Campylobacter infections are among the most common bacterial infections in humans. They produce both diarrheal and systemic illnesses.[1] In industrialized regions, enteric Campylobacter infections produce an inflammatory, sometimes bloody, diarrhea or dysentery syndrome.[2]
Campylobacter jejuni is a common food-borne pathogen that can cause diarrhea in all age groups, with peak incidence from age 1 to 5 years. It is a leading cause of food poisoning in the United States, sometimes causing more cases of diarrhea than Salmonella and Shigella combined. In infants, it can also lead to meningitis. In developing regions, diarrhea caused by C jejuni may be watery.[1, 2]
![]() View Image | Scanning electron microscope image of Campylobacter jejuni, illustrating its corkscrew appearance and bipolar flagella. Source: Virginia-Maryland Regi.... |
Campylobacter species, including C fetus, C coli, and C lari, are known to cause bacteremia and systemic manifestations in adults, particularly those with underlying medical conditions such as diabetes, cirrhosis, cancer, or HIV/AIDS. Although C fetus is less common than C jejuni, it is considered an opportunistic pathogen that primarily affects individuals with predisposing diseases, older adults, and pregnant patients, with pregnant individuals facing a significant risk for fetal loss, with rates as high as 70%. In healthy individuals, infections can be acquired through occupational exposure to animals carrying the bacteria. Patients with immunoglobulin deficiencies are at a higher risk of developing challenging and recurrent infections with Campylobacter species. Hypochlorhydria and achlorhydria also can predispose individuals to Campylobacter infections due to the bacteria's sensitivity to gastric acid.[1]
Campylobacter can manifest as a sexually transmitted infection, particularly among men who have sex with men (MSM), leading to gastrointestinal issues such as enterocolitis/proctocolitis syndrome.[1, 3] Bacteremia, including cases caused by Helicobacter species, can occur, with C jejuni often resulting in serious bacteremic conditions in individuals with AIDS.[4, 5] Furthermore, C lari has been associated with mild recurrent diarrhea in children, whereas C upsaliensis can cause diarrhea or bacteremia. Notably, C hyointestinalis, with biochemical features resembling C fetus, may cause sporadic bacteremia in immunocompromised individuals. These clinical presentations highlight the diverse and often severe consequences of Campylobacter infections in various patient populations.
Campylobacter organisms also may be an important cause of traveler's diarrhea, especially in Thailand and surrounding areas of Southeast Asia. In a study of American military personnel deployed in Thailand, more than half of those with diarrhea were found to be infected with Campylobacter species.[6]
Campylobacter is said to be prevalent in food animals such as poultry, cattle, pigs, sheep, and ostriches, as well as pets, including cats and dogs.
The known routes of Campylobacter transmission include fecal-oral, person-to-person sexual contact (uncommon),[1] unpasteurized raw milk and poultry ingestion, and waterborne (ie, through contaminated water supplies). Exposure to sick pets, especially puppies, also has been associated with Campylobacter outbreaks.[2]
Transmission of Campylobacter organisms to humans usually occurs via infected animals and their food products. Most human infections result from the consumption of improperly cooked or contaminated foodstuffs. Chickens may account for 50-70% of human Campylobacter infections. Most colonized animals develop a lifelong carrier state.
Campylobacter has been found in shellfish.[7, 8]
The infectious dose is 1000-10,000 bacteria. Campylobacter infection has occurred after ingestion of 500 organisms by a volunteer; however, a dose of fewer than 10,000 organisms is not a common cause of illness. Campylobacter species are sensitive to hydrochloric acid in the stomach. Conditions in which acid secretion is blocked, for example, by antacid treatment or disease, predispose patients to Campylobacter infections.
Symptoms of Campylobacter infection begin after an incubation period of up to a week. The sites of tissue injury include the jejunum, the ileum, and can extend to involve the colon and rectum. Campylobacter jejuni appears to invade and destroy epithelial cells; it is attracted to mucus and fucose in bile, and the flagella may be important in both chemotaxis and adherence to epithelial cells or mucus. Adherence also may involve lipopolysaccharides or other outer membrane components. Such adherence would promote gut colonization. PEB 1 is a superficial antigen that appears to be a major adhesin and is conserved among C jejuni strains.
Some strains of C jejuni produce a heat-labile, cholera-like enterotoxin, which is important in watery diarrhea observed in infections. Infection with the organism produces diffuse, bloody, edematous, and exudative enteritis. The inflammatory infiltrate consists of neutrophils, mononuclear cells, and eosinophils. Crypt abscesses develop in the epithelial glands, and ulceration of the mucosal epithelium occurs.
