Bioterrorist Agents

Bioterrorist Agents in Adults¶

Duration of therapy represents total treatment time..

‡Patients who remain critically ill after Doxycycline 200 mg (IV) q12h ×3 days should continue receiving 200 mg (IV) q12h for the full course of therapy.. For patients who have improved after 3 days, the dose may be decreased to 100 mg (IV or PO) q12h to complete the course of therapy.. Total duration of IV + PO therapy = 60 days..

*Ciprofloxacin 400 mg (IV) q12h or 500 mg (PO) q12h or Levofloxacin 500 mg (IV or PO) q24h..

¶Additional information can be obtained at www..bt..cdc..gov.. For post-exposure prophylaxis, see p.. 358..

174 A n t i b i o t i c E s s e n t i a l s

Bioterrorist Agents in Adults¶ (cont’d)

Duration of therapy represents total treatment time..

*Ciprofloxacin 400 mg (IV) q12h or 500 mg (PO) q12h or Levofloxacin 500 mg (IV or PO) q24h..

¶Additional information can be obtained at www..bt..cdc..gov.. For post-exposure prophylaxis, see p.. 358..

‡Patients who remain critically ill after Doxycycline 200 mg (IV) q12h ×3 days should continue receiving 200 mg (IV) q12h for the full course of therapy.. For patients who have improved after 3 days, the dose may be decreased to 100 mg (IV or PO) q12h to complete the course of therapy.. Total duration of IV + PO therapy = 60 days..

Anthrax (B. anthracis)

Clinical Presentation:  Bioterrorist anthrax usually presents as cutaneous or inhalational anthrax.. Cutaneous anthrax has the same clinical presentation as naturally-acquired anthrax: Lesions begin as painless, sometimes mildly pruritic papules, usually on the upper extremities, neck, or face, and evolve into a vesicular lesion which may be surrounded by satellite lesions.. A “gelatinous halo” surrounds the vesicle as it evolves into an ulcer, and a black eschar eventually develops over the ulcer.. Inhalational anthrax is a biphasic illness.. Initially, there is a viral illness-like prodrome with fever, chills, and myalgias with chest discomfort 3–5 days after inhaling anthrax spores.. Bacteremia is common.. Patients often improve somewhat over the next 1–2 days, only to rapidly deteriorate and become critically ill with high fevers, dyspnea, cyanosis, crushing substernal chest pain, and shock.. Oropharyngeal anthrax presents with fever, soft tissue edema, painful cervical adenopathy.. Lesions in oropharynx ulcerate in ~ 2 weeks. . GI anthrax presents with fever, malaise ± syncope, followed in 24 hours by mild nausea/vomiting, severe abdominal pain, and then ascites, ↑ abdominal pain, flushed face, and shock..

Diagnostic Considerations:  Cutaneous anthrax is a clinical diagnosis suggested by the lack of pain relative to the size of the lesion. . A presumptive microbiologic diagnosis is made by finding gram-­positive bacilli in the fluid from the gelatinous halo surrounding the ulcer or from under

the eschar. . Blood cultures may reveal B. . anthracis. . Definitive diagnosis depends on identifying B. . ­anthracis from culture of the skin lesions or blood cultures. . Inhalation anthrax is suspected in patients with fevers, chest pain, and mediastinal widening accompanied by bilateral pleural effusions on chest x-ray.. If chest x-ray findings are equivocal, then a chest CT/MRI is recommended to demonstrate mediastinal lymph node enlargement.. Inhalational anthrax presents as a hemorrhagic mediastinitis, not community-acquired pneumonia.. The diagnosis is clinical but supported by Gram stain of hemorrhagic pleural fluid demonstrating gram-positive bacilli. . Patients with inhalational anthrax often have positive blood cultures and may have associated anthrax meningitis.. If meningitis is present, the CSF is hemorrhagic and CSF Gram stain shows gram-positive bacilli, which, when cultured, is B.. anthracis..

Pitfalls:  Cutaneous anthrax is most often initially confused with ringworm or a brown recluse spider bite.. Subacute/chronic lesions may initially resemble ringworm, but the skin lesion in ringworm has an annular configuration, is painless, and is accompanied by prominent pruritus, particularly at the edges of the lesion.. Patients with ringworm have no fever or systemic symptoms.. Brown recluse spider bites produce extremely painful lesions with irregular edges, which eventually develop a necrotic center followed by eschar formation.. The lesions of the brown recluse spider bite are irregular, not accompanied by fever, and intensely painful.. In contrast, cutaneous anthrax lesions are painless, round, and are not primarily pruritic in nature.. Be alert to the possibility of smallpox following outbreaks of other bioterrorist agents such as anthrax, as the genome of smallpox is easily modified and can be incorporated into bacteria..

