Chapter 180

Gram-Negative
Coccal and Bacillary
Infections
Myron S. Cohen & David J. Weber

INFECTIONS DUE TO NEISSERIA

GONORRHOEAE (GONOCOCCUS)
Neisseria gonorrhoeae are nonmotile, nonspore
forming, Gram-negative cocci that typically grow
in pairs (i.e., diplococci). They closely resemble
Neisseria meningitides in appearance. Traditionally,
Gonococci are differentiated from other Neisseria
species by their ability to grow on selective media.
Gonococci are intolerant of drying, and therefore
patient samples should be immediately inoculated
onto the appropriate culture medium.
Neisseria gonorrhoeae primary infects columnar or
cuboidal epithelium. Attachment to mucosal epithelium is mediated in part of pili and Opa (opacity
related proteins or protein II). Infection is characterized by four stages: (1) attachment to the mucosal
cell surface; (2) local penetration to the submucosal
tissues; (3) local proliferation; and (4) a local inflammatory response or dissemination.
Generally, human serum will kill circulating Gonococci via activation of the complements system.
However, strains causing disseminated gonococcal
infection (DGI) are typically serum resistant and
induce defective deposition of complement on the
outer membranes.54 Gonococci have developed
multiple mechanisms for evading host defenses
including antigenic and phase variation of pili and
Opa, masking of gonocococcal antigen, release of
IgA1 proteases, and production of blocking antigen.
Gonorrhea is the second most commonly reported communicable disease in the United States
with more than 300,000 cases reported annually.
From the mid-1970s through the mid-1990s, the
incidence of gonorrhea declined approximately
75%. However, in the past 15 years, the incidence
appears to have stabilized at around 110120 cases
per 100,000 population. The incidence of gonorrhea is lower in Western European countries.
The highest rates of gonococcal infection are
reported in adolescents and young adults, minori-

ties, and persons living in the Southeastern United

States. Traditionally, higher rates have been reported in men as compared to women. However, most
recently nearly equal rates have been reported in
men and women. Risk factors for infection include
a new sexual partner or multiple sexual partners,
younger age, minority ethnicity, low education and
socioeconomic levels, substance abuse, unmarried
status, and previous infection. The attack rate after
sexual exposure has often been documented to be
50% or greater.
Over the years, N. gonorrhoeae has demonstrated
the ability to develop resistance to clinically
important antibiotic therapies. In the 1980s, N.
gonorrhoeae developed resistance to penicillin and
tetracycline. More recently, fluoroquinolone resistance has been reported across the Unites States
with prevalence up to 20% in parts of California and
Hawaii.
Gonococcal infections lead to different clinical
syndromes in men and women. In men genital
infections are generally symptomatic. Most commonly infection leads to urethritis, but may occasionally progress to periurethral abscess or acute
prostatitis. Infection may involve the pharynx or
rectum, especially in men who have sex with men.
Disseminated infection is less common in men
compared to women.
Urethritis is characterized by penile discharge and
dysuria. The discharge may be purulent or mucopurulent in color and copious. Microscopic analysis
of the urethral secretions reveals white blood cells.
Epididymitis characterized by testicular pain and
swelling, which is usually unilateral, may occur. Epididymitis must be distinguished from other causes
of testicular pain such as torsion or trauma.
In women, as in men, gonorrhea can involve any
portion of the genital tract. Women are more likely
than men to have asymptomatic infection. The
most common site of mucosal infection in women
is the cervix. Symptomatic infection is characterized by vaginal pruritis and/or a mucopurulent
discharge. Pain is uncommon. Women may also
develop urethritis, anorectal infection, or proctitis. Pharyngeal infection may occur and is usually
asymptomatic. Cervical gonorrhea leads to pelvic
inflammatory disease in 10%40% of women. Even
in the absence of symptoms, substantial scarring
and inflammation may occur resulting in decreased
fertility. Symptoms of pelvic inflammatory disease
include pelvic and abdominal pain, vaginal bleeding, and dyspareunia.

