Infections Due to Campylobacter and Related Organisms¶

Chapter 169 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 169

Key Clinical Points¶

C. jejuni accounts for 80–90% of recognized campylobacter illnesses; C. fetus is the major cause of extraintestinal illness.
Primary antibiotic resistance to macrolides is high in most locales; regimens containing clarithromycin often fail.
Azithromycin (500 mg daily for 3 days) is the regimen of choice for uncomplicated enteritis.
Carbapenems (imipenem or meropenem) are first-line for bacteremic infections due to C. fetus or immunocompromised hosts.
Campylobacter enteritis mimics inflammatory bowel disease (IBD); infection must be ruled out before diagnosing Crohn's or UC.
Campylobacter infections trigger 20–40% of all Guillain-Barré syndrome cases via molecular mimicry.
C. jejuni and C. coli are resistant to trimethoprim and beta-lactam antibiotics (penicillin, cephalosporins).
Incidence peaks during summer and early autumn; attack rates are highest among young children and young adults.
C. fetus infections are most common among compromised hosts (AIDS, immunoglobulin deficiency, neoplasia, liver disease, diabetes).
Use of antimotility agents is not recommended as they may prolong symptoms and are associated with toxic megacolon.

1. DEFINITION & OVERVIEW¶

Bacteria of the genus Campylobacter and related genera (Arcobacter, Helicobacter) cause diverse inflammatory conditions.

Definition (Harrison's 22e): Bacteria of the genus Campylobacter and of the related genera Arcobacter and Helicobacter (Chap. 168) cause a variety of inflammatory conditions.

Acute diarrheal illness is most common, but infections can occur in all body parts, especially in immunocompromised hosts.

Etymology: The term 'Campylobacter' derives from Greek for 'curved rod,' reflecting the organism's vibrio-like morphology.

1.1 Taxonomy & Morphology¶

• Classification: Originally classified as Vibrio fetus, reclassified in 1973 due to distinct characteristics. • Diversity: Over 20 species identified; divided into three genera: Campylobacter, Arcobacter, Helicobacter. • Pathogen Groups: ◦ Diarrheal agents: C. jejuni, C. coli ◦ Extraintestinal agents: C. fetus • Microbiology: Microaerophilic, non-spore-forming, curved gram-negative rods adapted for gastrointestinal mucous layer survival.

2. EPIDEMIOLOGY¶

Campylobacter species are zoonotic pathogens found in poultry, cattle, and pets.

• Transmission Routes: ◦ Contaminated food (especially undercooked poultry) ◦ Unpasteurized milk ◦ Untreated water ◦ Contact with infected animals/pets ◦ Travel to developing countries ◦ Oral-anal sexual contact

• Incidence: ~20 cases/100,000 in developed countries; higher in children <2 years in low-income settings.

2.1 Risk Factors¶

• Modifiable: Foodborne exposure, travel, animal contact, and oral-anal sexual contact. • Non-modifiable: Age (young children/adults for C. jejuni; extremes of age for C. fetus), immunocompromise (AIDS, Ig deficiency, diabetes, etc.), pregnancy. • Medication: Proton pump inhibitor use increases risk.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

C. jejuni infections may be subclinical in immunocompetent hosts with prior exposure.

• Pathogenesis: Adherence to host tissues and motility contribute to disease; cytolethal distending toxin is not a major virulence factor. • Immune Response: Antibodies play key role; immunity is short-lived without continuous exposure.

3.1 C. fetus Pathogenesis¶

• S-layer protein capsule: Provides resistance to complement and opsonization. ◦ Enables bacteremia and seeding of distant sites (meninges, bones, etc.). • Antigenic variability: Via S-layer switching; contributes to chronicity/recurrence.

3.2 Atypical Species¶

Table 169-1 details clinical features of atypical species.

• C. fetus: Causes systemic infections, bacteremia, sepsis, and meningitis; common in immunocompromised hosts. • C. coli: Clinically indistinguishable from C. jejuni; can cause systemic infection/meninges involvement. • H. cinaedi: Best treated with fluoroquinolones; identified in healthy hamsters. • C. upsaliensis: Difficult to isolate due to cephalothin susceptibility.

4. CLINICAL FEATURES¶

Symptoms vary by species and host immune status.

