Chapter 183

Miscellaneous
Bacterial Infections
with Cutaneous
Manifestations
Scott A. Norton

PLAGUE
Laboratory Findings
In bubonic plague, organisms can be cultured from
lymph node aspirates and blood; in pneumonic
plague, sputum, or tracheal washes. Lymph node
aspirates are obtained by using a sterile syringe
to inject 1 mL of saline into the center of a bubo
and withdrawing purulent material until the pus
is tinged with blood. Special transport medium
(e.g., Cary-Blair medium) is helpful but the culture
may be performed in standard brain-heart nutrient
broth. The organisms appear as Gram-negative coccobacilli with a Gram stain but their bipolar bacillary appearance is more distinctive with WrightGiemsa or Wayson stains.36,43 Bacilli can sometimes be
seen on stained buffy coat smears. Leukocytosis occurs in all forms of the disease. Renal failure and DIC
may occur in severe cases. Bacteria can be cultured
on standard blood agar media. Direct fluorescent
antibody assays, enzyme-linked immunosorbent
assay, and polymerase chain reaction testing are
useful when available, but serologic tests are less
reliable.42,44 Histopathologically, acute inflammatory
changes are seen in the involved nodes. Immunohistochemical stains of tissue biopsy specimens
may show organisms.45

BRUCELLOSIS
Etiology and Epdemiology
Brucellosis is caused by any of four species of
Brucella, which ordinarily infect livestock, especially
cattle, sheep, and goats. It is transmitted to humans
by contact with infected animals or animal products, ingestion of unpasteurized or contaminated
dairy products, and, rarely, by inhalation of aerosolized bacteria. Worldwide there are approximately
500,000 human cases per year. The highest incidence is in underdeveloped agrarian areas where

there are poor health controls for herds, where

people consume raw dairy products, and the populations are nomadic with less access to medical care.
These regions include East Africa, grazing areas of
upland South and Central America, and the belt of
nations extending from Spain and Portugal across
the Mediterranean basin, through Asia from Turkey
and the Middle East, and across the former Soviet
republics to Mongolia. Domesticated animals are
reservoirs for Brucella, and the two species that
most commonly infect humans are Brucella melitensis (from Malta, where the disease was first
described) and Brucella abortus, Brucella suis, and
Brucella canis are less common pathogens.4751
In the United States, brucellosis has largely been
eliminated by proper animal husbandry practices.
Still, there are 100200 cases annually, mostly in
travelers who ate raw dairy products in endemic
areas or in people who consume illegally imported
unpasteurized Mexican dairy products. Those at
high risk include herders, farmers, veterinarians,
and abattoir workers. Hunters who handle carcasses of large game such as deer, elk, and wild pigs are
also at risk.
People can become infected by ingestion or
inhalation of the pathogens or via contact through
conjunctiva or open skin. The bacteria then invade
reticuloendothelial tissues and typically evade host
defenses as intracellular pathogens.51
Contaminated unpasteurized milk or cheese is
the most common source for human infection.
Also, direct contact with infected animals, their
placentae, or excreta may allow organisms to enter
through abraded skin. Droplet inhalation can occur
in abattoir workers. Brucella multiply intracellularly
in many tissues and may persist for prolonged periods, leading to acute and chronic disease. Although
Brucella is an intracellular pathogen, acquired immunodeficiency syndrome (AIDS) patients do not
have more frequent or severe disease.
In the past, most US infections were due to B.
abortus after contact with infected cattle and dairy
products. This species may cause bovine abortions
and stillbirths, so handling infected fetuses or placentae is risky. Dog owners are at increased risk of
infections with B. canis.49

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270 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

Clinical Findings
HISTORY.
The incubation period varies and is usually 13
weeks, but may be 2 months or longer. The disease presents either as an acute febrile, flu-like
bacteremic syndrome or as a chronic disease with
nonspecific signs and symptoms such as weakness,
anorexia, headache, and low-grade fever. Relapses
occur in approximately 15% of patients, often after
an ineffective antibiotic regimen.
CUTANEOUS LESIONS.
Skin manifestations occur in fewer than 5% of
patients and are more common in children than
in adults. Furthermore, skin lesions, when present, vary widely, appearing as vasculitis, erythema
nodosum, panniculitis, abscesses, and polymorphous papules, pustules, and papulosquamous
lesions. This is because cutaneous brucellosis can
be related to direct inoculation, hematogenous
spread, deposition of antigenantibody complexes,
or hypersensitivity reactions. Children with acute
cutaneous brucellosis typically have a violaceous
papulonodular eruption primarily on the trunk and
lower extremities. Rarely, Brucella-related osteomyelitis or suppurative lymph nodes may create
cutaneous abscesses or sinuses.5257
A rare but distinctive dermatosis is seen in veterinarians or farmers who handle infected animals or
tissues58 and develop a severe contact hypersensitivity reaction to brucella antigens. This presents
with discrete, elevated, red papules on the hands or
arms that may ulcerate. Needle-stick injuries while
handling the live attenuated Brucella vaccine also
causes local reactions.44
RELATED PHYSICAL FINDINGS.
Brucellosis can involve every organ system, although there are no pathognomic clinical findings.
The disease can be debilitating but it is rarely fatal.
Joints, reproductive organs, liver, and the central
nervous system are, in order, the most frequently
involved. Nearly all patients have a characteristic
undulant fever (alternating pattern of several febrile
days followed by several afebrile days). Arthritis can
be axial (e.g., sacroiliitis) or peripheral. The disease
shows a predilection for reproductive organs, which
leads to miscarriages, stillbirths, mastitis, prostatitis, orchitis, and epididymitis. Spinal osteomyelitis

is well described, and endocarditis can be fatal.

