Gram-Positive Rod Infections

The Pathogen

Bacillus species are large, aerobic or facultatively anaerobic, spore-forming, gram-positive bacilli ( Fig. 272-1 ). The major pathogenic species of the B. cereus group have plasmids that carry genes for toxin proteins.

Bacillus anthracis

Anthrax occurs most commonly in Africa, India, the Middle East, Southeast Asia, and parts of Central and South America. Anthrax is enzootic in sub-Saharan Africa, where cases occur in wildlife and domestic animals that ingest or inhale B. anthracis spores from the soil while grazing. Cases may be sporadic or occur as part of an outbreak. Human cases in Africa outnumber human cases in most of the rest of the world. In Europe and North America, animal cases are sporadic and human cases are rare. Even a single case in a nonendemic area should generate concern for an act of bioterrorism ( Chapter 19 ).

Human cases of anthrax are usually associated with exposure to infected animals or their products. Cases can occur sporadically or be associated with outbreaks. Implicated products include meat, bone, wool (wool sorters disease), hair, hides, and items made from these materials. Transmission from flies has been reported to cause cutaneous infection.

Inhalational anthrax occurs from breathing in spores from contaminated animal products or after intentional release of spores during an act of bioterrorism. Gastrointestinal anthrax is acquired by ingesting spores or vegetative forms in the meat of infected animals or from contaminated water. Injectional anthrax infections have been reported in injection drug users who used heroin contaminated with anthrax spores.

Several outbreaks have been reported. In a 1979 outbreak in Sverdlovsk, Russia, 70 cases of confirmed inhalational anthrax occurred after an accidental release of spores from a military facility. In the largest human outbreak, approximately 10,000 cases, almost all of which were cutaneous, and 182 deaths occurred over a 6-year period from 1979 through 1985 in Zimbabwe. In 2001, letters containing anthrax spores were sent via the U.S. Postal Service to recipients in Florida, New York City, and Washington, D.C. Ultimately, 22 people were infected, with 11 cutaneous infections, 11 inhalational infections, and 5 deaths. Approximately 10,000 U.S. citizens received postexposure antibiotic prophylaxis to contain the outbreak.

Bacillus cereus

The foods most commonly associated with B. cereus food poisoning include meats, vegetables, and sauces. The emetic form of B. cereus food poisoning is frequently associated with starchy foods such as rice, especially fried rice, and potato salad. Improper storage and handling of food is the most likely cause. Contaminated rice has often been stored at room temperature to preserve its texture and then been reheated. Reheating may eliminate the organism and the diarrheal toxin but not the emetic toxin.

B. cereus , which is the most frequent bacteria that contaminates breast milk, can cause severe infection in very low-birthweight newborns. B. cereus can contaminate the product during collection, storage, or delivery. Cases of keratitis have been linked to contamination of contact lenses.

Bacillus anthracis

Cutaneous anthrax occurs when B. anthracis spores are introduced through microscopic or gross breaks in the skin, and injectional anthrax occurs via direct injection through intact skin. In classic cutaneous anthrax, a pustule forms at the inoculation site and ulcerates as the result of coagulation necrosis. Extensive edema surrounds the lesion. The organism multiplies locally and may spread to the blood stream or other organs via the lymphatics. The site of injectional anthrax has extensive edema but lacks the other findings of cutaneous anthrax.

Upon inhalation, B. anthracis spores are transported by alveolar macrophages and dendritic cells to regional lymph nodes. The spores germinate in blood and tissue. Following germination, vegetative cells produce an antiphagocytic capsule and anthrax toxin proteins, which are important virulence factors. Anthrax toxin consists of three proteins: protective antigen, edema factor, and lethal factor. These toxins neutralize the innate and adaptive immune systems to cause fatal disease. The capsule not only prevents phagocytosis but also enhances cytotoxicity and induces production of cytokines. Pulmonary infiltrates, which are seen radiographically in approximately a third of cases, are areas of pulmonary edema and hyaline membrane formation, not bacterial pneumonia. Pleural effusions are caused by blockage of normal lymphatic flow in the mediastinum.

