Version May 2024
INTRODUCTION — Campylobacter infection is an important cause of acute diarrhea worldwide; the organism also may produce systemic illness. Campylobacter enteritis is typically caused by Campylobacter jejuni or Campylobacter coli. The organism inhabits the intestinal tracts of a wide range of animal hosts, notably poultry; contamination from these sources can lead to foodborne disease. Campylobacter infection can also be transmitted via water-borne outbreaks and direct contact with animals or animal products.
Issues related to clinical manifestations, diagnosis, and treatment of Campylobacter infection will be reviewed here. Issues related to microbiology, pathogenesis, and epidemiology of Campylobacter infection are discussed separately, as are issues related to less-common Campylobacter species. (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology" and "Campylobacter: Infection with less common species and related bacteria".)
CLINICAL MANIFESTATIONS — The clinical features of Campylobacter enteritis due to C. jejuni and C. coli are clinically indistinguishable from one another and from illness due to other bacterial pathogens, such as Salmonellae or Shigellae.
Incubation period — The mean incubation period is three days (range one to seven days) (figure 1) [1-3].
Asymptomatic infection — Asymptomatic infection in both adults and children is rare in resource-rich settings but is more common in resource-limited countries. Asymptomatic infections in children may impact growth in early life [4].
Common presenting features
Adults — Early symptoms include abrupt onset of abdominal pain and diarrhea. In about one-third of cases, a prodromal period characterized by high fever accompanied by rigors, generalized aches, dizziness, and delirium is observed. It may last for one day (rarely two or three days) prior to onset of gastrointestinal symptoms. Patients presenting with prodromal symptoms tend to have more severe disease than those presenting with diarrhea.
The acute illness is characterized by cramping, periumbilical abdominal pain, and diarrhea. Patients frequently report ten or more bowel movements per day [5]. Bloody stools are observed on the second or third day of diarrhea in about 15 percent of patients; infection with an organism containing plasmid pVir may be correlated with more severe invasive disease and higher likelihood of bloody diarrhea [6,7].
Abdominal pain also may occur without diarrhea [8]. The pain may become continuous and radiate to the right iliac fossa, mimicking acute appendicitis. Nausea is common; approximately 15 to 25 percent of patients report vomiting.
Diarrhea is self-limited and lasts for a mean of seven days [9,10]. Abdominal pain may persist after resolution of diarrhea, and weight loss of 5 kg or more may be observed. Organisms may be excreted in the feces for several weeks after clinical recovery. One study reported a mean excretion period of 38 days [1]. Chronic carriage can occur in patients with immune deficiency, although follow-up cultures are not necessary in the absence of clinical symptoms. Relapse may occur in 5 to 10 percent of patients.
The case fatality rate is low and most deaths occur in older adults or others with comorbid conditions [11-13].
Children — Clinical manifestations in children include diarrhea, fever, abdominal pain, and vomiting. Bloody stools may be present in more than half of children. Fever tends to be pronounced in children over one year of age and convulsions may occur. In a large milk-borne outbreak of Campylobacter enteritis affecting 2500 children, 9 were hospitalized with grand mal seizures [14]. The seizures arose prior to onset of diarrhea and their illnesses were unusually severe. Meningismus and encephalopathy have also been reported [15].
In infants, vomiting and bloody stools are frequently observed; abdominal pain and fever are less common than in older children [16]. The presentation of bloody stools in the absence of diarrhea or fever can mimic intussusception. (See "Intussusception in children".)
Among neonates with C. jejuni infection, grossly bloody stools or fever may be the only manifestations of infection. Neonatal infection is usually acquired at the time of birth from a mother who is excreting Campylobacter organism in her stools (with or without a history of recent diarrhea). Nosocomial infection in neonatal nurseries has been reported [17].
People with HIV — There is an increased incidence of Campylobacter infection in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) [18,19]. Long-term carriage can occur, which can be associated with recurrent episodes of enteritis and bacteremia. Campylobacter infection in patients with HIV infection has been associated with severe, debilitating illness [19]. Antiretroviral therapy may reduce the risk of Campylobacter infection [20].