Persistent neuropsychiatric findings occur in 5% of
patients.51

Laboratory Findings
Patients often have leukopenia, anemia, and
elevated liver enzymes. Blood cultures may be positive during the acute illness. Because organisms
are easily aerosolized and highly infectious, culture
must be under Biosafety Level III conditions. Brucella are nonmotile, coccobacillary Gram-negative
rods that grow best in enriched media and hypercapnic conditions with 8%10% CO2. Serodiagnosis
is challenging.51

Histopathology
The papulonodular eruption shows focal perivascular and periadnexal lymphohistiocytic granulomatous inflammation. Macular lesions have a
nonspecific mild lymph perivascular infiltrate. The
panniculitis usually shows septolobular inflammation with abundant plasma cells. Hepatic and
splenic lesions contain small, noncaseating granulomas. Caseation necrosis and calcification may occur
in B. suis infections.48,49

Differential Diagnosis
The clinical diagnosis of brucellosis is challenging
and the epidemiologic suspicion is often delayed.
Confirmation by culture or by serological techniques is necessary but the laboratory techniques
are difficult.51 The diagnosis is usually made on the
basis of epidemiologic information, coupled with
isolation of the organism, finding high or rising
agglutination titers, or detecting organisms from
a clinical specimen by direct fluorescent antibody
technique. For cultures, bone marrow specimens
have the highest yield. An agglutination titer of
greater than 1:160 is sufficient to begin treatment.
Confirmatory titers should be obtained 714 days
later. In chronic disease, IgG antibodies indicate
continuing or recrudescent infection. Cross-reactions with Francisella tularensis, the cause of tularemia, are known, and recent cholera vaccination may
stimulate a false-positive Brucella agglutination.
The differential diagnosis includes other acute
bacterial infections such as salmonellosis, listeriosis,
tuberculosis, and endocarditis. Hodgkin disease

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 271

may mimic many findings of brucellosis. Vertebral

osteomyelitis is sometimes the sole manifestation
of brucellosis.

Treatment
Brucellosis requires prolonged multidrug therapy
with antimicrobials that penetrate into cells. Optimal therapy consists of doxycycline combined with
either streptomycin, which is difficult to obtain,
or gentamicin. The World Health Organization
recommends an oraloral regimen of doxycycline
and rifampin (see Table 183-1). Treatment should
last at least 6 weeks; shorter courses carry a risk for
relapse.51

Prognosis and Clinical Course

Perhaps 5% of brucellosis patients die, mostly because of B. melitensis endocarditis. Early treatment
results in rapid improvement but relapses occur in
about 10%15% of patients with suboptimal treatment. Chronic brucellosis can cause disabling fevers,
arthritis, fatigue, and nonspecific neuropsychiatric
changes.50

Prevention
In Western nations, brucellosis is largely preventable through occupational precautions such as
wearing gloves when handling game or products
of conception from livestock. People should avoid
unpasteurized dairy products and be especially
vigilant when traveling in endemic countries. Vaccines exist for animals but not humans. Brucellosis
is a reportable disease and any occurrence should
initiate a search forand possible destruction of
the animal or food source. The Centers for Disease
Control and Prevention (CDC) categorizes Brucella
as a Category B bioweapon so a criminal source
must be considered as well.49,51

GLANDERS
Etiology and Epidemiology
Glanders is a rare zoonosis caused by the Gramnegative bacillus Burkholderia mallei (formerly
Pseudomonas mallei). Glanders occurs mostly in
horses, mules, donkeys, and related species, and exists focally in Asia and the Middle East. The disease
is usually fatal in donkeys and mules but may cause

a chronic suppurative condition, called farcy, in

horses. Human cases are usually the result of direct
exposures to animal reservoirs. In endemic areas,
animal handlers, veterinarians, and abattoir workers
have the greatest risks of exposure.5961

Clinical Findings
HISTORY.
Human glanders may present in several ways,
depending whether the disease is transmitted via
cutaneous inoculation or respiratory inhalation:62,63:
acute localized infection, chronic cutaneous infection, acute pulmonary disease, and septicemia.
Most cases are acquired transcutaneously, and a local ulcer develops within 15 days. Regional lymph
nodes may then enlarge, producing a ulceroglandular syndrome.
CUTANEOUS LESIONS.
Two types of cutaneous glanders are: (1) an acute,
febrile, disseminated, infectious process that may
resolve in a few weeks or (2) an indolent, relapsing, chronic infection, with multiple cutaneous
or subcutaneous abscesses and draining sinuses.
Abscesses may develop in muscle, liver, or spleen.
In acute glanders, a nodule surrounded by cellulitis appears at the site of inoculation (see Table
183-1). Local swelling and suppuration occur, the lesion ulcerates, and regional lymphadenopathy develops. The ulcer is painful and has irregular edges
with a grayyellow base. Nodules rapidly develop
along lymphatics that drain the initial lesion. These
become necrotic and ulcerated, forming sinuses.
Widespread dissemination quickly follows, with
multiple nodular necrotic abscesses in subcutaneous tissues and muscle. Lesions frequently coalesce
into gangrenous areas.
During bacteremic spread, patients have fevers,
rigors, and night sweats. The characteristic eruption is composed of crops of papules, bullae, and
pustules. These may be generalized or localized to
the face and neck, in which case involvement of
the nasal mucosa, either initially or by secondary
spread, is prominent. Mucopurulent, bloody nasal
discharge is common. Infection may spread to the
paranasal sinuses, pharynx, and lungs.
In chronic glanders, cutaneous and subcutaneous
nodules appear on the extremities and occasionally on the face. The lesions ulcerate, and draining

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272 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

sinuses develop. Ulceration of the hard palate and

perforation of the nasal septum can occur. If the
organisms are inhaled, pulmonary disease may produce pneumonia, pulmonary abscesses, or pleural
effusions. Septicemic glanders is usually fatal.

Laboratory Findings
Histopathologic examination of the skin and
other involved organs shows a suppurative, necrotic process containing numerous intracellular
and extracellular bacteria. Chronic glanders causes
granulomatous changes.

Differential Diagnosis
The diagnosis is made on an epidemiologic basis,
examination of Gram-stained smears of pus, and
isolation of the organism from abscesses. Furthermore, in the pulmonary and septicemic forms,
organisms may be recovered from blood, sputum,
or urine. Acute glanders may resemble miliary
tuberculosis. The multiple subcutaneous abscesses
suggest staphylococcal or deep fungal infections
or melioidosis. Lymphonodular disease resembles
sporotrichosis, nocardiosis, tularemia, New World
leishmaniasis, and Mycobacterium marinum infection.

