Infectious Disease Emergencies: Cleveland Clinic

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/infectious-disease-emergencies/

Infectious disease emergencies are conditions that have potential for significant harm to the patient if not recognized and treated promptly. Timely and appropriate intervention may significantly improve outcomes. The following is a discussion of important infectious disease emergencies.Acute Bacterial MeningitisDefinition, Etiology, and IncidenceBacterial meningitis is an inflammation of the meninges caused by bacterial infection. Acute meningitis is characterized by the development of meningeal signs over the course of a few hours to a few days. The important causes of bacterial meningitis are outlined in Table 1.Table 1. Important Causes of Bacterial Meningitis*In AdultsIn Children After Neurosurgery

Streptococcus pneumoniae Neisseria meningitidis Listeria monocytogenes Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Streptococcus agalactiae(in neonates) Escherichia coli (in neonates) Staphylococcus aureus Pseudomonas aeruginosa Enteric gram-negative bacteria

*Mycobacterium tuberculosis is also a bacterium and can cause meningitis, but it is usually discussed separately as tuberculous meningitis.A passive survey conducted in the United States between 1978 and 1981 revealed an annual incidence rate for bacterial meningitis of 3.0 cases per 100,000 population.1 During this period, bacterial meningitis was predominantly a disease of children, the most common offending pathogen being Haemophilus influenzae. The introduction of routine immunization of children against H. influenzae type B in the late 1980s dramatically reduced the incidence of infection with this microorganism. As a consequence, the overall incidence of bacterial meningitisand particularly of meningitis caused by H. influenzaedecreased, so that bacterial meningitis is now a disease predominantly of adults.2PathophysiologyThe initial event is usually nasopharyngeal colonization with a pathogenic microorganism.3 This is followed by mucosal invasion, bacteremia, and meningeal invasion.4 A marked inflammatory response occurs in the subarachnoid space, but this response is inadequate to control the infection. This inflammatory response results in increased permeability of the blood-brain barrier. This is responsible for the increased cerebrospinal fluid (CSF) protein content seen in patients with meningitis. Progression of meningitis leads to the development of cerebral edema, resulting in increased CSF pressure. Inflammation of blood vessels traversing the subarachnoid space may lead to their thrombosis. This can result in ischemia and infarction of the underlying brain.Clinical PresentationPatients with acute bacterial meningitis usually present with headache, neck stiffness, fever, projectile vomiting, and photophobia. In more advanced disease, there is progressive clouding of consciousness. On examination, neck rigidity may be seen and Kernigs and Brudzinskis signs may be elicited. Cranial nerve palsies or focal neurologic signs may be seen in a minority of patients. The presence of petechial skin lesions should raise suspicion for meningococcemia.DiagnosisThe differential diagnosis includes viral and tuberculous meningitis, viral meningoencephalitis, subarachnoid hemorrhage, and primary amebic meningoencephalitis. Differentiation from viral meningitis on clinical grounds is usually difficult, and requires laboratory testing. Where tuberculosis is prevalent, it must be recognized that tuberculous meningitis can sometimes manifest acutely and could be mistaken for bacterial meningitis. Viral meningoencephalitis may manifest somewhat similarly with headache and fever, but patients would usually have more profound alteration in the sensorium early in the illness and neck stiffness may not be prominent. The most prominent symptom of subarachnoid hemorrhage is severe headache with a rapid onset. Primary amebic meningoencephalitis is a rare condition with a presentation similar to that of acute bacterial meningitis, but cultures are negative and amebae can be detected in the CSF by careful microscopic examination. There is usually a recent history of swimming in a warm freshwater lake or pond.The most important diagnostic test is a lumbar puncture, which should always be performed in all patients with suspected acute meningitis. Imaging tests do not help in making the diagnosis or identifying the cause of bacterial meningitis. It is not necessary to obtain a computed tomography (CT) scan before performing a lumbar puncture unless there are focal neurologic deficits.5 The CSF should be sent for cell count, protein and glucose levels, and Gram staining and culture. Typical CSF findings in acute bacterial meningitis include an elevated opening pressure, increased CSF white blood cell (WBC) count (100-10,000 cells/mcL), usually with a predominance of neutrophils, increased CSF