Campylobacter Infections

13 Interesting Facts of Campylobacter Infections 

1. Campylobacter infections are the leading cause of bacterial gastroenteritis in humans worldwide and are responsible for most pathogen-confirmed cases of traveler’s diarrhea in people returning to the United States from abroad
2. Most common organisms include Campylobacter jejuni and Campylobacter coli
3. Transmitted through consumption of contaminated food or water or direct contact with fecal material from infected animals or humans; birds and food animals are the most common reservoir 
4. Clinical manifestations frequently include watery and/or bloody diarrhea with cramping, abdominal pain, fever, nausea, and vomiting 
5. Can mimic appendicitis when presenting primarily with severe abdominal pain; can mimic inflammatory bowel disease when presenting primarily with bloody stools
6. Campylobacter fetus has a predilection for bacteremia and dissemination, especially in persons with comorbidity or in a immunocompromised state; parenteral and prolonged antibiotic treatment is required
7. Bacterial culture is the gold standard diagnostic test to confirm infection in any sample; obtain antibiotic susceptibility testing on isolates when antimicrobial treatment is a consideration 
8. Most patients recover from the illness with supportive care (eg, hydration; frequent, small meals; possibly probiotics) and do not require antibiotic therapy 
9. Azithromycin or erythromycin is first line antibiotic therapy indicated for patients with severe or prolonged symptoms, patients with bacteremia or extraintestinal infections, neonates, elderly people, pregnant people, immunocompromised patients, patients with severe debilitating comorbidity, and those meeting criteria for traveler’s diarrhea treatment 
10. Fluoroquinolone and macrolide resistance is high among Campylobacter isolates, especially when Campylobacter is acquired in developing countries
11. Possible complications include dehydration, bacteremia and extraintestinal infection, Guillain-Barré syndrome, reactive arthritis, and postinfectious irritable bowel syndrome 
12. Usually a mild, self-limiting illness, with mortality confined to very young and elderly people and patients with severe underlying disease 
13. Prevention of infection is paramount, including practicing proper handwashing hygiene; avoiding consuming undercooked poultry, foods contaminated by uncooked poultry, unpasteurized raw milk, and potentially contaminated untreated water; and taking traveler’s diarrhea chemoprophylaxis (select at-risk people)

Pitfalls

• Abdominal pain mimicking appendicitis is sometimes the predominant presenting feature, resulting in unnecessary diagnostic tests (eg, ultrasonography, CT) and procedural intervention (eg, laparotomy) 
• Campylobacter is a fastidious organism; it can be difficult to isolate and most diagnostic laboratories do not have the capability to detect non–Campylobacter jejuni and non–Campylobacter coli species. Use of preferred filtration culture technique increases yield of other atypical Campylobacter species
• Symptoms mimic several gastrointestinal infections (eg, viruses, protozoa, other bacterial pathogens). Avoid empiric treatment until culture results are available unless patient meets other criteria for empiric antibiotic treatment (eg, traveler’s diarrhea, immunocompromised state, concern for bacteremia)
• Not all Campylobacter enteric infections require oral antibiotics; avoid antibiotics in otherwise healthy people without severe or prolonged symptoms because the infection is usually self-limited in this population
• Avoid empiric antibiotic treatment of bloody diarrhea in children younger than 3 years until Escherichia coli O157:H7 pathogen is excluded by stool culture, owing to increased risk of hemolytic uremic syndrome in this patient population
• Resistance to antibiotics is high among Campylobacter species; suspect resistant strain in travelers failing empiric antibiotic treatment for traveler’s diarrhea and obtain bacterial stool cultures with sensitivities to identify resistant strains in travelers who remain symptomatic despite empiric therapy

• Campylobacter infections are the leading cause of bacterial gastroenteritis in human beings worldwide and are responsible for most pathogen-confirmed cases of traveler’s diarrhea in people returning to the United States from abroad 
• Disease is typically acute, self-limiting, and characterized by diarrhea, abdominal cramps, and fever 

Diagnosis

Clinical Presentation

History

• Clinical course of illness
  • Up to 50% of infected persons may be asymptomatic during outbreaks 
  • Severity of illness ranges from mild gastrointestinal symptoms to a choleralike illness with massive watery diarrhea to a more fulminant colitis 
  • 10% to 20% of patients develop a longer diarrheal illness (lasting more than 1 week); 5% to 10% of patients not treated with antibiotics relapse 
  • Severe or persistent infection mimics acute inflammatory bowel disease with gastrointestinal bleeding
  • Occasionally, patients present clinically with severe abdominal pain and minimal diarrhea, mimicking appendicitis or intussusception
• Symptoms typically present within 2 to 5 days of exposure to organism; illness lasts 3 to 7 days 
  • Prodrome
    • Fever, myalgia, and malaise may precede gastrointestinal symptoms by 12 to 24 hours 
  • Diarrhea
    • Usually loose and watery
    • Average is 8 to 10 bowel movements per day during peak of illness 
    • Bloody diarrhea develops in anywhere from 45% to 90% of patients 
    • Classically, infants and young children present with bloody diarrhea but without fever or other clinical manifestations
  • Abdominal pain
    • Present in up to 80% of patients 
    • Often diffuse, intermittent, crampy, and relieved by defecation
    • May be the most prominent feature
    • Can be severe and localized in the right lower quadrant when associated with mesenteric adenitis
  • Fever
    • Present in up to 80% of patients 
    • Can be low grade or very high (ie, greater than 40 °C) in severe cases 
  • Nausea and vomiting
    • Nausea is common in up to 53.6% of patients 
    • Nonbilious, nonbloody vomiting is common in about 19% to 55% of patients 
  • Tenesmus
    • Occurs in up to 33.3% of patients 
  • Headache
    • Occurs in anywhere from 12% to 82% of patients 
    • Nonspecific and diffuse, without meningismus
• Symptoms of dehydration may be present
  • Lack of tear production
  • Decreased urine output