Treatment
The CDC recommends treatment with sulfadiazine, although in vitro data indicate that B. mallei is
susceptible to ceftazidime, gentamicin, doxycycline,
imipenem, and ciprofloxacin. Patients with subcutaneous or visceral abscesses may require treatment
for up to 1 year.6264 Because the disease has largely
disappeared, few evidence-based recommendations are available.

Prognosis, Clinical Course, and

Complications
Untreated septicemic glanders causes widespread
abscesses in lungs, liver, spleen, muscles, and is
nearly always fatal.

Prevention
The usual way to control zoonotic or epizootic
glanders has been to destroy infected animals.
Such measures have nearly eradicated this once

common equine infection and eliminated transmission to humans in industrialized countries. In

the United States, glanders is a reportable disease.
There are no vaccines against B. mallei infection for
humans or animals. However, vaccines might be
developed because of the bioweapon potential of
this pathogen.61

RAT-BITE FEVER
Etiology and Epidemiology
The term rat-bite fever applies to two clinically
similar zoonoses that are both attributable to
contact with rats or their excreta. The more common form is caused by Streptobacillus moniliformis,
a pleomorphic Gram-negative rod found in the
nasopharyngeal flora of most wild and laboratory
rats, which are asymptomatic carriers, and is excreted in their urine.76 Carnivores that prey on wild
rodents may also transmit infection. Infections with
S. moniliformis arise in two ways: (1) direct contact
with infected animals, usually through a bite, or
(2) ingestion of food or drink contaminated by rat
urine, feces, or other secretions.77 In both forms, patients have an acute flu-like infection characterized
by a clinical triad of fever, polyarthralgias or arthritis,
and rash. In 1926, an outbreak in Haverhill, Massachusetts, caused by consumption of milk tainted by
rat excreta led to the designation Haverhill fever or
erythema arthriticum epidemicum.
The other pathogen implicated in rat-bite fever is
Spirillum minus, a Gram-negative spirochete. Spirillary rat-bite fever differs in its geographic distribution, incubation period, and milder arthritis. It
occurs almost exclusively in East Asia. Its Japanese
name is sodoku.75
Both diseases are most common where people
live in crowded, unsanitary conditions ideal for rats.
Although streptobacillary fever occurs worldwide,
it is most common in Asia. Most US cases occur in
children with a new pet rat. Person-to-person transmission is unknown. Rat-bite fever is nonreportable
so its exact incidence is not known.78

Clinical Findings
HISTORY.
Streptobacillary disease has an asymptomatic
incubation period of 17 days, and, in rare cases, as
long as 3 weeks. Often, the rat bite has healed by
the time a flu-like illness begins with fever, chills,
headache, stiff neck, nausea and vomiting, and

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 273

myalgias. A rash begins to appear several days later.

Spirillary rat-bite fever has an incubation period of
longer than 14 days.
CUTANEOUS LESIONS.
Approximately 75% of patients with streptobacillary fever develop a morbilliform eruption, usually
23 days after the fever. Individual lesions can be
macular, morbilliform, or petechial. Lesions are
most prominent on the palms, soles, and around
joints but may become generalized, resembling
measles.7880 There can be hemorrhagic acral
vesicles, resembling lesions of gonococcemia.81
Notably, when the rash appears, the rat bite has
usually healed and only rarely shows evidence of
infection, inflammation, or regional adenopathy. A
week or so after resolution of the disease, the palms
and soles have a characteristic desquamation that
may resemble Kawasaki disease.
In contrast, the bite producing spirillary fever is
usually tender, red, indurated, or ulcerated when
the rash appears.82 Cutaneous lesions are larger and
are prominent on the abdomen, thus resembling
the rose spots of typhoid. There can be tender regional lymphadenopathy and lymphangitis.83
RELATED PHYSICAL FINDINGS.
Within a week of the febrile symptoms, arthritis
usually develops, predominantly involving large
joints. The arthritis may be an asymmetric polyarthritis resembling rheumatoid arthritis but is rarely
suppurative. Regional lymphadenopathy may be
present. Infection may involve the liver, kidneys,
meninges, and heart valves.76 Arthritis is uncommon in S. minus infection.81

which characteristic puff-ball colonies are seen.

Anaerobic culture media, which lack the sulfonates,
permits slow growth and should be held for several
additional days. Histopathologic examination of
purpuric lesions shows a lymphocytic vasculitis
with focal intravascular thrombi.80 In fulminant
cases, filamentous organisms have been seen in
silver-stained tissues.78 Approximately one-third
of patients have false-positive venereal disease
research laboratory but no specific serologic tests
are currently available.
S. minum cannot be cultured in vitro. Darkfield
microscopy may reveal characteristic spirochetes.

Differential Diagnosis
The diagnosis should be suspected in any person
with unexplained fevers and recent rat exposure.78
The triad of fever, arthritis, and acral rash, accompanied by a history of a recent rat bite, should raise
suspicion. The differential diagnosis should also
include other causes of fever, rash, and arthralgias,
such as meningococcemia, disseminated gonococcemia, acute rheumatic fever, endocarditis, Lyme
disease, viral exanthems (e.g., from Coxsackie virus),
ehrlichiosis and rickettsioses, leptospirosis, secondary syphilis, typhoid, and Pasteurella multocida
infection.
Blood cultures are the best way to confirm the
diagnosis of streptobacillary rat-bite fever. Several
features help differentiate the two types of rat-bite
fever. In S. moniliformis infection the incubation period is shorter (usually <10 days vs. >14 days),84 the
bite site usually heals before systemic symptoms
begin, the rash is more peripheral, and arthritis is
more common (60% vs. 20%).