protein level (> 50 mg/dL), and decreased CSF glucose level (< 40% of simultaneously measured serum glucose level).6 Gram staining may reveal the presence of microorganisms and, if so detected, would be helpful for guiding therapy. In viral meningitis, the CSF WBC count is elevated, but the cells are usually predominantly lymphocytes, and the CSF glucose level may be normal or marginally decreased. The best way to confirm a diagnosis of viral meningitis is by specific polymerase chain reaction (PCR) testing, if available.TreatmentThe management of bacterial meningitis includes appropriate antibiotic therapy and adjunctive corticosteroids.7,8 Ideally, the lumbar puncture should be done before the administration of antibiotics. However, antibiotic administration should not be delayed for any reason if the lumbar puncture cannot be immediately performed. A lumbar puncture should be performed as soon as possible, even if antibiotics have already been administered; the possibility of being able to make a definite causal diagnosis, and its value in guiding subsequent therapy and managing possible complications, are fully worth the effort. Empiric antibiotics should be selected based on the expected pathogens. The patients age, presence or absence of risk factors such as middle ear or sinus disease, or recent neurosurgery provide clues about the cause and pathogenesis.It is recommended that patients be started on adjunctive dexamethasone 10 mg IV every 6 hours for 4 days with the first dose of antibiotics. This has been shown to improve outcomes in patients with bacterial meningitis.7 Antibiotic selection and dosing should also take into consideration the agents ability to cross the blood-brain barrier and achieve an effective concentration in the CSF. In adults, initial empiric treatment should provide adequate therapy for Streptococcus pneumoniae and Neisseria meningitidis. Increasing resistance of S. pneumoniae to beta-lactam antibiotics (including ceftriaxone) has prompted recommendations to initiate empiric antibiotic therapy with a regimen consisting of vancomycin and ceftriaxone.6 If Listeria monocytogenes is a possibility (eg, in older adults, pregnant women, and those with cellular immune deficits), ampicillin should be added. If Pseudomonas aeruginosa is a possibility, as after neurosurgical procedures, ceftazidime should be used instead of ceftriaxone. Antibiotic therapy should be adjusted once the causative microorganism has been identified. Duration of therapy for bacterial meningitis has not been adequately defined. For meningococcal meningitis, 7 days of therapy is considered adequate. S. pneumoniae should be treated for 10 to 14 days. L. monocytogenes should be treated for at least 21 days.9Summary The differential diagnosis of acute bacterial meningitis includes viral meningitis and meningoencephalitis, tuberculous meningitis, primary amebic meningoencephalitis, and subarachnoid hemorrhage. Lumbar puncture should be performed as soon as possible. Dexamethasone plus empiric antibiotics should be started without delay. Antibiotics should be adjusted subsequently, based on culture and susceptibility data.Back to TopAcute MeningococcemiaDefinition, Etiology, and IncidenceAcute meningococcemia is a disseminated infection caused by Neisseria meningitidis, with high mortality rates in those with fulminant disease. Meningococcal infection occurs in an endemic pattern, with periodic epidemics. There are substantial cyclic variations in disease incidence. In the United States, epidemics account for less than 5% of the reported cases. The incidence of meningococcal disease in the United States peaked at 1.7 cases per 100,000 population in 1997.10PathophysiologyThe pathogenesis of meningococcal infection begins with nasopharyngeal colonization. About 10% of the population has asymptomatic nasopharyngeal carriage of N. meningitidis during nonepidemic periods. A small proportion of carriers go on to develop invasive meningococcal disease. People who develop invasive disease generally do so soon after acquisition of carriage.11 Factors that facilitate invasive disease include agent factors, such as virulence, and transmissibility and host factors.Patients with deficiencies of the late components of the complement pathway are at markedly increased risk of developing recurrent episodes of meningococcal infections.12 Genetic variants of mannose-binding lectin (MBL), a plasma opsonin that initiates the MBL pathway of complement activation, may also make patients more susceptible to meningococcal infections.13Clinical PresentationMeningococcal infection can manifest in a variety of forms: bacteremia without sepsis, meningitis (with or without meningococcemia), acute meningococcemia (with or without meningitis), a meningoencephalitic picture, or chronic meningococcemia. The most fulminant form is acute meningococcemia, in which death may ensue within hours of the onset of symptoms.

