Chapter 183. Miscellaneous Bacterial Infections with Cutaneous Manifestations

This chapter focuses on a group of unrelated bacterial diseases that are rarely encountered in a conventional urban or suburban setting but are acquired after a distinctive environmental exposure, such as saltwater immersion, animal bites, handling of an infected animal carcass, or travel to specific areas around the world. Several of these diseases present primarily as cutaneous disorders with rare systemic involvement (e.g., erysipeloid); others present primarily as systemic disorders with rare cutaneous involvement (e.g., brucellosis). Several of the pathogens can be aerosolized and disseminated for respiratory transmission, naturally or with human intervention. The ease of dissemination and the potential virulence of several organisms make them suitable for intentional spread as biologic weapons. The intentional spread of these diseases is discussed in greater detail in Chapter 213.

In this chapter, these infections are grouped by their most common, natural means of transmission to humans: atraumatic exposure to animals, animal bites, and contact with contaminated water (Fig. 183-1).

Etiology and Epidemiology

Anthrax is a zoonotic infectious disease caused by Bacillus anthracis, a large aerobic, spore-forming Gram-positive rod.1 Anthrax occurs naturally in ruminant mammals, such as sheep, cattle, and goats. Human disease is seen most often in agrarian, livestock-dependent regions. Consequently, human anthrax usually follows agricultural or industrial exposure, either through direct handling of infected animals or contaminated soil or through the processing of hides, wool, hair, or meat.2 Anthrax has potential as a class A bioweapon (Table 183-1; see also Chapter 213).

The clinical presentation of human anthrax depends on the route of inoculation. In 95% of human cases, the disease is acquired through percutaneous inoculation of anthrax spores. Human anthrax can also be acquired as inhalational and gastrointestinal disease. Recent cases in the United States of both forms have been associated with recreational use of drums made of unprocessed animal hides imported from West Africa.3,4 Each of anthrax's form has distinctive clinical, epidemiologic, and prognostic features.5

Outbreaks still occur in endemic areas.6–11 During the late twentieth century, thousands of people in the African nations of Zambia and Zimbabwe developed anthrax.12 More than 90% of cases were cutaneous and the remainder represented an equal mix of inhalational and gastrointestinal disease. Dying animals typically release vegetative bacilli into the environment, which then convert into the dormant, yet infectious, spores. There are ongoing outbreaks of animal anthrax among free-ranging wood bison (Athabaskan buffalo) in Northern Canada,13 several species of antelope in Zambia,14 hippopotami in Uganda, and domesticated grazing animals in North Dakota.15

Clinical Findings

History

After an incubation period of 1–7 days, patients may experience low-grade fever and malaise and develop a painless papule at the exposed site. As the lesion enlarges, the surrounding skin becomes increasingly edematous. Pain, if present, is usually due to edema-associated pressure or secondary infection.

Cutaneous Lesions

Cutaneous anthrax develops when spores enter minor breaks in the skin, especially on exposed parts of the hands, legs, and face (Fig. 183-2). In the hospitable environment of human skin, spores revert to their rod forms and produce their toxins. A dermal papule, often resembling an arthropod bite reaction, develops over several days, and then progresses through vesicular, pustular, and escharotic phases. Lesions are surrounded by varying degrees of edema. Depending on the manner of inoculation, one to several lesions may appear, and there may be regional lymphadenitis, malaise, and fever. Individual lesions may appear pustular, leading to the name “malignant pustule,” but they do not suppurate. In anthrax, true pustules are rare; a primary pustular lesion is unlikely to be cutaneous anthrax.

The lesion enlarges into a glistening pseudobulla that becomes hemorrhagic with central necrosis and may be umbilicated (see Fig. 183-2). The necrotic ulcer is usually painless, which is an important feature in differentiating it from a brown recluse spider bite. There may be small satellite papules and vesicles that may extend along lymphatics in a sporotrichoid manner. An area of brawny, nonpitting edema (“malignant edema”) often surrounds the main lesion. Lesional progression is due to toxins and is unaffected by antibiotic therapy. Fatigue, fever, chills, and tender regional adenopathy may cause an ulceroglandular syndrome. The eschar dries and separates in 1–2 weeks.16–20

Related Physical Findings

Cutaneous anthrax may cause fever, tachycardia, and hypotension.

Histopathology

The prominent features are hemorrhagic edema, dilated lymphatics, and epidermal necrosis. Bacilli may be found in the eschar. Anthrax is toxin-mediated and induces scant inflammatory infiltrate. Immunohistochemical stains are quite useful.21

Treatment

Naturally occurring anthrax is treated with penicillin or doxycycline. Weaponized anthrax, on the other hand, may be resistant to these antibiotics, and, therefore, a fluoroquinolone is recommended for the initial treatment of confirmed or suspected bioterrorism-associated anthrax, even in pregnant women and children. Once drug sensitivities have been established, the patient may be switched to another antibiotic as clinically indicated. Antibiotics will kill activated B. anthracis bacilli but will not alter tissue damage already caused by toxins.22,23 To neutralize the anthrax toxins, the Centers for Disease Control and Prevention (CDC) now possesses human antianthrax immunoglobulin and monoclonal antibodies directed against the toxins are in development.

Although cutaneous anthrax is usually an uncomplicated and readily treatable infection, public health concerns warrant hospitalization. Standard universal precautions are appropriate but specific measures against secondary respiratory transmission are unnecessary because anthrax is not transmitted from person-to-person.