Laboratory Findings
Gram stains of S. moniliformis shows Gram-negative filamentous branching chains, interspersed
with bead-like swellings, hence the name moniliformis, meaning necklace-shaped. The organisms,
however, are pleomorphic in shape and staining
qualities, possibly resembling Gram-positive rods.76
If cultured properly, the organism can be recovered
from blood, joint fluid, or palmar pustules. It is
fastidious in culture; growth is inhibited by the sodium polyanethol sulfonate found in most aerobic
blood-culture bottles. It grows best on trypticasesoy broth or supplemented thioglycolate broth in

Treatment
The treatment of choice for someone who becomes ill after a rat bite is amoxicillin/clavulanic
acid. In patients allergic to penicillins, doxycycline
is acceptable. Once S. moniliformis is identified,
penicillin is the drug of choice. In general, rat bites
should be cleansed promptly and thoroughly.
Tetanus immunization status should be checked.
Although there are no established guidelines, one
might consider a prompt prophylactic course of
penicillin or doxycycline after any rat bite.77

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274 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

Prognosis, Clinical Course, and

Complications
Untreated disease may last for a few days to several weeks and 10%20% are fatal, usually due to
endocarditis. If diagnosed early, appropriate antibiotics produce a prompt clinical response although
migratory arthritis may persist after bacteriologic
cure.

hue, and usually extends beyond the original entry

site. Mycobacterium marinum infection is usually
painless and indolent. Seal pox is an orthopoxvirus
infection transmitted through contact with mouths
of seals and other pinnipeds. Staphylococcal or
streptococcal pyodermas may have a similar picture.
Herpetic whitlow can also cause a painful distal
phalanx. Culture should be attempted on special
mycoplasma media.

Treatment

Prevention
To prevent rat-bite fever, dwellings should be rat
proofed and open water supplies should be protected from contamination by rat excreta. Persons
who handle rats should wear gloves, wash their
hands frequently, and avoid hand-to-mouth contact when around rats. Children with pet rats should
be taught these simple precautions.79

SEAL FINGER
Etiology and Epidemiology
Seal finger is an occupational zoonosis that occurs
only after direct contact with seals, sea lions, and
similar marine mammals (order Pinnipedia), transmitted via bites or through open skin after handling
seals or their carcasses. Seal finger is characterized
by intensely painful red nodules, usually on the distal phalanx. Untreated, it can evolve into tenosynovitis, osteitis, and joint destruction.84,85 Although this
has not been fully confirmed, seal finger appears to
be caused by a group of Mycoplasma that is part of
the normal oropharyngeal flora of pinnipeds.86

Clinical Findings
People at risk include hunters, zookeepers, and
marine biologists. Seal finger is common in cold
water coastal areas around Scandinavia, Greenland,
Newfoundland, and similar environments in the
Southern Hemisphere. Most cases occur during the
spring sealing season. Incubation is usually approximately 4 days, rarely as long as 3 weeks. A furunclelike lesion appears at the inoculation site, followed
by severe pain, marked swelling, and stiffness.8789

Differential Diagnosis
The differential diagnosis includes other pathogens transmitted in a cold marine environment.
Erysipeloid is less painful, has a more violaceous

Seal finger does not respond to the -lactam

antibiotics frequently prescribed presumptively for
cellulitis caused by Staphylococcus, Streptococcus,
or Erysipelothrix. The lack of response to -lactams
further suggests seal finger. Tetracyclines are the
treatment of choice and must be continued for 46
weeks (see Table 183-1). Older accounts describe
occasional sealers who amputated their own fingers to rid themselves of the excruciatingly painful
digit.85

OTHER CUTANEOUS Vibrio

INFECTIONS
Etiology and Epidemiology
A. hydrophila is a facultatively anaerobic, Gramnegative bacillus that causes opportunistic human
infections. Except for the freshwater habitat of
Aeromonas, its taxonomic, ecologic, and epidemiologic profiles resemble those of Vibrio sp. Aeromonads are found in fresh and brackish water worldwide and are natural pathogens of many aquatic
animals, including fish, amphibians, and reptiles.
Human Aeromonas infections are usually associated
with exposure to contaminated fresh or brackish
water. The organism is typically linked with gastroenteritis,107 but in an increasing number of cases, it
has been implicated in skin, soft tissue, and muscle
infections, as well as in septicemic disease.108,109
An increasing number of soft tissue infections are
associated with the medical use of leeches.110,111
Recent reports describe a generalized folliculitis acquired after exposure to presumably contaminated
waters of hot tubs or childrens inflatable swimming
pools.112,113
Fish tanks, swimming pools, and tap water have
been contaminated with these organisms, leading
to occasional small common-source outbreaks.114
After the 2004 tsunami off the coast of Sumatra, approximately one-quarter of the isolates from hun-

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 275

dreds of patients hospitalized after prolonged water

exposure were due to Aeromonas spp.115 Other traumatic events, during occupational or recreational
exposure to contaminated aquatic environments,
are frequently associated with Aeromonas skin and
soft tissue infections.108

Clinical Findings
HISTORY.
The key historical feature is the contact of open skin
with fresh or brackish water. In healthy individuals,
Aeromonas infections may remain localized, but
compromised hosts are at risk for severe soft tissue
and septicemic disease.73,116
CUTANEOUS LESIONS.
The most common presentation is cellulitis associated with a laceration, often followed by abscess
formation or spread to deeper subcutaneous
tissues. Myonecrosis or necrotizing fasciitis may
mimic clostridial gas gangrene in its rapid onset
(12 days after exposure) and swift progression
with severe pain, marked swelling, serosanguineous bullae, crepitation, and systemic toxicity. The
exudate often has a foul or fishy odor. Occasionally,
bacteremia produces ecthyma gangrenosum-like
lesions.73,117,118 The folliculitis associated with hot
tubs clinically resembles Pseudomonas-induced hot
tub folliculitis.112
RELATED PHYSICAL FINDINGS.
Jaundice and other evidence of underlying disease
may be present.

cellulitis (including Streptococcus pyogenes or Streptococcus iniae), clostridial myonecrosis, necrotizing

fasciitis, and Vibrio vulnificus infection.

