Page 1014 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 81: Biological Warfare 745

overcome any dilution factor. Furthermore, boiling water and cooking Blood cultures are almost always positive within 24 hours; however, lab-
food destroys most agents. A recent study warns of the United States’ oratories may presumptively assume a contamination of specimens with
vulnerability to such an attack based on very centralized food process- Bacillus cereus. Thus microbiology labs need to be notified of the sus-
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ing methods and distribution of the foods over large areas. Likely agents picion, so they may use selective media to isolate anthrax. Confirmatory
are botulinum toxin, Salmonella, Shigella, Escherichia coli, and Vibrio testing such as growth on special nutrient agars, susceptibility to lysis by
cholera. 11 gamma phage, direct fluorescence antibody staining, nucleic acid signa-
Contact with intact skin with any of these agents is unlikely to result tures, and enzyme-linked immunosorbent assay (ELISA) for protective
in disease. However, if the skin integrity is compromised, the potential and capsule antigens are performed at level B and C laboratories of the
for disease exists. Current studies suggest that thorough washing with Laboratory Response Network (LRN) for Bioterrorism, CDC, or the U.S.
soap and water is sufficient to overcome even this threat. Army Medical Research Institute of Infectious Diseases (USAMRIID).
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Serological testing of acute and convalescent serum is useful only
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ANTHRAX retrospectively.
Postexposure prophylaxis for adults (including pregnant women and
Bacillus anthracis is a gram-positive spore-forming bacterium. It is an the immunosuppressed) is initially with ciprofloxacin 500 mg orally
encapsulated, nonmotile, and nonhemolytic organism, and usually every 12 hours or doxycycline 100 mg every 12 hours. If the strain is
grows within 6 to 24 hours on conventional culture media. The vegeta- susceptible, then amoxicillin 500 mg orally every 8 hours or the above
tive form is incapable of surviving outside of a warm-blooded host, and dose of doxycycline can be taken. These regimens should be taken for
colony counts are undetectable in water after 24 hours. As a biological 60 days owing to the unpredictable latency of inhalational anthrax. An
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weapon it is likely to be delivered as an aerosol. Clinically this would aluminum hydroxide adsorbed, licensed vaccine made of noninfectious
produce inhalational anthrax, the deadliest and rarest form of the dis- sterile culture filtrate from attenuated B anthracis is available in highly
ease. The cutaneous form is not considered lethal with current antibiotic limited supply, and only currently provided to the military; evidence
regimens, and the gastrointestinal form is exceedingly rare with essen- shows it to protect against aerosol challenge. However, currently it is
tially no cases having been reported in the United States. 12,13 not recommended for postexposure prophylaxis in either health care
Inhalational anthrax occurs after spores are ingested by alveolar mac- workers or the public. 32
rophages and transported via regional lymphatics to mediastinal lymph Current CDC recommendations for empiric treatment of inhala-
nodes. Germination takes place in 2 to 5 days, but can be delayed as tional anthrax in adults (including pregnant women and immunosup-
much as 60 days, after which disease rapidly occurs. The major viru- pressed) are ciprofloxacin 400 mg intravenously every 12 hours or
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lence factors are the antiphagocytic capsule and three toxin components doxycycline 100 mg intravenously every 12 hours. These should be
(lethal factor, edema factor, and protective antigen). The three toxins given with another one or two additional antibiotics that have in vitro
cause edema, hemorrhage, and necrosis, producing a thoracic lymphad- activity against anthrax (rifampin, penicillin, ampicillin, vancomycin,
enitis and hemorrhagic mediastinitis. Death can occur despite antibiotic imipenem, clindamycin, chloramphenicol, or clarithromycin). If the
administration if toxin levels have reached a critical threshold. 13 strain of the organism is susceptible, then 4 million units of penicil-
Clinically anthrax presents as a biphasic illness. The first stage is char- lin G intravenously every 4 hours can be used. High-dose intravenous
