of blood cultures should be obtained if endocarditis is suspected. Examination of the blood smear is useful in asplenic pts (to document Howell-Jolly bodies that indicate the absence of splenic function) and in cases of suspected malaria, babesiosis, and ehrlichiosis. Microscopic examination of a gram-stained buffy coat may reveal organisms in asplenic pts, given the high- grade bacteremia associated with sepsis in these pts. Pts with suspected meningitis should undergo LP before initiation of antibiotics; if brain imaging is needed before LP, antibiotics should be administered prior to imaging but after blood has been drawn for cultures. Imaging is indicated in pts with abnormal sensorium or focal neurologic signs. Appropriate radiographic examination and echocardiography are important, especially in cases that may merit emergent surgical intervention.

TREATMENT
The most important task of the physician is to recognize the acute infectious emergency and proceed with appropriate urgency. Table 42-1 lists first-line treatments for the infections considered in this chapter. The acutely ill febrile pt requires close observation and, in most cases, admission to the ICU for aggressive supportive therapy. For infections such as necrotizing fasciitis, myonecrosis, subdural empyema, spinal epidural or brain abscess, mucormycosis, or acute endocarditis, rapid surgical intervention supersedes other diagnostic or therapeutic maneuvers.

Bibliography

For a more detailed discussion, see Barlam TF, Kasper DL: Approach to the Acutely Ill Infected Febrile Patient, Chap. 19, p. 102, in HPIM-15.

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