Parenteral crystalline penicillin G (2 million units every 6 hours) was the treatment of choice prior to the 2001 bioterrorism outbreak. In one study, smears and cultures from vesicles or from the necrotic tissue beneath the eschar became negative within 6 hours of initiation of penicillin therapy. Treatment of primary cutaneous anthrax is continued with parenteral therapy until the local edema disappears or the lesion dries up over 1–2 weeks. When the edema resolves, the patient may complete the 60-day treatment with oral therapy.

Other than to obtain material for culture or histopathology, incision and debridement of the cutaneous lesion is unnecessary. First of all, the lesions contain no purulent material needing evacuation and, second, without effective antibiotics, these procedures increase the risk of bacteremic spread of the disease.

Prognosis and Clinical Course

Untreated cutaneous anthrax, particularly if nonedematous, is a largely self-resolving disease. In contrast, some lesions, especially ones with massive edema, pose the risk of bacteremia with subsequent septicemia. Thus, the mortality rate of untreated cutaneous anthrax is roughly 5%–20%. With prompt and appropriate antibiotics, there is rapid defervescence and clinical improvement. Massive facial edema associated with cutaneous lesions of the head or neck may lead to respiratory compromise, requiring intubation or tracheostomy and systemic corticosteroids. Palpebral lesions may scar the eyelids and edema-associated seventh-nerve palsy may occur.24 Hospitalization in an intensive care unit is recommended for any patient with inhalational or gastrointestinal anthrax.

Prevention

In nonendemic areas, any case of anthrax requires immediate reporting to public health authorities and a prompt public health response because of the threat of intentional criminal or terroristic release. Although anthrax is a dangerous disease, it is not transmitted from person-to-person. Instead, the spore is the infectious propagule. Therefore patients with anthrax—of whatever clinical presentation—do not require isolation.

An anthrax vaccine has been in use since 1954 for people with occupational exposure to natural anthrax (e.g., veterinarians, wildlife biologists). The CDC recently released new guidelines on its use in the post-9/11 era for routine occupational use and for pre- and postoutbreak exposure use.25

Although cutaneous anthrax is usually an uncomplicated and readily treatable infection, public health concerns warrant hospitalization. Standard universal precautions are appropriate but specific measures against secondary respiratory transmission are unnecessary because anthrax is not transmitted from person-to-person.

Etiology and Epidemiology

Tularemia is a zoonotic infectious disease caused by Francisella tularensis, a pleomorphic Gram-negative coccobacillus found in many species of mammals, most important, lagomorphs (rabbits and hares) and rodents, and in their immediate environments. The bacteria are highly infectious, can be transmitted in many ways, and cause at least eight different patterns of disease.

Tularemia occurs solely in temperate and cold regions of the Northern Hemisphere. The most common form in the United States is ulceroglandular disease in which organisms are inoculated directly into the skin by minor trauma or by bites of infected arthropods that maintain the enzootic cycle. Before 1950, most US infections occurred in hunters who handled infected rabbits and hares. Two incidence peaks each year corresponded with summer and winter hunting seasons. Currently, 100–150 US cases occur each year, mostly in Arkansas, Missouri, and Oklahoma, with transmission of the organism largely via tick bites. The most common tick vectors are Dermacentor variabilis, Amblyomma americanum, and, in Europe, Ixodes sp.26–30

Of several subspecies, the most virulent (F. tularensi subspecies tularensis) lives only in the North America. A more benign one (F. tularensis subspecies holarctica) is the only subspecies in Eurasia. Although these bacteria do not produce spores, they can survive environmentally—and maintain infectivity—for months.28,29

Tularemia is transmitted in other ways, too. Other arthropod vectors include the deerfly (Chrysops discalis) in the Western United States, and mosquitoes in Scandinavia and the Baltic region.31 An outbreak of pulmonary tularemia on Martha's Vineyard, Massachusetts, was associated with springtime mowing of tall grass.32 The precise environmental source was not clear, perhaps aerosolization of animal excreta in the grass. Domestic cats may spread the organism via direct contact, bite, or aerosol. In parts of Europe, aquatic rodents (muskrats and beavers), household rodents, and drinking water contaminated by these animals are the major sources of infection. Rarely, direct inoculation into conjunctivae or ingestion of poorly cooked, contaminated meat causes infection. There is no human-to-human transmission. A second species, Francisella philomiragia, can infect patients with inherited defects in phagocytosis such as chronic granulomatous disease (OMIM #306400).

Clinical Findings

History

Duration of incubation varies with size of inoculum, ranging from 2–10 days. All forms of tularemia present as a sudden flu-like illness characterized by fever, headache, malaise, and myalgias.

Cutaneous Lesions

In ulceroglandular tularemia, a painful red papule appears at the inoculation site (Fig. 183-3). It enlarges rapidly and evolves into a necrotic chancriform ulcer often covered by a black eschar. Regional lymph nodes are large and tender.32 Bacteremia may cause sepsis and virulent pneumonia. In two recent Scandinavian outbreaks with the less virulent holarctica type of tularemia, due primarily to mosquito-borne ulceroglandular disease, approximately one-third of nearly 300 patients developed nonspecific secondary cutaneous manifestations, such as erythema nodosum, erythema multiforme, or an asymptomatic id-like papular eruption on the extremities.31,33

Related Physical Findings

In oculoglandular tularemia, organisms are introduced directly into the conjunctivae, for example, after handling an infected tick or rabbit. This causes purulent conjunctivitis with pain, edema, and local adenopathy. In a recent outbreak in Bulgaria, more than 90% of cases were oropharyngeal, reflecting transmission via contaminated well water. Swallowing the organism may cause ulcerative pharyngotonsillitis with cervical adenopathy or may cause “typhoidal” tularemia.34 Pulmonary tularemia may be primary (i.e., due to inhalation of organisms) but is more often because of bacteremic spread from another focus.

