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Antibiotic Treatment

Recommendations for the use of antibiotics for thetreatment of cholera

Summary recommendations

1. Oral or intravenous hydration is the mainstay of cholera treatment.

2. In conjunction with hydration, treatment with antibiotics is recommended forseverely ill patients. It is particularly recommended for patients who are severely or

moderately dehydrated and continue to pass a large volume of stool duringrehydration treatment. Antibiotic treatment is also recommended for all patients whoare hospitalized.

3. Antibiotic choices should be informed by local antibiotic susceptibility patterns. In

most countries, Doxycycline is recommended as first-line treatment for adults, whileazithromycin is recommended as first-line treatment for children and pregnantwomen. During an epidemic or outbreak, antibiotic susceptibility should be monitoredthrough regular testing of sample isolates from various geographic areas.

4. None of the guidelines recommend antibiotics as prophylaxis for choleraprevention, and all emphasize that antibiotics should be used in conjunction withaggressive hydration.

5. Education of health care workers, assurance of adequate supplies, and monitoringof practices are all important for appropriate dispensation of antibiotics.

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Background1. Mainstay of cholera treatment is hydration 

Intravenous 1 and oral 2 hydration are both associated with greatly decreasedmortality and remain the mainstay of treatment for cholera.

2. 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 theeffectiveness of selected antibiotics on three main outcomes: stool output,

duration of diarrhea, and bacterial shedding.These studies compared outcomesfor cholera patients who were given both intravenous (IV) fluids and antibiotictreatment with those given IV fluids only. Findings indicate that antibioticsreduced 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 stoolvolume, antibiotics result in more rapid recovery and shorter lengths of inpatient stay, both of which contribute to optimizing resource utilization in anoutbreak setting.

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• 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 antibioticson mortality cannot be assessed. In the absence of adequate rehydration,

antibiotics alone are not sufficient to prevent cholera mortality.

3. Antibiotic regimens for the treatment of cholera Tetracycline has been shown to be effective treatment for cholera 2, 3 and is superiorto furazolidone 8, cholamphenicol 9 and sulfaguanidine 9 in reducing cholera morbidity.

Treatment with a single 300mg dose of doxycycline has shown to be equivalent totetracycline treatment 10. Erythromycin is effective for cholera treatment, andappropriate for children and pregnant women 11. Orfloxacin 12, trimethoprim-sulfamethoxazole (TMP-SMX) 13, and ciprofloxacin 14 are effective, but doxycyclineoffers advantages related to ease of administration and comparable or superioreffectiveness. Recently, azithromycin has been shown to be more effective thanerythromycin and ciprofloxacin 15, 16 and is an appropriate first line regimen forchildren and pregnant women.

4. Antibiotic resistance 

Resistance to tetracycline and other antimicrobial agents among V. cholerae has beendemonstrated in both endemic and epidemic cholera settings. Resistance can beacquired through the accumulation of selected mutations over time, or theacquisition of genetic elements such as plasmids, introns, or conjugative elements,which confer rapid spread of resistance. A likely risk factor for antimicrobialresistance is widespread use of antibiotics, including mass distribution for prophylaxisin asymptomatic individuals. Antibiotic resistance emerged in previous epidemics inthe context of antibiotic prophylaxis for household contacts of cholera patients 17, 18.

5. Unanswered questions 

Inadequate information still exists with respect to antibiotics in the following areas:

α. Effect of antibiotics on secondary transmission:

• There are insufficient data examining the effect of antibiotics onsecondary transmission of cholera. However, in published studies to dateantibiotics have not been shown to decrease secondary transmission of cholera within households 19, 20.

β. 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 insettings where this is not possible remains unclear.

2. Summary of Antibiotic Treatment GuidelinesVarious organizations that participate in cholera responses recommend the use of 

antibiotics in cholera-infected patients with moderate or severe illness and who havebegun IV hydration. None of the guidelines recommend antibiotics as prophylaxis for

cholera prevention, and all emphasize that antibiotics should be used in conjunctionwith aggressive hydration. In addition, the guidelines recommend that antimicrobial

susceptibility testing should inform local drug choices. Available guidelines aresummarized below.

3. 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.

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• 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 fromany outbreak is essential for understanding and minimizing the spread of 

resistance.

Rehydration TherapyRehydration 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  [PDF - 21 pages] (see Part A, Step 3) 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 andtime intervals shown are guidelines provided on the basis of usual needs.

o 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 adequaterehydration. If hydration is not improving, give fluids more rapidly. 200ml/kgor more of intravenous fluids may be needed during the first 24 hours of treatment.

o 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.