Gastrointestinal anthrax may be classified as primary or secondary. Primary gastrointestinal anthrax occurs after the ingestion of meat from an animal infected with anthrax, whereas secondary gastrointestinal anthrax results from B. anthracis bacteremia. Spores invade the gastrointestinal mucosa, where they cause necrosis and ulceration that may lead to hemorrhage. Spores are then transported to mesenteric lymph nodes where they replicate and cause bacteremia.

Meningitis, which may occur as a complication of any form of anthrax, results from hematogenous seeding of the meninges. The meninges are edematous and hemorrhagic. Diffuse cerebral arteritis may occur.

Bacillus cereus

The pathogenic potential of B. cereus is highly variable and is based on a number of virulence factors. Enterotoxins ingested with contaminated foods cause diarrhea. These toxins are heat labile and may be removed by heating food to high temperatures that kill the organism and neutralize the toxin. In addition to ingestion of preformed toxin in food, the organism can produce toxin within the gastrointestinal tract. Emesis is caused by the toxin, cereulide, which is heat stable and preformed in food. Cereulide toxin genes are found only in certain strains of B. cereus , whereas enterotoxin genes are found more broadly. Some highly pathogenic strains of B. cereus, which possess B. anthracis virulence plasmids that express anthrax toxins and have a capsule, have been isolated from animals in sub-Saharan Africa and from human cases. These strains produce a large amount of sphingomyelinase, which contributes to the pathogenicity.

Bacillus anthracis

Anthrax manifests as four types of infection: cutaneous, inhalational, gastrointestinal, and injectional. Most common is the cutaneous form, which accounts for approximately 95% of cases. Two to five days after inoculation of spores into the skin, a pruritic lesion appears as a painless papule that evolves into a vesicular stage and then to a painless black eschar surrounded by edema and a ring of vesicles, described as a “pearly wreath” ( Fig. 272-2 ). Injectional anthrax is an unusual form of cutaneous anthrax that has been reported in injection drug users who injected heroin contaminated with B. anthracis into the skin or the blood stream. Skin lesions are not typical for cutaneous anthrax. Edema is prominent at the injection site.

For inhalational anthrax, the incubation period is usually 1 to 7 days but can be up to 60 days. The initial clinical presentation is nonspecific and consistent with an influenza-like illness with fever, malaise, dry cough, dyspnea, and chest pain. The hallmarks of inhalational anthrax are mediastinal lymphadenopathy, hemorrhagic mediastinitis, and pleural effusions. A chest radiograph or computed tomography (CT) scan reveals a widened mediastinum, as well as large, serosanguinous or hemorrhagic, usually bilateral pleural effusions ( Fig. 272-3 ). High levels of lethal factor toxin have been found in pleural fluid. If treatment is delayed, patients develop severe respiratory distress and septic shock.

Gastrointestinal anthrax, which is very uncommon and is responsible for only 1% of cases, may manifest as oropharyngeal or intestinal disease. Symptoms usually occur 1 to 5 days after ingestion of contaminated meat or drinking water. Symptoms of oropharyngeal anthrax include severe pharyngitis, dysphagia, odynophagia, and fever. Edema and lymphadenopathy may be so severe that they may cause respiratory distress. An ulcerative lesion may be seen in the mouth or pharyngeal area. Pseudomembranes may form over the lesion and may mimic diphtheria. Intestinal anthrax presents with nausea, vomiting, and fever followed by abdominal pain that may be so severe that it mimics an acute abdomen. Patients may have hematemesis, bloody diarrhea, and ascites. Secondary meningitis may occur. Gastrointestinal anthrax is likely to be associated with bacteremia/sepsis and seeding of other organs.