Laboratory Findings

Laboratories should be notified of suspected tularemia so that cultures can be set under biohazard conditions to avoid aerosolization. F. tularensis grows best on cysteine-supplemented blood agar, producing nonmotile, nonsporulating, pleomorphic, Gram-negative coccobacilli. Some reference laboratories also use animal inoculation techniques.

Histopathology

The pathogen survives intracellularly in phagocytes, and small granulomas develop in lymph nodes, liver, and spleen. Some lesions may caseate and progress to frank abscess formation. Hepatic granulomas may resemble tuberculosis or brucellosis.

Differential Diagnosis

The primary lesion of tick-transmitted tularemia resembles a furuncle, paronychia, common ecthyma, the initial lesion of anthrax, Pasteurella multocida infection, or sporotrichosis. Prominent regional adenopathy may suggest cat-scratch disease, plague, or melioidosis. Fever after a tick bite might suggest Rocky Mountain spotted fever, but that usually has an exanthem rather than a chancriform lesion. Other tick-borne febrile diseases include other rickettsioses, ehrlichiosis, babesiosis, and viral tick fevers. F. tularensis is difficult to grow so the diagnosis is usually made by serologic tests showing a rise in titers. Although the subspecies of F. tularensis are clinically and epidemiologically distinct, they are serologically indistinguishable.28

Treatment

A presumptive diagnosis of tularemia on clinical and epidemiologic grounds is sufficient to initiate treatment while awaiting serologic confirmation (see Table 183-1). Treatment consists of an aminoglycoside antibiotic, such as gentamicin, or a fluoroquinolone; these should be given for at least 10 days. A tetracycline antibiotic, such as doxycycline, given for at least 15 days is an acceptable alternative. Patients improve within 24–48 hours, but treatment should continue for at least 7–10 afebrile days to reduce the risk of relapse.

Course, Prognosis, and Complications

Untreated pulmonary and typhoidal tularemia have mortality rates of about 30%. Without antibiotics, ulceroglandular disease lasts many weeks and has a mortality rate of 5%. Brief courses of antibiotics may permit relapse but, with proper treatment, uncomplicated recovery is expected.

Prevention

Hunters and animal handlers should wear impervious gloves when handling game, especially rabbits. Game meat should be cooked thoroughly, even if stored frozen for long periods. A live-attenuated (but rarely used) vaccine was developed in Russia; the US government is currently funding vaccine research. The disease is reportable in the United States and any cluster of pulmonary tularemia cases should raise concerns of bioterrorism.29,35

Etiology and Epidemiology

Plague is a severe, acute, febrile zoonosis caused by the aerobic Gram-negative bacillus Yersinia pestis. Plague exists in an enzootic cycle, infecting humans through contact with rodent reservoirs or flea vectors. Human plague has three clinical forms: (1) bubonic; (2) bubonic septicemic, a more virulent form due to secondary bacteremia and sepsis; and (3) pneumonic (fulminant disease due to respiratory spread). Distal purpura and gangrene associated with septicemic plague likely gave rise to the term black death. The plague bacillus likely evolved from the fecal–oral pathogen, Y pseudotuberculosis, by acquiring several virulence plasmids.36

Endemic or sylvatic plague occurs in wild rodents in the Western United States, parts of South America, much of sub-Saharan Africa, and across Southern Asia. In most places, plague is sporadic but Madagascar currently has epidemic plague.37,38 There are several thousand cases of plague worldwide each year and the disease prevalence is increasing across Africa; Madagascar alone account for nearly half the number of human cases each year.36,39

In this country, human disease is almost always transmitted by fleas. Direct handling of infected rodents, rabbits, or their carcasses can also transmit plague. Some cases are transmitted by direct contact with pet dogs or cats that become ill after contact with infected wild animals. Between 1990 and 2005, 107 plague cases, more than 80% bubonic, were reported in the United States, averaging seven per year, mostly in summertime. In Western States, winter cases are often linked with handling of animal carcasses while hunting. In recent years, epizootics have occurred among prairie dogs, and sporadic human cases were seen on several Indian reservations, associated with ground squirrels. Rarely, bacteremic bubonic disease may evolve into pneumonic plague and further initiate respiratory spread to others.40,41

The flea associated with epidemic plague in the Old World is Xenopsylla cheopis, but fleas in other genera (e.g., Anomiopsyllus, Aetheca, Pulex) are also vectors in the United States.

Because Y. pestis can be aerosolized, is devastatingly lethal, and can spread from person-to-person, it is considered a Category A biologic weapon (see Table 183-1). Y. pestis produces an intracellular toxin and virulence factors (see Chapter 213).

Clinical Findings

History

Bubonic plague incubates for roughly 2–6 days, followed by the sudden onset of high fever, prostration, malaise, myalgias, backache, and tachycardia. Primary pneumonic plague has a shorter incubation time.

Cutaneous Lesions

In bubonic plague, the initial skin lesion is related to the fleabite and may appear as papular urticaria. However, the hallmark of bubonic plague is prominent, exquisitely tender regional lymphadenopathy with extensive subcutaneous edema. Inguinal buboes are most common in adults; cervical and axillary buboes are more common in children.36

Any form of plague can lead to overwhelming endotoxic septicemia accompanied by disseminated intravascular coagulopathy (DIC) (see Chapter 144 and 181). Subsequent purpura and gangrene are most severe on distal extremities.42

Related Physical Findings

Primary septicemic plague lacks buboes and presents with typical Gram-negative sepsis. Many patients also have severe abdominal pain, nausea, vomiting, and bloody diarrhea. Pneumonic plague has an abrupt onset with high fever, tachycardia, tachypnea, chest pain, and dyspnea. Within 24 hours of onset, the patient is critically ill and producing bloody sputum laden with Y. pestis. Meningitis may complicate all forms of plague.