Prognosis and Clinical Course

With extensive surgical intervention and appropriate antimicrobial therapy, patients improve rapidly.
Prognosis is excellent except in immunocompromised individuals with bacteremia.

Treatment
Prompt surgical exploration and debridement
are essential, guided radiographically, if possible. A.
hydrophila produces -lactamase and is resistant
to first-generation penicillins and cephalosporins.
Most isolates are susceptible to third-generation
cephalosporins, fluoroquinolones, and aminoglycosides (but not streptomycin). Aeromonas, particularly in the developing world, are developing
resistance to several antibiotics so it is essential to
conduct antibiotic sensitivity tests.109 Consideration
must be given to the polymicrobial nature of these
infections, so results of Gram-staining and culture
should guide antimicrobial selection. Two other
less pathogenic species of Aeromonas, Aeromonas
caviae and Aeromonas sobria, have similar antibiotic
sensitivity profiles.73,117
There are no current recommendations for the
treatment of pool water-associated Aeromonas
folliculitis. The case reports describe the condition
in immunocompetent individuals who were treated
with either topical gentamicin or oral fluoroquinolones.112,113

Laboratory Findings
Gram-stained aspirates from abscesses or bullae
may contain Gram-negative bacilli. Wound cultures
yield multiple microbes in more than 50% of cases,
and specimens should be plated on both sheep
blood agar and MacConkeys agar. Blood cultures
are rarely positive for the organism. A radiograph
may detect gas in deeper soft tissues.

Differential Diagnosis
A history of open skin exposed to fresh or brackish water, followed by local cellulitis (often with
gas formation), increasing pain, and foul discharge
suggests Aeromonas infection. The differential
diagnosis includes staphylococcal or streptococcal

Prevention
Individuals who are immunocompromised or
who have chronic liver disease should promptly
clean any wounds or open skin that are exposed to
fresh or brackish water. In addition, they should not
undergo leech therapy.

MELIOIDOSIS
Etiology and Epidemiology
Melioidosis is caused by Burkholderia pseudomallei (formerly Pseudomonas pseudomallei), a motile,
pleomorphic, Gram-negative aerobic bacillus. The
organism is a natural saprophyte found in freshwater and damp soil in the humid tropics. Melioidosis

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276 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

infects humans, a variety of birds, and domestic

and wild mammals in endemic areas, but animals
are not regarded as reservoirs for human infection.
Although sporadic cases occur pantropically, melioidosis has its greatest incidence in Southeast Asia,
especially Singapore and Northeastern Thailand,
and in coastal areas of Australias Northern Territory.
Apart from rare laboratory-acquired infections, cases of melioidosis in the United States and Europe
have occurred only in people previously exposed in
endemic areas.119120
Most cases of melioidosis are transmitted by exposure of open skin to contaminated soil or water.
Cutaneous melioidosis can be a primary disease,
in which infection was acquired via percutaneous
inoculation and the principal manifestations of this
disease appear in the skin.
In Thailand, melioidosis is most common in rice
farmers and has a male:female ratio of 4:1, consistent with occupational exposure patterns. Serological surveys in endemic areas of rural Thailand
show that 5%20% of inhabitants have antibodies,
suggesting prior, presumably asymptomatic, infections. The frequency of pulmonary disease suggests
that melioidosis may also be acquired by inhalation
of contaminated droplets, soil, or dust.121,122 Individuals with diabetes mellitus, chronic renal disease,
alcoholic liver disease are at greater risk for infection and severe disease.
There is a marked seasonality in cases of melioidosis with peak incidence during rainy monsoon
seasons. After the December 2004 tsunami, hundreds of thousands of people were exposed to
flood waters and cases of severe postimmersion
pneumonic melioidosis were reported throughout
the region.123129
During the Vietnam War, extensive immersion in
rice paddies and similar conditions led to cases of
melioidosis among American servicemen. Several
cases were reported in Vietnam veterans whose disease appeared decades later, and the only plausible
exposure was to rice paddies long before.125
Direct human-to-human transmission is rare. B.
pseudomallei is infectious when aerosolized and is
regarded as a Category B bioweapon for its potential use on livestock or humans. If an individual
without characteristic travel or exposure history
develops melioidosis, or if there is a cluster of cases,
deliberate exposure may have occurred.126

B. pseudomallei is phylogenetically close to

Burkholderia mallei, the cause of glanders, and the
clinical presentations of both diseases are often
similar. However, the organisms have different
environmental niches and the diseases occur after
different exposures.

Clinical Findings
HISTORY.
Melioidosis has two principal clinical presentations: (1) acute melioidosis with suppurative skin
lesions, pneumonia, or septicemia; and (2) chronic
melioidosis, the more common form of the disease,
with involvement of the lungs, skin (subcutaneous
abscesses and draining sinuses), bones, joints, liver,
and spleen. Approximately 50% of cases involve
the lungs, caused either by inhalation of pathogens or by bacteremia from a cutaneous exposure,
although most patients have no obvious breaks in
the skin. Human immunodeficiency virus infection does not appear to increase either the risk of
acquiring the disease or its severity.119,127
The incubation period can be as brief as 23 days.
Acute pneumonic melioidosis usually starts abruptly with fever, chills, cough, dyspnea, and chest pain.
Acute septicemic melioidosis may also arise from a
cutaneous focus. In one-half the patients, no source
for the bacteremia can be identified, but many individuals have minor abrasions on their feet.114
Chronic melioidosis may follow acute disease,
but more commonly starts as an indolent pulmonary infection or as a low-grade febrile illness with
multiple subcutaneous abscesses. Recrudescence
of latent infection years after exposure may be associated with a subsequent debility, presenting as
persistent, unexplained fever.130
CUTANEOUS LESIONS.
Cutaneous manifestations are nonspecific. The
inoculation site of primary cutaneous melioidosis,
seen primarily in children, is frequently an ulcer,
occasionally with a purulent exudate.131 Acute septicemia may follow minor cutaneous disease. Disseminated disease can produce multiple superficial
pustules or, more rarely, ecthyma gangrenosum or
necrotizing fasciitis. In chronic melioidosis, draining
sinuses and subcutaneous abscesses, particularly
of the scalp, are common. In children, a common
presentation is acute suppurative parotitis, usually
unilateral, associated with parotid pain and fever.119120,128,129,131133

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 277

RELATED PHYSICAL FINDINGS.