Figure 1: Click to Enlarge The most common manifestation of acute meningococcemia is fever with rash. The rash usually begins with petechiae, initially with a few discrete lesions 1 to 2 mm in diameter that often progress and coalesce to form larger ecchymotic lesions (Figure 1). In cases of associated meningitis, meningeal signs and symptoms may also be present.The shock state is a dominant feature in patients with acute meningococcemia, and is often accompanied by disseminated intravascular coagulation (DIC). Meningococcemia can lead to complications such as massive adrenal hemorrhage; DIC; arthritis; heart problems such as pericarditis and myocarditis; neurologic problems such as deafness and peripheral neuropathy; and peripheral gangrene.14 In epidemic settings in Third-World countries, case-fatality rates as high as 70% have been recorded. In endemic settings in industrialized countries, the mortality rate is approximately 8%, but might be as high as 19%.Meningococcemia does not always manifest in a fulminant manner. An unusual manifestation of meningococcal infection is chronic meningococcemia, which manifests with low-grade fever, rash, and arthritis. This manifestation is identical to that of chronic gonococcemia.DiagnosisWhen patients present with an acute febrile illness with the characteristic ecchymotic rash, the diagnosis is not difficult to make. Early infection could be missed if a careful physical examination is not carried out in a patient with an acute febrile illness. Definitive diagnosis requires isolation of the microorganism from a normally sterile site. Samples for blood cultures should be obtained before the administration of antibiotics, if possible. Antibiotic therapy rapidly sterilizes the blood and CSF in patients with meningococcal infection.15,16 CSF cultures are often positive for microorganisms, even in patients who do not have clinical evidence of meningitis,17 and should always be examined when meningococcemia is suspected. Microorganisms may also be identified in the biopsy of petechial skin lesions.TreatmentThe treatment of acute meningococcemia involves appropriate antibiotic therapy, along with supportive therapy for shock, heart failure, DIC, and other complications. Early antibiotic therapy has been conclusively shown to improve outcomes in patients with meningococcal disease.18 The recommended treatment for severe meningococcal infection is a third-generation cephalosporin with good CSF penetration. Ceftriaxone, 1 g every 12 hours, is the most commonly used treatment.19 Cefotaxime and ceftazidime should be equally efficacious alternatives. Patients who are allergic to cephalosporins may be treated with chloramphenicol, 100 mg/kg, in 4 divided doses. The maximum total dosage is 4 g/day.20 High doses of penicillin G should also usually be adequate; however, small numbers of resistant N. meningitidis have been reported, and therefore penicillin G is not ordinarily the first-choice antibiotic in the absence of susceptibility data. The shock state is a dominant part of the clinical picture of meningococcemia and supportive management is important. The use of steroids for meningococcemia is controversial, and a recommendation for the routine use of steroids for treatment of this condition cannot be made.ProphylaxisHousehold contacts are at significantly higher risk of infection.21 Chemoprophylaxis is recommended for household contacts, daycare center staff and clients, and anyone exposed to the patients oral secretions. Among health care workers, this includes people who intubated the patient and who provided suction to clear secretions. Effective prophylactic treatments include a single 1-g dose of ceftriaxone intravenously or intramuscularly, a single 500-mg dose of ciprofloxacin, a single 500-mg dose of azithromycin, and 600 mg of rifampin every 12 hours for 2 days.18Summary The classic presentation of meningococcemia is fever and rash. Prompt antibiotic therapy can be lifesaving. Shock is a dominant clinical finding and supportive management is important. People who have come in close contact with the patient should receive chemoprophylaxis.Back to TopCranial Subdural EmpyemaDefinition, Etiology, and IncidenceSubdural empyema is a condition in which there is collection of pus in the region between the dura and the arachnoid. The most common causes of subdural empyema are aerobic and anaerobic streptococci (especially the S. milleri group), Staphylococcus aureus and, to a lesser extent, aerobic gram-negative bacilli.22,23 Studies have found anaerobic infections in varying proportions of infections. However a high proportion of patients have had anaerobic microorganisms recovered.24 This raises the possibility that these infections are usually polymicrobial, with anaerobic microorganisms usually present. Subdural empyemas account for 15% to 20% of all localized intracranial infections.23PathophysiologyCranial subdural empyema is usually a complication of infection of the paranasal