Physical examination

• Signs of dehydration may be present secondary to excessive gastrointestinal losses without fluid replacement 
  • Weight loss
  • Tachycardia
  • Abnormal orthostatic vital signs
  • Prolonged capillary refill time
  • Dry mucous membranes
  • Decreased skin turgor
  • Sunken eyes
  • Decreased level of consciousness
• Abdominal tenderness
  • Mild, diffuse abdominal tenderness without peritoneal signs or signs of obstruction may be present

Causes

• Campylobacter is a small (0.3-0.6 μm in diameter), gram-negative, spiral-shaped, microaerophilic motile bacterium; several species can cause symptomatic infection in humans
• Campylobacter jejuni and Campylobacter coli are most frequently identified in human disease
  • Campylobacter jejuni is the most common cause of bacterial gastroenteritis worldwide 
    • 89% of reported cases of Campylobacter infections are caused by Campylobacter jejuni 
  • Campylobacter coli accounts for 8% of all enteric Campylobacter infections 
    • Gastroenteritis caused by Campylobacter coli is clinically indistinguishable from that caused by Campylobacter jejuni 
  • Campylobacter upsaliensis, Campylobacter lari, Campylobacter concisus, and Campylobacter ureolyticus are atypical pathogenic enteric species of recently recognized clinical significance 
    • Responsible for gastroenteritis with overall milder symptoms than those caused by Campylobacter coli and Campylobacter jejuni 
    • Previously underrecognized owing to difficulty culturing atypical organisms with conventional selective media culture technique (ie, nonfiltration technique) 
  • Campylobacter fetus predominantly causes systemic infection in neonates and debilitated patients (eg, patients with bacteremia or meningitis) 
    • Bacteremia occurs after oral ingestion and intestinal colonization with or without diarrheal symptoms 

Incubation

• Typically 2 to 5 days 

Reservoirs

• Organism is prevalent as normal flora in the gastrointestinal tract of many wild, agricultural, and domestic animals (eg, birds, chickens, ostrich, cattle, swine, sheep, rodents, shellfish) 
  • Birds and food animals are the primary reservoir for Campylobacter jejuni 
  • Cattle, sheep, and reptiles are the primary reservoir for Campylobacter fetus 
  • Swine are the primary reservoir for Campylobacter coli and Campylobacter hyointestinalis
  • Dogs are the primary reservoir for Campylobacter upsaliensis
• Occasionally detected in the gastrointestinal tracts of pets (eg, cats, dogs, hamsters, birds) 

Transmission 

• Contaminated food is the most common vehicle of transmission
  • Most infections are isolated, sporadic events related to consuming undercooked poultry and foods contaminated by raw poultry
    • Campylobacter is isolated from the feces of 30% to 100% of healthy chickens, turkey, and water fowl 
  • Consuming contaminated unpasteurized milk or untreated water can result in outbreaks: 
    • Unpasteurized milk contaminated with Campylobacter when the cow’s udder is colonized or the milk is contaminated with manure
    • Water contaminated by infected feces from chickens, turkeys, wild birds, or cows
• Direct contact with feces from an infected animal
  • Farm animals (eg, chickens, cows)
  • Domestic animals, especially young ones (eg, kittens, puppies) with diarrhea 
• Human-to-human transmission is uncommon and occurs by fecal-oral route 

Risk factors and/or associations

Age

• Most prevalent in 2 age groups in industrialized nations:
  • Children younger than 5 years 
  • Adolescents and adults aged 15 to 44 years 

Sex

• More common in males 

Other risk factors/associations

• Factors that increase infection risk
  • Consuming undercooked poultry, undercooked meat, raw seafood, or raw milk 
  • Being in contact with a pet puppy with diarrhea or in direct contact with farm animals 
  • Drinking untreated water from a lake, river, or stream
  • Traveling to or living in high-risk developing geographic areas (eg, Mexico, Latin America, South America, Africa, South and Southeast Asia) 
• Patients taking proton pump inhibitors and H₂ blockers are more susceptible to infection. Intact stomach acid barrier is an effective deterrent against infection 
• Consuming an organism in items that favor penetration through gastric acid barrier increases risk of symptomatic infection (eg, milk, fatty foods, water) 
• Immunocompromised status (eg, HIV, hypogammaglobulinemia) increases risk of infection, severe infection, prolonged infection, relapsing infection, and extraintestinal infections 
• Neonates, elderly people, pregnant people, and patients with life-threatening comorbid disease are at increased risk for extraintestinal infections 
• Disease is seasonal in developed nations, with peak infection in summer and early fall. Disease occurs year-round in developing countries 