4.1 Intestinal Phase (C. jejuni)¶

• Prodrome: Fever, headache, myalgia, malaise (12–48 h before diarrhea). • Diarrhea: Watery to bloody (approx. 10% of adults); ≥10 bowel movements/day. • Abdominal Pain: Cramping, generalized or localized; may mimic appendicitis. • Fever: May be the sole initial manifestation. • Course: Self-limited in 80–90%; >1 week in 10–20%; relapses in 5–10%.

4.2 Systemic Phase (C. fetus)¶

• Presentation: Prolonged relapsing illness with fever, chills, myalgias, and bacteremia. • Tropism: Preference for vascular sites; no obvious primary source. • Complications: Secondary seeding of organs (meninges, brain, bone, etc.). • Severity: Fulminant course possible in immunocompromised hosts.

5. DIFFERENTIAL DIAGNOSIS¶

Campylobacter enteritis mimics several other conditions.

• Mimics: Ulcerative colitis, Crohn's disease, Salmonella, Shigella, Yersinia, EHEC. • Key Differentiating Features: ◦ Fever + fecal leukocytes/erythrocytes = inflammatory diarrhea. ◦ History of travel, animal contact, or immunodeficiency increases suspicion. ◦ Biopsy may not distinguish IBD from infectious colitis.

5.1 Mimics¶

• Ulcerative colitis • Crohn's disease • Salmonella • Shigella • Yersinia • Enterohemorrhagic E. coli

5.2 Key Differentiating Features¶

• Fever + fecal leukocytes/erythrocytes = inflammatory diarrhea. • History of foreign travel, animal contact, immunodeficiency increases suspicion. • Biopsy may not distinguish between IBD and infectious colitis.

6. INVESTIGATIONS & DIAGNOSIS¶

Diagnosis relies on stool culture, PCR, and microscopy.

• Stool Culture: Gold standard; requires selective media. • PCR/CIDTs: More sensitive than culture; may detect nonviable bacteria. • Microscopy: Gram/Wright stain; phase-contrast/dark-field for 'darting' motility. • MALDI-TOF: Species identification.

6.1 Diagnostic Tests¶

• Stool Culture: Gold standard; requires selective media. • PCR/CIDTs: More sensitive than culture; may detect nonviable bacteria. • Microscopy: Gram/Wright stain; phase-contrast/dark-field for 'darting' motility. • MALDI-TOF: Species identification.

6.2 Diagnostic Algorithm¶

Suspect based on inflammatory diarrhea (fever, fecal leukocytes/erythrocytes).
Perform Gram/Wright-stained fecal smear → identify vibrioid morphology and 'darting' motility.
Culture stool on Campylobacter-specific media (selective media).
Confirm with MALDI-TOF or PCR if needed.
Consider blood culture for systemic infections (C. fetus) or septic abortion/thrombophlebitis.

7. MANAGEMENT & TREATMENT¶

Treatment focuses on hydration and targeted antibiotics.

• Uncomplicated Enteritis: Azithromycin (500 mg/day ×3 days) is first-line; macrolide resistance <10%. • Systemic/Bacteremic Infections: Carbapenems (imipenem/meropenem) are first-line; gentamicin added for life-threatening cases. • Resistance Patterns: Fluoroquinolone resistance ~27% in US; C. jejuni/C. coli resistant to trimethoprim/beta-lactams.

7.1 Antibiotic Regimens¶

Uncomplicated Enteritis: • Azithromycin: 500 mg once daily ×3 days OR 1000 mg single dose. • Fluoroquinolones (if needed): Ciprofloxacin 500 mg BID ×3 days (Note: ~27% resistance in US) or Levofloxacin 750 mg QD ×3 days. • Note: Macrolides are preferred due to <10% resistance.
Systemic/Bacteremic Infections: • Carbapenems: Imipenem 500 mg every 6 h OR Meropenem 1–2 g every 8 h. • Gentamicin (life-threatening): 1.0–1.7 mg/kg IV every 8 h (Loading dose 1.5–2 mg/kg).
Duration of Therapy: • Immunocompromised uncomplicated: 7–14 days. • Systemic infections: 7–14 days. • Immunocompromised systemic: Up to 4 weeks. • Recurrent infections: Lifelong therapy/prophylaxis.