sinuses.23 Less commonly, it results from spread from the middle ear.25 It may also occur as a complication of trauma or neurosurgery. Infection spreads intracranially through the emissary veins that communicate between the veins draining the facial structures and intracranial venous channels. In a small proportion of cases, subdural empyema may occur by metastatic spread, usually from a pulmonary infection, for an unexplained reason.Clinical PresentationPatients with this condition usually present acutely, with headache and vomiting. Most patients have an altered mental status at presentation and the level of consciousness deteriorates rapidly. Patients may have neurologic deficits and complications such as local cerebritis, cerebral abscesses, and septic dural venous thromboses may occur.DiagnosisThe diagnosis should be considered in any patient who presents with features suggestive of meningitis and a focal neurologic deficit or rapid deterioration in the level of consciousness. If recognized, lumbar puncture should not be performed because of the risk of cerebral herniation.23 CSF findings would be nonspecific, with an elevated opening pressure, neutrophilic or mixed pleocytosis, and elevated protein level. Gram staining and culture of CSF are usually negative. The diagnostic procedure of choice is magnetic resonance imaging (MRI). If not available, CT scanning with contrast should be done. CT is inferior to MRI in detecting empyemas at the base of the brain and in the posterior fossa.TreatmentEffective treatment for cranial subdural empyema requires a combined surgical and medical approach. Empiric antibiotic therapy should be broad spectrum and include coverage for gram-positive pyogenic bacteria and anaerobes. Vancomycin is a reasonable choice. Cultures obtained at the time of surgery will help tailor antibiotic treatment. The goal of surgery is complete evacuation of the purulent collection, which may be accomplished by craniotomy or through burr holes, depending on the circumstances of the case. It is important to evacuate the collection completely, and a craniotomy or multiple surgical procedures may be necessary to accomplish this. Up to 50% of patients who are treated with burr hole drainage require reoperation, compared with 20% of those treated with craniotomy.26 The duration of antibiotic therapy is usually 3 to 4 weeks after adequate drainage. If there is associated osteomyelitis of the skull, treatment should be extended to approximately 6 weeks.Summary MRI or CT scanning should be performed promptly when cranial subdural empyema is suspected. Treatment requires a combined medical and surgical approach. Empiric broad-spectrum antibiotic therapy should be started promptly. Cultures obtained at the time of surgery will help tailor antibiotic therapy. Multiple operations may be necessary.Back to TopNecrotizing Soft Tissue InfectionsDefinition, Etiology, and IncidenceThis term encompasses several specific clinical entities characterized by disease processes that produce necrosis of subcutaneous tissue, muscle, or both, and that progress rapidly and require a combined emergent surgical and medical approach for optimal outcomes. These entities include necrotizing fasciitis, streptococcal necrotizing myositis, clostridial myonecrosis (gas gangrene), and nonclostridial crepitant myositis.Type I necrotizing fasciitis is a mixed infection caused by an anaerobic bacterium (usually Bacteroides or Clostridium) in association with a facultative anaerobic microorganism, such as a streptococcus or a member of the Enterobacteriaceae. Type II necrotizing fasciitis, hemolytic streptococcal gangrene, is caused by group A, B, C, or G streptococci. Other microorganisms may be present in the mix. Community-associated methicillin-resistant S. aureus (CA-MRSA) has recently been described as a cause of necrotizing fasciitis.27Clostridial myonecrosis, also commonly known as gas gangrene, and streptococcal necrotizing myositis, as their names imply, are caused by Clostridium spp. and by beta hemolytic streptococci, respectively.Nonclostridial crepitant myositis encompasses several clinical entities that may result from mixed infection caused by: anaerobic streptococci, along with group A streptococci or S. aureus (anaerobic streptococcal myonecrosis); a mixture of anaerobic and facultatively anaerobic microorganisms (synergistic nonclostridial anaerobic myonecrosis, or Meleneys bacterial synergistic gangrene); Proteus spp., Bacteroides spp., and anaerobic streptococci in devitalized limbs (infected vascular gangrene); Vibrio vulnificus; and Aeromonas hydrophila.As a group, these illnesses are uncommon but not rare, and prompt recognition and appropriate management can significantly improve outcomes.PathophysiologyNecrotizing fasciitis usually begins with the introduction of the offending microorganism into the subcutaneous structures, usually as a result of minor trauma. Gas gangrene occurs in situations in which muscle injury