Communicability

• Infectious dose is small; ingestion of fewer than 500 organisms can cause disease 
• Human excretion of organism usually lasts 2 to 3 weeks without treatment but can last up to 7 weeks; with effective antibiotic treatment, organism excretion is eliminated after 2 to 3 days 

Diagnostic Procedures

Primary diagnostic tools

• History and physical examination are integral to the diagnosis. Diarrhea with high fever, blood, or tenesmus are features suggestive of bacterial enteritis 
  • Identify possible risk factors for foodborne illness (eg, consumption of undercooked poultry, recent travel, contact with an infected person) 
• Obtain stool culture in patients with suspected infectious diarrhea (eg, fever, bloody or mucoid stools, severe abdominal cramping or tenderness) for which antimicrobial agents may confer benefit 
  • Laboratory diagnosis can be difficult because Campylobacter is a fragile and fastidious organism that is difficult to grow, isolate, and identify 
  • Culture requires specialized media and specialized conditions (eg, reduced oxygen, increased carbon dioxide, elevated temperatures, prolonged incubation time of at least 2 days owing to slow growth of organism) 
• Bacterial culture is the gold standard diagnostic test to confirm infection 
  • Definitive diagnosis is made by isolating Campylobacter from a clinical sample (eg, stool, blood) or observing organism on direct smear of fresh specimen 
  • Obtain stool cultures in patients:
    • With symptoms suggestive of foodborne illness or bacterial cause of diarrhea (eg, high fever, bloody stool)
    • With immunocompromised status or significant comorbidity who present with severe acute gastroenteritis
  • Guidelines support testing of adults with moderate to severe disease when significant symptoms last more than 7 days and when a symptomatic individual is at high risk of spreading disease to others (eg, day care workers, food handlers, residents of institutional facilities) 
  • Routine antimicrobial susceptibility testing is indicated: 
    • For infants younger than 6 months
    • For elderly or immunocompromised patients
    • For patients with prolonged or severe disease
    • When Campylobacter is isolated from extraintestinal sites
    • When antimicrobial treatment is under consideration
  • Blood cultures are indicated:
    • In neonates with fever
    • In very ill-appearing patients in whom concern exists for sepsis or meningitis
    • In immunocompromised people
    • In patients with significant debilitating comorbidity (eg, chronic alcoholism, liver disease, diabetes, malignancy)
• Probable laboratory diagnosis can be made using a culture-independent diagnostic test (ie, rapid antigen or rapid nucleic acid amplification test) on an enteric specimen 
  • Major limitation to culture-independent diagnostic testing is lack of antibiotic susceptibility data
  • Advantage over culture is a more rapid presumptive diagnosis
  • Culture-independent methods are recommended at least as adjunct to traditional methods of isolation for some adults, particularly when culture methods fail to isolate causative organism 
• Report Campylobacter infection to the local health department. If multiple coinciding cases are reported, local officials will need to investigate to determine source of outbreak 