Acute pulmonary presentations range from
bronchitis to acute pneumonia, lung abscess, or
empyema. Septicemia can lead to jaundice, hepatosplenomegaly, miliary pulmonary disease, myocarditis, and severe gastroenteritis. Chronic pulmonary
melioidosis resembles fibrocavitary tuberculosis
or lung abscesses both clinically and radiologically.
The disseminated form of chronic disease may
extend over many months, causing septic arthritis,
osteomyelitis, suppurative lymphadenopathy, and
visceral abscesses.

Laboratory Findings
B. pseudomallei grows on ordinary agar but the
addition of gentamicin prevents overgrowth by
other bacteria. The laboratory should be alerted of
possible melioidosis so that special media can be
used.134,135 Polymerase chain reaction tests are more
rapid than culture.136,137 On histopathologic examination, sharply circumscribed abscesses are found
in many organs and in the subcutaneous tissues,
often with a surrounding granulomatous response.

Differential Diagnosis
The disease is a great imitator and diagnosis
requires confirmed identification of the organism. Acute melioidosis may mimic typhoid fever,
staphylococcal pneumonia, disseminated fungal
infections (particularly due to Penicillium marneffei in Thailand), glanders, or septicemia. Chronic
melioidosis resembles pulmonary tuberculosis,
nocardiosis, deep fungal infection, and bacterial
lung abscess. Chronic skin infections and draining
sinuses in individuals from endemic areas should
raise the possibility of melioidosis, as should an
acute suppurative parotitis in a child from an endemic area.138
The diagnosis is supported by a history of recent
or remote history of travel to Southeast Asia or
Northern Australia in a patient with unexplained
sepsis. The finding of bipolar-stained Gram-negative bacilli strengthens the diagnosis. Culture of the
organism establishes the etiology. Rising antibody
titers also confirm the diagnosis. The indirect hemagglutination assay is the most commonly used test
in Southeast Asia because it is simple to perform
and cheap.136,137,139

Treatment
Antibiotic susceptibility must be determined for
each isolate. In Australias Northern Territory, where
melioidosis is relatively common, treatment consists of at least 2 weeks of intravenous antibiotics
(usually ceftazidime and carbipenem). This should
be followed by several months of high-dose oral
therapy with an antibiotic such as trimethoprimsulfamethoxazole131 or amoxicillin/clavulanic acid
(or longer in the case of osteomyelitis or multiple
suppurative foci) to reduce the risk of relapse.120,140
Abscesses should be drained surgically, but only
after the patient is taking appropriate antibiotics to
help prevent bacteremia.

Prognosis, Clinical Course, and

Complications
In septicemic melioidosis accompanied by shock
and dissemination to skin and viscera, mortality is
approximately 50%. In localized cutaneous melioidosis without bacteremia, mortality is <9%.

Prevention
There are no vaccines against melioidosis. People
with diabetes or chronic renal disease should
avoid exposure to fresh water when in endemic
areas, particularly if they have open skin wounds.
After such exposures, the skin should be cleansed
thoroughly but there are no data on antibiotic
prophylaxis.

STREPTOCOCCUS INIAE
INFECTIONS
Etiology and Epidemiology
S. iniae is a recently recognized Gram-positive
coccus that colonizes the skin of freshwater fish,
particularly those raised in intense aquaculture.
It has been found in tilapia, hybrid bass, rainbow
trout, coho salmon, and other species, and can
cause fatal epizootics of piscine meningoencephalitis.145 The species name derives from the Amazonian
freshwater dolphin, Inia geoffrensis, from which it
was first isolated. In dolphins, S. iniae causes slowgrowing nodular abscesses of the skin and subcutaneous tissues, giving it the vernacular name golf
ball disease. The condition has been noted only in
captive dolphins that presumably are exposed to S.

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278 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

iniae in the fish in their diets.146

In humans, S. iniae infection usually causes hand
cellulitis after the handling of live freshwater fish,
particularly farm-raised tilapia (Tilapia sp. and
Oreochromis sp.). Most cases have been reported in
cities in China and in Asian communities in North
America, particularly Toronto, where the practice of
buying live fish for home preparation, rather than
buying fresh fish that have already been killed and
cleaned, is common.147 Because of these cultural
practices, most people who develop S. iniae infection are elderly (average age >65 years) individuals of East Asian descent. Furthermore, most have
underlying medical conditions, such as diabetes
mellitus or cirrhosis, that predispose them to infection.148

Clinical Findings
HISTORY AND CUTANEOUS LESIONS.
The key element in the history is the rapid onset of
hand cellulitis within 13 days after the handling of
live farm-raised fish. Ascending lymphangitis and
fever are early features, but neither skin necrosis
nor bullae occur.149
RELATED PHYSICAL FINDINGS.
Bacteremia frequent complicates S. iniae cellulitis
and may lead to septic arthritis, meningitis, osteomyelitis, and endocarditis.149

Laboratory Findings
Cellulitis with S. iniae is probably underdiagnosed
because many practitioners treat hand cellulitis
empirically as if it were caused by Staphylococcus
aureus or Streptococcus pyogenes. Furthermore,
confirmation by culture of S. iniae is difficult because the organism exhibits variable hemolysis and
cannot be placed into a Lancefield group. In culture,
it resembles Streptococcus viridans, Streptococcus
uberis, and Streptococcus dysgalactiae.

Differential Diagnosis
To date, all reported cases have followed the culinary handling of live freshwater fish, usually tilapia.
The diagnosis should be considered in individuals
who develop hand cellulitis after such exposure,
with or without recognized percutaneous injury.

Other common causes of cellulitis (S. pyogenes, S.

aureus) as well as other freshwater and fish-borne
pathogens (Aeromonas hydrophila and Vibrio vulnificus) should be considered.