Cytotoxin production has been reported in Campylobacter strains from patients with bloody diarrhea. In a small number of cases, the infection is associated with the hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura through a poorly understood mechanism. Endothelial cell injury, mediated by endotoxins or immune complexes, is followed by intravascular coagulation and thrombotic microangiopathy in the glomerulus and the gastrointestinal mucosa.
Campylobacter species produce the bacterial toxin cytolethal distending toxin (CDT), which produces a cell block at the G2 stage preceding mitosis. Cytolethal distending toxin inhibits cellular and humoral immunity via the destruction of immune response cells and necrosis of epithelial-type cells and fibroblasts involved in the repair of lesions. This leads to slow healing and results in disease symptoms.[9]
In patients with HIV infection, Campylobacter infections may be more common, may cause prolonged or recurrent diarrhea, and may be more commonly associated with bacteremia and antibiotic resistance.
Campylobacter fetus is covered with a surface S-layer protein that functions like a capsule and disrupts c3b binding to the organisms, resulting in both serum and phagocytosis resistance.
Campylobacter jejuni infections also show recurrence in children and adults with immunoglobulin deficiencies. Acute C jejuni infection confers short-term immunity. Patients develop specific immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies in serum; IgA antibodies develop in intestinal secretions as well. The severity and persistence of C jejuni infections in individuals with AIDS and hypogammaglobulinemia indicate that both cell-mediated and humoral immunity are important in preventing and terminating infection.
Campylobacter infections in kidney transplant recipients have been associated with factors such as the use of corticosteroids for immunosuppression, low eGFR, low lymphocyte counts, and acute rejection.
The oral cavity contains numerous Campylobacter species, such as Campylobacter concisus, that have been associated with a subtype of inflammatory bowel disease.[10, 11] Campylobacter gracilis is associated with periodontal disease,[12] pleuropulmonary disease, and bacteremia[13]
United States
An estimated 1.5 million cases of Campylobacter infections occur annually in the United States.[14]
In 2020 the incidence of Campylobacter was 20 per 100,000 population. FoodNet surveillance tracks eight foodborne pathogens (including Campylobacter), and a 26% reduction was noted in 2020 as compared to 2017-2019.[15]
International
Campylobacter jejuni infections are extremely common worldwide, although exact figures are not available, particularly in low- and middle-income countries. In high-income countries, the incidence has been estimated to be 4.4 to 9.3 per 1000 population.[16] In the UK, 500,000 cases are estimated to occur annually. Campylobacter jejuni and C coli account for 91% and 8% of cases, respectively.[17] The Czech Republic reported the highest national campylobacteriosis rate in 2019, at 126.1 per 100,000 that year.[18]
Campylobacter infections usually are self-limited and rarely cause mortality. Exact figures are unavailable, but occasional deaths have been attributed to Campylobacter infections, typically in elderly or immunocompromised persons and secondary to volume depletion in young, previously healthy individuals.
Campylobacter infections have no clear racial predilection.
Campylobacter organisms are isolated more frequently from males than females. Homosexual men appear to be at increased risk for infection with atypical Campylobacter species such as H cinaedi and H fennelliae.
Campylobacter infections can occur in all age groups.
Studies show a peak incidence in children younger than 1 year and in persons aged 15 to 29 years. The age-specific attack rate is highest in young children. In the United States, the highest incidence of Campylobacter infection in 2010 was in children younger than 5 years and was 24.4 cases per 100,000 population,[19] However, the rate of fecal cultures positive for Campylobacter species is greatest in adults and older children.
Asymptomatic Campylobacter infection is uncommon in adults.
In developing countries, Campylobacter infection is very common in the first 2 years of life. Asymptomatic infection is also more common.[20]
For additional information on pediatric Campylobacter infections, see Campylobacter Infections.
Campylobacter infections can range from asymptomatic to, rarely, severe life-threatening colitis with toxic megacolon.[21]
All Campylobacter species associated with enteric illnesses cause identical clinical manifestations.
The symptoms and severity of the gastroenteritis produced can vary.
Patients may have a history of ingestion of inadequately cooked poultry, unpasteurized milk, or untreated water. The incubation period is 1 to 7 days and probably is related to the dose of organisms ingested.
A brief prodrome of fever, headache, and myalgias lasting up to 24 hours is followed by crampy abdominal pain, fever as high as 40°C, and as many as 10 watery, frequently bloody, bowel movements per day. Fever, which develops in more than 90% of patients, may be low or high grade and can persist for a week.