Therapeutic Considerations:  B.. anthracis is highly susceptible to nearly all antibiotics; in the U..S.. bioterrorist experience, no strains were resistant to antibiotics.. Traditionally, penicillin has been used to treat natural anthrax, but because of concern for resistant bioterrorist strains, doxycycline or quinolones are preferred.. Because meningitis is frequently associated with inhalational anthrax, penicillin in (IV) meningeal doses may be added as a second or third antibiotic to quinolones or doxycycline.. For meningeal anthrax use penicillin G or meropenem in meningeal doses. . Clindamycin is active against B.. anthracis and has been used in combination therapy because of its potential anti-exotoxin activity. . Some patients seemed to respond somewhat better when clindamycin 600 mg (IV) q8h or 300 mg (PO) q8h plus rifampin 300 mg (PO) q12h is added to either a quinolone or doxycycline.. Corticosteroids should be considered for severe mediastinal edema or meningitis.. Depending upon antimicrobial susceptibility testing, rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin or clarithromycin may be added if the need arises. . Prolonged therapy of 100 days with or without anthrax vaccine has been recommended by some authors.. Three doses of anthrax vaccine (BioThraxT, formerly AVA - anthrax vaccine absorbed) have been recommended by the ACIP and the John Hopkins Working Group on Civilian Bio-Defense with antimicrobials for prophylaxis after aerosolized exposure, but as it is not licensed, it must be administered under an IND application.. Some B.. anthracis strains produce cephalosporinase and inducible beta-lactamase that make penicillins drugs less suitable for initial therapy.. In general, the organism is resistant to trimethoprim-sulfamethoxazole..

Prognosis:  Prognosis of cutaneous anthrax is uniformly good.. With inhalational anthrax, prognosis is related to the inhaled dose of the organism, underlying host status, and rapidity of initiating antimicrobial therapy.. Inhalational anthrax remains a highly lethal infectious disease, but with early intervention/ supportive care, some patients survive.. Patients with associated anthrax meningitis have a poor prognosis..

Tularemic Pneumonia (F. tularensis)

Clinical Presentation:  Fever, chills, myalgias, headache, dyspnea and a nonproductive cough may occur, but encephalopathy is absent.. Chest x-ray resembles other causes of community-acquired pneumonia, but tularemic pneumonia is usually accompanied by hilar adenopathy and pleural effusion, which is serosanguineous or frankly bloody.. Cavitation sometimes occurs.. Relative bradycardia is not present and serum transaminases are not elevated..

Diagnostic Considerations:  Tularemic pneumonia can resemble other atypical pneumonias, but in a patient presenting with community-acquired pneumonia, the presence of hilar adenopathy with pleural effusions should suggest the diagnosis.. F.. tularensis may be seen in the Gram stain of the sputum or bloody pleural effusion fluid as a small, bipolar staining, gram-negative bacillus.. Diagnosis is confirmed serologically or by culture of the organism from respiratory fluid/blood..

Pitfalls:  Gram-negative bacilli in the sputum may resemble Y.. pestis but are not bipolar staining.. Chest x-ray may resemble inhalational anthrax (hilar adenopathy/mediastinal widening).. Both tularemic pneumonia and inhalational anthrax may be accompanied by bloody pleural effusions.. In contrast to inhalational anthrax (which may be accompanied by anthrax meningitis), CNS involvement is not a feature of tularemic pneumonia..

Therapeutic Considerations:  Streptomycin is the antibiotic traditionally used to treat tularemia.. Gentamicin may be substituted for streptomycin if it is not available.. Doxycycline, chloramphenicol, or a quinolone are also effective..

Prognosis:  Depends on inoculum size and health of host.. Mortality rates for severe untreated infection can be as high as 30%, although early treatment is associated with mortality rates < 1%..

Pneumonic Plague (Y. pestis)

Clinical Presentation:  Bioterrorist plague presents as pneumonic plague and has the potential for per- son-to-person spread.. After an incubation period of 1–4 days, the patient presents with acute onset of fever, chills, headache, myalgias and dizziness, followed by pulmonary manifestations including cough, chest pain, dyspnea.. Hemoptysis may occur, and increasing respiratory distress and circulatory collapse are common.. Compared to community-acquired pneumonia, patients presenting with plague pneumonia are critically ill.. Sputum is pink and frothy and contains abundant bipolar staining gram-negative bacilli.. Chest x-ray is not diagnostic..

