Version May 2024
INTRODUCTION — Campylobacter infection usually consists of acute enteritis caused by Campylobacter jejuni or Campylobacter coli. The genus Campylobacter comprises 20 species isolated from humans and many more isolated from animals. New species are identified regularly [1]. These organisms can cause a variety of infections including intestinal, systemic, fetal/placental (abortion, stillbirth), and oral (periodontitis). Certain closely related species of Arcobacter and Helicobacter also cause human infection and may be provisionally identified as campylobacters in clinical laboratories.
The clinical relevance of less common Campylobacter infections will be reviewed here [2]. Issues related to C. jejuni and C. coli are discussed separately. (See "Campylobacter infection: Microbiology, pathogenesis, and epidemiology" and "Campylobacter infection: Clinical manifestations, diagnosis, and treatment".)
INTESTINAL AND SYSTEMIC INFECTION — Infections with the less common Campylobacter species and related organisms are observed more frequently among individuals in resource-limited settings than among individuals in developed countries [2]. Bacteremia has been observed in the setting of malnourished children with diarrhea and patients with immunodeficiency.
Campylobacter upsaliensis — Campylobacter upsaliensis is the most important Campylobacter species after C. jejuni and C. coli [3]. It is commonly found in younger dogs and cats, and interestingly, dogs fed homemade cooked food appear to have a higher risk of carrying this organism [4]. These animals were once considered likely sources of human infection; however, genetic studies have demonstrated that human and canine strains are distinct [5].
Considerable variation in isolation rates has been reported, which may be partly due to methodologic differences rather than differences in prevalence. The selective culture media used for C. jejuni and C. coli are unsuitable for C. upsaliensis, which requires filtration on nonselective agar or a special selective medium.
In Europe, C. upsaliensis comprises about 1 to 2 percent of clinical Campylobacter isolates. One Belgian survey noted C. upsaliensis comprised about 13 percent of isolates, which was likely attributable to immigrant children from Morocco and Turkey [6]. In Cape Town, C. upsaliensis has been observed in 23 percent of isolates [2].
C. upsaliensis infection typically causes watery diarrhea and abdominal pain, usually without fever. It is probably less pathogenic than C. jejuni. An outbreak among 44 children in day care centers in Brussels has been described [7]. In an Australian study, C. upsaliensis was associated with prolonged diarrhea of mild to moderate severity in HIV-infected patients [8]. Rare cases of extraintestinal infection (including isolation from a giant hepatic cyst), bacteremia, and death caused by this organism have been reported [9-12].
Campylobacter jejuni subspecies doylei — Campylobacter jejuni subspecies doylei is a slower growing, more fastidious organism that is phylogenetically distinct from C. jejuni subspecies jejuni (referred to as C. jejuni) [13]. It requires the special filtration method for its isolation from feces and an incubation temperature of 37°C rather than 42 to 43°C.
Subspecies doylei is generally observed among children living in resource-limited settings and is a cause of systemic infection. It was first isolated from Aboriginal Australian children and has also been identified in South African children [2]. In Aboriginal Australian children, subspecies doylei accounted for 85 percent of all campylobacters isolated from blood in one series [14]. In South African children, this organism accounted for 24 percent of blood isolates [2].
Most C. doylei strains are susceptible to both nalidixic acid and cephalothin [9].
Campylobacter lari — Campylobacter lari shares many of the features of C. jejuni and C. coli, including the ability to grow freely at 43°C and on conventional Campylobacter-selective agars. C. lari is found in abundance in natural water and is a normal inhabitant of the intestinal tract of seagulls (genus Larus), other birds, and shellfish [15].
C. lari accounts for less than 1 percent of campylobacters isolated from humans. It was implicated in a water-borne outbreak of diarrhea in Canada [16] and occasionally is isolated from blood cultures, but many strains are clearly nonpathogenic. The organism has been isolated from a patient who had experienced only a mild afebrile diarrheal illness [17]. C. lari has been reported as a cause of a permanent pacemaker infection [18] and prosthetic joint infection, sepsis [19,20], cellulitis and bacteremia in a patient with lymphoma [21], and death in a healthy older person [19].
Patients with diarrheal illness may not require antimicrobial therapy. The organism is generally susceptible to erythromycin, chloramphenicol, clindamycin, aminoglycosides, and carbapenems. Some isolates are susceptible to fluoroquinolones, but the rate of resistance is growing. A few reports have suggested C. lari is resistant to all cephalosporins, penicillin, trimethoprim-sulfamethoxazole, and vancomycin [22,23].