Laboratory

• Stool culture
  • Isolation of Campylobacter confirms the disease
    • Optimally, collect stool specimen during acute phase of disease and before initiation of antibiotic treatment 
      • May use rectal swabs if a stool sample cannot be obtained from infants or young children
      • Although 1 specimen is usually sufficient, 2 specimens may be necessary depending on clinical scenario and degree of clinical concern (eg, concern about inadequate sample on rectal swab being falsely negative)
      • A single negative culture result does not exclude infection, especially if preferred or optimal filtration method for primary isolation is not used
    • Process specimens within 2 hours of collection
      • Bacteria are fragile and easily killed by oxygen and in dry environments
    • If the specimen cannot be processed within 2 hours, place in Cary-Blair transport medium and refrigerate at 4 °C until processing 
    • Filtration culture technique
      • Optimal method for primary isolation of bacteria; provides improved stool culture yield for Campylobacter jejuni, Campylobacter coli, Campylobacter fetus, and other less common or atypical species 
      • 0.45 or 0.65 μm filtration technique that excludes enteric flora owing to small size and motility of the bacteria before culture on nonselective rich media (eg, chocolate agar) at 37 °C in microaerobic atmospheric conditions for 72 to 96 hours 
    • Conventional culture technique
      • Incubate stool sample for 72 to 96 hours at 42 °C on selective media in a microaerobic atmosphere (ie, 5% oxygen, 10% carbon dioxide, 85% nitrogen) to optimize recovery of Campylobacter jejuni and Campylobacter coli while preventing overgrowth of enteric organisms 
        • Using only 1 medium is often sufficient; using multiple media increases likelihood of Campylobacter jejuni and Campylobacter coli isolation
        • Commonly used media include:
          • Modified charcoal cefoperazone-deoxycholate agar
          • Campy-CVA agar (cefoperazone, vancomycin, and amphotericin B)
          • Skirrow agar
          • Karmali agar
      • Conventional stool culture favors isolation of Campylobacter jejuni and Campylobacter coli; no single culture method currently available isolates all Campylobacter species 
    • Campylobacter appears as gray, flat colonies on plated media and often spreads along the streak lines. Characteristic microscopic appearance, presence of a positive oxidase reaction, and hippurate hydrolysis testing further characterize species level of common Campylobacter strains
• Hippurate hydrolysis test 
  • Use to differentiate Campylobacter jejuni from Campylobacter coli
  • Campylobacter jejuni is capable of hippurate hydrolysis and Campylobacter coli is not; glycine and benzoic acid are detectable in samples when hippurate is hydrolyzed by Campylobacter jejuni strain
• Stool analysis by direct visualization with stool phase contrast or dark-field microscopy and Gram stain
  • Campylobacter can be detected on fresh stool samples by direct visualization of morphologic appearance (ie, curved, spiral, S-shaped rods resembling Vibrio cholerae with darting motility)
  • Not routinely performed because method is less sensitive than culture and microscopic expertise is required
  • Fresh specimen Gram stain with gram-negative vibrioid rods is very specific but relatively insensitive finding (ie, 50%-70% sensitivity) 
  • Up to 75% of patients will have associated RBCs and neutrophils present on Gram stain 
• Rapid antigen assay
  • Commercially available rapid enzyme immunoassays detect Campylobacter surface antigen shared between Campylobacter jejuni and Campylobacter coli species; test does not differentiate between species 
    • Test will not provide epidemiologic data for public health surveillance because it does not identify species
  • Method does not allow for antibiotic susceptibility testing
  • Sensitivity and specificity of commercially available antigen tests are highly variable; overall moderate sensitivity (80%-90%) and high specificity (greater than 95%) compared with stool culture are reported
  • Positive antigen test result must be confirmed by culture 
• Rapid multiplex nucleic acid amplification assay
  • Test method uses amplification of genetic material specific for Campylobacter
  • Method does not allow for antibiotic susceptibility testing and requires a high degree of technical laboratory training to perform accurately, and results do not yield isolates that can be reported to public health laboratories 
  • Some tests can identify species of organism, including less common Campylobacter species missed by conventional culture 
  • Offers improved sensitivity and specificity over rapid antigen testing and stool culture techniques; limited data about test performance characteristics are available
  • Current list of FDA-licensed multiplex nucleic acid–based tests is available 
  • To confirm diagnosis in patients with serious infection, isolation of the organism is currently preferred, as antibiotic susceptibility testing is required on positive specimen samples 
• Blood, wound, and cerebrospinal fluid cultures
  • Routine anaerobic cultures occasionally isolate organism. Extend incubation of cultures to 2 weeks when organism is suspected, owing to very slow growth in culture
    • Isolation of Campylobacter fetus from blood culture takes from 4 to 14 days 
  • Standard collection and transport procedures apply for nonenteric specimen sources
  • Incubate in a microaerobic atmosphere at 37 °C if isolate does not grow on subculture in an attempt to characterize organism
• Other molecular tests to identify species of uncommon Campylobacter organisms 
  • Nonmolecular laboratory-based phenotypic characterization cannot readily identify non–Campylobacter jejuni and non–Campylobacter coli species, and additional molecular testing is necessary to identify other less common Campylobacter species
  • Use species-specific polymerase chain reaction, single-target gene sequencing, or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to further characterize uncommon Campylobacter species
• Electrolytes
  • Children with longer duration of diarrhea, moderate to severe dehydration, or atypical clinical presentation may require measurement of electrolytes 
  • Patients with moderate to severe dehydration or presentation consistent with electrolyte abnormalities (eg, hyponatremia) may require assessment of electrolytes