Laboratory features — Transient bacteremia may be present in the early stages of infection. In the United States and Europe, bacteremia has been reported to occur in 0.1 to 1 percent of Campylobacter cases [11,21-23]. Bacteremia appears to occur more frequently among immunosuppressed patients or those with other comorbidities [12,21,24,25], although a surveillance study in Finland noted that 53 of 76 cases of bacteremia (70 percent) occurred in patients without any underlying disease [22].
A mild neutrophilic leukocytosis with bandemia is common [26]; although mild, transient leukopenia has also been reported [27].
Unique manifestations — Patients with Campylobacter infection can present with clinical manifestations mimicking other diseases (eg, "pseudoappendicitis" and colitis).
Pseudoappendicitis — Severe abdominal pain prior to onset of diarrhea can mimic acute appendicitis. In some cases, diarrhea is absent (this is most frequently observed among children aged 6 to 15 years). The pain is caused by acute ileocecitis. On clinical examination, tenderness may be observed; rebound tenderness and guarding are usually absent.
Ultrasound or computed tomography examination may be useful for differentiating bacterial ileocecitis from acute appendicitis. In one series of 533 patients with suspected acute appendicitis or appendiceal mass, 61 had ultrasonographic findings indicating enlarged mesenteric lymph nodes and mural thickening of the terminal ileum and cecum, but there was no image of the appendix [28]. Of these 61 patients, 41 had confirmed infection (21 with Yersinia enterocolitica and 15 with C. jejuni).
Among patients with Campylobacter infection who undergo appendectomy, in most cases the removed appendix shows little or no inflammation, although evidence of Campylobacter infection has been found in up to 3 percent of inflamed appendices removed surgically [29]. Thus, Campylobacter-induced appendicitis is probably a real, though uncommon, entity.
Colitis — Campylobacter infection usually starts in the jejunum and ileum and progresses distally to affect the cecum and colon. However, some patients present with acute colitis and bloody diarrhea, which can mimic the acute colitis of inflammatory bowel disease (IBD) [30]. Histologic examination of the rectal or colonic mucosa in patients with Campylobacter colitis demonstrates acute inflammation without the chronic changes and crypt distortion usually seen in IBD [31].
It has been suggested that Campylobacter infection may play a role in the pathogenesis of IBD [32,33]. (See "Definitions, epidemiology, and risk factors for inflammatory bowel disease", section on 'Infection and the immune response'.)
Lymphoma — Biopsy specimens from patients with immunoproliferative small intestinal disease have demonstrated evidence of C. jejuni, suggesting the possibility of an association between C. jejuni infection and lymphoma [34]. Additional investigation may lead to new insights into the pathogenesis of C. jejuni infection.
Complications
Acute onset — Acute complications of Campylobacter enteritis include [5]:
●Cholecystitis, with or without preceding diarrhea [35].
●Peritonitis in patients on continuous ambulatory peritoneal dialysis, usually with preceding diarrhea [36,37].
●Rash (such as urticaria, erythema nodosum, vasculitis, cellulitis) [38].
●Osteomyelitis [24,39].
●Meningitis [40].
●Septic pseudoaneurysm [41].
●Pericarditis and myocarditis [42-45]. The typical clinical presentation involves acute chest pain, with electrocardiogram changes, and elevated levels of cardiac enzymes, in association with antecedent or coincident enteritis.
Focal extraintestinal infections with C. jejuni and C. coli occur uncommonly, with or without preceding diarrhea. Examples include septic arthritis, bursitis, osteitis, soft tissue infections, nodular skin eruptions [46], and fetal/placental infection [5]. Campylobacter abortion is also caused by Campylobacter fetus but is rarely associated with C. jejuni infection [47]. (See "Campylobacter: Infection with less common species and related bacteria".)
Late onset — There are two major late onset complications of Campylobacter infection: reactive arthritis and Guillain-Barré syndrome (GBS).
