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Cholera

Medication

Medication Summary

Antimicrobial therapy for cholera is an adjunct to fluid therapy and is not an essential therapeutic component. However, an effective antibiotic can reduce the volume of diarrhea in patients with severe cholera and shorten the period during which Vibrio cholerae O1 is excreted. In addition, it usually stops the diarrhea within 48 hours, thus shortening the period of hospitalization. No other drugs besides antibiotics should be used in the treatment of cholera.

The choice of antibiotics is determined by the susceptibility patterns of the local strains of V cholerae O1 or O139.

If antimicrobial therapy is to be initiated, it should be given when the patient is first seen and cholera is suspected. Little reason exists to wait for culture and susceptibility reports.

Furazolidone has been the agent routinely used in the treatment of cholera in children; however, resistance has been reported, and ampicillin, erythromycin, and fluoroquinolones are potentially effective alternatives. The use of quinolones is contraindicated in children with cholera.

Travelers to cholera-affected regions should receive a cholera vaccine. The cholera vaccine Vaxchora is the only one approved by the FDA for cholera prevention. It is a live, weakened vaccine administered as a single, oral liquid dose of about three fluid ounces at least 10 days before travel to a cholera-affected region. The only other existing cholera-prevention vaccines require 2 doses, according to the Centers for Disease Control and Prevention (CDC). A single-dose vaccine is especially beneficial to a person who needs to travel to a cholera-affected region on short notice.^[20]

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Although not necessarily curative, treatment with an antibiotic to which the organism is susceptible diminishes the duration and volume of the fluid loss and hastens clearance of the organism from stool. Pharmacotherapy plays a secondary role in the management of cholera; fluid replacement is primary.

Emerging drug resistance in certain parts of the world is a concern, as some V cholerae strains contain plasmids that confer resistance to many antibiotics. In areas of known tetracycline resistance, therapeutic options include ciprofloxacin and erythromycin. Strains resistant to ciprofloxacin have been reported from Calcutta, India.

Chemoprophylaxis of household contacts is not necessary.

Doxycycline (Adoxa, Vibramycin, Doxy)

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Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Tetracycline

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Tetracycline inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). This agent treats gram-positive and gram-negative organisms and mycoplasmal, chlamydial, and rickettsial infections.

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)

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This combination agent inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.

Trimethoprim is a dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. It is active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens (eg, Enterobacteriaceae and Staphylococcus saprophyticus). Resistance is usually mediated by decreased cell permeability or alterations in amount or structure of dihydrofolate reductase. It demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production.

Ciprofloxacin (Cipro, Proquin XR)

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Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), S epidermidis, and most gram-negative organisms. It does not have activity against anaerobes. This agent inhibits bacterial DNA synthesis and, consequently, growth.

Ampicillin

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Ampicillin has bactericidal activity against susceptible organisms.

Erythromycin (E.E.S., Erythrocin, Ery-Tab)

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Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer RNA (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. Erythromycin is used for treatment of staphylococcal and streptococcal infections. In children, age, weight, and severity of infection determine proper dose. When twice-daily dosing is desired, half the total daily dose may be taken q12h. For more severe infections, double the dose.

Azithromycin (Zithromax, Zmax)

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This agent acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

It concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. This agent is used to treat mild-to-moderate microbial infections.

Norfloxacin (Noroxin)

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Norfloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms. It does not have activity against anaerobes. It inhibits bacterial DNA synthesis and growth.

Class Summary

In June, 2016, the first U.S. cholera vaccine was approved by the FDA.^[20]

Cholera vaccine (Vaxchora)

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Contains live attenuated cholera bacteria that replicate in the gastrointestinal tract of the recipient to provide immunity. It is indicated for active immunization against disease caused by Vibrio cholerae serogroup O1 in persons aged 2-64 y traveling to cholera-affected areas.

Questions

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Media Gallery

Electron microscopic image of Vibrio cholera.
Scanning electron microscope image of Vibrio cholerae bacteria, which infect the digestive system.
This scanning electron micrograph (SEM) depicts a number of Vibrio cholerae bacteria of the serogroup 01; magnified 22371x. Image courtesy of CDC/Janice Haney Carr.
This patient with cholera is drinking oral rehydration solution (ORS) in order to counteract the cholera-induced dehydration. Image courtesy of the CDC.

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Table 1. Assessment of the Patient With Diarrhea for Dehydration (based on WHO classification)

Sensorium	Eyes	Thirst	Skin Pinch	Decision
Abnormally sleepy or lethargic	Sunken	Drinks poorly or not at all	Goes back very slowly (>2 sec)	If the patient has 2 or more of these signs, severe dehydration is present
Restless, irritable	Sunken	Drinks eagerly	Goes back slowly (< 2 sec)	If the patient has 2 or more signs, some dehydration is present
Well, alert	Normal	Drinks normally, not thirsty	Goes back quickly	Patient has no dehydration

