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Colistin - Uses, Dosage, Side Effects, Warnings, and Precautions

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Colistin is a Polymyxin antibiotic for treating bacterial infections caused by susceptible gram-negative bacteria.

Medically reviewed by

Dr. Kaushal Bhavsar

Published At March 28, 2023
Reviewed AtMarch 28, 2023

Overview

Colistin is an antibiotic used for treating various types of bacterial infections. The drug treats a serious type of infection that usually does not respond to any other antibiotics. It works by killing the bacteria by destroying the bacterial cell membrane. The drug is also useful for treating stomach and intestinal infections caused by sensitive gram-negative bacteria. It is also used to prevent bowel sterilization before any surgery is performed.

Dosage and Administration

The dosage should be given as follows:

Susceptible Infections:

  • 2.5 to 5 milligrams per kilogram per day divided every 6 to 12 hours intravenously or intramuscularly, and it should not exceed 5 milligrams per kilogram per day.

Renal Impairment:

  • Creatinine Clearance Greater Than 80 Milliliters per Minute: No dosage adjustment required.

  • Creatinine Clearance 50 to 79 Milliliters per Minute: 2.5 to 3.8 milligrams per kilogram per day intravenously or intramuscularly divided every 12 hours.

  • Creatinine Clearance 30 to 49 Milliliters per Minute: 2.5 milligrams per kilogram per day intravenously or intramuscularly once daily or divided every 12 hours.

  • Creatinine Clearance 10 to 29 Milliliters per Minute: 1.5 milligrams per kilogram intravenously or intramuscularly every 36 hours.

What Is the Clinical Use of Colistin?

Colistin, or Polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant gram-negative infections, including pneumonia. These may involve Klebsiella pneumoniae, Pseudomonas aeruginosa, or Acinetobacter. It comes in two forms: Colistimethate sodium, which can be injected into a vein, muscle, or inhaled. Colistin sulfate is applied to the skin or taken by mouth.

Warnings:

  • Do not use Colistin to treat patients with a history of hypersensitivity to Colistin or its components.

  • The use of inhaled Colistin may result in bronchoconstriction. In patients with hyperactive airways, use caution. Consider the administration of a bronchodilator within 15 minutes before the administration of Colistin.

  • Colistin is toxic to the central nervous system (CNS) and can cause temporary neurological disturbances like tingling, dizziness, numbness, vertigo, and slurred speech. Hence patients should avoid activities that require mental alertness.

  • Colistin is also toxic to the kidneys. The therapy should be discontinued if there are signs of impaired kidney function.

  • Respiratory arrest has also been reported with Colistin use, and this risk increases with impaired kidney function. Hence in patients with kidney disease, it should be used with caution. Respiratory arrest risk also increases in patients with myasthenia gravis and concurrent use of anesthetics or any other neuromuscular blocking drugs.

  • Prolonged Colistin use can cause fungal or bacterial superinfection, including colon inflammation and Clostridium difficile-associated diarrhea (CDAD).

Use in Specific Population

  1. Pregnancy- Colistin, given intramuscularly during organogenesis to rabbits at 4.15 and 9.3 milligrams per kilogram, resulted in talipes varus in 2.6 percent and 2.9 percent of fetuses, respectively. The doses are 0.25 and 0.55 times the maximum daily dose from humans based on milligrams per meter square. In addition, increased resorption occurred at 9.3 milligrams per kilogram. Colistin was not teratogenic in rats at 4.15 or 9.3 milligrams per kilogram. The doses are 0.13 and 0.30 times the maximum daily dose from humans dose based on milligrams per meter square. There are no adequate and well-controlled studies on pregnant women. Since Colistin is transferred across the placental barrier in humans, it should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

  2. Lactation- It is unknown whether Colistin sodium is excreted in human breast milk. However, Colistin sulfate is excreted in human breast milk. Therefore, caution should be exercised when Colistin is administered to nursing women.

