Organism	Source	Spectrum of Disease in Humans
C. concisus, C. curvus, C. rectus, C. showae	Humans	Periodontal disease; gastroenteritis (?)
C. gracilis	Humans	Deep-tissue infections: head, neck, and viscera; gingival crevices
C. coli	Pigs, poultry, sheep, bulls, birds	Gastroenteritis * Septicemia
C. jejuni subsp. jejuni	Poultry, pigs, bulls, dogs, cats, birds, and other animals	Gastroenteritis * Septicemia Meningitis Proctitis
C. jejuni subsp. doylei	Humans	Gastroenteritis * Gastritis Septicemia
C. lari	Birds, poultry, other animals; river and seawater	Gastroenteritis * Septicemia Prosthetic joint infection
C. hyointestinalis subsp. hyointestinalis	Pigs, cattle, hamsters, deer	Gastroenteritis
C. upsaliensis	Dogs, cats	Gastroenteritis Septicemia abscesses
C. fetus subsp. fetus	Cattle, sheep	Septicemia Gastroenteritis Abortion Meningitis
C. fetus subsp. venerealis	Cattle	Septicemia
C. sputorum biovar sputorum	Humans, cattle, pigs	Abscesses Gastroenteritis
Arcobacter cryaerophilus	Pigs, bulls, and other animals	Gastroenteritis * Septicemia
A. butzleri	Pigs, bulls, humans, other animals; water	Gastroenteritis * Septicemia

Epidemiology and Pathogenesis

The majority of Campylobacter species are pathogenic and associated with a wide variety of diseases in humans and other animals. These organisms demonstrate considerable ecologic diversity. Campylobacter spp. are microaerophilic (5% to 10% O₂) inhabitants of the gastrointestinal tracts of various animals, including poultry, dogs, cats, sheep, and cattle, as well as the reproductive organs of several species. When random fecal samples from chicken carcasses from butcher shops in the New York City area were tested for Campylobacter, 83% of the samples yielded more than 10 colony-forming units per gram of feces. In general, Campylobacter spp. produce three syndromes in humans: febrile systemic disease, periodontal disease, and, most commonly, gastroenteritis. Arcobacter species appear to be associated with gastroenteritis. Studies have indicated that A. butzleri was the fourth most common Campylobacter-like organism isolated from stool and was associated with a persistent, watery diarrhea. In addition, more recent data indicate that Arcobacter is underreported in gastrointestinal infections and diarrhea throughout many European countries. The organism is found in the environment and in untreated water. It is also prevalent in commercially prepared meats including chicken, beef, pork, lamb, and poultry.

Within the genus Campylobacter, C. jejuni and C. coli are commonly associated with infections in humans and are transmitted via contaminated food, milk, or water. Outbreaks have been associated with contaminated drinking water and improperly pasteurized milk, among other sources. In contrast to other agents of foodborne gastroenteritis, including Salmonella and staphylococci, Campylobacter spp. does not multiply in food. Other campylobacters have been isolated from patients as a result of consumption of untreated water, immunocompromised patients, or patients recently returned from international travel. C. jejuni subsp. doylei has been isolated from children with diarrhea and from gastric biopsies in adults. In developed countries, the majority of C. jejuni infections are transmitted by direct contact during the preparation and eating of chicken. Person-to-person transmission of Campylobacter infections plays only a minor role in the transmission of disease. There is a marked seasonality with the rates of C. jejuni infection in the United States; the highest rates of infection occur in late summer and early fall. Campylobacter spp. has been recognized as the most common etiologic agent of gastroenteritis in the United States.

Although infections with C. jejuni are evident as a result of acute inflammatory enteritis of the small intestine and colon, the pathogenesis remains unclear. However, multiplication of organisms in the intestine leads to cell damage and an inflammatory response. Blood and polymorphonuclear neutrophils are often observed in patient stool specimens. Most strains of C. jejuni are susceptible to the nonspecific bactericidal activity of normal human serum; this susceptibility probably explains why C. jejuni bacteremia is uncommon.

Spectrum of Disease

As previously mentioned, Campylobacter species are the causative agent of gastrointestinal or extraintestinal infections. An increase in extraintestinal disease, including meningitis, endocarditis, and septic arthritis has been reported in patients with acquired immunodeficiency syndrome (AIDS) and other immunocompromised individuals. The different campylobacters and the associated diseases are summarized in Table 34-1. Gastroenteritis associated with Campylobacter spp. is usually a self-limiting illness and does not require antibiotic therapy. Most recently, postinfectious complications with C. jejuni have been recognized and include reactive arthritis and Guillain-Barré syndrome, an acute demyelination (removal of the myelin sheath from a nerve) of the peripheral nerves. Studies indicate that 20% to 40% of patients with this syndrome are infected with C. jejuni 1 to 3 weeks prior to the onset of neurologic symptoms.