Campylobacter hyointestinalis — Campylobacter hyointestinalis is normally found in the gut of pigs. It has occasionally been isolated from patients with diarrhea [24], including a patient with infection acquired from a pig [25]. In one series of stool isolates from South African children, it accounted for 1.3 percent of campylobacters isolated [3]. C. hyointestinalis also has been detected in gastric biopsy specimens of patients with gastritis but associated with less inflammation than H. pylori [26].
The presence of hydrogen is essential for culture. In vitro and animal studies have shown that C. hyointestinalis is susceptible to many antimicrobial agents including ciprofloxacin, doxycycline, ampicillin, amoxicillin, and amoxicillin-clavulanate [27,28]. The organism may be resistant to metronidazole, lincomycin, tetracycline, and erythromycin [27,28].
Campylobacter concisus — Campylobacter concisus has been isolated from the stool of about 10 percent of children and adults with and without diarrhea [2,29,30]. In some communities, this organism has been isolated with high frequency from patients with enteric illness or has been associated with prolonged diarrhea, but in the absence of a control group, no conclusion about its pathogenicity may be made [31-35]. Evidence is accumulating that C. concisus may be associated with microscopic colitis and Crohn’s disease [32,36-41]. Studies using polymerase chain reaction (PCR) assays identified the organism more frequently in the stool samples of children recently diagnosed with Crohn’s than in samples from controls [42-44]. C. concisus is a part of oral flora; it may contribute to the development of periodontal disease. Additionally, the organism has been identified in a brain abscess in a patient with chronic sinusitis [45]. Bacteremia almost never occurs, probably because the organism is highly susceptible to the killing effects of normal human serum [46].
Most C. concisus isolates are susceptible to macrolides, ciprofloxacin, tetracycline, ampicillin, and gentamicin; susceptibility to cephalosporins is variable [47].
Other campylobacters — Other subsequently identified Campylobacter species that may be clinically relevant include C. urealyticus [48-51], C. troglodytis [52], C. lari subspecies concheus, C. testudinum [53], and C. peloridis [54].
Arcobacter — Arcobacter species, including A. butzleri and A. cryaerophilus (formerly A. cryaerophila), are occasionally isolated from humans. In some regions, particularly when enrichment culture techniques are used, these bacteria are identified with increasing frequency [55].
Both organisms cause intestinal infection; persistent watery diarrhea appears to be the main symptom [56,57]. A. butzleri has been reported in 2.4 percent of children with diarrhea in Thailand [58]. It has also been isolated from the peritoneal fluid of several patients with acute appendicitis, and occasional cases of bacteremia have been reported [56,59]. One outbreak, attributed to a single strain (Lior serogroup 1) of A. butzleri, affected 10 children in an Italian primary school. None of the children had diarrhea, but all suffered from intermittent abdominal cramps lasting for 5 to 10 days [60]. In a study of 1380 persons with diarrhea in New Zealand, A. butzleri was isolated from seven (0.5 percent) and A. cryaerophilus was isolated from five (0.4 percent) [61]. In another study of 201 travelers with diarrhea, Arcobacter species were isolated from the stool of 8 percent [62]. Nevertheless, the pathogenic role of Arcobacter species in such studies cannot be established because they lacked an appropriate control group.
Arcobacter species have also been isolated from the peritoneal fluid of several patients with acute appendicitis, and occasional cases of bacteremia have been reported [56,57]. Patients with gastrointestinal infection typically have self-limited disease and do not require antimicrobial therapy. However, for more severe and invasive infections when antimicrobial treatment is warranted, fluoroquinolones, aminoglycosides, or tetracyclines may be used, as most in vitro studies show the organisms are susceptible to such agents [47,63]. Most A. butzleri strains are susceptible to ciprofloxacin, but about half of A. cryaerophilus are resistant to this agent [64]. More than 20 percent of Arcobacter isolates are resistant to ampicillin and erythromycin [47,63].
Helicobacter cinaedi and Helicobacter fennelliae — Formerly classified as campylobacters, these two species have been isolated from up to 8 percent of gay men with diarrhea or proctitis [65]. They have also been found in South African children with diarrhea [2]. In the latter group, Helicobacter fennelliae accounted for 7 percent and Helicobacter cinaedi 0.8 percent of campylobacters isolated. Both species have caused cellulitis, osteomyelitis, infected subdural hematoma, and bacteremia, mainly in immunocompromised patients, particularly those with hematologic malignancies or HIV infection [13,66-71]. H. cinaedi has been identified in resected aortic aneurysms using 16S rRNA gene sequencing [72]. There are only isolated reports of H. cinaedi bacteremia in immunocompetent persons [73,74]. Recurrence of H. cinaedi bacteremia has been reported; in one series of 168 patients, recurrent bacteremia was identified in 20 percent and was associated with recent cancer chemotherapy or steroids [75]. Bacterial translocation from the gastrointestinal tract in the setting of mucosal damage is a postulated mechanism for primary bacteremia. Some have also speculated that these organisms may play a role in triggering inflammatory bowel disease [76].