Differential Diagnosis

Most common

• Other infectious enteritis/colitis
  • Other bacterial gastroenteritis
    • Other bacteria can cause forms of gastroenteritis that are essentially clinically indistinguishable from Campylobacter enteritis and present with diarrhea, bloody stools, abdominal pain, nausea, vomiting, and fever; these include species of pathogenic Escherichia coli, Salmonella, Shigella, and Yersinia enterocolitica
      • As in enteric infections with Yersinia enterocolitica and Salmonella enteritidis, patients with Campylobacter jejuni can present with pseudoappendicitis
    • Many are foodborne pathogens with modes of transmission similar to those of Campylobacter; minor clinical differences are as follows:
      • Yersinia enterocolitica 
        • Encountered much less frequently than Campylobacter. Symptoms typically last longer in patients with Yersinia infection: 1 to 3 weeks in Yersinia infections, as opposed to 3 to 6 days in Campylobacter infections
      • Salmonella and Shigella 
        • More commonly responsible for community outbreaks (eg, day care center epidemics) owing to increased person-to-person transmission
    • Differentiate other common bacterial pathogens responsible for gastroenteritis from Campylobacter by bacterial stool culture
  • Clostridium difficile colitis
    • Colitis caused by overgrowth of toxin-producing Clostridium difficile bacteria, resulting in colonic inflammation and mucosal damage; usually associated with use of antibiotics
    • As in Campylobacter infection, patients with Clostridium difficile colitis present with watery diarrhea, fever, and abdominal pain
    • Unlike in Campylobacter infection, diarrhea is rarely bloody in Clostridium difficile colitis and patients often present after or during a course of antibiotics
    • Differentiate by clinical presentation and stool culture test result negative for Campylobacter
    • Polymerase chain reaction test to detect toxin-producing gene or positive toxin radioimmunoassay are diagnostic
  • Viral gastroenteritis
    • As in Campylobacter infection, patients with viral gastroenteritis present with fever, vomiting, and watery diarrhea
    • Typically, viral gastroenteritis does not cause bloody diarrhea and has a milder presentation than Campylobacter infection. Usually, infection is self-limited and resolves within a few days
    • Clinical presentation and course of illness most often differentiate viral gastroenteritis from bacterial enteritis
    • Stool cultures are not often indicated in patients presenting with typical viral gastroenteritis; however, when obtained, they will exclude Campylobacter as a causative organism in patients presenting with unusually severe viral gastroenteritis course (eg, prolonged illness, bloody stools, prolonged high fever)
    • Rapid viral antigen testing of the stool for rotavirus and enteric adenovirus and polymerase chain reaction for norovirus can confirm these causative viral pathogens if the diagnosis remains in question
  • Parasitic gastroenteritis
    • Diarrhea-causing infection by intestinal parasites (eg, Giardia, Entamoeba histolytica, Cryptosporidium, Cyclospora) can present similar to bacterial enteritis with abdominal pain and diarrhea
    • Often, incubation is longer and symptoms are milder and prolonged in patients with a parasitic cause for diarrheal illness; stool can be bloody but usually does not have fecal leukocytes
    • Patients often share a similar history of exposure to potential contaminated sources (eg, water from streams, international travel)
    • Occasionally, contaminated swimming pools are responsible for Giardia infection, whereas appropriate levels of chlorine are lethal to Campylobacter species 
    • Some parasitic infections are more likely to be spread in day care centers than Campylobacter (eg, Cryptosporidium)
    • Clinical presentation and clinical course usually differentiate parasitic from bacterial enteric disease; patients with parasitic disease have negative bacterial stool culture results
    • Giardia, Cryptosporidium, and Entamoeba histolytica stool antigen testing and stool samples for ova and parasite testing will confirm parasitic disease if parasitic pathogens remain in question
• Appendicitis
  • Patients present with sudden onset of diffuse abdominal pain that often localizes in the right lower quadrant
  • An uncommon presentation for patients with Campylobacter colitis is pseudoappendicitis when abdominal pain is pronounced and diarrhea is minimal
  • With appendicitis, pain is typically more severe and peritoneal signs are more pronounced; additionally, diarrhea is not characteristic
  • Acutely differentiate Campylobacter infection from appendicitis by imaging with surgical consultation (ultrasonography and/or CT depending on patient age at presentation); rapid test result for Campylobacter is negative in patients with appendicitis
• Inflammatory bowel disease
  • Patients with inflammatory bowel disease (ie, ulcerative colitis, Crohn disease) can present with bloody stools and abdominal pain. They may have a family history of inflammatory bowel disease and extraintestinal manifestations (eg, arthritis, weight loss, dermatologic disease, ocular disease) preceding bowel symptoms
  • Difficult to distinguish inflammatory bowel disease clinically from infectious enterocolitis without stool cultures
  • Distinguish inflammatory bowel disease from infectious colitis by negative stool cultures and consultation with gastroenterologist for further diagnostic considerations (eg, endoscopy with biopsy showing diagnostic pathology)
• Ileocolic intussusception
  • Young patients with ileocolic intussusception present with crampy, diffuse, intermittent abdominal pain; vomiting; and occasionally bloody stool, which can mimic early Campylobacter enteritis. Diarrhea is present in a minority of children with intussusception
  • Patients with ileocolic intussusception may present with a distinct, sausage-shaped, tender right upper quadrant mass; otherwise, diseases can be difficult to clinically distinguish without imaging
  • Ultrasonography can differentiate ileocolic intussusception from infectious enteritis; air, water, or barium enema is gold standard to diagnose and treat intussusception when not contraindicated by peritoneal signs, signs of perforation, or concern for significant bowel ischemia

Treatment Goals

• Promote eradication of infection with antibiotics in select high-risk patient populations
• Decrease risk of complications
• Promote antibiotic stewardship with judicious use of antibiotics only when indicated

Disposition

Admission criteria

Patients who develop complications may require admission

• Ill-appearing patients with suspected bacteremia or serious extraintestinal infectious disease manifestations require hospital admission for IV antibiotic therapy
• Patients with significant dehydration or inability to tolerate oral fluids require hospital admission for IV hydration
• Patients who develop neurologic signs or concern for Guillain-Barré syndrome require hospital admission for monitoring and supportive care

Criteria for ICU admission

• Admit patients with progressive respiratory depression or concern for respiratory muscle paralysis with Guillain-Barré syndrome to the ICU for ventilatory support and advanced supportive care

Recommendations for specialist referral

• Consult infectious disease specialist for further diagnostic and treatment recommendations for the following:
  • Patients with serious extraintestinal infections (eg, bacteremia, meningitis)
  • Failure of usual therapy for enteric infections
  • Patients with underlying immunocompromised state or severe debilitating comorbidity
• Consult neurologist for patients who develop Guillain-Barré syndrome

Treatment Options

Supportive care

• Initiate rehydration
  • Most patients require only supportive care with rehydration and electrolyte replacement owing to self-limited nature of the disease in most otherwise healthy and immunocompetent persons 
  • Use rapid parenteral (IV or intraosseous) volume expansion for any patient with severe signs of dehydration, unstable vital signs, or signs of shock 
• Antimotility agents (eg, loperamide)
  • May improve symptoms in adults and individuals with traveler’s diarrhea 
  • May prolong symptoms; antimotility agents have been associated with an increased risk of death in certain patient populations 
  • Contraindicated in infants and children, elderly patients, and patients with fever, severe pain, or dysenteric stools 
• Probiotic use is controversial
  • May shorten duration and diminish stool frequency; optimum dose/regimen is not currently available 
  • Routine use is not recommended for most adult and child populations 
• Use ondansetron for patients with significant nausea and vomiting
  • 1 dose in children administered in the emergency setting can prevent need for parenteral rehydration and hospitalization 
  • Multiple-dose therapy in children lacks proven efficacy and may lead to increase in diarrheal episodes 