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264 Chapter 180: Gram-Negative Coccal and Bacillary Infections

Disseminated gonococcal infection (DGI) occurs

in 1%3% of persons infected with N. gonorrhoeae.
Most patients with DGI are less than 40 years of age.
Both males and females may be affected, although
DGI is approximately three times more common
in women than men. Risk factors for DGI include
recent symptomatic genital infection in both men
and women, recent menstruation, pregnancy, congenital or acquired complement deficiencies (C5,
C6, C7, or C8), and systemic lupus erythematosus.
DGI typically present with one of two syndromes.5560 First, a triad of tenosynovitis, dermatitis, and polyarthralgias without purulent arthritis.
Second, purulent arthritis without associated skin
lesions. Frequently there is overlap between these
two syndromes. In the tenosynovitis, dermatitis,
polyarthralgias syndrome, the acute phase is characterized by fever, chills, and malaise. Tenosynovitis
is classic. Skin lesions are the most common manifestation of DBI and occur in 50%70% of patients.
The eruption typically appears during the first-day
symptoms and may recur with each episode of
fever. The skin lesions associated with DGI begin as
tiny red papules or petechiae 15 mm in diameter,
many of which evolve rapidly through vesicular or
pustular stages to develop a gray, necrotic center,
often on a hemorrhagic base. Papules, bullae, pustules, and hemorrhagic lesions, all may be present
simultaneously. The lesions tend to be scanty but
widely distributed. The distal portions of the extremities are most commonly involved with sparing
of scalp, face, trunk, and oral mucous membranes.
Histologic exam reveals leukocytoclastic vasculitis
with fibrin thrombi. Circulating immune complexes
may play a role in the pathogenesis of DGI-associated skin lesions and arthritis/tenosynovitis.
Uncomplicated urogenital and anorectal infection
is best diagnosed using nucleic acid amplification.
In men, this may be performed on urethral discharge or urine and in women on cervical, vaginal,
or urine samples. Culture remains the gold standard
with samples immediately plated on ThayerMartin
medium. While culture is 100 specific, sensitivity is
only between 65% and 85% in women. Urogenital
and anorectal infection should be treated with
a single injection of ceftriaxone.61 Alternatively,
cefixime may be used for oral therapy. In patients
who have a severe allergy to -lactam antibiotics
and cannot undergo desensitization, azithromycin
should be used. However, more than 5% of recent
strains have demonstrated decreased susceptibility
to this drug. Spectinomycin is another alternative
therapy in the -lactam allergic patient.

In patients who present with DGI, it is best

established via synovial fluid analysis that generally reveals around 50,000 cells/mm3. Patients
with tenosynovitis, dermatitis, and polyarthralgia
typically have negative synovial fluid cultures. All
patients with suspected DGI should have two sets
of blood cultures prior to therapy. Although blood
cultures are frequently negative, when positive they
confirm the diagnosis. Patients should also have synovial, skin, urethral or cervical cultures, and rectal
cultures immediately plated on appropriate media.
Approximately, 50% of patients will have a positive
mucosal culture. More recently, molecular diagnostics have been used to diagnose culture-negative
DGI include real-time PCR of synovial fluid62 and
nucleic acid amplification of a skin biopsy sample.63
A variety of syndromes may mimic DGI including
acute hepatitis B, bacterial arthritis, acute rheumatic
fever, infective endocarditis, Reiter syndrome, HIV
seroconversion syndrome, rheumatoid arthritis, and
psoriatic arthritis. DGI may be treated with intravenous ceftriaxone or cefotaxime with the treatment
course being completed with oral cefixime. All
patients with DGI should be evaluated for Chlamydial infection and HIV. Whenever possible, sexual
partners should be identified and offered treatment.
Patients with recurrent DGI should be screened for
deficiencies of the terminal components of complements.

