Colistimethate Sodium - Indication, Dosage, Side Effects, and Pharmacological Aspects

Overview:

An antibiotic called Colistimethate sodium is used to treat bacterial infections, especially those brought on by Gram-negative bacteria that are resistant to several drugs, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Its risk for kidney damage and neurotoxicity makes it a treatment of last resort. Colistimethate sodium causes cell death in bacteria by rupturing their cell membrane. The United States Food and Drug Administration (USFDA) approved Colistimethate sodium for managing bacterial infections in 1970.

Drug Group:

Colistimethate sodium is a member of the class of medications called polymyxins. Antibiotics called polymyxins are mostly used to treat bacterial infections, particularly those brought on by bacteria that are resistant to drugs, like Acinetobacter baumannii and Pseudomonas aeruginosa. Colistimethate sodium causes cell death in bacteria by rupturing their cell membrane. When all other antibiotics have failed owing to bacterial resistance or when the infection is severe, it is frequently administered as a last option.

Dosages:

Colistimethate sodium is administered parenterally in two to four different doses per day for patients of all ages. Patients with normal kidney function should take 2.5 to 5 mg/kg (milligrams per kilogram) daily; the precise dosage within this range will depend on the severity of the illness. If the patient is obese, determine the dosage by taking into account their optimal body weight.

For Patients:

What Are Bacterial Infections?

When pathogenic bacteria enter the body and proliferate, they can cause bacterial infections and illness. Several physiological systems, including the digestive system, skin, urinary tract, and respiratory system, can be impacted by these illnesses. The type of bacteria present and the affected part of the body determine the symptoms, which might include fever, inflammation, discomfort, and general malaise. Bacterial infections are usually treated with antibiotics.

What Is the Management of Bacterial Infections?

• Antibiotics: Antibiotics can kill or stop the growth of bacteria to treat bacterial infections (bacteriostatic). The type of bacteria causing the infection and its sensitivity to medications determine which drug is best.

• Supportive Care: Includes actions like keeping the patient hydrated, and managing a fever, relieving pain, and making sure the patient is getting enough nutrients to support the body's immune response.

• Surgical Intervention: Surgical drainage or debridement may be required in certain situations, such as abscesses (inflammation and pus) or infected tissues that cannot be adequately treated with antibiotics alone.

• Prevention: Strategies for prevention include wound care, immunization (where available), basic hygiene, and infection control in medical settings.

• Antibiotic Stewardship: Antibiotics should only be administered sparingly and when essential to reduce adverse effects and prevent antibiotic resistance. This includes making the right diagnosis, choosing the best antibiotic, and making sure the dosage and course of treatment are suitable.

• Monitoring and Follow-up: To ensure full resolution of the infection and to address any consequences, patients should be continuously watched for any improvement or worsening of symptoms. Follow-up sessions may also be required.

How Does Colistimethate Sodium Work?

Gram-negative bacteria, in particular, have their outer membranes ruptured by an antibiotic called Colistimethate sodium. It attaches itself to lipopolysaccharides in the outer membrane, allowing intracellular fluids to seep out and eventually kill bacterial cells. Treatments for infections brought on by Gram-negative bacteria resistant to multiple drugs sometimes involve the use of Colistimethate sodium.

How Should the Drug Be Taken?

Colistimethate sodium parenteral is supplied in vials containing 150 mg of colistin base activity. Each vial of Colistimethate sodium contains To prepare for intravenous or intramuscular use; the 150 mg vial should be mixed with 2 mL (milliliter) of sterile water for injection. The resulting solution contains Colistimethate sodium at a concentration of 75 mg/mL (milligram per milliliter) of colistin base activity. When reconstituting, gently swirl to prevent frothing. Before administration, visually inspect the solution for any particulate matter or discoloration. If either is present, refrain from using the product.

What Are the Benefits of Using Colistimethate Sodium-Bacterial Infections?