Antibiotics shorten duration of illness, shorten period of organism excretion in stool, and prevent relapse if given early in the course of illness 

• Usual duration of oral antibiotic therapy is 3 to 5 days 
• Intestinal symptoms are reduced by about 1.3 days with appropriate antimicrobial therapy 
• Endovascular infections caused by Campylobacter fetus require a minimum of 4 weeks of therapy 
• Central nervous system infections require 2 to 3 weeks of therapy 

Start empiric oral antibiotics in select patient populations

• Infants younger than 3 months with suspected bacterial cause
• Pregnant and elderly patients
• Adults with inflammatory features (eg, dysentery, high fever)
• Patients who present with concerns for sepsis or who are severely ill 
• Immunocompromised patients (eg, patients with HIV or who are hypogammaglobulinemic)
• Patients with significant debilitating comorbidity (eg, chronic alcoholism, liver disease, diabetes, malignancy) or risk factors for complications
• Travelers to endemic areas who develop moderate to severe enteritis symptoms (eg, significant diarrhea, bloody stools, diarrhea with fever, significant abdominal pain)

Antibiotics are indicated only for certain patient populations with confirmed culture-positive Campylobacter enteritis, including: 

• Patients with severe enteric disease (eg, temperature over 40 °C, significant bloody stools)
• Patients in whom there is concern for bacteremia and/or sepsis
• Patients with prolonged illness (symptoms longer than 1 week) or worsening symptoms 
• Patients with relapse of symptoms or recrudescent disease
• Patients who otherwise meet empiric treatment criteria (eg, patients who are extremely old or young, are pregnant, are immunocompromised, have significant comorbidity)

Antibiotic selection is guided by positive bacterial stool culture results 

• First line oral antibiotic drug of choice is azithromycin or erythromycin 
• Ciprofloxacin is the oral drug of choice when bacterial strain is resistant to azithromycin
• Antibiotic resistance rates are high among Campylobacter isolates; highest resistance is to fluoroquinolones and emerging resistance to macrolides is evident. Most isolates are resistant to penicillin, cephalosporins, and sulfonamides 
  • Campylobacter strains acquired in developing countries are more likely to be resistant 
  • When infection is acquired in a developing country, consider initially treating with alternate antibiotic class until antibiotic susceptibilities are known 
• Alternate antibiotic classes to which Campylobacter is usually susceptible include tetracyclines, aminoglycosides, clindamycin, amoxicillin–clavulanic acid, and imipenem 
• Further refine antibiotic selection based on antibiotic sensitivity results, when available

Select parenteral antibiotics for invasive or systemic infections (eg, very ill-appearing patients, patients with extraintestinal infection, patients with Campylobacter fetus infection) in consultation with an infectious disease specialist 

• Preferred initial empiric parenteral antibiotics include aminoglycosides or imipenem
• Campylobacter fetus is usually susceptible to aminoglycosides, extended-spectrum cephalosporins, meropenem, imipenem, ampicillin, and erythromycin
• Refine antibiotic selection based on antimicrobial susceptibility results and individual patient response

Drug therapy

• Antibiotic therapy
  • Macrolides
    • Azithromycin
      • Azithromycin Oral suspension; Children: 10 mg/kg/dose (Max: 500 mg/dose) PO once daily for 3 days.
      • Azithromycin Oral tablet; Adults: 500 mg PO once daily for 3 days.
    • Erythromycin
      • Erythromycin Estolate Oral suspension; Infants, Children, and Adolescents: 40 mg/kg/day (Max: 2 g/day) PO in 4 divided doses for 5 days.
      • Erythromycin Oral tablet; Adults: 500 mg PO q6h for 7 days has been used.
  • Fluoroquinolones
    • Ciprofloxacin
      • Ciprofloxacin Oral suspension; Infants, Children, and Adolescents: 15 mg/kg/dose (Max: 500 mg) PO every 12 hours for 5 days.
        • Note: risks versus benefits must be considered before fluoroquinolone therapy initiated in children younger than 18 years.
      • Ciprofloxacin Hydrochloride Oral tablet; Adolescents†: 500 to 750 mg PO every 12 hours for 7 to 10 days for HIV-infected patients; at least 14 days if bacteremic; 2 to 6 weeks for recurrent bacteremia. Add aminoglycoside if bacteremic.
      • Ciprofloxacin Hydrochloride Oral tablet; Adults: 500 mg PO every 12 hours for 5 to 7 days. 500 to 750 mg PO every 12 hours for 7 to 10 days for HIV-infected patients; at least 14 days if bacteremic; 2 to 6 weeks for recurrent bacteremia. Add aminoglycoside if bacteremic.
      • Consider using IV ciprofloxacin for patients with severe diarrhea and bacteremia. Administer via IV until bacteremia is cleared and patients are able to absorb antibiotics orally.
  • Parenteral antibiotics
    • For invasive or systemic infections
    • Aminoglycoside
      • Gentamicin
        • Gentamicin Sulfate Solution for injection; Infants, Children, and Adolescents: 5 to 7.5 mg/kg/dose IV/IM every 24 hours.
        • Gentamicin Sulfate Solution for injection; Adults: 5 to 7 mg/kg/dose IV/IM. Dosing interval often determined via nomogram and adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.
    • Carbapenem
      • Imipenem
        • Imipenem, Cilastatin Sodium Solution for injection; Infants, Children, and Adolescents 3 months to 17 years: 15 to 25 mg/kg/dose IV every 6 hours (Max: 2 g/day for fully susceptible organisms; 4 g/day for moderately susceptible organisms).
        • Imipenem, Cilastatin Sodium Solution for injection; Adults: 500 mg IV every 6 hours or 1 g IV every 8 hours for fully susceptible organisms and 1 g IV every 6 hours for organisms with intermediate susceptibility.
• 5-HT₃ receptor antagonist
  • Ondansetron
    • Ondansetron Hydrochloride Oral solution; Infants and Children 6 months and older weighing 8 to 15 kg: 2 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
    • Ondansetron Hydrochloride Oral solution; Children weighing 15 to 30 kg: 4 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
    • Ondansetron Oral disintegrating tablet; Children and Adolescents weighing more than 30 kg: 6 to 8 mg PO as a single dose. Alternatively, 0.2 mg/kg/dose PO every 8 hours for 3 doses has also been studied.
    • Ondansetron Oral disintegrating tablet; Adults: 4 to 8 mg PO as a single dose.