Reactive arthritis — The reactive arthritis associated with Campylobacter enteritis is similar to arthritis that can occur following Salmonella, Shigella, and other bacterial diarrheal infections. The rate of reactive arthritis is fairly low (up to 2.6 percent) [5,48-50], although the prevalence of joint symptoms may be as high as 9 to 13 percent [51,52]. The likelihood of developing reactive arthritis following C. jejuni infection appears to be unrelated to the severity of diarrheal illness [53]. Reactive arthritis occurs more commonly among patients with the HLA-B27 phenotype.
Joint pain and swelling typically appear one to two weeks (or occasionally several weeks) after the onset of diarrhea. Symptoms may mimic septic arthritis [54]. The ankles, knees, wrists, and small joints of the hands are most frequently affected, often with considerable incapacity [55]. The duration of arthritis ranges from one week to several months. The prognosis is usually good; most patients remit spontaneously or with NSAID therapy within six months of onset. (See "Reactive arthritis".)
Guillain-Barré syndrome — C. jejuni infection has been established as a trigger of GBS, an acute immune-mediated polyneuropathy [56,57]. It has been estimated that 30 to 40 percent of GBS illness is attributable to Campylobacter infection, which typically occurs between one and two weeks before the onset of neurologic symptoms [57]. In resource-limited settings, the proportion of GBS cases preceded by Campylobacter infection may be even higher [58].
Campylobacter-associated GBS is more likely to be associated with the axonal form of GBS (as opposed to the demyelinating form). In both the demyelinating and direct axonal injury forms of Campylobacter-associated GBS, the pathogenic mechanism is likely due to molecular mimicry between the surface structures of the inciting pathogen and components of the axon or myelin [59]. GBS occurring after infection with C. jejuni has a worse prognosis than other forms of GBS; recovery is slower, and the likelihood of residual neurologic disability is greater than with other forms of GBS [60]. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Guillain-Barré syndrome in adults: Treatment and prognosis".)
The risk for developing GBS during the two months following a symptomatic episode of C. jejuni infection is approximately 100-fold higher than the risk of developing GBS in the general population [61,62]. In the United States, about 1 in 1000 patients with Campylobacter enteritis develops GBS [57]. Subclinical cases of Campylobacter infection can also trigger GBS [63].
GBS associated with C. jejuni infection is likely caused by antibodies formed in response to epitopes expressed by the infecting Campylobacter strain that are cross-reactive to GM1 ganglioside (present in high concentrations in peripheral nerve myelin) [64-66]. Many Campylobacter strains isolated from patients with GBS belong to specific serotypes, notably Penner O19 and O41 strains [67-69]. In 2019 a large outbreak of GBS triggered by Campylobacter serotype O41 occurred in Peru; 59 patients were hospitalized [70].
The production of antibodies to GM1 ganglioside may also occur due to mechanisms other than molecular mimicry [56], and many patients with Campylobacter infection form these antibodies in the absence of neurologic symptoms [64]. Some studies have suggested there may be an association between certain HLA types and the likelihood of developing GBS following C. jejuni infection [38,71,72]. Others have been unable to confirm this association [73].
The Miller-Fisher variant of GBS, in which the cranial nerves are more prominently affected, has also been associated with Campylobacter infection. Cross-reacting antibodies to GQ1b ganglioside (which is present in cranial nerve myelin) have been observed in these cases [56]. The most common serotype observed in C. jejuni-associated Miller-Fisher syndrome is Penner O2 [74].
DIAGNOSIS
Clinical suspicion — Campylobacter enteritis should be suspected in the setting of severe abdominal pain with diarrhea. In particular, the following exposures or circumstances should prompt consideration of Campylobacter infection [75]:
●Diarrheal illness in the setting of a foodborne outbreak
●Consumption of raw or undercooked poultry
●Consumption of unpasteurized dairy products
●Travel to resource-limited settings
●Swimming in untreated freshwater
●House pet with diarrhea
●Other animal contact (eg, farm or petting zoo)
Microbiologic diagnosis of acute disease — The diagnosis is established by stool culture (or, in cases complicated by bacteremia, by blood culture) or by culture-independent assays, such as molecular testing, on stool.