• Effective Against Resistant Bacteria: When other antibiotics are ineffective because of bacterial resistance, Colistimethate sodium is frequently utilized. It works against strains of Gram-negative bacteria, including those that are resistant to Carbapenems and other antibiotics.

• Management of Severe Infections: It is used to treat severe infections like bloodstream infections, pneumonia, urinary tract infections, and infections of the abdomen brought on by susceptible bacteria.

• Broad Spectrum: Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacter species are only a few of the Gram-negative bacteria that Colistimethate sodium is effective against.

• Intravenous Administration: When treating severe infections, it can be given intravenously, which enables quick delivery and absorption.

• Restricted Options: When it comes to treating some infections, particularly those brought on by bacteria with a high level of resistance, there are occasionally few options. In such cases, Colistimethate sodium offers an alternative.

• Therapeutic Experience: Colistimethate sodium has been in use for a long time, and its safety profile and therapeutic effectiveness in certain patient populations are well-established.

What Must the Patient Inform the Doctor Before Taking Colistimethate Sodium?

Before taking Colistimethate sodium, patients should inform their doctor about any existing medical illnesses, such as myasthenia gravis (autoimmune disease that lasts a long time and causes skeletal muscular weakening by blocking the nerves' ability to communicate with muscles), Parkinson's disease (a progressive illness affecting the neurological system and the body's nerve-controlled regions), renal issues, neurological abnormalities, breathing issues, sensitivities to Polymyxin medications, and muscle weakness disorders. It is important to let the doctor know about all the drugs, vitamins, and herbal products that the patient is taking because some of them can interact negatively with Colistimethate Sodium. Additionally, to guarantee the safe use of Colistimethate Sodium, it is crucial to inform the doctor about any pregnancy, plans to become pregnant, or breastfeeding.

What Are the Side Effects of Using Colistimethate Sodium?

• Nausea.

• Vomiting.

• Diarrhea.

• Headache.

• Dizziness.

• Fever.

• Rash.

• Kidney problems.

• Neuromuscular blockade (in high doses).

For Doctors:

Description:

Colistimethate for injection is a sterile parenteral antibiotic medication that, once reconstituted, can be administered intramuscularly or intravenously. Each vial holds Colistimethate sodium or pentasodium colistin methanesulfonate, equivalent to 150 mg of colistin base activity. Colistimethate sodium is an antibiotic polypeptide with an estimated molecular weight of 1750 and an empirical formula of C58H105N16Na5O28S5.

Therapeutic Uses of Colistimethate Sodium:

• Pneumonia: Colistimethate sodium is a common treatment for pneumonia caused by multidrug-resistant bacteria, particularly in individuals who are critically ill or immunocompromised.

• Ventilator-Associated Pneumonia (VAP): Treatment for ventilator-associated pneumonia (VAP), which is brought on by Gram-negative bacteria, is beneficial for patients requiring mechanical ventilation.

• Exacerbations of Cystic Fibrosis: Pseudomonas aeruginosa, a prevalent infection in these patients, is the cause of exacerbations of cystic fibrosis. Colistimethate sodium is widely used to treat this condition.

• Urinary Tract Infections (UTIs): Multidrug-resistant Gram-negative bacteria can occasionally be treated with Colistimethate sodium.

• Skin and Soft Tissue Infections: Colistimethate sodium is a therapy for serious infections of the skin and soft tissues caused by susceptible organisms.

• Intra-abdominal Infections: Treatment for severe intra-abdominal infections resulting from bacteria resistant to many drugs may include the use of Colistimethate sodium.

• Septicemia: Colistimethate sodium may be used in the therapy regimen for septicemia brought on by Gram-negative bacteria resistant to several drugs.

Dosage Forms and Strengths:

For both adults and pediatric patients, Colistimethate sodium parenteral should be administered intravenously or intramuscularly at a dosage ranging from 2.5 to 5 mg/kg per day of colistin base, divided into two to four doses daily, considering the severity of the infection and normal renal function. In obese individuals, dosing should be calculated based on their ideal body weight. Individuals with impaired kidney function should be administered less frequently and at a reduced daily dose.

