What antibiotics are effective against common gastrointestinal (GI) pathogens such as Salmonella, Shigella, Campylobacter, and Escherichia coli (E. coli)?

Antibiotic Selection for Common GI Pathogens

For empiric treatment of moderate-to-severe bacterial gastroenteritis with suspected invasive pathogens, azithromycin is the first-line antibiotic, given as either a single 1000 mg dose or 500 mg daily for 3 days. 1, 2

Pathogen-Specific Treatment Recommendations

Campylobacter Species

• Azithromycin is the drug of choice with a 96% clinical cure rate, particularly when started within 72 hours of symptom onset 1
• Azithromycin reduces symptom duration from 50-93 hours to 16-30 hours when given early 1
• Erythromycin is an alternative if azithromycin is unavailable, though less effective 1
• Avoid fluoroquinolones due to widespread resistance exceeding 90% in Southeast Asia and increasing globally, with clinical failure rates of 33% when the isolate is resistant 1, 3
• Fluoroquinolone resistance has increased from 0% before 1991 to 84% by 1995 in Thailand 3

Shigella Species

• Azithromycin or ciprofloxacin are first-line agents for shigellosis 4
• Ciprofloxacin demonstrates strong efficacy in randomized controlled trials 4
• Azithromycin is an effective alternative, particularly in regions with fluoroquinolone resistance 4, 5
• Trimethoprim-sulfamethoxazole (TMP-SMZ) can be used in children when susceptibility is confirmed, though resistance exceeds 90% in many regions 4, 3
• Antibiotic treatment is indicated for all confirmed Shigella infections to reduce duration and shedding 4

Salmonella Species (Non-typhoidal)

• Ciprofloxacin is the primary treatment when systemic spread is suspected or in high-risk patients 4
• For severe disease or bacteremia, combination therapy with ceftriaxone plus ciprofloxacin is recommended initially, with de-escalation to monotherapy based on susceptibility results 4
• Alternative agents include TMP-SMZ or amoxicillin based on susceptibility testing 4
• Avoid routine antibiotic treatment in uncomplicated cases as antibiotics may prolong shedding of non-typhi Salmonella 4
• Treatment is warranted for children <6 months, immunocompromised patients, or when systemic spread is suspected 4
• Ceftriaxone and ciprofloxacin are recommended for salmonellosis requiring antibiotic therapy 5

E. coli (Enterotoxigenic and Enteropathogenic)

• Ciprofloxacin or azithromycin are effective for enterotoxigenic E. coli (ETEC) 4, 6
• Rifaximin is effective for non-invasive diarrhea caused by diarrheagenic E. coli but fails in up to 50% of invasive infections 4
• Do NOT treat Shiga toxin-producing E. coli (STEC/E. coli O157:H7) with antibiotics as this increases the risk of hemolytic uremic syndrome (HUS) 4
• Avoid antimotility agents in suspected STEC infections 4

Yersinia Species

• Fluoroquinolone or TMP-SMZ or doxycycline for standard infections 4
• For severe disease, third-generation cephalosporin combined with gentamicin is preferred 4

Empiric Treatment Algorithm

When to Treat Empirically

• Moderate-to-severe diarrhea with fever, bloody stools, or signs of invasive disease warrants empiric antibiotic treatment after obtaining stool specimen 4
• Patients with >3 days of diarrhea plus fever, vomiting, myalgias, or headache have 87% probability of Salmonella, Shigella, or Campylobacter infection 4
• Immunocompromised patients should receive empiric treatment even for less severe illness 4, 1

Geographic Considerations

• In Southeast Asia, azithromycin should be the default first-line agent regardless of severity due to fluoroquinolone resistance exceeding 85-90% for Campylobacter 2
• In regions with high fluoroquinolone resistance, azithromycin is superior to fluoroquinolones 4, 2

Dosing Regimens

• Azithromycin: 1000 mg single dose OR 500 mg daily for 3 days 1, 2, 7
• Single-dose regimens are preferred for better compliance 2
• Ciprofloxacin: 500 mg twice daily for 3-5 days for susceptible organisms 6
• For severe infections requiring IV therapy: azithromycin 500 mg IV daily for 2-5 days, then transition to oral when tolerated 7

Combination Therapy

• Azithromycin plus loperamide reduces illness duration from 59 hours to approximately 1 hour in moderate-to-severe cases 2
• Loperamide dosing: 4 mg initially, then 2 mg after each liquid stool, maximum 16 mg/24 hours 2
• Never combine loperamide with suspected or confirmed STEC infection 4

Critical Resistance Patterns and Pitfalls

Fluoroquinolone Resistance

• Ciprofloxacin resistance in Campylobacter has increased dramatically worldwide, with rates of 10.2% in Minnesota and 84% in Thailand by 1995 4, 3
• Nalidixic acid resistance in Shigella dysenteriae 1 reached 97-100% between 1992-1995, indicating first-step gyrA mutations 3
• Among Salmonella, 16.2% in Europe and 12.9% in Latin America show nalidixic acid resistance, suggesting possible fluoroquinolone treatment failure 8

Emerging Multi-Drug Resistance

• Multiple-drug resistance including quinolones has emerged in clinical Salmonella strains 4
• Resistance to TMP-SMZ exceeds 90% in Shigella and 40% in ETEC and Salmonella in Thailand 3
• Azithromycin resistance has been detected in 7-15% of Campylobacter, 15% of ETEC, and 3% of Salmonella isolates 3
• Co-resistance to ciprofloxacin, azithromycin, and ceftriaxone has emerged worldwide 9

Common Pitfalls to Avoid

• Using fluoroquinolones empirically without considering local resistance patterns leads to treatment failure and prolonged illness 1
• Delaying azithromycin treatment beyond 72 hours reduces effectiveness significantly 1
• Treating STEC O157 with antibiotics increases HUS risk; several retrospective studies show higher HUS rates in treated patients 4
• Prescribing antibiotics to reduce secondary transmission is not indicated; hand-washing achieves the same goal without selecting for resistance 4
• Using antibiotics for uncomplicated non-typhi Salmonella may prolong shedding 4

Special Populations

Immunocompromised Patients

• Always treat severely ill and/or immunocompromised individuals with systemic antibiotics 4
• For Salmonella bacteremia in immunocompromised patients, combination therapy with ceftriaxone plus ciprofloxacin is recommended 4

Pediatric Patients

• TMP-SMZ is preferred over fluoroquinolones in children for susceptible Shigella and Campylobacter 4
• Ciprofloxacin is FDA-approved for complicated UTI and pyelonephritis in children 1-17 years, but is not first-choice due to increased adverse events including joint-related issues 6
• Azithromycin is recommended for pediatric gastroenteritis based on local susceptibility patterns 2, 5

Severe Disease Requiring IV Therapy

• IV azithromycin 500 mg daily for 2-5 days is first-line for severe bacterial gastroenteritis when oral therapy is not tolerated 7
• Transition to oral therapy when clinical improvement occurs 7

When NOT to Use Antibiotics

• Mild, self-limited diarrhea in immunocompetent patients typically resolves in 3-5 days without antibiotics 1
• Suspected or confirmed STEC O157 infection should never receive antibiotics or antimotility agents 4
• Uncomplicated non-typhi Salmonella in immunocompetent adults does not require treatment 4