Laboratory Findings

Differential Diagnosis

Most patients with bubonic plague present with the rapid onset of a toxic febrile illness, painful buboes, and evidence of an arthropod bite without surrounding cellulitis. Bubonic plague should be distinguished from tularemia, lymphogranuloma venereum, cat-scratch disease, chancroid, Kikuchi's disease, and suppurative lymphadenitis due to staphylococcal or streptococcal infections. Pneumonic plague must be differentiated from other acute bacterial pneumonias. Epidemiologic considerations and the tempo of the illness are major points in the differential diagnosis. The diagnosis is made by examining Gram-stained (or specific fluorescent antibody stained) smears of infected material or by culturing organism from blood, sputum, or aspirated buboes. Serologic methods help retrospectively by demonstrating a fourfold or greater rise in titers. A convalescent passive hemagglutination titer of >1:16 suggests the diagnosis.

Treatment

Because the original drug of choice, streptomycin, is not widely available, another aminoglycoside antibiotic, gentamicin, is the preferred treatment (although the US Food and Drug Administration has not approved it for this indication) (see Table 183-1). Doxycycline is also effective and maybe the treatment of choice when oral therapy is required or to use as postexposure prophylaxis. Cotrimoxazole is useful when combination therapy is desired.43 Patients with pneumonic plague must be placed in respiratory isolation to prevent further transmission. The course of treatment, irrespective of medication, is 10 days. Ordinarily, buboes should not be drained until they are well-localized and antibiotic therapy has been started.46

Prognosis and Clinical Course

Pneumonic and septicemic plague, if untreated, are nearly always fatal. Untreated bubonic plague has a mortality rate of roughly 50% but early antibiotic therapy has reduced this to 5%–10%. Because primary septicemic plague lacks telltale buboes, the clinical suspicion of plague is often delayed, hence antibiotics are started late and mortality is high.

Prevention

Most cases in the United States are acquired peridomestically so it is important in endemic areas to control rodents around homes. Children should be taught to avoid rodent nests, burrows, and dead animals. Pets should be given regular flea treatments, examined properly when ill, and trained not to hunt small mammals or eat sick or dead mammals. Rabbit hunters should wear gloves when handling carcasses. With pneumonic cases, respiratory isolation is mandatory and close contacts should receive antibiotic prophylaxis with doxycycline or cotrimoxazole. Plague vaccine is no longer available. Because the disease is a zoonosis, it is considered ineradicable, so prevention through rodent control is the most important way to prevent plague.36,39

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Histopathology

Differential Diagnosis

Treatment

Prognosis and Clinical Course

Prevention

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Laboratory Findings

Differential Diagnosis

Treatment

Prognosis, Clinical Course, and Complications

Prevention

Etiology and Epidemiology

P. multocida is a small, ovoid, Gram-negative rod that can cause local skin infection with regional adenitis after a superficial animal bite, scratch, or lick,65 or septic arthritis and osteomyelitis after a deeper animal bite. Respiratory infections unassociated with trauma occur in rare cases, and bacteremia may accompany meningitis or osteomyelitis.

P. multocida commonly colonizes the oropharynx and nasopharynx of healthy cats, dogs, rats, mice, pigs and other livestock, and poultry. Nearly all patients with P. multocida infection have had animal exposure, most commonly a dog or cat bite. Cat teeth are often longer and sharper than those of dogs and therefore may penetrate more deeply to cause septic arthritis or osteomyelitis. Compromising conditions such as cirrhosis, malignancy, and chronic obstructive pulmonary disease coexist in most severe cases.66–71

Neonatal pasteurellosis can be acquired by exposure to animals, usually pet dogs and cats in the household, even without known or recognized traumatic contact, possibly via respiratory droplets from the animal, or via vertical transmission from an asymptomatic mother.72

Clinical Findings

History

Local pain and swelling occur within a few days of an animal bite or contact exposure. Fever is uncommon.

Cutaneous Lesions

Redness, swelling, ulceration, and seropurulent drainage develop at the bite site. Cellulitis may progress rapidly and extensively, producing lymphangitis. Local necrosis may follow, and necrotizing fasciitis with septic shock has been reported.66,73

Related Physical Findings

Regional adenopathy may be present. Deep bites may introduce organisms into a joint or beneath periosteum and cause septic arthritis or osteomyelitis.

Laboratory Findings

Mild leukocytosis is present. After several weeks, a radiograph of underlying bone may show osteomyelitis. The organism is Gram-negative, and Wright–Giemsa stain reveals a bipolar appearance. Histopathologically, an acute pyogenic response is seen.67

Differential Diagnosis

The diagnosis is suspected when a painful infection develops rapidly (<2 days) at the site of an animal bite. Approximately 75% of infected cat bites are caused by P. multocida. Local ulceration and proximal lymphadenitis mimic ulceroglandular tularemia, but P. multocida characteristically produces a necrotizing cellulitis and not chancriform syndrome. The diagnosis is confirmed by isolation of the organism, although treatment is often initiated according to an animal bite protocol or based on the history of a rapidly appearing painful cellulitis after a dog or cat bite.73,74

Treatment

Because most animal bite wounds show polymicrobial contamination, an amoxicillin/clavulanic acid preparation should be started after a dog or cat bite. Although P. multocida is a Gram-negative organism, most strains are susceptible to penicillin, which is the drug of choice if only Pasteurella is cultured. If one suspects that the bite reached periosteum, parenteral penicillin should be given until the local lesion is well healed. P. multocida is also susceptible to doxycycline, later-generation cephalosporins, and trimethoprim-sulfamethoxazole (see Table 183-1).