Dosage and Administration:

• It is critical to remember that each vial of Colistimethate sodium parenteral has 150 mg of colistin base activity.

• Reconstitution with 2 mL sterile water for injection, is required for the 150 mg vial to be administered intravenously or intramuscularly. Colistimethate sodium is available in the reconstituted solution at a concentration equal to 75 mg/mL colistin base activity.

• To prevent foaming during reconstitution, gently swirl.

• Parenteral medication preparations should be visually scrutinized for discoloration and particle debris before being administered. The product should not be used if these conditions are found.

Indications:

Colistimethate sodium is prescribed for treating acute or chronic infections caused by susceptible strains of certain Gram-negative bacilli, especially Pseudomonas aeruginosa. It is not suitable for infections caused by Proteus or Neisseria. This antibiotic has demonstrated clinical effectiveness against Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterobacter aerogenes. It can be used to start treatment for severe illnesses thought to be caused by Gram-negative bacteria in organisms and for treating infections caused by susceptible Gram-negative pathogenic bacilli.

To mitigate the emergence of drug-resistant bacteria and uphold the efficacy of other antibacterial medications, Colistimethate sodium ought to be reserved for treating or preventing infections that are confirmed or highly suspected to be caused by susceptible bacteria. When there is access to culture and susceptibility data, it should guide the choice or adjustment of antibacterial treatment. In the absence of such information, local epidemiological trends and susceptibility profiles may inform the empirical selection of therapy.

Contraindications:

Patients with a history of sensitivity to Colistimethate sodium or any of its components should not use the medication due to contraindications.

Warnings and Precautions:

The maximum recommended daily dose for patients with normal kidney function based on colistin-based activity is 5 mg/kg/day (milligrams per kilogram per day). Patients should be cautioned about potential transient neurological side effects such as tingling sensations, numbness, dizziness, and speech difficulties, which may impair their ability to operate vehicles or machinery. Close observation is recommended, and changing the dosage might help reduce these symptoms. Nephrotoxicity is a possible adverse effect, typically reversible upon discontinuation of the antibiotic. Overdosing may lead to renal insufficiency, muscle weakness, and breathing difficulties. Intramuscular administration of Colistimethate sodium can even cause respiratory arrest, especially in patients with impaired kidney function. Proper dosing according to renal function guidelines is crucial. The use of Colistimethate sodium, like other antibiotics, can also lead to Clostridium difficile-associated diarrhea (CDAD), ranging from mild to severe and even fatal colitis. CDAD should be considered in patients presenting with diarrhea post-antibiotic therapy, and appropriate management, including fluid and electrolyte balance, protein supplementation, and targeted antibiotic treatment, should be initiated promptly if CDAD is suspected or confirmed.

What Are the Pharmacological Aspects of Colistimethate Sodium?

Mechanism of Action:

Colistimethate functions as a surface-active agent, penetrating and disrupting the bacterial cell membrane. It possesses both hydrophobic and lipophilic properties, enabling interaction with the bacterial cytoplasmic membrane, altering its permeability, and exerting a bactericidal effect. Additionally, polymyxins like Colistimethate have been shown to enter the cell and precipitate cytoplasmic components, particularly ribosomes.

Pharmacodynamics:

Colistimethate, a type of polymyxin antibiotic, was initially believed to be less harmful than Polymyxin B. However, when administered at equivalent doses, their toxicities can be comparable. Polymyxins, which are cationic polypeptides, disrupt bacterial cell membranes through a detergent-like process. Due to the emergence of less harmful alternatives like extended-spectrum Penicillins and Cephalosporins, the use of parenteral polymyxins has largely been discontinued, except for treating multidrug-resistant pulmonary infections in cystic fibrosis patients. In recent times, the resurgence of multidrug-resistant Gram-negative bacteria like Pseudomonas aeruginosa and Acinetobacter baumannii, coupled with the absence of novel antimicrobial treatments, has prompted a renewed interest in employing polymyxins.