Table 2. Fluid Replacement for Dehydration

Severe dehydration	Intravenous (IV) drips of Ringer Lactate or, if not available, normal saline and oral rehydration salts as outlined below	100 mL/kg in 3-h period (in 6 h for children < 1 y) Start rapidly (30 mL/kg within 30 min, then slow down) Total amount for first 24 h: 200 mL/kg
Some dehydration	Oral rehydration salts (amount in first 4 h)	Infants < 4 mo (< 5 kg): 200–400 mL Infants 4–11 mo (5–7.9 kg): 400–600 mL Children 1–2 y (8–10.9 kg): 600–800 mL Children 2–4 y (11–15.9 kg): 800–1200 mL Children 5–14 y (16–29.9 kg): 1200–2200 mL Patients >14 y (≥30 kg): 2200–4000 mL
No dehydration	Oral rehydration salts	Children < 2 y: 50–100 mL, up to 500 mL/day Children 2–9 y: 100–200 mL, up to 1000 mL/day Patients >9 y: As much as wanted, up to 2000 mL/day

Table 3. Approximate Amount of Oral Rehydration Solution to Administer in the First 4 Hours

Age	< 4 mo	4-11 mo	12-23 mo	2-4 y	5-14 y	≥15 y
Weight	< 5 kg	5-7.9 kg	8-10.9 kg	11-15.9 kg	16-29.9 kg	≥30 kg
ORS solution in mL	200-400	400-600	600-800	800-1200	1200-2200	2200-4000

Table 4. Estimate of Oral Rehydration Solution Packets to Be Administered at Home

Age	Amount of Solution After Each Loose Stool	ORS Packets Needed
< 24 mo	50-100 mL	Enough for 500 mL/d
2-9 y	100-200 mL	Enough for 1000 mL/d
≥10 y	As much as is wanted	Enough for 200 mL/d

Table 5. Oral Replacement Solution for Maintenance of Hydration

Age	Amount of Solution After Each Loose Stool
< 24 mo	100 mL
2-9 y	200 mL
≥10 y	As much as is wanted

Table 6. Antimicrobial Therapy Used in the Treatment of Cholera*

Antibiotic	Single Dose (PO)	Multiple Dose (PO)
Doxycycline^†	7 mg/kg; not to exceed 300 mg/dose^‡	2 mg/kg bid on day 1; then 2 mg/kg qd on days 2 and 3; not to exceed 100 mg/dose
Tetracycline^†	25 mg/kg; not to exceed 1 g/dose^‡	40 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Furazolidone	7 mg/kg; not to exceed 300 mg/dose	5 mg/kg/d divided qid for 3 d; not to exceed 400 mg/d
Trimethoprim and sulfamethoxazole	Not evaluated	< 2 months: Contraindicated ≥2 months: 5-10 mg/kg/d (based on trimethoprim component) divided bid for 3 d; not to exceed 320 mg/d trimethoprim and 1.6 g/d of sulfamethoxazole
Ciprofloxacin^§	30 mg/kg; not to exceed 1 g/dose^‡	30 mg/kg/d divided q12h for 3 d; not to exceed 2 g/d
Ampicillin	Not evaluated	50 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Erythromycin	Not evaluated	40 mg/kg/d erythromycin base divided tid for 3 d; not to exceed 1 g/d
^* Antimicrobial therapy is an adjunct to fluid therapy of cholera and is not an essential component. However, it reduces diarrhea volume and duration by approximately 50%. The choice of antibiotics is determined by the susceptibility patterns of the local strains of V cholerae O1 or O139. ^† Tetracycline and doxycycline can discolor permanent teeth of children younger than 8 years. However, the risk is small when these drugs are used for short courses of therapy, especially if used in a single dose. ^‡ Single-dose therapy of these drugs has not been evaluated systematically in children, and recommendations are extrapolated from experience in adults. ^§ Fluoroquinolones (eg, ciprofloxacin) are not approved in the United States for use in persons younger than 18 years. When given in high doses to juvenile animals, they cause arthropathy. Clinical experience indicates that this risk is very small in children when used for short courses of therapy.

Table 7. WHO Guidelines for Cholera Management

Steps in the treatment of a patient with suspected cholera are as follows:

1. Assess for dehydration (see Table 1)

2. Rehydrate the patient and monitor frequently, then reassess hydration status

3. Maintain hydration; replace ongoing fluid losses until diarrhea stops

4. Administer an oral antibiotic to the patient with severe dehydration

5. Feed the patient

More detailed guidelines for the treatment of cholera are as follows:

Evaluate the degree of dehydration upon arrival

Rehydrate the patient in 2 phases; these include rehydration (for 2-4 h) and maintenance (until diarrhea abates)

Use the intravenous route only (1) during the rehydration phase for severely dehydrated patients for whom an infusion rate of 50-100 mL/kg/h is advised, (2) for moderately dehydrated patients who do not tolerate the oral route, and (3) during the maintenance phase in patients considered high stool purgers (ie, >10 mL/kg/h)

During the maintenance phase, use oral rehydration solution at a rate of 800-1000 mL/h; match ongoing losses with ORS administration

Discharge patients to the treatment center if oral tolerance is greater than or equal to 1000 mL/h, urine volume is greater than or equal to 40 mL/h, and stool volume is less than or equal to 400 mL/h.