Prognosis and Treatment

The infection will respond within 24 days to
penicillin, the treatment of choice. The pathogen
is also susceptible to cephalosporins, macrolides,
quinolones, and vancomycin but is resistant to
tetracyclines. Treatment should be maintained
for 10 days or longer if there are extracutaneous
complications.149

CHROMOBACTERIUM
VIOLACEUM INFECTIONS
C. violaceum is a facultatively anaerobic, Gramnegative, motile, flagellated bacillus found as a
saprophyte in tropical and subtropical freshwater
and soil. It is rarely pathogenic except to people
with disorders of neutrophil function, especially
inherited chronic granulomatous disease, who have
difficulty generating an adequate host response
to catalase-producing organisms, such as C. violaceum. Infection occurs after open skin is exposed
to a contaminated source, such as stagnant or
muddy water. Nearly all US cases have occurred
in Southeastern States during summer months.
After exposure, cellulitis and fevers soon develop.
Pustules and nodules may appear, followed by regional adenopathy. The organisms may disseminate
hematogenously, causing ecthyma gangrenosum,
visceral abscesses, abdominal pain, septic shock,
and death. C. violaceum should be cultured on a
tryptophan-supplemented medium, where it will
produce water-insoluble, metallic-appearing, dark
purple colonies. It is often misidentified as a Vibrio
or Aeromonas or regarded as a contaminant, which
delays proper treatment, possibly leading to fatal
consequences in the immunodeficient patients
vulnerable to this organism. Biopsy shows a necrotizing vasculitis, bacilli in the vessels, and minimal
neutrophilic infiltrate.
Treatment consists of surgical drainage of cutaneous and visceral abscesses, along with several
weeks of parenteral antibiotics. Limited data show
that parenteral carbapenems, chloramphenicol
with gentamicin, and fluoroquinolones are effective. A prolonged course of oral doxycycline or

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 279

cotrimoxazole is necessary to reduce risk of relapse.

Subsequent fevers or abdominal pain may indicate
need for abdominal computed tomography or ultrasounds to screen for abscesses. Melioidosis has a
similar epidemiology, occurring in people exposed
to stagnant water in tropical and subtropical environments, skin and soft tissue lesions, sepsis and
visceral abscesses, with shock and death. Anyone
with C. violaceum infection requires evaluation for
immunodeficiency, particularly chronic granulomatous disease.150153

DIPHTHERIA
Etiology and Epidemiology
Diphtheria is an acute febrile illness caused by
Corynebacterium diphtheriae that in 90% of cases
affects the pharynx and mucous membranes of the
upper respiratory tract. The clinical manifestations
of diphtheria are caused by (1) acute membranous
obstruction of the airway, and (2) the tardive effects
of a potent exotoxin on the myocardium and on
cranial and peripheral nerves. The classic oropharyngeal lesion is a gray, leathery membrane along
the tonsils and soft palate. Cutaneous diphtheria,
which is far less common, can present either as a
primary skin lesion or as a secondary infection of
an existing break in the skin. Cutaneous diphtheria
occurs most commonly in people living in or returning from tropical areas.160
Although diphtheroids are widespread in nature,
humans are the only natural host for C. diphtheriae,
which colonizes the pharynx of asymptomatic individuals. Disease occurs when a nonimmune person,
usually someone very young or very old, is infected
by a toxigenic strain of C. diphtheriae. Epidemics occur when such strains become widespread among
nonimmune individuals. Diphtheria has been
largely controlled in Western nations by routine
childhood immunization, which is directed against
diphtherias exotoxin, not against the bacteria itself.
With the decline of the public health system in the
former Soviet states, epidemic diphtheria began
there in the early 1990s, infecting >150,000 people
and causing >5,000 deaths. In the United States,
diphtheria occurs mainly in marginalized populations (such as homeless people or migrant workers)
who live in crowded, unhygienic conditions and
lack periodic reimmunizations. Three outbreaks
among in indigent alcoholics in Seattle between
1972 and 1982 involved >1,000 cases, of which 86%
were cutaneous.163

Because of the widespread use of toxoid immunization, the disease is rare in this country. It should
be stressed, however, that this protection does not
prevent the development of the carrier state and
subsequent spread of organisms to susceptible
nonimmunes.

Clinical Findings
HISTORY.
Classic diphtheria presents with pharyngitis and
low-grade fever 25 days after exposure to a carrier
or, much more rarely, to fomites. A thick or leathery
grayish white membrane adheres to pharyngeal
walls and tonsillar pillars, and usually spreads asymmetrically onto the soft palate and uvula. As the disease progresses, the patients neck becomes painful
and swollen. There is often a unilateral bloody nasal
discharge. Patients appear to have a toxic process,
and ensuing tracheal edema may obstruct the
airway, causing lethal suffocation.
Cutaneous diphtheria typically affects the lower
extremity, involves one or more sites, and may
occur with or without concomitant pharyngeal
disease. In roughly one-third of patients with cutaneous diphtheria, the same strain of C. diphtheriae
can be recovered from the respiratory tract, which
suggests inadvertent autoinoculation as the cause
of the skin lesions.
CUTANEOUS LESIONS.
There are two types of skin involvement. The first is
primary cutaneous diphtheria, which starts acutely
as a tender pustule and then breaks down to form
an enlarging oval punched-out ulcer with a gray
membrane at the base (see Table 183-1). Later, the
membrane becomes dark brown, and the ulcers
border acquires edematous, rolled, bluish margins.160,161,166
Wound diphtheria is a secondary infection by
C. diphtheriae of an existing break in the skin. This
type accounts for almost all cases of cutaneous
diphtheria reported in the United States. Preexisting skin lesions affected include those caused by
abrasions, chronic dermatoses (e.g., eczema or
scabies), and common pyodermas already infected
with Staphylococcus or Streptococcus. A painful ulcer is partly covered by a brownish gray membrane,
drains pus, and is surrounded by edema and erythema. In the outbreak in Seattle among indigent
alcoholics, coinfection with S. pyogenes occurred in

