What is the drug of choice for treating Campylobacter (C.) jejuni infection?

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Last updated: December 27, 2025View editorial policy

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Drug of Choice for Campylobacter jejuni

Azithromycin is the drug of choice for Campylobacter jejuni infection, with a dosing regimen of either 1000 mg as a single dose or 500 mg daily for 3 days. 1

First-Line Treatment Recommendation

  • The Infectious Diseases Society of America and American College of Physicians recommend azithromycin as first-line therapy for C. jejuni infections due to its superior efficacy (96% clinical cure rate) and persistently low resistance rates (approximately 4% globally). 1

  • Early treatment within 72 hours of symptom onset maximizes benefit, reducing illness duration from 50-93 hours to 16-30 hours. 1, 2

  • For severe cases with dysentery or high fever, the single 1000 mg dose is preferred for immediate high tissue concentrations. 2

  • For less severe cases, 500 mg daily for 3 days provides equivalent efficacy with sustained therapeutic levels. 2

Why Fluoroquinolones Are No Longer First-Line

  • Fluoroquinolone resistance in C. jejuni has reached epidemic proportions globally, rendering ciprofloxacin and other quinolones unreliable for empiric therapy. 3

  • Resistance rates exceed 90% in Southeast Asia, 73-90% in Peru, and 60% in travel-related infections in the United States. 3

  • Clinical failure occurs in 33% of patients treated with fluoroquinolones when the isolate is resistant, directly translating resistance into poor patient outcomes. 3, 1

  • While ciprofloxacin is FDA-approved for C. jejuni infectious diarrhea 4, this approval predates the current resistance crisis and should not guide contemporary practice.

Geographic Considerations

  • In Southeast Asia, India, Mexico, and South America, azithromycin should be used empirically without exception due to near-universal fluoroquinolone resistance (78-83%). 3, 1

  • Even in regions with lower resistance rates, the Centers for Disease Control and Prevention recommends considering local resistance patterns, which increasingly favor azithromycin as default therapy. 1

Special Populations Requiring Treatment

  • Immunocompromised patients must receive antibiotic treatment even for mild infections due to high risk of bacteremia and systemic spread. 1

  • Infants under 6 months warrant prompt azithromycin treatment as they are at higher risk for severe disease and complications. 1

  • Elderly patients require close monitoring for dehydration but receive standard azithromycin dosing. 2

Alternative Treatment Options

  • Erythromycin 50 mg/kg/day divided every 6-8 hours for 5 days may be used if azithromycin is unavailable, though it is less effective and requires more frequent dosing. 1

  • Fluoroquinolones (ciprofloxacin 500 mg twice daily for 3 days or levofloxacin 500 mg daily for 3 days) should only be considered in documented low-resistance areas with confirmed susceptibility testing. 1, 2

Resistance Trends and Mechanisms

  • Macrolide resistance in C. jejuni remains stable at approximately 4% for travel-related infections, though some regions (notably Iquitos, Peru) have seen increases from 2.2% to 14.9%. 3

  • Resistance is primarily mediated by A2075G point mutations in the 23S rRNA gene, which confer high-level resistance but impose fitness costs that limit transmission. 5

  • The emergence of erm(B)-mediated resistance in C. coli (primarily in China) is concerning but has not yet significantly affected C. jejuni treatment outcomes. 5

Critical Pitfalls to Avoid

  • Never use fluoroquinolones empirically without susceptibility data—this leads to treatment failure and prolonged illness in one-third of resistant cases. 3, 1

  • Do not delay treatment beyond 72 hours, as antibiotic effectiveness decreases significantly after this window. 1, 2

  • Avoid antimotility agents (loperamide) in suspected invasive diarrhea with blood or high fever, as they can worsen outcomes. 1

Supportive Care Essentials

  • Maintain aggressive oral rehydration with 8-10 large glasses of clear liquids daily, using oral rehydration solutions (Ceralyte, Pedialyte) for moderate-to-severe dehydration. 1, 2

  • Implement dietary modifications: avoid lactose, alcohol, and high-osmolar supplements; consume bland foods (bananas, rice, applesage, toast). 2

When to Reassess

  • If no improvement occurs within 48 hours of azithromycin initiation, obtain stool culture with susceptibility testing and consider alternative diagnoses. 1

  • Presence of blood in stool, fever >38.5°C persisting beyond 48 hours, or signs of severe dehydration (decreased urination, dizziness, dry mouth) require immediate medical re-evaluation. 2

  • Monitor for post-infectious complications including Guillain-Barré syndrome, reactive arthritis, and rarely hemolytic-uremic syndrome, which can develop weeks after acute infection. 1

References

Guideline

Treatment of Campylobacter Infections

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Treatment of Campylobacter jejuni Diarrhea

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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