Cholera Treatment

Most persons infected with the cholera bacterium have mild diarrhea or no symptoms at all. Only a small proportion, about 10%, of persons infected with Vibrio cholerae O1 have illness requiring treatment at a health center.

Cholera patients should be evaluated and treated quickly. With proper treatment, even severely ill patients can be saved. Prompt restoration of lost fluids and salts through rehydration therapy is the primary goal of treatment.

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Rehydration Therapy

Rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well under 1%.

Low-osmolarity oral rehydration solution and cereal-based oral rehydration solution are the preferred replacement fluids for most patients. However, a modified rehydration solution called ReSoMal was formulated for rehydration of severely malnourished children. Breastfed children should also continue to breastfeed. Other types of fluids, such as juice, soft drinks, and sports drinks should be avoided. Safe (treated) water should be used to prepare oral rehydration solutions.

Reassess the patient every 1-2 hours and continue hydrating. The volumes and time intervals shown are guidelines provided on the basis of usual needs.
- If necessary, the rate of fluid administration can be increased, or the fluid can be given at the same rate for a longer period, to achieve adequate rehydration. If hydration is not improving, give fluids more rapidly. 200ml/kg or more of intravenous fluids may be needed during the first 24 hours of treatment.
- Similarly, the amount of fluid can be decreased if hydration is achieved earlier than expected.
Switch from intravenous hydration to oral rehydration solution once hydration is improved and the patient can drink. This will conserve IV fluids and reduce the risk of phlebitis and other complications.
Nasogastric tubes can be used to administer oral rehydration solution if patient is alert but unable to drink sufficient quantities independently.
Patients should continue to eat a normal diet and breastfeeding children should continue to breastfeed during rehydration.

Antibiotic Treatment

Recommendations for the use of antibiotics for the treatment of cholera

Oral or intravenous hydration is the mainstay of cholera treatment.
In conjunction with hydration, treatment with antibiotics is recommended for severely ill patients. It is particularly recommended for patients who are severely or moderately dehydrated and continue to pass a large volume of stool during rehydration treatment. Antibiotic treatment is also recommended for all patients who are hospitalized.
Antibiotic choices should be informed by local antibiotic susceptibility patterns. In most countries, Doxycycline is recommended as first-line treatment for adults, while azithromycin is recommended as first-line treatment for children and pregnant women. During an epidemic or outbreak, antibiotic susceptibility should be monitored through regular testing of sample isolates from various geographic areas.
None of the guidelines recommend antibiotics as prophylaxis for cholera prevention, and all emphasize that antibiotics should be used in conjunction with aggressive hydration.
Education of health care workers, assurance of adequate supplies, and monitoring of practices are all important for appropriate dispensation of antibiotics.

Background

Mainstay of cholera treatment is hydration
Intravenous 1 and oral 2 hydration are both associated with greatly decreased mortality and remain the mainstay of treatment for cholera.
Antibiotic effectiveness for the treatment of cholera
- Antibiotics have been used as an adjunct to hydration treatment for cholera since 1964. Findings from randomized controlled trials evaluated the effectiveness of selected antibiotics on three main outcomes: stool output, duration of diarrhea, and bacterial shedding.These studies compared outcomes for cholera patients who were given both intravenous (IV) fluids and antibiotic treatment with those given IV fluids only. Findings indicate that antibiotics reduced volume of stool output by 8-92%, duration of diarrhea by 50-56%, and duration of positive bacterial culture by 26-83% 3–7.
- Antibiotic use for moderately and severely ill patients is also likely to reduce resource requirements. By decreasing duration of diarrhea and stool volume, antibiotics result in more rapid recovery and shorter lengths of inpatient stay, both of which contribute to optimizing resource utilization in an outbreak setting.
- The majority of published studies exploring effectiveness of antibiotics for cholera patients have been done in patients who were adequately rehydrated. In these studies, there was no mortality and therefore the impact of antibiotics on mortality cannot be assessed. In the absence of adequate rehydration, antibiotics alone are not sufficient to prevent cholera mortality.
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Antibiotic regimens for the treatment of cholera
Tetracycline has been shown to be effective treatment for cholera 2, 3 and is superior to furazolidone 8, cholamphenicol 9 and sulfaguanidine 9 in reducing cholera morbidity. Treatment with a single 300mg dose of doxycycline has shown to be equivalent to tetracycline treatment 10. Erythromycin is effective for cholera treatment, and appropriate for children and pregnant women 11. Orfloxacin 12, trimethoprim-sulfamethoxazole (TMP-SMX) 13, and ciprofloxacin 14 are effective, but doxycycline offers advantages related to ease of administration and comparable or superior effectiveness. Recently, azithromycin has been shown to be more effective than erythromycin and ciprofloxacin 15, 16 and is an appropriate first line regimen for children and pregnant women.
Antibiotic resistance
Resistance to tetracycline and other antimicrobial agents among V. cholerae has been demonstrated in both endemic and epidemic cholera settings. Resistance can be acquired through the accumulation of selected mutations over time, or the acquisition of genetic elements such as plasmids, introns, or conjugative elements, which confer rapid spread of resistance. A likely risk factor for antimicrobial resistance is widespread use of antibiotics, including mass distribution for prophylaxis in asymptomatic individuals. Antibiotic resistance emerged in previous epidemics in the context of antibiotic prophylaxis for household contacts of cholera patients 17, 18.
Unanswered questions
Inadequate information still exists with respect to antibiotics in the following areas:
1. Effect of antibiotics on secondary transmission:
  - There are insufficient data examining the effect of antibiotics on secondary transmission of cholera. However, in published studies to date antibiotics have not been shown to decrease secondary transmission of cholera within households 19, 20.
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2. Utility of antibiotics when aggressive rehydration is not possible:
  - Because studies on antibiotic treatment for cholera were conducted in patients who received adequate rehydration, the effect of antibiotics in settings where this is not possible remains unclear.
Summary of Antibiotic Treatment Guidelines
Various organizations that participate in cholera responses recommend the use of antibiotics in cholera-infected patients with moderate or severe illness and who have begun IV hydration. None of the guidelines recommend antibiotics as prophylaxis for cholera prevention, and all emphasize that antibiotics should be used in conjunction with aggressive hydration. In addition, the guidelines recommend that antimicrobial susceptibility testing should inform local drug choices. Available guidelines are summarized below.

Considerations
- Over-emphasizing antibiotics for treatment of cholera could divert resources from oral and intravenous rehydration.
- Doxycycline costs approximately $0.02 per 100mg tablet. Azithromycin costs approximately $0.16 per 250mg tablet.
- Antibiotics can cause nausea and vomiting. Gastrointestinal side effects should be carefully monitored, especially in dehydrated patients.
- Antibiotics are not needed and should not be given to patients with cholera who have only mild or no diarrhea and dehydration.
- Prospective surveillance for antibiotic resistance among bacterial isolates from any outbreak is essential for understanding and minimizing the spread of resistance.

Zinc Treatment

A study in Bangladesh showed that zinc supplementation significantly reduced the duration and severity of diarrhea in children suffering from cholera 1. The study was conducted with 179 children, 3-14 years old, who were admitted to a hospital within 24 hours of the onset of cholera symptoms. In the study, all children received antibiotics and rehydration therapy as needed, but those in the intervention group also received zinc supplementation.

Children who received zinc supplementation had 8 fewer hours of diarrheal illness and 10% less diarrheal stool volume, on average. Zinc has also been shown to have a similar effect in children with diarrhea caused by infections other than cholera, and is recommended for the treatment of pediatric diarrhea more generally 2.