INFECTIONS WITH OTHER

GRAM-NEGATIVE BACILLI
THAT HAVE CUTANEOUS
MANIFESTATIONS
Aeromonas
Aeromonas was first isolated more than 60 years
ago.107 Aeromonas are ubiquitous in the environment and can be isolated from aquatic habitats,
fish, foods, domesticated pets, invertebrates, birds,
ticks and insects, leeches, and the soil. The current
taxonomy of this genus is in transition.107 Three species (Aeromonas hydrophila, Aeromonas caviae, and
Aeromonas veronii bv. Sobria) are responsible for
more than 85% of human infections. Humans most
commonly acquire infection from injuries suffered
in fresh or brackish water, animal bites (especially
snakes, alligators, and reptiles), and consumption of
contaminated foods.
The most common site for isolation of aeromonas
is the gastrointestinal tract, although their etiologic role in gastroenteritis is still being elucidated.

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Chapter 180:

Gram-Negative Coccal and Bacillary Infections 265

Aeromonas sp. have been linked to a nonspecific

enteritis and less commonly to a dysenteric form of
disease. On extremely rare occasions, Aeromonas
has been linked to a cholera-like syndrome.
The second most common clinical syndrome
caused by Aeromonas is skin and soft tissue infections. Most commonly these infections result from
injuries sustained in the water (during occupation,
swimming, boating, fishing) or bites by reptiles.
Occasionally, Aeromonas infection may occur as a
result of medical procedures including medicinal
leech therapy, elective bowel surgery, or orthopedic
procedures. Burn wounds contaminated with water
may subsequently develop serious Aeromonas secondary infection.108 Skin infections range from mild
topical problems such as pustular lesions to severe
and life-threatening infections. Aeromonas folliculitis may occur as a consequent of spa bathing.109 Severe infections usually start as subcutaneous infection (cellulitis) but may progress to involve deeper
layers of skin and subcutaneous tissue with spread
along facial planes (i.e., necrotizing fasciitis). These
infections have a high mortality, often exceeding
50%. Necrotizing fasciitis is most commonly seen
in patients with liver disorders or malignancy. Keys
to a favorable outcome include early recognition,
prompt antibiotic therapy, and appropriate and
rapid surgical intervention (debridement, irrigation).

often present with overwhelming sepsis (mortality

>25%50%) without an obvious infectious source.
The distinctive skin lesions associated with this syndrome are large bullous lesions filled with hemorrhagic fluid.111 Lesions can also present as erythema,
necrotic ulcers, necrotizing fasciitis, vasculitis, pustules, petechiae, purpura, generalized papules or
macules, gangrene, urticaria, or erythema multiforme-like lesions.112 The lesions are typically on the
extremities, usually the legs. V. vulnificus also causes
severe wound infections, usually after trauma with
exposure to salt or brackish water. Cleaning fish or
shellfish is a common method of injury. The wound
infection is characterized by swelling and intense
pain at the wound site. The wound generally has
intensive erythema with swelling that may progress
to bullous lesions with vasculitis and ultimately to
frank gangrene. The differential diagnosis includes
infections due to Group A streptococcal, S. aureus, P.
aeruginosa, Pasteurella multocida, and Aeromonas
hydrophila.113 Treatment includes prompt antibiotics and debridement.

Vibrio species
Vibrio species are small, straight, slightly curved,
curved, or comma-shaped Gram-negative rods.
They are motile with polar flagella when grown in
liquid media. Vibrio species are primarily aquatic
and are very common in marine and estuarine
environments. Seafood often harbors Vibrio species
including oysters, clams, mussels, crabs, shrimp,
and prawns.
Vibrio species usually cause either gastrointestinal
disease extraintestinal infections. Vibrio cholerae
O1 and O139 are an important cause of epidemic
gastroenteritis worldwide.110 More recently, Vibrio
parahaemolyticus has emerged as an important
cause of acute gastroenteritis.
Vibrio vulnificus has been linked with two disease
syndromes: (1) primary sepsis and (2) severe wound
infections.110 Primary sepsis most commonly occurs in patients with preexisting liver disease (e.g.,
hemachromatosis) and follows either a wound
infection with V. vulnificus or ingestion from contaminated food most commonly shellfish. Patients

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