Nondrug and supportive care

• Rehydrate with fluid and electrolyte replacement 
  • Encourage commercially available oral rehydration solutions, which are effective in most patients
    • Balanced electrolyte solutions (ie, sodium of 60-75 mEq/L and glucose of 75-90 mmol/L) are preferred in: 
      • Infants and young children 
      • Elderly people with severe diarrhea 
      • Individuals with voluminous, choleralike watery diarrhea 
    • Oral rehydration therapy is contraindicated in: 
      • Initial management of severe dehydration
      • Children with paralytic ileus
      • Frequent and persistent vomiting (ie, more than 4 episodes per hour)
      • Painful oral conditions such as moderate to severe thrush (eg, oral candidiasis)
    • Amount of recommended oral rehydration therapy for mild to moderate dehydration in children
      • 50 to 100 mL/kg over 3 to 4 hours followed by additional replacement of ongoing losses (eg, 50-100 mL for each diarrheal stool or vomiting episode) 
    • Recommend water, sports drinks, soups, and saltines in other adults with mild to moderate acute diarrhea 
  • Nasogastric administration is an alternate effective route for enteral fluid administration in patients who do not tolerate oral fluids
    • May be most appropriate for malnourished or lethargic children but not feasible for otherwise healthy, active, older children 
  • Administer IV fluid for patients with significant dehydration
    • Common indications for IV fluid include:
      • Continuing rapid stool loss (more than 15-20 mL/kg/hour) 
      • Frequent, severe vomiting
      • Insufficient intake of oral rehydration solution owing to fatigue or lethargy
      • Severe dehydration 
    • Avoid hypotonic D5 1/4 NS replacement solution in patients with severe dehydration secondary to diarrheal disease 
• Encourage early refeeding with regular age-appropriate diet to promote enteral recovery 
  • Recommend frequent, small meals throughout the day; energy- and micronutrient-rich foods are ideal (eg, grains, eggs, meats, fruits, vegetables) 
  • Avoid hyperosmolar canned fruit juices because they can aggravate diarrhea 
  • For nursing infants, continue breastfeeding, as tolerated 
  • Avoid lactose during symptomatic diarrhea owing to risk of interval lactose intolerance with temporary lactase deficiency, particularly in infants and children
• Standard infection-control and contact precautions are required for all hospitalized patients

Special populations

• Avoid empiric antibiotic treatment of bloody diarrhea in children younger than 3 years until Escherichia coli O157:H7 pathogen is excluded by stool culture owing to increased risk of hemolytic uremic syndrome in this patient population 
• Treat children younger than 18 years with azithromycin; fluoroquinolones are not approved to treat Campylobacter enteritis in otherwise healthy children in this age group 
• Hypogammaglobulinemic patients may require the addition of fresh frozen plasma or oral immune globulin to antibiotic therapy to eradicate infection and treat recurrent infection 
• Immunocompromised people require a prolonged curative antibiotic treatment course; occasionally, lifelong suppression therapy is required 
• Children with longer duration of diarrhea, moderate to severe dehydration, or atypical clinical presentation may require measurement of electrolytes and correction of dehydration or electrolyte abnormalities 

Monitoring

• Obtain follow-up blood cultures for Campylobacter fetus after antibiotic treatment to ensure it is eradicated 