Anthrax meningitis occurs when bacteremia seeds the meninges during cases of inhalational or gastrointestinal anthrax. It occurs in up to 50% of inhalational cases. Symptoms and signs include severe headache, alteration of mental status, nuchal rigidity, other meningeal signs, and diffuse or focal neurologic findings. The course is frequently fulminant, with the development of delirium, seizures, and coma usually occurring within hours of initial presentation. Cerebrospinal fluid (CSF) is hemorrhagic. Hemorrhage may also be found in the brain parenchyma and the subarachnoid space. Cerebral edema may be present.

Bacillus cereus and Other Bacillus Species

B. cereus causes two types of food poisoning: a diarrheal syndrome and an emetic syndrome. Similar to other toxin-mediated food poisoning ( Chapter 262 ), the onset of symptoms with B. cereus occurs within 24 hours of eating the contaminated food item and usually within 8 to 16 hours. Cardinal symptoms of the diarrheal syndrome include profuse diarrhea and cramping abdominal discomfort. Fever and vomiting are rare. Onset of symptoms with the emetic form is very rapid and usually occurs within 1 to 5 hours, a time frame that is similar to food poisoning caused by Staphylococcus aureus ( Chapter 267 ). Symptoms include nausea and vomiting. Diarrhea has been reported in approximately one third of cases. Both syndromes are usually self-limited and resolve within 24 hours. Rarely, the Bacillus toxin may lead to acute liver failure. In addition to B. cereus , other Bacillus species have been linked to food poisoning and outbreaks.

Of the systemic infections caused by Bacillus species, bacteremia is the most common presentation, and B. cereus is the most common species isolated. B. cereus may also cause a variety of local and systemic infections such as endocarditis; pneumonia; central nervous system (CNS) infection ; and infections of the urinary tract, skin, soft tissue, muscle, and wounds. Many of these infections are health care–associated ( Chapter 261 ). Bacteremia can lead to dissemination to other body sites. Endocarditis may occur in prosthetic valves, and rare cases of native valve endocarditis are usually associated with bacteremia secondary to injection drug use. B. cereus can also cause eye infections, such as endophthalmitis and keratitis. CNS infections, including meningitis and brain abscess, tend to occur in immunocompromised hosts, especially when they are neutropenic. When the bone marrow recovers and neutropenia resolves, immune reconstitution syndrome can be associated with a transient exacerbation of symptoms of meningitis and brain abscess.

Bacillus anthracis

For cutaneous anthrax, a Gram stain of vesicular fluid, a scraping from the base of the lesion, or a skin biopsy may show the organism. Gram stain of vesicular fluid reveals bacilli but very few leukocytes. The direct fluorescent antibody test and PCR testing can provide a rapid diagnosis. Cultures are frequently positive.

In inhalational cases, the direct fluorescent antibody test and PCR should be performed on body fluids and tissues. A Gram stain of pleural fluid may also reveal the organism. Blood and pleural fluid cultures are positive.

For suspected gastrointestinal anthrax, PCR testing as well as blood and stool cultures should be obtained. A swab of the base of an oropharyngeal lesion may reveal gram-positive bacilli; culture is frequently positive. If ascites is present, fluid should be cultured and sent for PCR testing.

Bacillus cereus and Other Bacillus Species

Both the diarrheal and emetic form of B. cereus food poisoning can be diagnosed by culturing the organism from food, stool, or vomitus. Bacillus species are easily cultured, but testing is not routinely performed when stool cultures are requested. PCR testing is also useful. Commercial assays for toxin testing are not widely available.

Differentiating Bacillus infection from contamination may be difficult. Repeated isolation from a normally sterile body fluid or site indicates infection. Most cases of true bacteremia occur in the presence of an intravascular catheter.

Serology plays a role in diagnosis and may be particularly useful when cultures and PCR are negative. Anti-protective antigen antibody is detectable approximately 1 week after the start of symptoms. Acute and convalescent samples for anti-protective antigen antibody response should be obtained in the first 7 days of illness and repeated at 14 to 28 days.