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Oral antibiotics for suspected cholera

Oral antibiotics for suspected cholera
Class Antibiotic Adult dose Pediatric dose* Comments
Tetracyclines Doxycycline 300 mg (single dose) 4 to 6 mg/kg (single dose)¶[1]
  • Antibiotic resistance to all tetracyclines is common[2]
  • Empiric use is appropriate in epidemics caused by documented susceptible isolates
  • Not recommended for pregnant patients and children <8 years of age if other agents are appropriate and availableΔ
Tetracycline 500 mg 4 times per day for 3 days 12.5 mg/kg per dose, 4 times per day for 3 days
Macrolides Azithromycin 1 g (single dose) 20 mg/kg (single dose)
  • Single-dose azithromycin is preferred therapy[3,4]
  • Rare reports of macrolide resistance
  • Azithromycin is associated with less gastrointestinal distress (eg, vomiting) than erythromycin
Erythromycin 500 mg 4 times per day for 3 days[5] 12.5 mg/kg per dose, 4 times per day for 3 days
Fluoroquinolones Ciprofloxacinפ 500 mg twice daily for 3 days 15 mg/kg per dose, twice daily for 3 days
  • Reduced susceptibility to fluoroquinolones has been reported in Asia and Africa[3,6]
  • Not recommended for pregnant patients and children <8 years of age if other agents are appropriate and available¥
Rapid rehydration therapy and electrolyte replacement is critical; oral antibiotics may be indicated depending on severity of dehydration and other clinical factors (eg, pregnancy, malnutrition). Selection should be guided by local isolate susceptibility and availability. Refer to UpToDate content on treatment and prevention of cholera.

* Maximum pediatric dose is not to exceed adult dose listed.

¶ A pediatric dose of 4 mg/kg is roughly equivalent to an adult dose of 200 mg; a pediatric dose of 6 mg/kg is roughly equivalent to an adult dose of 300 mg. In children >6 years of age, the higher dose of 6 mg/kg has been associated with shorter duration of diarrhea compared with lower doses[7].

Δ Single-dose doxycycline is unlikely to cause dental staining or adverse effects in children, and short-term use is permitted by American Academy of Pediatrics in children of all ages[8]; Centers for Disease Control and Prevention (CDC) and Global Task Force on Cholera Control (GTFCC) consider single-dose doxycycline appropriate for use in children and pregnant patients in the absence of resistance[9,10].

◊ Dose reduction may be needed in patients with kidney impairment (CrCl <30 mL/minute).

§ We recommend a 3-day course of ciprofloxacin in the setting of decreasing susceptibility to fluoroquinolones[11]. For isolates with decreased fluoroquinolone susceptibility (identified by resistance to nalidixic acid), fluoroquinolone regimens administered for 3 days have been associated with higher rates of clinical and bacteriologic response than single-dose regimens.

¥ CDC and GTFCC consider ciprofloxacin appropriate for use in children and pregnant patients in the absence of resistance[9,10].
References:
  1. Kanungo S, Azman AS, Ramamurthy T, et al. Cholera. Lancet 2022; 399:1429; supplementary appendix table S3.
  2. Yamamoto T, Nair GB, Albert MJ, et al. Survey of in vitro susceptibilities of Vibrio cholerae O1 and O139 to antimicrobial agents. Antimicrob Agents Chemother 1995; 39:241.
  3. Saha D, Karim MM, Khan WA, et al. Single-dose azithromycin for the treatment of cholera in adults. N Engl J Med 2006; 354:2452.
  4. Khan WA, Saha D, Rahman A, et al. Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial. Lancet 2002; 360:1722.
  5. Saha D, Khan WA, Karim MM, et al. Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial. Lancet 2005; 366:1085.
  6. Islam MS, Midzi SM, Charimari L, et al. Susceptibility to fluoroquinolones of Vibrio cholerae O1 isolated from diarrheal patients in Zimbabwe. JAMA 2009; 302:2321.
  7. De S, Chaudhuri A, Dutta P, et al. Doxycycline in the treatment of cholera. Bull World Health Organ 1976; 54:177.
  8. Red Book Online 2021-2024 Report of the Committee on Infectious Diseases (32nd ed), Kimberlin DW, Barnett ED, Lynfield R et al (Eds), American Academy of Pediatrics. https://publications.aap.org/redbook/book/347/Red-Book-2021-2024-Report-of-the-Committee-on.
  9. Centers for Disease Control and Prevention (CDC). Cholera - Vibrio cholerae infection. Antibiotic treatment: recommendations for the use of antibiotics for the treatment of cholera. https://www.cdc.gov/cholera/treatment/antibiotic-treatment.html. Updated June 2022.
  10. Global Task Force on Cholera Control (GTFCC). Cholera outbreak response field manual. https://www.gtfcc.org/wp content/uploads/2020/04/gtfcc-cholera-outbreak-response-field-manual.pdf. Published October 2019.
  11. Khan WA, Saha D, Ahmed S, et al. Efficacy of ciprofloxacin for treatment of cholera associated with diminished susceptibility to ciprofloxacin to Vibrio cholerae O1. PLoS One 2015; 10:e0134921.
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