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Zinc TreatmentA 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.

zinc Pengobatan

Sebuah penelitian di Bangladesh menunjukkan bahwa suplementasi zinc secara

signifikan mengurangi durasi dan keparahan diare pada anak-anak yang

menderita kolera 1. Penelitian ini dilakukan dengan 179 anak, 3-14 tahun, yang

dirawat di rumah sakit dalam waktu 24 jam dari timbulnya gejala kolera. Dalam

studi tersebut, semua anak menerima antibiotik dan terapi rehidrasi yang

diperlukan, tetapi mereka dalam kelompok intervensi juga menerima suplemen

seng. Anak-anak yang menerima suplemen zinc memiliki 8 jam lebih sedikit dari

penyakit diare dan volume tinja 10% lebih sedikit diare, rata-rata. Zinc juga telah

terbukti memiliki efek yang sama pada anak-anak dengan diare yang disebabkanoleh infeksi selain kolera, dan dianjurkan untuk pengobatan diare anak lebih

umum 2.

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Five Basic Cholera Prevention Messages1. Drink and use safe water*

• Bottled water with unbroken seals and canned/bottled carbonated

beverages are safe to drink and use

• Use safe water to brush your teeth, wash and prepare food, and to make

ice

• Clean food preparation areas and kitchenware with soap and safe water

and let dry completely before reuse

*Piped water sources, drinks sold in cups or bags, or ice may not be safeand should be boiled or treated with chlorine. 

To be sure water is safe to drink and use:

• Boil it or treat it with a chlorine product or household bleach

• If boiling, bring your water to a complete boil for at least 1 minute

• To treat your water with chlorine, use one of the locally available

treatment products and follow the instructions. For a list of products distributedby country, visit CDC’s Safe Water System website

• If a chlorine treatment product is not available, you can treat your water

with household bleach. Add 8 drops of household bleach for every 1 gallon of 

water (or 2 drops of household bleach for every 1 liter of water) and wait 30minutes before drinking

• Always store your treated water in a clean, covered container

A woman collecting water

2. Wash your hands often with soap and safe water*

• Before you eat or prepare food

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• Before feeding your children

• After using the latrine or toilet

• After cleaning your child’s bottom

•After taking care of someone ill with diarrhea

* If no soap is available, scrub hands often with ash or sand and rinse withsafe water.

3. Use latrines or bury your feces (poop); do not defecate in any body of water

• Use latrines or other sanitation systems, like chemical toilets, to dispose of 

feces

• Wash hands with soap and safe water after defecating

• Clean latrines and surfaces contaminated with feces using a solution of 1

part household bleach to 9 parts water

What if I don’t have a latrine or chemical toilet?

• Defecate at least 30 meters away from any body of water and then bury

your feces

• Dispose of plastic bags containing feces in latrines, at collection points if 

available, or bury it in the ground. Do not put plastic bags in chemical toilets

• Dig new latrines or temporary pit toilets at least a half-meter deep and at

least 30 meters away from any body of water

4. Cook food well (especially seafood), keep it covered, eat it hot, and peel

fruits and vegetables*

• Boil it, Cook it, Peel it, or Leave it

• Be sure to cook shellfish (like crabs and crayfish) until they are very hot

all the way through

*Avoid raw foods other than fruits and vegetables you have peeled yourself.5. Clean up safely—in the kitchen and in places where the family bathes and

washes clothes

• Wash yourself, your children, diapers, and clothes, 30 meters away from

drinking water sources

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DiseaseCholera is an acute, diarrheal illness caused by infection of the intestine with the

bacterium Vibrio cholerae and is transmitted by contaminated food or water. The

infection is often mild or without symptoms, but sometimes it can be severe.

A young boy being checked for dehydration

Approximately 5-10% of persons will have severe cholera which in the early stages

includes:

• profuse watery diarrhea, sometimes described as “rice-water stools,” 

• vomiting

• rapid heart rate

• loss of skin elasticity

• dry mucous membranes

• low blood pressure

• thirst

• muscle cramps

• restlessness or irritability

Persons with severe cholera can develop acute renal failure, severe electrolyte

imbalances and coma. If untreated, severe dehydration can rapidly lead to shock and

death.

Profuse diarrhea produced by cholera patients contains large amounts of 

infectious Vibrio choleraebacteria that can infect others if ingested, and when these

bacteria contaminate water or food will lead to additional cases.

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Person washing hands

Persons caring for cholera patients can avoid acquiring illness by washing their

hands after touching anything that might be contaminated and properly disposing of 

contaminated items.

Infected persons, when treated rapidly, can recover quickly, and there are typically no

long term consequences. Persons with cholera do not become carriers of the disease

after they recover, but can be reinfected if exposed again.