Prognosis and Clinical Course

Infection usually responds promptly to antibiotic therapy. Osteomyelitis, abscesses, and remnant foreign bodies should be treated surgically as well as medically. P. multocida infections may be more severe or lead to sepsis in immunocompromised or acquired immunodeficiency syndrome (AIDS) patients.

Prevention

A great many animal bites are unprovoked by family pets onto a child's hand, therefore judicious selection of pets and instruction to children are useful, but not guaranteed, ways to reduce domestic animal bites.75

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Differential Diagnosis

Treatment

Prognosis, Clinical Course, and Complications

Prevention

Etiology and Epidemiology

Clinical Findings

Differential Diagnosis

Treatment

Etiology and Epidemiology

L. monocytogenes is an anaerobic Gram-positive bacillus found widely in soil, water, vegetation, and the gut flora of humans and other animals. Exposure to this organism occurs through fecal–oral contamination, but the disease has an opportunistic nature, appearing in very young, very old, pregnant, or immunocompromised individuals. L. monocytogenes is found in the feces of many domestic and wild animals and birds, and is therefore widespread in the environment.90 Typically, livestock become infected by eating manure-contaminated silage; this can cause abortions, septicemia, and a peculiar form of encephalitis called circling disease.91

Human listeriosis is uncommon but occurs in three typical settings: (1) sporadic disease in pregnant women and neonates; (2) sporadic disease in AIDS patients; and (3) food-borne outbreaks.92 Humans usually become infected by eating contaminated, unpasteurized, or improperly pasteurized dairy products. In adults, the disease can present as septicemia, meningitis, vaginal infection, pneumonitis, or oculoglandular syndrome and can cause miscarriages and stillbirths.62 Infantile listeriosis presents acutely with septicemia, meningitis and meningoencephalitis, and septic granulomatosis.

Approximately 5% of humans are fecal carriers of Listeria. Higher rates of carriage have been observed in family contacts of patients with listeriosis. Several outbreaks have implicated unpasteurized soft cheeses imported from Mexico or vegetables from farms that fertilize crops with manure.93

The highest incidence of human listeriosis is seen among infants in the perinatal period, which suggests that the transmission occurs in utero or at birth. One-fourth of adult cases occur in pregnant women. Many other adult cases occur in patients with altered cellular immunity, such as those with Hodgkin disease, leukemia, or AIDS or those who have undergone organ transplantation. Hepatic disorders such as cirrhosis and iron overload also predispose to infection. Recent reports suggest that biological therapies that interfere with tumor necrosis factor activity, such as treating psoriatic arthritis with infliximab, may increase the risk for listeriosis.94

Clinical Findings

History

Early-onset neonatal listeriosis develops in infants infected in utero by untreated bacteremic mothers shortly before labor begins. Findings are evident at birth or become apparent within the first few days. These neonates are acutely ill and have generalized pustular, papular, or petechial skin lesions. Late-onset neonatal listeriosis occurs several weeks after a healthy birth, is presuably acquired postpartum, and usually presents as meningitis.93,95,96

Listeriosis from food-borne organisms usually causes outbreaks of acute gastroenteritis in families or communities. Patients have fever, vomiting, and nonbloody diarrhea, but this form lacks skin lesions.

Cutaneous Lesions

In septic infants, cutaneous lesions appear as generalized petechiae, papules, or pustules. Veterinarians or farmers who handle infected bovine fetuses may develop an acute febrile illness with headache, malaise, and regional adenopathy. Tender red papules develop on exposed surfaces and may evolve into pustules over 2–3 days. These contain the characteristic Gram-positive rods.

Related Physical Findings

Neonates with early onset listeriosis are often meconium-stained at birth, lethargic, and have an enlarged liver and spleen. Central nervous system listeriosis has a spectrum of neurologic manifestations, ranging from typical acute bacterial meningitis, abscesses, encephalitis, and infarcts.96

Laboratory Findings

L. monocytogenes is a small pleomorphic bacillus that often appears coccoid in infected tissues and body fluids. Pustules, meconium, cerebrospinal fluid (CSF), or blood cultures reveal the characteristic Gram-positive rods. The organism is β-hemolytic when cultured on sheep blood agar and exhibits a characteristic tumbling motility when grown in broth. In adults with meningitis, the CSF contains neutrophils, but about one-third of meningitic infants have a mononuclear response.

Histopathology

Skin lesions show focal necrosis, neutrophilic infiltrates, and monocytes around blood vessels. In septic patients, viscera may show abscesses and granulomas.

Differential Diagnosis

Neonatal listeriosis should be suspected in a meconium-stained newborn with intrauterine growth retardation who develops a papular skin eruption or subsequently failure to thrive. The differential diagnosis includes other in utero neonatal infections such as toxoplasmosis, cytomegalovirus infection, rubella, disseminated herpes simplex infection, and disseminated bacterial infections, such as those caused by group B Streptococci, Escherichia coli, Salmonella, and Pseudomonas.