7.2 Resistance Patterns¶

• Macrolide resistance: Usually <10%. • Fluoroquinolone resistance: ~27% in US (2014); higher in many other countries. • Trimethoprim/Beta-lactam resistance: C. jejuri/C. coli resistant. • Travel-related infections: Consider a priori fluoroquinolone-resistant.

8. PROGNOSIS & COMPLICATIONS¶

Most patients recover spontaneously; however, several complications may occur.

• Mortality: ~12% overall; primarily due to volume depletion or systemic C. fetus infections.

8.1 Postinfectious Sequelae¶

• Reactive Arthritis: • Incidence: Up to 2.5%. • Presentation: Nonspecific symptoms (~10%); typically several weeks after infection. • Joints: Knees most frequent; others include ankles, wrists, and small joints of hands (avg 3.2 joints). • Guillain-Barré Syndrome (GBS): • Incidence: 1/1000–2000 cases generally; 1/100–200 for specific serotypes like O19. • Prevalence: 20–40% of all GBS cases attributed to Campylobacter via molecular mimicry (sialylated lipopolysaccharides). • Variant: Miller Fisher (cranial polyneuropathy). • MALToma: - Association: Immuno-proliferative small-intestinal disease. - Treatment: Antimicrobial therapy leads to improvement.

9. SPECIAL CONSIDERATIONS¶

Considerations for specific populations and settings.

• Immunocompromised hosts: Prolonged therapy (up to 4 weeks) often required; lifelong prophylaxis for recurrent infections. • Developing countries: Hyperendemic C. jejuni infections associated with stunting and microbiome changes. • C. fetus in immunocompetent hosts: May cause prolonged systemic illness without localizing signs.

10. KEY PEARLS & CLINICAL TRAPS¶

Critical clinical insights and pitfalls.

• Diagnostic Clues: ◦ Bloody diarrhea + fever → suggests Campylobacter over Salmonella/Shigella. ◦ Biopsy findings resembling IBD must prompt infectious workup. ◦ C. fetus in immunocompetent hosts may present as prolonged systemic illness without localizing signs. • Clinical Traps: ◦ Overlooking Campylobacter as the cause of GBS (molecular mimicry is key). ◦ Misdiagnosing IBD without ruling out infectious colitis. ◦ Use of antimotility agents in Campylobacter enteritis → risk of toxic megacolon.

10.1 Diagnostic Clues¶

• Bloody diarrhea + fever → suggests Campylobacter over Salmonella/Shigella. • Biopsy findings resembling IBD must prompt infectious workup. • C. fetus in immunocompetent hosts may present as prolonged systemic illness without localizing signs.

Reference Tables¶

Harrison's 22e, p.1304

SPECIES	COMMON CLINICAL FEATURES	LESS COMMON CLINICAL FEATURES	ADDITIONAL INFORMATION
Campylobacter coli	Fever, diarrhea, abdominal pain	Bacteremiaa	Clinically indistinguishable from C. jejuni
	Bacteremiaa, sepsis, meningitis, vascular infections	Diarrhea, relapsing fevers
Campylobacter upsaliensis	Watery diarrhea, low-grade fever, abdominal pain	Bacteremiaa, abscesses	Difficult to isolate because of cephalothin susceptibility
	Abdominal pain, diarrhea	Colitis, appendicitis
Campylobacter hyointestinalis	Watery or bloody diarrhea, vomiting, abdominal pain	Bacteremiaa	Causes proliferative enteritis in swine
	Chronic mild diarrhea, abdominal cramps, proctitis	Bacteremiaa
Helicobacter cinaedi	Chronic mild diarrhea, abdominal cramps, proctitis	Bacteremiaa	Best treated with fluoroquinolones; identified in healthy hamsters
	Diarrhea	Chronic gastritis, bacteremiab
Arcobacter cryaerophilus	Diarrhea	Bacteremiaa	Poultry, seafood sources. Cultured under aerobic conditions
	Fever, diarrhea, abdominal pain, nausea; or asymptomatic	Bacteremiaa, appendicitis
Campylobacter sputorum	Pulmonary, perianal, groin, and axillary abscesses; diarrhea	Bacteremia	Three clinically relevant biovars: sputorum, faecalis, and paraureolyticus