  3. Geriatric Use- Clinical studies of Colistin did not include sufficient numbers of patients aged 65 years and above to determine whether they respond differently from younger patients. Generally, the dose selection for an older patient should be made with caution, usually starting with a low end of the dosing range, who reflects a greater frequency of decreased renal, hepatic, or cardiac function and other concomitant disease or drug therapy. Colistin is known to be excreted by the kidney, and the risk of toxic reactions to this drug may be higher in patients with impaired renal function. As elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

  4. Pediatric Use- Colistin was administered to the pediatric population in clinical studies. Although adverse reactions appeared similar in adult and pediatric patients, subjective symptoms of toxicity may not be reported by the pediatric population. Hence, close clinical monitoring is recommended in pediatric patients.

Drug Interactions-

  • Certain antibiotics like Aminoglycosides and Polymyxin have also been reported to interfere with nerve transmission at the neuromuscular junction.

  • Curariform muscle relaxants like Tubocurarine and other drugs, such as ether, Succinylcholine, Gallamine, Decamethonium, and Sodium citrate, potentiate the neuromuscular blocking effect and should be used with precaution in patients being treated with Colistin.

  • Sodium cephalothin may enhance the nephrotoxicity of Colistin. The consequent use of sodium cephalothin and Colistin should be avoided.

For Patients:

What Are Gram-negative Bacterial Infections?

In healthcare settings, gram-negative bacteria cause pneumonia, bloodstream infections, wound or surgical site infections, and meningitis. Gram-negative bacteria are resistant to multiple drugs and also resistant to most of the available antibiotics. Gram-negative bacteria have a great ability to cause disease in humans. They can reach almost all body systems, such as the digestive, nervous, urinary, and bloodstream, causing diarrheal gastroenteritis until severe meningitis.

Why Is Colistin Prescribed?

Colistin injection is used for treating certain infections caused by bacteria. Colistin injection comes under a class of medications called antibiotics and works by killing bacteria. Antibiotics like Colistin injection will not work for colds, flu, or any other viral infections. Using antibiotics when they are not required can increase the risk of getting an infection later that resists antibiotic treatment.

How Should Colistin Be Taken?

Colistin injection comes in a powder form to be mixed with a liquid and injected intravenously over three to five minutes. Colistin injections may also be injected into the muscles of the buttocks or thighs. It is usually given every six to twelve hours. Colistin injection may also be a constant intravenous infusion over 22 to 23 hours. The length of the treatment depends on the general health, the infection type, and how well one responds to the medication.

One can take a Colistin injection in a hospital or administer it at home. If a patient takes a Colistin injection at home, a healthcare provider will guide them on how to use it.

One might begin to feel better during the first few days of treatment with the Colistin injection. If the symptoms do not improve or get worse, contact the doctor.

Colistin injection should be used as written in the prescription, even after the patient feels better. If the patient stops using a Colistin injection too soon or skips doses, the infection may not be completely treated, and the bacteria may become resistant to antibiotics.

What Special Precautions Should Be Taken?

  • The doctor and pharmacist should be informed if the patient is allergic to Colistin or other ingredients present in Colistin. Ask the doctor or pharmacist if the person is unsure whether the medication they are allergic to belongs to one of these medications.

  • The doctor should be informed about the prescription or nonprescription medications that the patient is taking. They should also inform about the patient's herbal products or dietary or vitamin supplements.

  • The doctor should be informed if the patient has had kidney disease.

  • The doctor should be informed if the patient is pregnant, or if they are planning to become pregnant or breastfeeding. Contact the doctor immediately if the patient becomes pregnant while using the Ceftaroline injection.

  • Be sure to mention drugs like Amikacin, Amphotericin B, Capreomycin, Gentamicin, Kanamycin, Neomycin, Paromomycin, Polymyxin B, Sodium citrate, Streptomycin, Tobramycin, or Vancomycin.

Side Effects:

  • Upset stomach.

  • Hives.

  • Rash.

  • Numbness and tingling of the arms, legs, hands, feet, or tongue

  • A sensation of insects crawling under the skin

  • Itching.