Treatment

Neonates with listeriosis should be treated with intravenous ampicillin (or penicillin) (see Table 183-1). Penicillin-allergic patients may be treated with cotrimoxazole or erythromycin. Cephalosporins are generally ineffective.90

Prognosis, Clinical Course, and Complications

In neonatal septicemia or meningitis, mortality is around 50%, even with treatment. In adults, prompt treatment is usually effective, unless there is a severe underlying debility. Pregnant woman, even if treated, are at risk for miscarriage.

Prevention

Prepartum strategies to reduce neonatal group B streptococcal infections may also reduce risk of neonatal listeriosis.96

Farmers should not feed contaminated silage to livestock nor use untreated manure to fertilize crops. Still, it is almost impossible to guarantee Listeria-free foods. Therefore, people at greatest risk should avoid foods typically linked to listeriosis, such as raw (unpasteurized) dairy products, unwashed vegetables, and poorly cooked meats. Veterinarians and farmers should use gloves and protective garments when handling aborted fetuses or placentae.95

Etiology and Epidemiology

Vibrio are facultatively anaerobic, pleomorphic, Gram-negative rods found in marine waters, estuaries, brackish lakes, and their sediments wherever the water temperature is above 20°C (68°F). The most well-known vibriosis is cholera, caused by antigenic strains of Vibrio cholerae. Although cholera organisms do not infect the skin, many other Vibrio do. The most important of these, V. vulnificus can cause fulminant cellulitis, myositis, necrotizing fasciitis, and death.97

People become infected with V. vulnificus through oral or percutaneous exposure. After eating contaminated raw or undercooked seafood, people who have chronic liver disease or diabetes mellitus, or who are otherwise immunocompromised, are at risk for primary septicemia. Percutaneous infections are acquired by handling raw seafood, by entering saltwater with an open wound, or by experiencing skin trauma while in or around saltwater. Immunocompromised individuals are again at increased risk for secondary septicemia.98,99

V. vulnificus lives in warm seawater, where it colonizes the skin of fish and is concentrated in filter-feeding shellfish, such as oysters. Infections are particularly common along the Gulf of Mexico and, because of global warming, are now found in increasingly higher latitudes, such as on the Baltic Sea.100–102

Most cases of wound infection are sporadic and depend more on host susceptibilities than environmental conditions. However, after Hurricane Katrina struck the Gulf Coast in 2005, thousands of people were exposed to brackish floodwaters. There were 18 known cases of Vibrio wound infections—14 due to V. vulnificus, 3 due to V. parahaemolyticus, and 1 unspeciated case.103

Clinical Findings

History

There is nearly always a history of contact with saltwater, injury while ocean fishing, or consumption or handling of shellfish. After oral exposure, primary septicemia often begins with watery diarrhea, fever, chills, nausea, vomiting, and abdominal pain. People with wound infections usually recall an open skin lesion present before the saltwater exposure or a percutaneous injury during the exposure. Vibrio cellulitis is painful and has a rapid onset within 12–24 hours of exposure. Secondary bacteremia with sepsis may occur several days later.104

Cutaneous Lesions

Infected wounds may present as pustules, lymphangitis, or cellulitis. These infections may be mild or may develop into rapidly progressive, painful cellulitis with extensive skin necrosis, myositis, and necrotizing fasciitis (Fig. 183-4). Secondary bacteremia may cause metastatic cutaneous lesions.98,105 In septic patients, large hemorrhagic bullae commonly arise on the extremities or trunk and usually progress to necrotic ulcers and necrotizing fasciitis (see Table 183-1; see also Chapter 179).

Related Physical Findings

V. vulnificus septicemia causes high fever, tachycardia, and hypotension. One-third of patients develop Gram-negative septic shock.

Laboratory Findings

In primary septicemia, leukopenia is more common than leukocytosis. Thrombocytopenia is typical and may be part of disseminated intravascular coagulation. Usually, there is laboratory evidence for the person's predisposing condition (e.g., diabetes). All Vibrio species can be grown in regular blood culture media and cause hemolysis on sheep blood agar, but only V. vulnificus ferments lactose on MacConkey's agar. Histopathology shows noninflammatory bulla, epidermal necrosis, hemorrhage, and bacteria in dermal vessels. Radiographic studies show accumulations of nonspecific soft tissue edema.

Differential Diagnosis

A cirrhotic or diabetic patient with fever, shock, and hemorrhagic bulla within several days of saltwater exposure or eating raw oysters should alert the physician to possible Vibrio septicemia, especially along the American Gulf Coast.

Similar presentations include disseminated intravascular coagulation, clostridial myonecrosis, meningococcemia, purpura fulminans, any form of necrotizing fasciitis, and other aggressive soft tissue infections. Wound infections sustained in fresh water suggest infection with Aeromonas rather than Vibrio. Clostridial myonecrosis may present with necrotizing fasciitis and shock, but is further suggested by local wound crepitus and the finding of Gram-positive rods.

Treatment

Primary or secondary septicemia due to V. vulnificus (or other Vibrio sp.) requires prompt management of hypotensive shock, parenteral administration of antibiotics, and vigorous debridement of necrotic lesions. Amputation of the affected limb may be necessary. The antibiotics of choice are a combination of doxycycline and ceftazidime (see Table 183-1). Alternatives to doxycycline include chloramphenicol, ciprofloxacin, and minocycline. Alternatives to ceftazidime include cefotaxime. Application of compresses with modified Dakin's solution (0.025% sodium hypochlorite) may help arrest the progression of the cutaneous lesions.106

Prognosis, Clinical Course, and Complications

The mortality rate for V. vulnificus primary septicemia is approximately 50%, about three times higher than the mortality for wound infections caused by the same organism.