Complications

• Acute complications
  • Dehydration
    • Electrolyte and metabolic abnormalities are possible in association with dehydration secondary to excessive gastrointestinal fluid losses
  • Extraintestinal infections are rare in otherwise healthy patients
    • More common in immunocompromised people, neonates, elderly people, and pregnant women 
    • Bacteremia
      • Campylobacter jejuni and Campylobacter coli rarely cause bacteremia in immunocompetent people (1.5 cases per 1000 intestinal infections) 
      • Campylobacter fetus infection has a predilection for spreading from gastrointestinal tract to bloodstream and distant foci 
      • Atypical Campylobacter species bacteremia is relatively commonly in immunocompromised people 
      • Most cases occur in patients with underlying comorbid debilitating disease (eg, cirrhosis, malignancy, diabetes, chronic alcoholism) 
      • 30-day mortality rate associated with Campylobacter bacteremia is approximately 15% 
    • Meningitis
      • Can rarely result from Campylobacter jejuni infection; more often a result of Campylobacter fetus dissemination 
      • Campylobacter fetus can cause neonatal meningitis
    • Other rare complications of infection include: 
      • Abscess and cellulitis 
      • Endocarditis 
      • Septic abortion
      • Osteomyelitis
  • Gastrointestinal complications
    • Mesenteric adenitis
      • Mimics appendicitis
    • Other gastrointestinal complications are very rare and include:
      • Toxic megacolon 
      • Pseudomembranous colitis
      • Massive lower gastrointestinal hemorrhage
      • Ischemic bowel disease in older patients
  • Febrile seizures
    • In young children, may occur as a result of infection-related high fever
• Subacute complications can occur during convalescence
  • Relapse of enteritis
    • About 5% to 10% of patients relapse after apparent resolution of initial illness 
  • Immunoreactive complications
    • Reactive arthritis
      • Inflammatory arthritis after an infection occurs in 1% to 5% of patients infected with Campylobacter 
      • Joint pain and swelling usually involve the hands, feet, ankles, and knees; may occur up to several weeks after infection and can persist from 1 week to several months 
      • More common in people with HLA-B27 phenotype 
    • Guillain-Barré syndrome
      • Acute demyelinating disease of the peripheral nervous system representing the most common cause of acute neuromuscular paralysis; up to 30% of Guillain-Barré syndrome cases are attributed to Campylobacter infection 
      • Usually occurs from 1 to 3 weeks after onset of Campylobacter enteritis symptoms 
      • Approximately 1 in every 1000 patients with Campylobacter enteritis will develop Guillain-Barré syndrome 
      • Associated with certain serotypes, particularly Campylobacter jejuni serotype O:19 
      • About 20% of cases require intensive care; case fatality rate in high-income countries is 3% to 10% 
    • Other less common subacute immunoreactive complications include: 
      • Reiter syndrome (ie, arthritis, urethritis, and bilateral conjunctivitis)
      • Myopericarditis
      • Hepatitis
      • Erythema nodosum
      • Renal complications (eg, IgA nephropathy, interstitial nephritis, hemolytic uremic syndrome) 
  • Immunoproliferative small intestinal disease
    • Mucosa-associated lymphoid tissue changes have unusually been associated with infection 
• Chronic complications
  • Postinfectious irritable bowel syndrome
    • Irritable bowel syndrome develops in up to 36% of patients within 1 to 2 years after Campylobacter infection 
    • Risk is higher among those with more severe acute disease 

Prognosis

• Most commonly, illness is mild, self-limiting, and associated with a good prognosis 
  • Infection resolves without antimicrobial treatment in 3 to 7 days in most healthy people 
  • Relapse occurs in 5% to 10% of patients untreated with antibiotics 
• Case fatality rate for enteric Campylobacter infection is very low (0.1%)
  • Mortality is typically limited to very young or elderly people, those with severe comorbid disease or immunocompromise, and those with Campylobacter fetus infection
  • Mortality rates are higher (up to 15%) among immunocompromised people with bacteremia 
• 12% to 21% of culture-confirmed cases of Campylobacter infection in the United States require hospitalization 

Prevention 

• General preventive measures
  • Good personal hygiene with frequent hand washing using soap, especially in certain high-risk scenarios, including:
    • Food preparation
    • Travel to areas of endemicity
    • Possible contact with pet feces, especially the diarrhea of puppies and kittens
    • Possible contact with contaminated human stool
  • Proper disposal systems of human and animal waste
    • General measures for interrupting enteric transmission in day care centers are warranted (eg, exclude infants and children in diapers from contact with asymptomatic children) 
  • Proper handling and preparation of food and drinks; advise patients as follows: 
    • Avoid drinking untreated surface water or unpasteurized raw milk 
    • Avoid eating raw or undercooked poultry, meat, and shellfish 
    • Avoid cross-contamination during food preparation; store raw food away from cooked food and use separate utensils and chopping boards for raw food
    • Avoid eating at restaurants that appear unsanitary; avoid eating poultry prepared at restaurants 
    • Thoroughly cook food to hotter than 70 °C and serve hot food at hotter than 60 °C
    • Do not leave food at room temperature longer than 2 hours and refrigerate all perishable food (to less than 5 °C)
    • Understand that freezing reduces, but does not eliminate, bacteria on raw meat
• Travelers at high risk (eg, patients on proton pump inhibitors, immunocompromised patients, patients with underlying chronic gastrointestinal disease, healthy travelers with critical duties or history of moderate to severe traveler’s diarrhea) who go to endemic areas may benefit from traveler’s diarrhea chemoprophylaxis (eg, bismuth subsalicylate, antibiotics, probiotics) 

References

Kaakoush NO et al: Global epidemiology of Campylobacter infection. Clin Microbiol Rev. 28(3):687-720, 2015