Patients with C jejuni infection who report vomiting, bloody diarrhea, or both, tend to have a long illness and require hospital admission.[22]
Abdominal pain and tenderness may be localized. Pain in the right lower quadrant may mimic acute appendicitis (pseudoappendicitis).
Tenesmus occurs in approximately 25% of patients.
In some cases, acute abdominal pain is the only symptom, with pain typically in the right lower quadrant. Among the symptoms, abdominal pain is more likely to result from Campylobacter infection than from Salmonella or Shigella infections.
In contrast to C jejuni infection, C fetus infection often presents as a non-specific febrile illness. It causes diarrheal illness less frequently. It is the most commonly identified species in bacteremia. However, C fetus infection that produces diarrheal illness results in clinical manifestations that are similar to those of C jejuni infection. Campylobacter fetus is an opportunistic agent in debilitated and immunocompromised hosts,[23] but healthy hosts rarely may be affected.[24]
C fetus sometimes is isolated from the bloodstream, possibly as it resists the bactericidal activity of serum, whereas the more common C jejuni does not. Persons who develop Campylobacter bacteremia usually are older and are more likely to have cellulitis, endovascular infection, or a device-related infection.[25]
Systemic illness with a predilection for vascular sites is characteristic. Meningitis,[26] vascular infections, thrombophlebitis, peritonitis, and cellulitis can occur.[27]
Campylobacter fetus infection may cause intermittent diarrhea or nonspecific abdominal pain. It should be considered in individuals with nonspecific fever who are either immunocompromised or have had exposure to cattle and sheep.[28]
Patients with Campylobacter infection may appear to be ill.
Campylobacter infection commonly manifests as an acute gastrointestinal illness characterized by watery, occasionally bloody diarrhea. Systemic features of the infection also are notable, with a consistent fever of 38 to 40°C, which may exhibit a relapsing or intermittent pattern. Frequent accompaniments include abdominal pain, often mimicking appendicitis and localized to the right lower quadrant, alongside headaches and myalgias.
Complications can extend to subacute bacterial endocarditis—typically linked to C fetus—reactive arthritis that often impacts the knees and resolves spontaneously, meningitis, or a protracted fever with an elusive origin. Among other presenting features, there is a notable abdominal tenderness, frequently observed bilaterally in the lower quadrants.
It is particularly significant to note that abdominal pain is more prevalent in Campylobacter infections compared to other enteropathogens such as Salmonella and Shigella. This clinical differential is essential for appropriate diagnostic and therapeutic strategies.
Campylobacter organisms are curved or spiral, motile, non–spore-forming, gram-negative rods. Organisms from young cultures have a vibriolike appearance, but, after 48 hours of incubation, organisms appear coccoid. Campylobacter organisms are motile by means of unipolar or bipolar flagellae. They both are oxidase- and catalase-positive and microaerophilic, requiring reduced oxygen (5-10%) and increased carbon dioxide (3-10%). The organisms grow slowly, with 3 to 4 days required for primary isolation from stool samples, and even longer from blood.
Potential complications of Campylobacter infections include the following:
In the clinical diagnosis of Campylobacter infections, an array of laboratory techniques is essential for identifying the pathogen accurately and distinguishing it from other gastrointestinal illnesses.[1] From foundational microbiological assessments to sophisticated molecular and serological testing, these methods provide the critical data needed for effective clinical decision-making. Below, we detail the array of diagnostic tools employed in clinical settings, examining both their applications and the pivotal advancements that have refined the detection and management of Campylobacter infections.
Microbiological testing
Clinicians typically begin with microbiological evaluations, such as stool cultures or nucleic acid amplification tests (NAAT). In cases where symptoms suggest a focal infection or severe systemic disease, blood cultures are also recommended. Microscopic examination of stool smears generally reveals the presence of white blood cells, indicative of infection.
Advanced diagnostic tools
To enhance the accuracy of diagnostics, advanced tools like multiple enteric pathogen NAAT panels and antigen-based stool tests are employed. Gram staining of stool samples can detect Campylobacter’s characteristic curved rods, although its sensitivity varies between 50-75%. Leukocytes and erythrocytes, frequently present in fecal samples from patients with Campylobacter enteritis, can be visualized through direct light microscopy using either methylene blue or Gram stains.
Additional laboratory findings
Peripheral blood leukocytosis and clinical signs of dehydration in moderate to severely ill patients are common. Special culture conditions are necessary for infections suspected to be caused by C fetus or other atypical Campylobacter species, which includes incubation at 37°C without the use of cephalosporins.