acterized by nonspecific symptoms of fever, chills, weakness, headache, penicillin may provide better CNS penetration in cases associated with
vomiting, abdominal pain, dyspnea, cough, and chest pain, lasting for meningitis. Recent survivors of inhalational anthrax were treated with
hours up to a few days. This may be followed by a short period of appar- a combination of ciprofloxacin (based on official recommendations),
ent recovery. The second stage is characterized by sudden resurgence of rifampin (for increased gram-positive coverage and for its intracel-
fever, shortness of breath, profound sweating that drenches the patient, lular mechanism of action), and clindamycin (for its ability to prevent
and shock. Hypocalcemia, hypoglycemia, hyperkalemia, depression of expression of toxin). It is important to note that B anthracis isolates
the respiratory centers, and terminal acidosis are some of the biochemical produce cephalosporinase, making treatment with cephalosporins such
and physiologic signs that develop in severe infections. Delirium, men- as ceftriaxone useless. 25
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ingismus, obtundation, seizures, and coma secondary to hemorrhagic As person-to-person transmission does not occur, patients can be
meningitis occur in up to 50% of cases. Involvement of the gut is also cared for under standard precautions. However, it should be remem-
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a common feature of advanced disease and thought to be secondary to bered that in an act of suspected bioterrorism one would not imme-
hematogenous spread (different from primary gastrointestinal anthrax) diately know whether patients are affected with anthrax or a more
presenting as abdominal pain (33%), and can lead to necrotizing enteritis transmissible agent such as plague, which warrants respiratory isola-
of the bowel. The lag period between the initial exposure and the onset tion precautions as well (Table 81-3). Patients with cutaneous anthrax
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of symptoms seems to be inversely proportional to mortality. 17 should be cared for under contact isolation. Specimens should be
Diagnosis of inhalational anthrax clinically requires a high degree handled under Biosafety Level (BSL) 2 precautions. Decontamination
of suspicion given that the symptoms on initial presentation can easily of individuals exposed to the initial aerosol attack is not necessary, and
be confused with a seasonal viral syndrome. Presenting symptoms and washing with soap and water is sufficient to eliminate any secondary
routine laboratory tests are nonspecific, and the only clue prior to devel- aerosolization. For contaminated hospital areas, bleach solutions and
opment of fulminant disease may be a widened mediastinum on chest 0.5% hypochlorite solution are adequate for decontamination. 26
x-ray. 18,19 The recent series of cases in the United States suggest a paren-
chymal process is likely to be more common than previously thought. PLAGUE
Small pleural effusions that rapidly progress to a large size appears to
be a consistent finding and may correlate with the progression of the Yesinia pestis is a nonmotile, gram-negative bipolar coccobacillus that is
disease. Thoracentesis yields a hemorrhagic fluid with relatively few the causative agent of plague. Recently, the organism has been used as
white blood cells (WBCs), and is positive for the bacteria by Gram stain the hypothetical biological weapon in the TOPOFF scenario, theoreti-
and culture. Noncontrast computed tomography (CT) scan of the chest cally causing thousands of casualties and widespread disruption of the
is extremely helpful in determining the extent of mediastinal adenopathy public health system. The most likely route of delivery during an attack
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and edema. 20-22 would be via aerosol. 28
Meningeal signs develop in 50% of cases, with contrast CT scan of the Human plague occurs worldwide and is endemic to the southwestern
brain revealing diffuse leptomeningeal enhancement, with intracerebral United States, with an average of 10 cases reported each year. Its natural
and subarachnoid hemorrhages. Cerebrospinal fluid (CSF) is usually reservoirs are urban and rural rodents. The transmission vector is the
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bloody and gram-positive. Gram stains of sputum are typically negative, oriental rat flea (Xenopsylla cheopis). Humans become accidental hosts
while those of blood and pleural fluid are more likely to be positive. after being infected by an infected flea’s bite. Humans very rarely are

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