●Culture – Stool culture technique consists of plating on Campylobacter-selective media and incubation in a gas mixture of 5 to 10 percent oxygen, 1 to 10 percent carbon dioxide, and ideally some hydrogen (picture 1). Campylobacters have a characteristic appearance under the microscope, as curved rods that sometimes have a gull-wing formation when located end to end. Campylobacters can also take on a spiral shape. Its characteristic morphology, together with detection of oxidase and catalase positivity, is sufficient for diagnosis.
●Culture-independent assays – Use of culture-independent techniques, such as nucleic acid amplification tests (NAAT), including reverse transcription-polymerase chain reaction (RT-PCR), has been rapidly expanding [75]. NAATs are far more sensitive than culture, yielding rates of Campylobacter recovery in stool that are 20 to 40 percent higher [76] but have significant drawbacks. These techniques detect bacterial deoxyribonucleic acid (DNA), not viable organisms, and positive tests must therefore be interpreted with a high degree of clinical correlation. A further drawback of culture-independent techniques is that they impede outbreak detection and investigation; enhanced surveillance by using traditional cultures supplemented by molecular subtyping has resulted in the prevention of thousands of illnesses in the past. Furthermore, for the individual patient, use of culture-independent diagnostic technologies fails to provide information about antimicrobial susceptibility to guide management. Many clinical laboratories have adopted DNA-based syndromic panels, which often do not routinely reflex to stool cultures. (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology", section on 'Detection in the laboratory'.)
It is customary for laboratories to report the presence of "Campylobacter" or "C. jejuni" without differentiating C. jejuni from C. coli. This is acceptable for routine diagnostic purposes since the distinction is of no clinical consequence, but speciation and strain identification are sometimes needed for epidemiological purposes. (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology".)
In rare cases of acute colitis or suspected appendicitis in which a rapid diagnosis is needed for clinical management, presumptive identification is possible by stool microscopic examination using dark-field, phase-contrast, and stained smears. This technique is less sensitive than culture (50 versus 94 percent) and is not practiced routinely. Gram stain is even less sensitive. C. jejuni appear as faint, gram-negative curved rods (picture 2). (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology", section on 'Detection in the laboratory'.)
Late-onset complications — Patients with late onset reactive arthritis or Guillain-Barré syndrome (GBS) may have negative stool studies. Serologic tests can be used to detect recent Campylobacter infection in these patients. In one study, a complement fixation test (using whole-cell antigens) had greatest sensitivity compared with enzyme-linked immunosorbent assay (ELISA) and other tests [77]. In general, these tests are available only in reference laboratories. Whole genome sequencing of Campylobacter isolates may be available in the future for use in outbreak investigations and in further characterizing the epidemiology of these infections [78].
TREATMENT — Campylobacter infection is usually a mild, self-limited infection. The estimated mortality from symptomatic infection in the United States is 2.4 per 1000 culture-confirmed cases [79,80]. Maintenance of proper hydration and correction of electrolyte abnormalities should be the focus of therapy. Antibiotics are not needed for most cases of C. jejuni gastroenteritis.
In general, antimotility agents such as loperamide should be avoided, especially if the patient is febrile. (See "Approach to the adult with acute diarrhea in resource-abundant settings", section on 'Symptomatic therapy'.)
Antimicrobial therapy
Indications — The efficacy of antimicrobial therapy for Campylobacter infection has been addressed in a small number of randomized trials. A meta-analysis of 11 small randomized trials noted that antimicrobial therapy reduced the duration of intestinal symptoms by only 1.3 days (95% CI 0.6-2.0 days) [81]. There was a nonsignificant trend toward greater benefit for patients treated within the first three days of illness.
Given the self-limited nature of most Campylobacter infections and the limited efficacy of routine antimicrobial therapy, treatment is warranted only for patients with severe disease or risk for severe disease. Patients with severe disease include individuals with bloody stools, high fever, extraintestinal infection, worsening or relapsing symptoms, or symptoms lasting longer than one week [79]. Those at risk for severe disease include patients who are older, pregnant, or immunocompromised [82].