Pharmacokinetics:

It can be inferred that 80 percent of the dose remains unchanged in the urine, with no biliary excretion. The remainder of the drug is presumed to be deactivated in the tissues, though the mechanism remains unidentified. In adults and pediatric patients, including premature infants, effects typically manifest within two to three hours post intravenous or intramuscular administration.

Drug Interactions:

It has been documented that the neuromuscular junction can cause interference with nerve transmission with certain antibiotics like aminoglycosides and polymyxin. Therefore, caution is advised when administering them concurrently with Colistimethate sodium.

Muscle relaxants such as Tubocurarine and other drugs like Ether, Succinylcholine, Gallamine, Decamethonium, and Sodium citrate can potentiate the neuromuscular blocking effect and should be used cautiously in patients undergoing treatment with Colistimethate sodium. The use of Sodium cephalothin alongside Colistimethate sodium may increase the risk of nephrotoxicity and should be avoided.

Carcinogenicity, mutagenicity, and impairment of fertility studies have not been conducted extensively with Colistimethate sodium. In rats, doses up to 9.3 mg/kg/day (0.30 times the maximum amount of mg/m2 that a human can consume in a day) did not result in adverse effects on fertility or reproduction.

Use In Specific Populations:

• Pregnancy: During organogenesis, intramuscular administration of Colistimethate sodium to rabbits at doses of 4.15 and 9.3 mg/kg (milligrams per kilogram). Additionally, increased resorption occurred at the higher dose of 9.3 mg/kg. However, Colistimethate sodium did not exhibit teratogenic effects in rats at doses of 4.15 or 9.3 mg/kg, which correspond to 0.13 and 0.30 times the maximum daily human dose based on mg/m2(milligrams per square meter). There is insufficient data from adequate and well-controlled studies in pregnant women. Given that Colistimethate sodium crosses the placental barrier in humans, Only if the possible advantages of using it during pregnancy outweigh the possible hazards to the developing fetus should it be considered for use.

• Lactation: As for nursing women, it is unclear if human breast milk contains Colistimethate sodium excretion; colistin sulfate has been found in human breast milk. Thus, caution is advised when administering Colistimethate sodium to nursing women.

• Geriatrics: In geriatric patients, there were not enough subjects aged 65 and over in clinical studies to determine potential differences in response compared to younger subjects. However, elderly patients may have decreased hepatic, renal, or cardiac function, along with more frequent concomitant diseases or drug therapies. Elderly people should usually begin on the lower end of the dose range with caution. Because the kidneys eliminate Colistimethate sodium in large amounts, people with compromised renal function may be more susceptible to hazardous responses. Therefore, renal function monitoring is recommended, especially in elderly patients.

• Pediatrics: In pediatric use, clinical studies have included neonates, infants, children, and adolescents. While adverse reactions appear similar between adults and pediatric populations, pediatric patients may not report subjective symptoms of toxicity. Thus, close clinical monitoring of pediatric patients is advised.

Clinical Studies:

Twenty critically ill adult patients with infections caused by Colistin-susceptible multidrug-resistant (MDR) organisms and normal renal function received intravenous Colistimethate sodium. They were administered a loading dose of nine million units (equivalent to 270 mg colistin base activity) followed by a maintenance dose of three million units thrice daily, initiated 24 hours after the loading dose. Clinical cure (CC) was evaluated at the end of therapy. Patient characteristics and plasma concentrations of colistin were assessed at specific time intervals following the loading dose and during maintenance therapy.

Among the twenty evaluated patients, 60 percent had pneumonia, with predominant pathogens being Klebsiella pneumoniae and Acinetobacter spp. The clinical cure rate was 50 percent. Nephrotoxicity was observed in 5 percent of patients by day 7 of therapy. However, there was no significant correlation between bacteriological cure and pharmacokinetic/pharmacodynamic parameters.