These organisms are not associated with fatal illness, but clinical response to antimicrobial therapy is often slow and may therefore require longer courses of antimicrobial treatment. In vitro studies show the organisms are susceptible to ampicillin, tetracycline, nalidixic acid, rifampin, chloramphenicol, and gentamicin [77]. Many isolates are resistant to clindamycin, erythromycin, and trimethoprim-sulfamethoxazole. The best choice for treatment may be oral ciprofloxacin [78].
Other helicobacters — There are several intestinal Helicobacter species that have been isolated from patients with diarrhea [2]. Their status as pathogens is difficult to assess, since routine methods of detection are unsuitable for most of them. Treatment of helicobacters that have not been definitively associated with clinical illness is not advised, as some studies suggest that certain Helicobacter species may exert an immunomodulatory effect that might protect against development of inflammatory bowel disease [79].
Helicobacter westmeadii was isolated from the blood of two AIDS patients with diarrhea [80]. H. pullorum, a species found in poultry, has been isolated from several patients with diarrhea. H. canis, found in dogs and similar to H. fennelliae, was isolated from a boy with diarrhea.
Helicobacter bilis (formerly "Flexispira rappini," then Helicobacter rappini) has been isolated from patients with chronic diarrhea [81]; it has also been isolated from the blood of a child with pneumonia and the blood of a man undergoing hemodialysis. Most recently it was implicated as a cause of pyoderma gangrenosum in a boy with x-linked agammaglobulinemia [82]. This organism has a striking morphology consisting of a large fusiform body encased in spirally wound periplasmic fibers with bipolar tufts of sheathed flagella.
Campylobacter fetus — Campylobacter fetus is the species most frequently associated with systemic campylobacteriosis, which generally occurs among patients with immune deficiency or other underlying disease. Systemic campylobacteriosis can also be associated with focal infection such as cellulitis or septic arthritis.
There are two subspecies, C. fetus subspecies fetus and C. fetus subspecies venerealis. C. fetus subspecies fetus is the subspecies usually found in human infection (referred to as C. fetus). Human infection with C. fetus subspecies venerealis is limited to a small number of case reports [2]. C. fetus is an important cause of abortion in sheep and cattle. Cows are infected venereally from carrier bulls with C. fetus subspecies venerealis. C. fetus possesses a surface layer protein (SLP) that functions as a capsule and protects the bacterium from the bactericidal action of normal serum [83]. The SLPs are critical in virulence and undergo high-frequency phenotypic switching by recombination, resulting in antigenic variation [84]. The antigenic variation is thought to be responsible for the ability of the organism to persist in animal and human hosts and may account for relapsing human infection despite seemingly effective antibiotic therapies. Most other campylobacters (including C. jejuni and C. coli) do not possess SLP and are readily eliminated from the bloodstream.
C. fetus is found in various animals and animal products, mainly cattle and sheep, which are probably the main source of human infection. Food-borne sources of infection likely include raw milk products, raw liver, and raw meat of such animals [85,86]. Reports of a cluster of C. fetus cases among men who have sex with men suggest the possibility of person-to-person transmission [87].
Primary colonization takes place in the intestine, but in healthy individuals this seldom causes disease; when it does, enteritis is the primary manifestation [3,88,89]. Human infection is uncommon and generally limited to patients with immune deficiency [90]. Predisposing factors include:
●Liver disease (particularly alcoholic cirrhosis)
●Malignancy, leukemia, and other blood dyscrasias
●Diabetes mellitus
●AIDS and other immune deficiency states
●Older subjects
Such patients usually present with a nonspecific febrile illness. Localizing signs are usually absent, and the first indication of the nature of the illness is isolation of C. fetus from the blood. C. fetus has a tropism for endovascular tissue, so endocarditis [90], infected aneurysms [91,92], or septic thrombophlebitis may be observed. Other forms of focal infection can occur; these include meningoencephalitis, osteomyelitis, empyema, cholecystitis, pericarditis, myocarditis, peritonitis, and salpingitis [2,93].
Healthy persons who develop C. fetus gastroenteritis will usually recover without antibiotic therapy. However, immunocompromised persons or those with bacteremia or other extraintestinal infection may require a prolonged course of antimicrobial treatment. The organism is generally susceptible to ampicillin, third-generation cephalosporins, aminoglycosides, imipenem, and meropenem; these agents have been used effectively [94-96]. As an example, in a small series of patients with C. fetus bacteremia, all of six patients treated with imipenem and 7 of 11 treated with amoxicillin-clavulanate had favorable outcomes [94]. In contrast, use of fluoroquinolones was associated with death in a separate series of 94 cases of C. fetus bacteremia, among which the fluoroquinolone resistance rate was 33 percent [89]. Because many isolates are resistant, erythromycin should not be used [95].