Diagnostic Considerations:  Yersinia pestis may be demonstrated in sputum Gram stain (bipolar staining gram-negative bacilli) and may be recovered from blood cultures.. Laboratory confirmation requires isolation of Y.. pestis from body fluid or tissue culture.. Consider the diagnosis in any critically ill patient with pneumonia and bipolar staining gram-negative bacilli in the sputum..

Pitfalls:  Plague pneumonia can resemble tularemic pneumonia, but there are several distinguishing features.. Unlike plague, tularemic pneumonia is usually associated with hilar enlargement and pleural­ effusion.. Although gram-negative bacilli may be present in the sputum of patients with tularemia, the organisms are not bipolar staining..

Therapeutic Considerations:  Streptomycin is the preferred drug for pneumonic plague.. Doxycycline or a quinolone is also effective..

Prognosis:  Depends on inoculum size, health of the host, and the rapidity of treatment.. Left untreated, mortality rates exceed 50%.. ARDS, DIC, and other manifestations of gram-negative sepsis are more common when treatment is delayed..

Botulism (C. botulinum) (see p. 171)

Smallpox

Clinical Presentation:  After an incubation period of 1–12 days, typical smallpox is heralded by high fever, headache, and gastrointestinal complaints (vomiting, colicky pain).. No rash is present at this time.. After 1–2 days, the fever decreases to near normal level, and macules begin to appear on the head, usually at the hairline.. Macules progress to papules, then vesicles, then finally pustules.. The rash begins on the face/head and rapidly spreads to the extremities with relative sparing of the trunk.. The mucous membranes of the oropharynx and upper/lower airways are also affected early. . Lesions initially are umbilicated, then later lose their umbilication.. The fully formed smallpox pustule is located deep in the dermis.. The appearance of the pustules is accompanied by recrudescence of fever.. Hemorrhagic smallpox is a fulminant form of smallpox that begins with petechial lesions in a “swimming trunk” distribution and results in widespread hemorrhage into the skin and mucous membranes.. Patients look toxemic and have high fevers with no other signs of smallpox; death from toxemia often occurs before the typical rash appears..

Diagnostic Considerations:  Smallpox is most likely to be confused with chickenpox or drug eruptions.. Patients with chickenpox are less toxemic and the lesion distribution is different from smallpox.. Chickenpox lesions occur in crops for the first 72 hours, then stop.. The lesions of chickenpox are superficial, not deep in the dermis like smallpox, and chickenpox vesicles are predominantly centripetal rather than centrifugal.. The chickenpox vesicle has been described as a “dewdrop on a rose petal” because of its fragility and superficial location on the skin.. If there is any doubt, a Tzanck test should be performed by unroofing the vesicle, scraping cells from the base of the vesicle, and staining the cells.. A positive Tzanck test indicates chickenpox, not smallpox.. Alternatively, a monoclonal VZV test can be performed on vesicle base cells.. Drug eruptions are not accompanied by toxemia and are usually accompanied by relative bradycardia if fever is present..

Pitfalls:  Smallpox is easily missed before the rash and is difficult to diagnose.. Look for the combination of high fever/headache with gastrointestinal symptoms (e..g.., abdominal pain) that precedes the rash.. GI complaints may be confused with appendicitis.. A petechial rash in a swimming trunk distribution does not occur with any other infectious disease and should immediately suggest smallpox.. Recently human monkeypox has occurred in the Western Hemisphere after transmission via imported African rodent pets.. After an incubation period of 7–19 days, patients develop fever, headache, and malaise.. Skin lesions appear on head, trunk, and extremities (including palms/soles).. Rash begins like smallpox as macules, then papules, and finally umbilicated vesicles.. Some exudative pharyngitis/tonsillitis with cervical adenopathy may be present.. Encephalitis is very rare.. Laboratory results are nonspecific.. Unlike smallpox, human monkeypox patients are not toxic, have pharyngitis/tonsillitis with cervical adenopathy, and have focal hemorrhage into some lesions (in hemorrhagic smallpox, hemorrhages are extensive/widespread).. Patients immunized against smallpox are unlikely to acquire human monkeypox..

Therapeutic Considerations:  Smallpox vaccination should be initiated as soon as the diagnosis is suspected.. Smallpox vaccine may be given at full strength or in a 1:5 dilution, which is also protective.. Cidofovir may prove useful but dose for smallpox is not established..

Prognosis:  Variable in typical smallpox, with deep, permanent scarring, especially on the face.. Hemorrhagic smallpox is highly lethal..