Prevention

People with cirrhosis, diabetes, AIDS, and other immunocompromising illnesses should not eat raw shellfish and, if they have open skin wounds, should not enter seawater, estuaries, or brackish lakes. If an at-risk individual exposes open skin to saltwater, the site should be cleansed promptly with soap and clean water. Similarly, these individuals should not handle raw fish and shellfish. Vigilant attention to onset of illness is then required. Some authorities consider of a course of prophylactic oral doxycycline for an immunocompromised person with a high-risk exposure.

The most common other Vibrio to cause wound infections are Vibrio parahaemolyticus and nontoxigenic Vibrio cholerae (i.e., antigenic strains other than 01 and 139). Usually, these Vibrio cause an infection after oral exposure, producing an acute but self-limited noninflammatory gastroenteritis. Wound infections may occur after open skin is exposed to saltwater. The disease course is usually less severe than that of V. vulnificus although in an immunocompromised host, it may cause hemorrhagic bulla, shock, and necrotizing fasciitis.

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Differential Diagnosis

Prognosis and Clinical Course

Treatment

Prevention

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Differential Diagnosis

Treatment

Prognosis, Clinical Course, and Complications

Prevention

Etiology and Epidemiology

Erysipeloid, an acute infection of traumatized skin caused by Erysipelothrix rhusiopathiae (formerly Erysipelothrix insidiosa), occurs most frequently in fishermen, butchers, kitchen workers, and others who handle raw fish, poultry (especially turkey), and meat products.136,137,141–143 The disease is especially common in pigs, where it is known as swine erysipelas. In humans, erysipeloid occurs primarily during the summer months and can be considered an occupational dermatosis.

E. rhusiopathiae is a thin, Gram-positive, microaerophilic, nonmotile bacillus that is hardy enough to survive putrefaction of tissue and exposure to saltwater or freshwater. The organism is found in rats, birds, the slime on saltwater fish, and crabs and other shellfish, and is associated with poultry, meats, hides, and bones.

In humans, organisms usually enter broken skin on the hands and takes one of the four clinical forms: (1) a local nonsuppurative cutaneous infection (erysipeloid of Rosenbach); (2) a diffuse chronic cutaneous form consisting of multiple plaques with sharply defined angular borders; (3) subacute bacterial endocarditis, particularly of the aortic valve; or (4) a bacteremic form without endocarditis, usually found only in immunocompromised patients. The disease does not seem to confer lasting immunity.144

Clinical Findings

History

The patient is usually employed in the fishing or animal product industry. After inoculation, there is an incubation period of 2–7 days. Initially, burning pain occurs at the injured site, then a violaceous dermal plaque develops. Lymphangitis and regional adenopathy occasionally occur, as well as low-grade fever and malaise. Bacteremia and endocarditis are rare but serious sequelae. Untreated, erysipeloid usually heals on its own within 3 weeks.

Cutaneous Lesions

The distinctive erysipeloid lesion is usually on a finger or the back of the hand; is violaceous, warm, and tender; and has well-defined, raised margins with an angular or polygonal border (Fig. 183-5). It often involves the web spaces but spares the terminal phalanges and does not progress beyond the wrist. The borders usually expand, whereas the central region clears without desquamation or ulceration. Rarely, multiple lesions distant from the original site of injury arise, presumably through bacteremic spread. Postinflammatory hyperpigmentation may persist after the lesion resolves.

Related Physical Findings

Arthritis may be associated with the local lesion, and, in rare cases, distant joints are involved. Sepsis produces typical peripheral stigmata, including signs of endocarditis.142

Laboratory Findings

Gram stains rarely show E. rhusiopathiae although culturing tissue from the advancing edge may reveal the organism. Growth occurs best on serum-fortified media between 30°C and 37°C under hypercapnic conditions. Agar-gel diffusion precipitation or fluorescent antibody techniques are helpful in establishing the diagnosis.136,137

Histopathology

The findings are nonspecific but may include marked superficial dermal edema, vascular dilation, and mixed lymphocytic and neutrophilic perivascular infiltrates.

Differential Diagnosis

The character of the local lesion in a person handling fresh meat or fish products suggests the diagnosis. As its name suggests, erysipeloid resembles other forms of bacterial cellulitis or erysipelas. It may resemble a severe, acute irritant contact dermatitis. In erysipelas, the central area is most affected region compared with central clearing in erysipeloid. “Seal finger” may be mistaken for erysipeloid.

Treatment

The treatment of choice for erysipeloid is high-dose penicillin or ampicillin for 7–10 days. Patients who cannot take penicillins may be treated with a third-generation cephalosporin (such as ceftriaxone), imipenem, or ciprofloxacin (see Table 183-1). This recommendation is based primarily on in vitro studies, not clinical experience. If arthritis, septicemia, or endocarditis is present, the penicillin dosage should be increased and the drug should be administered intravenously for several weeks.142

Prognosis, Clinical Course, and Complications

Untreated lesions usually last for 2–3 weeks but may have waxing and waning cycles over several months. Improvement is often dramatic and recurrence is rare if penicillin is administered. The prognosis in systemic infections depends on early and appropriate treatment. The bacteremic form occasionally leads to endocarditis with its attendant morbidity and mortality.

Prevention

Erysipeloid can be prevented by wearing gloves when handling live animals or animal products and by washing skin wounds promptly with soap and water.

Etiology and Epidemiology

Clinical Findings

History and Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Differential Diagnosis

Prognosis and Treatment

Prevention

Aquaculture farms are becoming increasingly aware of S. iniae infections in their produce and have an economic incentive to maintain healthy fish. Nevertheless, cooks who prepare live-bought, aquaculture-raised fish will continue to be exposed to this pathogen.