is compounded by wound contamination with soil or other foreign material harboring spores of a tissue-invasive Clostridium, such as C. perfringens, C. novyi, and C. septicum. Such injuries include war injuries, compound fractures, and septic abortion. Most cases of streptococcal myositis appear to begin spontaneously. The different forms of nonclostridial myonecrosis usually begin with the introduction of the offending microorganisms at the time of usually minor trauma. Aeromonas hydrophila myonecrosis occurs as a result of inoculation of the microorganism at the time of penetrating injury in a freshwater setting or in association with fish or other aquatic animals. In all these conditions, there is rapid progression of disease, often with gas formation in the muscles and subcutaneous tissues, and in many cases associated with the development of gangrene.Diabetes mellitus is the most important risk factor for the development of necrotizing soft tissue infections.28 Other risk factors include alcoholism, corticosteroid use, and parenteral drug use.Clinical PresentationNecrotizing fasciitis is usually an acute process, with severe infection of the superficial and deep fascia. It most commonly occurs in the extremities. The affected area becomes erythematous, swollen, warm, and painful. The infection typically progresses rapidly, with the skin becoming darker, and over a few days bullae and skin breakdown develop. In the polymicrobial form, crepitations may be felt subcutaneously, indicating the presence of gas. Development of anesthesia over an erythematous area may precede development of skin breakdown and may serve as a warning sign that the disease process is more serious than cellulitis. Pain out of proportion to the skin changes also may be an indicator of a more serious infection. On palpation, the affected area has a woody hard feel. Increasing tissue edema may lead to the development of compartment syndrome.Necrotizing myositis or myonecrosis may occur without overt findings on the skin surface. The predominant symptom is intense muscle pain, usually accompanied by fever. Patients usually appear more ill than would be expected from the physical findings. Gas gangrene and other syndromes of necrotizing myositis caused by anaerobic microorganisms will also have crepitations because of the presence of subcutaneous gas.At initial presentation, it may not be possible to make a clinical distinction between necrotizing fasciitis and necrotizing myositis. Indeed, both processes may occur simultaneously, especially with streptococcal infection. Lack of involvement of the overlying skin does not exclude the presence of an underlying necrotizing process.Streptococcal necrotizing soft tissue infections are usually associated with the toxic shock syndrome. Acute vascular compromise from trauma or embolic occlusion leads to tissue infarction and may progress to infected vascular gangrene if the appropriate microorganisms gain access to the devitalized tissues.DiagnosisClinical suspicion is important in order to make an early diagnosis of a necrotizing soft tissue infection. A clue to the presence of a deep necrotizing process is the presence of tenderness clearly beyond the areas of apparent involvement in the skin. Leukocytosis is common. The creatine kinase (CK) level is usually elevated, but may be normal in cases of necrotizing fasciitis with minimal muscle involvement. Ultrasonography, CT scanning, or MRI will usually reveal muscle swelling and fluid in muscle compartments, but may not be apparent early in the disease process. Histopathologic examination will reveal the presence of sheets of neutrophils in fascial planes. Gram staining of tissue exudates will reveal the presence of microorganisms.TreatmentIt is not always obvious whether a skin or soft tissue infection is a necrotizing one. When considered a possibility, aggressive management is important. Clinical features cannot accurately predict the causative microorganism. A prudent approach would be to treat with antibiotics that are effective against group A streptococci, S. aureus, enteric gram-negative bacteria, and anaerobic microorganisms until the etiologic diagnosis has been established. The antibiotics of choice for initial empiric therapy are clindamycin plus ampicillin-sulbactam plus ciprofloxacin.29 If there is reason to suspect MRSA infection, vancomycin should be added. Antibiotic therapy should be modified when culture and susceptibility data become available. A lack of response to a reasonable trial of antibiotics should prompt emergent surgical intervention. Prompt and aggressive fasciotomy and debridement of devitalized tissue are necessary to gain control of the infection. Early surgical intervention reduces mortality.28 If infection is advanced, amputation may be necessary and lifesaving.Summary Clinical suspicion will facilitate the early diagnosis of necrotizing soft tissue infections. Skin surface findings may be minimal. Prompt and