Choice of drug — We suggest azithromycin for treatment of Campylobacter gastroenteritis, when indicated. Fluoroquinolones are an alternative option. Although both azithromycin and fluoroquinolones are highly effective against susceptible isolates, rates of resistance to fluoroquinolones are increasing worldwide and generally exceed those for azithromycin [83-86]. (See 'Resistance' below.)
In patients with uncomplicated Campylobacter infection at risk for severe disease, the dose of azithromycin is 500 mg orally daily for three days or until signs and symptoms of disease have improved. A single 1 g oral dose of azithromycin may be equally effective, and is more convenient, but can be associated with gastrointestinal upset; giving it as two divided doses on the same day may limit nausea. Fluoroquinolone doses for uncomplicated infection are levofloxacin 750 mg orally daily or ciprofloxacin 750 mg orally twice daily, each for three days or until signs and symptoms of disease have improved.
For those with complications or underlying immunosuppression, a longer course (7 to 14 days) of antibiotics may be warranted. For patients who are severely ill and cannot tolerate oral therapy, carbapenems are appropriate empiric therapy, but susceptibility testing should be performed to confirm that they are active. For those with life-threatening infections, the addition of an aminoglycoside to the regimen is reasonable.
C. jejuni and C. coli are usually sensitive to macrolides, fluoroquinolones, carbapenems, and aminoglycosides [87]; they are also typically sensitive in vitro to clindamycin, tetracyclines, and chloramphenicol, although there are no data indicating clinical efficacy of these agents. However, resistance to fluoroquinolones and macrolides has been described. C. jejuni and C. coli are inherently resistant to trimethoprim and beta-lactam antibiotics, including penicillin and most cephalosporins [88]. A few case reports have suggested Campylobacter may be effectively treated with fosfomycin, however laboratory studies to confirm susceptibility have not been done [89].
Resistance — The rate of macrolide-resistance among Campylobacter has remained stable at <5 percent in most parts of the world [90-93]. However, in some parts of the world, such as in Thailand and in Ireland, the macrolide-resistance rate is higher [94,95]. Despite an increase in macrolide resistance, macrolides are usually still effective in these areas. Drug susceptibility testing should be performed on isolates from patients failing therapy.
The prevalence of fluoroquinolone-resistant Campylobacter is rising. Fluoroquinolone-resistant Campylobacter is particularly prevalent in Southeast Asia, where resistance rates have been reported to exceed 80 percent [94,96]. Resistance rates of greater than 50 percent have been reported in France, Spain, Hungary, Iran, and several resource-limited countries [97,98]. Consideration of fluoroquinolone resistance is particularly important in the setting of significant diarrhea following foreign travel and/or after failed empiric treatment with a fluoroquinolone [99,100].
The rate of resistance to fluoroquinolones is also increasing in the United States [101]. In 1989, the rate of ciprofloxacin was 0 percent; between 2005 and 2014, it ranged from 20 to 27 percent [90,93]. Parallels in fluoroquinolone resistance have been observed between human isolates and strains isolated from poultry, reflecting the use of fluoroquinolones in food animals in the United States since 1995 [92,99,102-104]. In one study, ciprofloxacin-resistant Campylobacter was isolated from 10 percent of 180 chicken products from grocery stores in three states [90]. Molecular subtyping has confirmed the link between the human and poultry isolates [9]. Use of fluoroquinolones in poultry was withdrawn in the United States in 2005 [105]. Nonetheless, infections due to fluoroquinolone-resistant Campylobacter species are likely to persist due to continued circulation of such organisms in poultry flocks and from acquisition of quinolone-resistant infection during foreign travel. Following a United States outbreak of multidrug resistant Campylobacter jejuni infection linked to pet store puppies in 2017, ongoing surveillance studies suggest transmission of these resistant strains continues [106].