Etiology and Epidemiology

Leptospirosis is a waterborne zoonosis caused by Leptospira interrogans. The disease is found worldwide, except in the Polar Regions, wherever animal urine can contaminate bodies of freshwater. Rodents are the most important reservoirs, although over 160 species of mammals are known to harbor Leptospira, including wild, farm, pet, and laboratory animals. Infected humans can also serve as transient reservoirs, particularly in urban slums in the wet tropics. Reservoir animals excrete leptospires in their urine, which contaminate the environment. Humans generally acquire the disease through broken skin after direct contact with an infected animal or exposure to contaminated water or soil. People are infected less commonly through mucous membranes, ingestion of contaminated water, or inhalation of fomites.154,155

L. interrogans thrives in warm fresh water, so leptospirosis has its highest incidence in tropical areas, particularly those with inadequate sanitation and where people go barefoot. Leptospirosis is an important cause of undifferentiated fever in the developing world, along with dengue, malaria, and typhoid. Serological surveys in some endemic regions suggest that >80% of people had prior infection.156 The disease is most prevalent among children who play or swim in contaminated water and among adults with occupational exposures (e.g., sugarcane workers or rice farmers) to infected animals or to contaminated soil and water. Travelers to hyperendemic areas, particularly ecotourists or adventure travelers who are exposed to contaminated water, are at increased risk. Many outbreaks of leptospirosis have been reported after heavy rains and floods as they cause sewers to overflow.157,158 Hawaii has the highest incidence in the United States.157,159,160

Clinical Findings

History

Patients usually have had recent occupational or recreational contact with contaminated water or mud. Most human infections are asymptomatic, self-limited, and detectable only on serologic surveys. Ill patients have one of two clinical forms of the disease: (1) a mild anicteric form that resolves without complications, or (2) a severe, icteric form (Weil disease). Both forms typically have two phases: the acute bacteremic phase, followed by the delayed immune or convalescent phase. Incubation usually takes 5–14 days and then the leptospiremic phase begins suddenly with headache, fever, chills, nausea, vomiting, abdominal pain, and myalgias (particularly of the calves and thighs). This initial nonspecific phase continues for about a week, then defervescence occurs.159

After several relatively asymptomatic days, the second phase of illness begins with low-grade fever. In severe cases rash, meningitis, uveitis, and hepatic and renal failure may develop.

Cutaneous Lesions

In the first week of illness, the conjunctivae become suffused (red but not exudative). Skin lesions occur in fewer than 50% of cases. These consist of nonspecific macules, papules, urticaria, and petechiae, mostly on the trunk. Desquamation and infarcts have been observed on the hands or feet of some infected children. Weil disease has prominent hepatic (jaundice) and renal (hematuria, azotemia) components. Hemorrhages occur in a variety of organs, including the skin, and petechiae are common on the palate. A variant called pretibial fever or Fort Bragg fever, caused by L. interrogans serovariant autumnalis, has a distinctive rash that appears on the fourth or fifth day of illness, consisting of slightly raised, 1- to 5-cm, tender, erythematous papules on the shins. The rash subsides within 4–7 days.155

Related Physical Findings

Most patients present with a fever of unknown origin without localizing signs. Other physical findings depend on the severity of the presentation, ranging nuchal rigidity in aseptic meningitis; or jaundice, hepatomegaly, and interstitial nephritis in Weil's disease. Some patients have generalized hemorrhages with epistaxis, hematuria, and gastrointestinal bleeding, and pretibial fever with splenomegaly.

Laboratory Findings

Laboratory tests help establish the diagnosis and the disease's severity. Direct isolation of leptospires is possible from the blood or CSF during the acute phase or from urine during the convalescent phase. A recently developed serum dipstick assay rapidly detects antileptospire immunoglobulin M or IgM antibodies. Thrombocytopenia is common but the white blood cell count is widely variable, reaching levels up to 40,000/mm3 in Weil's disease. A CSF pleocytosis, with up to several hundred mononuclear cells, may be present. Liver function abnormalities and jaundice are common. Azotemia and hematuria occur in patients with renal involvement.159,161

Treatment

Public health authorities in endemic areas recommend starting antibiotic therapy early, perhaps presumptively, to reduce the risk of severe disease while laboratory confirmation is awaited. Doxycycline is effective and can be taken prophylactically for short-term exposure in a hyperendemic area. Penicillin has also been recommended, although controlled studies are lacking, and it may precipitate a Jarisch–Herxheimer reaction (see Table 183-1).

Prognosis, Clinical Course, and Complications

Perhaps 90% of patients have either asymptomatic or mild anicteric disease. Both forms resolve spontaneously without complications. In Weil's disease, close attention must be given to fluid and renal status. Untreated Weil's disease has a mortality rate of 5%–40%, usually due to renal failure, less often due to cardiopulmonary failure or pulmonary hemorrhage. Late sequelae among survivors of untreated illness include neuropsychiatric diseases.162

Prevention

Water sanitation and rodent control measures will reduce the incidence of leptospirosis in a community. There is no vaccine against leptospirosis. Individuals who expect frequent contact with contaminated water or soils (e.g., military personnel or adventure travelers) should consider protective clothing and other ways to limit exposures or they may decrease the risk of disease by taking prophylactic doxycycline 200 mg, once weekly during these periods.158,162

Etiology and Epidemiology

Clinical Findings

History

Cutaneous Lesions

Related Physical Findings

Laboratory Findings

Differential Diagnosis

Treatment

Prognosis, Clinical Course, and Complications

Prevention