  • Slurred speech.

  • Muscle weakness.

  • Shallow slowed or temporarily stopped breathing.

  • Decreased urination.

  • Severe diarrhea with or without fever and stomach cramps may occur up to two months after treatment.

What Should Be Done in Case of a Missed Dose?

The missed dose should be taken as soon as the patient remembers it. However, if it is almost time for the next dose, the missed dose can be skipped, and the patient can continue the regular dosing schedule. Do not use a double dose to make up for a missed one.

What Should Be in Case of Overdose?

In case of an overdose, the poison control helpline number should be contacted immediately. If the patient has collapsed, had a seizure, has trouble breathing, or cannot be awakened, immediately contact the emergency services.

Storage and Disposal:

A healthcare professional can guide how to store the medication. Store the medication only as directed. It is important to understand how to store the medication properly. Medications that are not required should be disposed of so that pets, children, and others cannot consume them. However, it should not be flushed down the toilet. Instead, the best way to dispose of the medication is through a medicine take-back program. Talk to the pharmacist or contact the local garbage or recycling department to learn about take-back programs in the community.

Other Information:

  • Keep all appointments with the doctor and the laboratory. The doctor may order certain lab tests to check the body's response to the Colistin injection.

  • Before having any laboratory test, inform the doctor and the laboratory personnel that the patient is taking a Colistin injection.

  • If a patient still experiences the symptoms of infection after finishing the treatment with Colistin, they should contact the doctor.

  • Keeping a written list of the patient's prescription and nonprescription medicines and any products such as vitamins, minerals, or other dietary supplements is important.

  • It is advisable to bring this list each time the patient visits a doctor or is admitted to a hospital.

  • It is also important to carry this list in case of emergencies.

For Doctors:

Indication-

Colistin is indicated for treating acute or chronic infections caused due to sensitive strains of certain gram-negative bacilli.

Pharmacodynamics:

Colistin is a Polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the cell membrane of the bacteria through a detergent-like mechanism. With the development of less toxic agents, like extended-spectrum Penicillins and Cephalosporins, parenteral Polymyxin was largely abandoned, except for treating multidrug-resistant pulmonary infections in patients with cystic fibrosis. Although, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have created options for the revived use of polymyxins.

Mechanism of Action:

Colistin is a surface-active agent that penetrates and disrupts the bacterial cell membrane. Colistin is polycationic and has both lipophilic and hydrophobic moieties, and it interacts with the cytoplasmic membrane of the bacteria, changing its permeability. This effect is bactericidal. It has also been reported that Polymyxins can enter the cell and precipitate cytoplasmic components, mainly ribosomes.

Pharmacokinetics:

  • Absorption- It is poorly absorbed from the gastrointestinal tract.

  • Metabolism- 80 percent of the dose was recovered in the urine unchanged; since there is no biliary excretion, it can be assumed that the remaining drug gets inactivated in the tissues, although the mechanism is unknown.

  • Half-Life- Five hours.

Dosage and Administration-

Intravenous Administration:

  • Direct Intermittent Administration- In this, slowly inject one-half of the daily dose for three to five minutes every twelve hours.

  • Continuous Infusion- In this, slowly inject one-half of the total daily dose over three to five minutes. Now add the remaining half of the total daily dose of Colistin to one of the following: 0.9 percent sodium chloride (NaCl), 5 percent dextrose in 0.9 percent NaCl, 5 percent dextrose in water, 5 percent dextrose in 0.45 percent NaCl, 5 percent dextrose in 0.225 percent NaCl lactated Ringer's solution, and 10 percent invert sugar solution. Administer the other second half of the total daily dose of Colistin by slow intravenous infusion, starting one to two hours after the initial dose, over the next 22 to 23 hours. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment. The fluid and electrolyte management requirements dictate the choice of intravenous solution and the volume to be employed. Any final intravenous infusion solution containing Colistin should be freshly prepared and used for no longer than 24 hours.