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280 Chapter 183: Miscellaneous Bacterial Infections with Cutaneous Manifestations

73% of diphtheritic skin lesions.157 C. diphtheriae has

been recovered from lesions resembling impetigo,
ecthyma, and infected insect bites. Whether these
are truly infected or merely colonized is not clear.
Mucosa of the nose, conjunctivae, or vagina can
exhibit membranous diphtheria, although these
cases are quite rare.
RELATED PHYSICAL FINDINGS.
The most important other manifestations of
diphtheria are the toxins effects on the heart and
nerves. Myocarditis and conductive heart block
may develop 12 weeks after onset, whereas
cranial or peripheral neuropathies may develop 2
weeks to several months after the primary lesion.
Neurologic manifestations include blurred vision,
diplopia, numbness of the tongue, palatal paralysis,
and peripheral motor and sensory neuropathies. A
GuillainBarr-like syndrome has been reported in
3%5% of patients with cutaneous diphtheria.

Laboratory Findings
C. diphtheriae can be isolated from either the skin
ulcer or pharyngeal membrane. It is a Gram-positive, club-shaped rod that exhibits metachromatic
bipolar granules on staining with methylene blue.
The organism grows well on standard culture media,
but other bacteria may obscure it. Therefore, selective media such as Lffler or tellurite agar should
be used. The histopathologic features of cutaneous
diphtheria are nondiagnostic, and the membrane
is composed of coagulation necrosis and inflammatory cells. Not all strains of C. diphtheriae produce
diphtheria toxin, so it is recommended that the
pathogen be sent to a reference laboratory to determine the toxigenicity of the particular strain.

Differential Diagnosis
Cutaneous diphtheria may resemble deep streptococcal or staphylococcal ecthyma, tropical ulcer,
Buruli ulcer, cutaneous anthrax, cutaneous tularemia, pyoderma gangrenosum, and other entities.
Tropical ulcer, also painful, usually extends into or
below the fascia. Buruli ulcer is painless. Most bacterially infected ulcers do not develop membranous
coverings. Cutaneous deep fungal infections (e.g.,
coccidioidomycosis) usually have irregular hyperkeratotic borders and lack surrounding erythema.

Diphtheria should be suspected in a patient with

membranous tonsillar pharyngitis with asymmetric
extension onto the soft palate and uvula. In methylene blue-stained smears from the edge of the
membrane, the characteristic beaded metachromatic rods can be seen, but confirmation requires
culture and demonstration of toxin production.
However, the presence of a classic pharyngeal
membrane is sufficient evidence to begin immediate treatment for diphtheria. Pharyngitis due to
Streptococci, gonococci, infectious mononucleosis,
primary syphilis, Vincents angina, or candidiasis
can resemble faucial diphtheria (or can complicate
the diagnosis of diphtheria).158,164

Treatment
Pharyngotonsillar diphtheria requires treatment
with antibiotics (to kill the bacteria) and antitoxin
(to neutralize the exotoxin). Treatment should be
started on clinical suspicion without awaiting culture confirmation, because toxin produced in the
interim might damage the myocardium irreversibly.
Cutaneous diphtheria must be treated with antibiotics and antitoxin (see Table 183-1). The antibiotic
of choice is high-dose intravenous penicillin or,
for those unable to take penicillin, erythromycin.
Diphtheria antitoxin, available from the CDC, is
administered intravenously after careful testing for
horse serum hypersensitivity. Injection of antitoxin
subcutaneously around and under the ulcer, along
with superficial application to the lesion, may be
beneficial, but data are incomplete. After antitoxin
and antibiotics are administered, the membrane
should be debrided and the ulcer kept clean.
Patients with either form of the disease should be
isolated for roughly 14 days.

Prognosis, Clinical Course, and

Complications
If treatment is started early, the prognosis is
excellent. Pharyngeal cultures should be repeated
2 weeks after completing treatment. In untreated,
unimmunized persons with cutaneous diphtheria,
ulcers may persist for as long as 6 months. Myocarditis and heart block may lead to congestive heart
failure. Neurologic signs may appear 5 weeks to 5
months after the onset of illness and almost always
resolve. Diphtheria deaths are usually due to acute
airway obstruction.

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Chapter 183:

Miscellaneous Bacterial Infections with Cutaneous Manifestations 281

Prevention
The disease is largely preventable through routine
immunizations. Many adults are unaware that they
should receive a dose of tetanus and diphtheria toxoid (called Td) every 10 years. If a case of cutaneous
or pharyngeal diphtheria does occur, close contacts,
even if asymptomatic, should undergo cultures of
their oro- and nasopharynx and of any skin lesions.
All contacts should receive antibiotic prophylaxis
with oral erythromycin or penicillin (or a single
intramuscular injection of benzathine penicillin). In
addition, contacts whose diphtheria immunization
status is unclear or incomplete should be immunized with diphtheria toxoid. For children, 7 years of
age and older, and adults, the adult formulation of
the combined Td preparation should be used rather
than the pediatric diphtheria, pertussis, and tetanus
(DPT) vaccine. Modern epidemics are controlled
through mass immunizations.

OTHER CUTANEOUS
DIPHTHEROID INFECTIONS
Corynebacterium ulcerans is a common commensal
organism in cattle. Humans are rarely infected but
can become ill after direct contact with cattle or
by drinking raw milk. Pharyngeal disease is most
common but cutaneous lesions, resembling those
caused by Corynebacterium diphtheriae, have been
reported. Some strains of Corynebacterium ulcerans
produce the same diphtheria exotoxin, albeit in
smaller quantities.167 Corynebacterium pseudotuberculosis, which causes caseous lymphadenitis in
ruminants, occasionally causes a similar necrotizing
lymphadenitis in humans.
An organism closely related to corynebacteria,
Rhodococcus equi (formerly Corynebacterium equi),
causes pulmonary disease in AIDS patients. Rarely,
this organism, which resembles C. diphtheriae
on Gram-staining, can cause skin and soft tissue
infections in healthy individuals, especially those
exposed to horse manure or after an injury contaminated with soil.

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