Serodiagnosis and molecular techniques
Serodiagnosis employing highly specific recombinant antigens in enzyme-linked immunoassay (ELISA) enhances specificity for detecting C jejuni infections.[46] Furthermore, real-time polymerase chain reaction (PCR) offers a rapid and precise method for the direct detection of C jejuni from diarrheal stools.[47]
Modern molecular biology techniques such as PCR and immunoenzymatic methods demonstrate greater sensitivity compared to traditional culture methods.[48, 49, 50] Culture-independent rapid tests for detecting antigens in stool specimens exist, but their reliability as standalone diagnostic tools is currently under debate,[51] underscoring the necessity for a comprehensive diagnostic protocol incorporating a blend of traditional and modern methods.[52, 53, 54]
Up to 80% of patients with Campylobacter infection demonstrate evidence of proctocolitis on sigmoidoscopy. However, findings may be identical to those observed in pseudomembranous colitis or inflammatory bowel disease. Sigmoidoscopic abnormalities range from focal mucosal edema and hyperemia with patchy petechiae to diffuse or aphthoid ulceration.
Most infections caused by Campylobacter jejuni in the gastrointestinal tract are self-limiting; however, in cases where recovery is delayed, azithromycin has proven beneficial. Azithromycin is also routinely administered to individuals at increased risk for severe or complicated infections, particularly those with compromised immune systems.[1]
The use of ciprofloxacin has fallen out of favor due to escalating resistance rates; it should be reserved for cases where susceptibility is confirmed, though resistance still may occur even during fluoroquinolone treatment.
For instances of Campylobacter infections that extend beyond the gastrointestinal tract, a prolonged antibiotic regimen, typically ranging from 2 to 4 weeks with agents such as imipenem, gentamicin, ampicillin, or erythromycin, is recommended to mitigate the risk for recurrence.
Replacement of fluids and electrolytes is the mainstay of therapy in patients with Campylobacter infections.[1] Rehydration is done with oral glucose-electrolyte solutions. Intravenous fluids are used if oral rehydration fails.
The use of antibiotics to treat uncomplicated Campylobacter infections is controversial, with studies showing that erythromycin rapidly eliminated Campylobacter organisms from the stool without affecting the duration of illness. Studies in children with C jejuni dysentery have shown benefit from early treatment with erythromycin. Antibiotics may be indicated if any of the following occur:
For toxic megacolon or infected aneurysms,[41] consult a surgeon.
For endovascular C fetus infections, consult an infectious disease specialist.
Azithromycin therapy would be a primary antibiotic choice for Campylobacter jejuni gastroenteritis when indicated (see Medical Care),[55] with a typical regimen of 500 mg/d for 3 days. However, erythromycin is the classic antibiotic of choice. Its resistance remains low,[56] and it can be used in pregnant patients and children. Self-limited diarrhea in a normal host may not need treatment.
Macrolides should not be used to treat serious infections (meningitis, bacteremia, and endovascular infections) caused by C fetus.
The use of fluoroquinolones in food animals has resulted in fluoroquinolone-resistant Campylobacter strains worldwide.[57, 58] Quinolone resistance of C jejuni and C coli is conferred by the mutation gyrA C-257-T, which can be identified with methods such as multiplex PCR.[59] A 2008 study from the United Kingdom found fluoroquinolone-resistant Campylobacter species in 22% of poultry and 75% of pig farms.[60] C jejuni with phenotypic resistance to ciprofloxacin increased from 13% in 2001-2005 to 47% in the 2011-2018 period.[17] High levels of ciprofloxacin resistance also have been reported in developing countries, with resistance ranging from 30% to greater than 70%.[61, 6] Some evidence has shown that multidrug resistance in pediatric patients in developing countries may be related to the food chain.[62] Consequently, their use as empiric therapy should be avoided.
Infections involving macrolide resistance could be treated with amoxicillin-clavulanate.[63]
Specific antibiotic doses to treat Campylobacter infections have not been fully defined for tetracycline; therefore, the doses below are empirical. Tetracyclines should be avoided in pregnancy and children.
Antibiotic treatment does not prolong carriage of C jejuni.[64]
CNS infections can be treated with meropenem in meningitis doses for 4 to 6 weeks of prolonged therapy.[38, 39, 65] Life-threatening infections can be treated with carbapenems.
Clinical Context: Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.
Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.
Treats mild-to-moderate microbial infections.
Plasma concentrations are very low, but tissue concentrations are much higher, giving it value in treating intracellular organisms. Has a long tissue half-life.