There are no therapeutic trials on which to base treatment duration recommendations. Endovascular infections should probably be treated for at least four weeks. Infection of the central nervous system should be treated for at least two to three weeks. Persistent or relapsing infection with C. fetus can occur, even years after the initial diagnosis [84,86].
FETAL/PLACENTAL INFECTION — Campylobacter enteritis during pregnancy occurs with relative frequency; a very small proportion of fetuses are affected. Approximately 30 instances of Campylobacter abortion, stillbirth, or congenital infection have been described [97]; roughly half are due to C. fetus, half to C. jejuni, and one each to C. coli and C. upsaliensis [98]. The stage of gestation ranged from 10 weeks to full term (average 19 weeks for C. jejuni, 28 weeks for C. fetus). It is probable that many gestational infections go undetected.
Infected pregnant women typically present with fever, with or without vaginal bleeding. Abortion can also occur without antecedent symptoms. Abdominal pain with or without diarrhea is present in at least half of patients with C. jejuni. Hematogenous spread from the gut is probably the main route of placental infection. Inflammation of the placenta with necrosis is almost always present. Campylobacter organisms can be isolated from blood cultures and from placental and fetal tissues. Ascending genital tract infection may occur in some cases [99].
In the setting of C. fetus infection, the fetal outcome is frequently death; survival is possible if the agent is C. jejuni and infection is at or near term [97]. Intrauterine infection at term may be difficult to distinguish from perinatal infection acquired during delivery from a mother with stool shedding of organisms. In such cases, the prognosis is relatively good with appropriate treatment, even in the setting of meningitis.
PERIODONTAL INFECTION — Six species of Campylobacter are part of the human oral flora: C. sputorum, C. concisus, C. rectus, C. curvus, C. showae, and C. gracilis [100]. C. rectus (formerly Wolinella recta) has a particularly strong association with periodontal infection and has a protective surface S-layer protein (as described above for C. fetus) [101]. Patients with periodontitis have a higher titer of IgG antibody to this protein than controls [102]. Cytotoxin production by C. rectus has also been reported [103]. (See 'Campylobacter fetus' above.)
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".)
SUMMARY
●The genus Campylobacter comprises 20 species isolated from humans. These organisms can cause a variety of infections including intestinal, systemic, fetal/placental (abortion, stillbirth), and oral (periodontitis). Certain closely related species of Arcobacter and Helicobacter also cause human infection and may be provisionally identified as campylobacters in clinical laboratories. (See 'Introduction' above.)
●Infections with the less common Campylobacter species and related organisms are observed more frequently among individuals in resource-limited settings than among individuals in developed countries. Campylobacter upsaliensis is the most prevalent Campylobacter species after C. jejuni and C. coli. C. jejuni subspecies doylei is a slower growing, more fastidious organism than C. jejuni subspecies jejuni (referred to as C. jejuni). (See 'Intestinal and systemic infection' above.)
●Campylobacter fetus is the species most frequently associated with systemic campylobacteriosis, which generally occurs among patients with immune deficiency or other underlying disease. C. fetus is found in various animals and animal products, which are probably the main source of human infection. Patients usually present with a nonspecific febrile illness. C. fetus has a tropism for endovascular tissue, so endocarditis, infected aneurysms, or septic thrombophlebitis may be observed. (See 'Campylobacter fetus' above.)
●Approximately 30 instances of Campylobacter abortion, stillbirth, or congenital infection have been described. Infected pregnant women typically present with fever, with or without vaginal bleeding. Abortion can also occur without antecedent symptoms. Hematogenous spread from the gut is probably the main route of placental infection. Campylobacter organisms can be isolated from blood cultures and from placental and fetal tissues. In the setting of C. fetus infection, the fetal outcome is frequently death; survival is possible if the agent is C. jejuni and infection is at or near term. (See 'Fetal/placental infection' above.)
●Six species of Campylobacter are part of the human oral flora: C. sputorum, C. concisus, C. rectus, C. curvus, C. showae, and C. gracilis. C. rectus (formerly Wolinella recta) has a particularly strong association with periodontal infection. (See 'Periodontal infection' above.)
●Enteric infections due to Campylobacter and related species do not necessarily warrant antimicrobial therapy. For patients with severe or systemic infection, antimicrobial therapy should be tailored to antibiotic susceptibility testing. The typical susceptibility profile varies by species. (See 'Intestinal and systemic infection' above.)
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