aggressive surgical debridement is the most important aspect of treatment. Empiric antibiotic therapy should consist of clindamycin plus ampicillin-sulbactam plus ciprofloxacin. Antibiotic therapy should be modified once culture data become available.Back to TopToxic Shock SyndromeDefinition, Etiology, and IncidenceToxic shock syndrome (TSS) is a severe toxin-mediated bacterial disease characterized by shock resulting from an excess of inflammatory cytokines. Two important syndromes, staphylococcal TSS and streptococcal TSS, are recognized to be caused by S. aureus and Streptococcus pyogenes, respectively. Both are uncommon diseases. The incidence rate of streptococcal TSS in the United States is 3.5 per 100,000 population per year. Staphylococcal TSS has an overall incidence of about 1 per 100,000, with menstrual TSS about twice as common as nonmenstrual TSS.30 At the peak of the epidemic of menstrual TSS, before the recognition of the association between the use of certain tampons and TSS, the incidence rate of menstrual TSS was as high as 10 per 100,000 population per year and accounted for over 90% of all cases of staphylococcal TSS.PathophysiologyToxic shock syndrome is a toxin-mediated disease.31 Several exotoxins of S. aureus and S. pyogenes are capable of stimulating excessive T cell responses, and are thus known as superantigens. These toxins include toxic shock syndrome toxin-1 (TSST-1) and staphylococcal exotoxins A, B, and C (SEA, SEB, SEC) of S. aureus, and streptococcal pyrogenic exotoxins A, B, and C (SPEA, SPEB, SPEC) of S. pyogenes. These toxins are capable of binding both major histocompatibility complex (MHC) class II molecules of antigen-presenting cells and the V region of T cell receptors, leading to broad-range induction of T cell proliferation. The resulting excessive production of inflammatory cytokines (interleukin-1 and -6 [IL-1, IL-6], tumor necrosis factors and [TNF-, TNF-], interferon gamma [IFN-]) leads to increased capillary permeability resulting in tissue damage to various organs and shock.Staphylococcal TSS is commonly associated with menstruation (menstrual TSS).32 The pathophysiology of menstrual TSS includes a high local protein level and relatively high local pH (caused by the presence of blood and blood products), high partial pressure of carbon dioxide (caused by higher than atmospheric Pco2 in blood), and high Po2 (introduced by high-absorbency tampons).31 The production of TSST-1 by colonizing S. aureus is stimulated in such an environment. Nonmenstrual TSS can be caused by S. aureus infection at any site in the body, including surgical wounds, the lungs, peritoneal dialysis catheters, and skin and mucosal infections. The illness is mediated by TSST-1 or SEA or SEB produced by the microorganisms at the site of infection.Clinical PresentationToxic shock syndrome manifests as a multisystem illness, with shock being a prominent feature.31 Clinical features include high fever, hypotension, tachycardia, tachypnea, anasarca, and a morbilliform rash. Many patients also have myalgias and gastrointestinal symptoms, such as vomiting, abdominal pain, and diarrhea. Patients may develop confusion. The disease progresses rapidly and, especially with streptococcal TSS, can lead to death within 24 to 48 hours. Menstrual TSS starts within 2 days of the beginning or end of menses in women using high-absorbency tampons.32 In many patients with nonmenstrual TSS, the site of infection may show minimal inflammation and may not be readily apparent.Streptococcal TSS is generally a more serious condition.33 In this condition, the site of infection with S. pyogenes may be obvious. It is usually a necrotizing soft tissue infection, but streptococcal TSS has been described in patients with pneumonia, meningitis, septic arthritis, peritonitis, and other deep infections.33 Patients are usually very ill and may develop acute respiratory distress syndrome (ARDS) or DIC. The mortality of adequately treated staphylococcal TSS is about 5%. The mortality of streptococcal TSS is about 50%.DiagnosisThe diagnostic criteria for TSS are outlined in Tables 2 and 3.34,35 In streptococcal TSS, streptococci can usually be detected in culture at the affected site or in blood culture. In staphylococcal TSS, it is rare to detect staphylococci, except if vaginal cultures are obtained from patients with menstruation-associated TSS. Prompt diagnosis requires recognition of the constellation of symptoms and signs, with confirmation by additional laboratory testing to look for abnormalities that indicate damage to the organ systems expected to be involved by the process. CT or MRI helps in defining the presence of deep soft tissue infection in patients with streptococcal TSS. Gas is not produced, but the diagnosis should not be excluded if imaging findings do not appear impressive when clinical features are suggestive of the disease.Table 2. Diagnostic Criteria for Staphylococcal Toxic Shock Syndrome*Diagnostic criteria include:

Fever: Temperature 102 F (38.9 C) Rash: Diffuse macular erythroderma Overt or orthostatic hypotension

Plus multisystem involvement ( 3 of the following):

Gastrointestinal: Vomiting or diarrhea at the onset of illness Muscular: Severe myalgia or creatine kinase level 2 the upper limit of normal Mucous membranes: Vaginal, oropharyngeal, or conjunctival hyperemia Renal: Blood urea nitrogen or creatinine level 2 the upper limit of normal or urinary sediment with pyuria ( 5 leukocytes per high-power field) in the absence of urinary tract infection Hepatic: Total bilirubin, aspartate transaminase, or alanine aminotransaminase level 2 the upper limit of normal Hematologic: Platelet count 100,000/mcL Central nervous system: Disorientation or alteration in consciousness without focal neurologic signs when fever and hypotension are absentNegative results on the following tests, if performed: Blood, throat, or cerebrospinal cultures (blood cultures may be positive for Staphylococcus aureus) Rise in antibody titer to Rocky Mountain spotted fever, leptospirosis, or rubeolaDesquamation 1-2 wk after onset of illness, particularly over palms and soles

*All 6 criteria have to be satisfied to make a definite diagnosis. Fulfillment of the first 5 criteria makes a probable diagnosis.Table 3. Diagnostic Criteria for Streptococcal Toxic Shock Syndrome*Diagnostic criteria include 1 of the following:

Isolation of Streptococcus pyogenes or Hypotension

Plus 2 or more of the following:

Renal impairment: Creatinine level 2.0 mg/dL or 2 the upper limit of normal for age Thrombocytopenia (platelet count 100,000/mcL) or disseminated intravascular coagulation Liver involvement: Aspartate transaminase, alanine aminotransaminase, or total bilirubin level 2 the upper limit of normal Acute respiratory distress syndrome Generalized macular erythrodermic rash that may desquamate Necrotizing soft tissue infection

*All 3 criteria must be met. If S. pyogenes is isolated from a normally sterile site, the diagnosis is definite; if isolated from a nonsterile site, the diagnosis is probable.TreatmentManagement of TSS includes eradication of the focus of infection plus supportive care, which includes fluid resuscitation and vasopressors, as necessary.36 Large volumes of crystalloids may be required because of the loss of intravascular volume caused by capillary leak. Circulating bacterial hemolysins may lead to moderate to severe anemia, necessitating blood transfusions. When the focus of infection is identified in staphylococcal TSS, it is important to drain abscesses and treat with appropriate antibiotics. If a hyperabsorbent tampon is in place, it should be removed. Patients who have streptococcal TSS do better with combinations of clindamycin and cell-wall active agents compared to patients who receive cell-wall active agents alone.37 Because clindamycin is not affected by bacterial inoculum or stage of growth, and because it inhibits synthesis of bacterial toxin, there are theoretical reasons why it would also be effective in these patients. Thus, in both staphylococcal and streptococcal toxic shock syndrome, clindamycin should be included initially.Staphylococcal TSS should also initially be treated with vancomycin. Antibiotic therapy can be modified once susceptibility data become available. MRSA infections should be treated with vancomycin; MSSA infections with oxacillin; and penicillin-susceptible S. aureus should be treated with penicillin G. Treatment of streptococcal TSS usually includes aggressive surgical debridement, with antibiotic therapy and supportive care. The antibiotic of choice is penicillin G.Summary The toxic shock syndromes are toxin-mediated diseases of S. aureus and S. pyogenes. The site of infection may not be readily apparent, especially in staphylococcal TSS. Streptococcal TSS is often associated with necrotizing soft tissue infections. Surgical debridement of the focus of infection may be necessary. Early antibiotic therapy should include clindamycin in addition to cell-wall active agents.Back to TopNeutropenic FeverDefinition, Etiology, and IncidenceFever in a neutropenic patient is defined as a single oral temperature > 101F (38.3C) or a temperature >100.4 (38.0C) sustained over a 1-hour period.38 Neutropenia is defined as an absolute neutrophil count (ANC) < 500 cells/mcL and/or ANC that is expected to decrease to 100.4 F (38.0 C) for more than 1 hour in a neutropenic patient (actual or predicted ANC