Effective against a wide range of organisms, including the most common gram-positive and gram-negative organisms. Has additional coverage of so-called atypical infections such as Chlamydia, Mycoplasma, and Legionella species.
Indicated for treatment of patients with mild-to-moderate infections, including acute bronchitic infections that may be observed with bronchiectasis.
Clinical Context: DOC for Campylobacter infections. Macrolide antibiotic that inhibits bacterial growth by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For C jejuni (not C fetus) infections.
Clinical Context: Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. For C jejuni (not C fetus) infections.
Clinical Context: For treatment of multiple organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential for toxicity. For C fetus (not C jejuni) infection.
Clinical Context: Aminoglycoside antibiotic. May be needed in severe infections. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. Can be used for C fetus infections. May be administered IV/IM.
Clinical Context: Inhibits cell-wall synthesis by binding to penicillin-binding proteins; resistant to most beta-lactamases. Can be used for C fetus meningitis.
Clinical Context: Broad-spectrum penicillin; interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms; alternative to amoxicillin when unable to take medication orally.
Clinical Context: Amoxicillin binds to penicillin-binding proteins, thus inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell walls; addition of clavulanate inhibits beta-lactamase-producing bacteria, allowing amoxicillin extended spectrum of action.
It is a semisynthetic antibiotic with a broad spectrum of bactericidal activity, covering both gram-negative and gram-positive microorganisms.
Clinical Context: Synthetic, broad-spectrum antibacterial compounds. Novel mechanism of action, targeting bacterial topoisomerases II and IV, leads to a sudden cessation of DNA replication. Oral bioavailability is nearly 100%. For C jejuni (not C fetus) infections.
Clinical Context: For pseudomonal infections and infections due to multidrug resistant gram-negative organisms. For C jejuni (not for C fetus) infections.
Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.
Sometimes systemic Campylobacter infections are diagnosed following empiric antibiotic therapy with clinical resolution. In such cases, follow-up blood cultures should be obtained, and treatment can be stopped if they are negative.
Oral erythromycin and azithromycin may not be adequate for systemic C jejuni or C fetus endovascular infections, and carbapenems such as meropenem and imipenem should be used.
Pasteurization of milk and chlorination of drinking water destroy Campylobacter organisms.
Unpasteurized milk and untreated surface water should not be consumed.
Raw milk may not be safe, even if it conforms to routine testing by somatic cell and coliform counts.[66]
Treatment with antibiotics can reduce fecal excretion.
Healthcare workers with Campylobacter infections should not provide direct patient care or prepare food while they have diarrhea or are shedding Campylobacter organisms in the stool. However, person-to-person transmission is unusual.
After diarrhea resolves, infective organisms may be present in the stool for up to 3 weeks.
Separate cutting boards should be used for foods of animal origin and other foods. After preparing raw food of animal origin, all cutting boards and countertops should be carefully cleaned with soap and hot water.[67, 68]
Chicken should be adequately cooked.
When outbreaks occur, community education can be directed at proper food-handling techniques, including thorough cooking of poultry.
As noted above, handling and consumption of poultry meat is a significant source of illness. One control strategy that has been suggested is to keep colonized and noncolonized flocks separate.[69]
Fresh chicken can be the dominant source of Campylobacter infection, and replacing this with frozen chicken can reduce Campylobacter levels.[18]
Eating raw animal products such as beef and cattle liver should be avoided.[70]
Cross-contamination of food items not normally associated with Campylobacter infections should be considered and prevented.[71]
Generally, Campylobacter infections carry an excellent prognosis. The disease is almost always self-limited, with or without specific therapy.
The illness usually lasts less than a week, but some patients develop a longer-relapsing diarrheal illness that lasts several weeks.
The occasional deaths attributable to C jejuni infection usually occur in elderly or immunocompromised hosts.
Attributable deaths may also occur in young, healthy individuals secondary to volume depletion.
The rarer C fetus infection may also be fatal in debilitated hosts.
Many Campylobacter infections are potentially preventable through education.
Meat and poultry should be cooked well and served while hot.
Avoid ice unless made from safe water.
If drinking water is of questionable quality it can be boiled or chemically purified.
Fruits and vegetables should be carefully washed if they are going to be eaten raw.
If possible, they should be peeled before consumption.
Hands should be washed carefully after preparing food.
Parents should be informed that sick pets (eg, puppies, kittens) may harbor human pathogens and must be kept away from young children.
Untreated surface water and unpasteurized milk should be avoided.