Laboratory Diagnosis

Specimen Collection, Transport, and Processing

There are no special requirements for the collection, transport, and processing of clinical specimens for the detection of campylobacters; the two most common clinical specimens submitted to the laboratory are feces (rectal swabs are also acceptable for culture) and blood. Specimens should be processed as soon as possible. Delays of more than 2 hours require the stool specimen to be placed either in Cary-Blair transport medium or in campy thio, a thioglycollate broth base with 0.16% agar and vancomycin (10 mg/L), trimethoprim (5 mg/L), cephalothin (15 mg/L), polymyxin B (2500 U/L), and amphotericin B (2 mg/L). Cary-Blair transport medium is suitable for other enteric pathogens; specimens received in transport medium should be processed immediately or stored at 4° C until processed.

Upon gram staining, Campylobacter spp. display a characteristic microscopic morphology as small, curved or seagull-winged, faintly staining, gram-negative rods (Figure 34-2). Polymerase chain reaction (PCR) amplification may provide an alternative to culture methods for the detection of Campylobacter spp. from clinical specimens. The detection of Campylobacter DNA in stools from a large number of patients with diarrhea suggests that Campylobacter spp. other than C. jejuni and C. coli may account for a proportion of cases of acute gastroenteritis in which no etiologic agent is identified.

Figure 34-2 A, Gram stain appearance of *Campylobacter jejuni* subsp. *jejuni* from a colony on a primary isolation plate. Note seagull and curved forms *(arrows).* B, Appearance of *Campylobacter jejuni* subsp. *jejuni* in a direct Gram stain of stool obtained from a patient with campylobacteriosis. *Arrows* point to the seagull form.

Antigen Detection

Several commercial antigen detection systems are available for the direct detection of Campylobacter in stool specimens. These enzyme immunoassays (EIA) can be used to detect antigens in stool samples for several days if stored at 4° C.

Media

Campy-BAP is an enriched selective blood agar plate used to isolate C. jejuni. The medium is composed of a Brucella agar base, sheep red blood cells and vancomycin, trimethoprim, polymyxin B, amphotericin B, and cephalothin. Campy medium (CVA) contains cefoperazone, vancomycin, and amphotericin B. The antibiotics in both media suppress the growth of normal fecal flora. Campylobacter agar base blood free (CCDA) is a modified agar that does not include blood. The blood is replaced with charcoal, sodium pyruvate, and ferrous sulfate. The medium supports growth of most Campylobacter spp.

Cultivation

Stool.

Successful isolation of Campylobacter spp. from stool requires selective media and optimum incubation conditions. Recommended inoculation of two selective agars is associated with increased recovery of the organisms. Because Campylobacter and Arcobacter spp. have different optimum temperatures, two sets of selective plates should be incubated, one at 42° C and one at 37° C. Extended incubation may be required, 48 to 72 hours, before there is evidence of visible growth. Table 34-2 describes the selective plating media and incubation conditions required for the recovery of Campylobacter spp. from stool specimens.

TABLE 34-2

Selective Media and Incubation Conditions to Recover Campylobacter and Arcobacter spp. from Stool Specimens

Organism	Primary Plating Media	Incubation Conditions
C jejuni C coli	Modified Skirrow’s medium: Columbia blood agar base, 7% horse-lysed blood, and antibiotics (vancomycin, trimethoprim, and polymyxin B) Campy-BAP: Brucella agar base with antibiotics (trimethoprim, polymyxin B, cephalothin, vancomycin, and amphotericin B) and 10% sheep blood Blood-free, charcoal-based selective medium: Columbia base with charcoal, hemin, sodium pyruvate, and antibiotics (vancomycin, cefoperazone, and cycloheximide) Modified charcoal cefoperazone deoxycholate agar (CCDA) Semisolid motility agar: Mueller-Hinton broth II, agar, cefoperazone, and trimethoprim lactate Campy-CVA: Brucella agar base with antibiotics (cefoperazone, vancomycin, and amphotericin B) and 5% sheep blood	42° C microaerobic conditions* for 72 hours
C fetus subsp. fetus^† C jejuni subsp. doylei C upsaliensis C lari C hyointestinalis	Modified Skirrow’s medium Blood-free charcoal-based selective media Campy-CVA CCDA Semisolid motility agar	37° C under microaerobic conditions for at least 72 hours up to 7 days^‡
A. cryaerophilus, A. butzleri	Campy-CVA	37° C under microaerobic conditions^§ for 72 hours