Instramuscular Administration:

  • For Intramuscular Injection, administer the deep intramuscular injection into a large muscle mass like the gluteal muscles or lateral part of the thigh. Store the solution for intramuscular injection in a refrigerator at 2 degrees Celsius to 8 degrees Celsius (36 to 46 degrees Fahrenheit) or between 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) and use within seven days.

Storage-

Colistin is supplied in vials as a white to the slightly yellow lyophilized cake. Store unreconstituted products between 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit). Store reconstituted solution in the refrigerator under 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit) or between 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) and use within seven days.

Adverse Effects-

The following adverse reactions have been reported:

  • Gastrointestinal: Gastrointestinal upset.

  • Nervous System: Tingling sensation of extremities and tongue, dizziness, slurred speech, vertigo, paresthesia, and seizures.

  • Integumentary: Generalized itching, rash, and urticaria.

  • Body as a Whole: Fever and anaphylaxis.

  • Laboratory Deviations: Increase in the blood urea nitrogen (BUN), elevated creatinine, and decreased creatinine clearance.

  • Respiratory System: Respiratory distress and apnea.

  • Renal System: Nephrotoxicity and decrease in urine output.

Frequently Asked Questions

1.

What Class of Drug Does Colistin Belong To?

Colistin belongs to the class of drugs called antibiotics. It is bactericidal, or it kills bacteria. They are narrow-spectrum antibiotics. The drug is effective against gram-negative bacteria and other multi-drug resistant variants.

2.

What Type of Drug Is Colistin?

Colistin is a polymyxin antibiotic. It helps to treat serious infections that usually do not respond to any other antibiotics or are drug resistant. The drug kills the bacteria by destroying its cell membrane.

3.

Can Colistin Be Taken in Oral Forms?

Yes, Colistin can be taken in oral forms. Oral forms of Colistin are available in powder, solution, premix, tablets, and paste formulations. It is used in the management of any stomach or intestinal infections which are caused by sensitive gram-negative bacteria.

4.

When Did Colistin Get Banned in India?

On July 19, the Union Ministry of Health and Family Welfare (MoHFW) declared a prohibition on the sale, manufacture, and distribution of Colistin and its formulations in food-producing animals, poultry, aqua farming, and animal feed supplements. It was brought about in order to regulate antibiotic misuse and antimicrobial resistance.

5.

How Does Colistin Work?

Colistin kills the bacteria by destroying its cell membrane. It removes the divalent cations of calcium and magnesium competitively, changing the lipopolysaccharide structure three-dimensionally. The drug then inserts its acyl fat chain, which is hydrophobic. This causes an expansion of the external outer membrane monolayer.

6.

Is Colistin Considered a Successful Drug?

The drug is found to be very successful, especially in gram-negative bacteria and multi-drug resistant conditions. The success rate for Colistin is about 89 percent. It has been found to be very successful in treating gram-negative bacteria and multi-drug-resistant conditions. It is considered a last-resort antibiotic.

7.

How Long Can Colistin Be Given?

Colistin is given for ten to fourteen days. However, the doses may vary. It will be adjusted in patients with renal impairments and high serum creatinine levels. Its dosage will vary in critically ill patients. This is because there can be fluctuations in their renal clearance.

8.

Is Colistin an Antibiotic?

Colistin is found to be very successful, especially in gram-negative bacteria and multi-drug resistant conditions. It has been found useful in Pseudomonas, Escherichia, and Klebsiella infections. It is often used as a last-resort antibiotic.

9.

Which Organ Is Affected by Colistin?

The kidneys are the most commonly affected organ due to Colistin. This is because the drug is excreted by the kidneys. Increased levels of the drug in the blood can also cause kidney damage.

10.

What Are the Side-Effects of Colistin?

The common side effects of the drug can include dizziness, numbness, tingling, or burning sensation in the extremities and the tongue. It can cause stomach upsets in some people. Skin irritations and blood in the urine are seen in some people. Some people find difficulty breathing after taking the drug.
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Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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