Prevention — Interruption of transmission from poultry is a major factor in preventing human Campylobacter infection. Chicken should be cooked thoroughly. Utensils, cutting boards, and other items used in preparation of raw poultry should be washed thoroughly. Avoidance of unpasteurized dairy products is also an important preventive measure [107].
Previous infection with Campylobacter is not necessarily protective of future symptomatic infections [108]. Thus, patients who have previously experienced symptomatic infections should also be advised to take such precautions.
Adults with Campylobacter enteritis do not require special isolation; standard precautions are sufficient. Nosocomial infection in neonatal nurseries has been described. Infants and younger children in diapers with C. jejuni enteritis should be excluded from routine childcare centers until diarrhea has resolved. (See 'Children' above.)
Individuals with an acute diarrheal illness should not prepare or handle food until symptoms have resolved.
Antibiotic prophylaxis is occasionally used in select high-risk travelers to prevent diarrhea. However, rifaximin, the agent recommended if antibiotic prophylaxis is given, is not effective in preventing Campylobacter infection. In a randomized human challenge trial, the rate of clinical Campylobacter infection was similarly high with rifaximin versus placebo, each given twice daily for four days around the time of ingestion of an infectious dose [109]. (See "Travelers' diarrhea: Treatment and prevention".)
There is no effective vaccine for prevention of Campylobacter infection [110].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
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●Basics topic (see "Patient education: Campylobacter infection (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Epidemiology and transmission − Campylobacter enteritis is an important cause of acute diarrhea worldwide. It is typically caused by Campylobacter jejuni or Campylobacter coli and is largely a foodborne disease. The organism inhabits the intestinal tracts of a wide range of animal hosts, notably poultry; contamination from these sources can lead to foodborne disease. Campylobacter infection can also be transmitted via water-borne outbreaks and direct contact with animals or animal products. (See 'Introduction' above.)
●Clinical manifestations
•Common features − The mean incubation period is three days (range one to seven days) (figure 1). Early symptoms include abrupt onset of abdominal pain and diarrhea. The acute illness is characterized by cramping periumbilical abdominal pain and diarrhea. Patients frequently report ten or more bowel movements per day. Bloody stools are observed on the second or third day of diarrhea in about 15 percent of adults; in children, bloody stools may be present in more than half of cases. Diarrhea is self-limited and lasts for a mean of seven days. (See 'Common presenting features' above.)
•Unique manifestations and complications − Patients with Campylobacter infection can present with clinical manifestations mimicking other diseases (eg, "pseudoappendicitis" and colitis). A variety of acute complications can occur. There are two major late onset complications of Campylobacter infection: reactive arthritis and Guillain-Barré syndrome (GBS). (See 'Unique manifestations' above and 'Complications' above.)
●Diagnosis − The diagnosis of Campylobacter enteritis is established by stool culture. Patients with late onset reactive arthritis or GBS may have negative stool studies; serologic tests can be used to detect recent Campylobacter infection in these patients. (See 'Diagnosis' above.)
●Management
•Supportive care − Campylobacter infection is usually a mild, self-limited infection. Maintenance of proper hydration and correction of electrolyte abnormalities should be the focus of therapy. Antibiotics are not needed for most cases of C. jejuni gastroenteritis. (See 'Treatment' above.)
•Role of antimicrobial therapy − For patients with severe disease or risk for severe disease, we suggest treatment with azithromycin (Grade 2C). A fluoroquinolone is an alternative, but susceptibility should be confirmed. For uncomplicated infections in patients at risk for severe disease, we typically use azithromycin 500 mg orally daily for three days or until signs and symptoms of disease have improved. For patients who cannot tolerate oral therapy, a carbapenem or an aminoglycoside are appropriate options. (See 'Antimicrobial therapy' above.)
•Resistance − Campylobacter resistance to macrolides and fluoroquinolones has been described. The rate of macrolide resistance among Campylobacter has remained stable at <5 percent in most parts of the world; the prevalence of fluoroquinolone-resistant Campylobacter is rising in many areas, particularly in Southeast Asia. (See 'Resistance' above.)
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