From the Guidelines
Colistin should be used as a last-resort antibiotic for treating severe infections caused by multidrug-resistant Gram-negative bacteria, with a recommended dosing regimen of 9 million IU of colistin methanesulfonate (CMS) initially, followed by 4.5 million IU CMS twice a day as the maintenance dose, as supported by the most recent and highest quality study 1.
Key Considerations
- Colistin is typically administered as colistimethate sodium, with dosing adjustments needed for patients with kidney impairment.
- A loading dose is often recommended to achieve optimal plasma levels quickly.
- Treatment duration ranges from 7-14 days, depending on infection severity and clinical response.
- Colistin works by disrupting bacterial cell membranes, leading to increased permeability and cell death.
- Important considerations include monitoring renal function closely, as nephrotoxicity occurs in 30-50% of patients, and watching for neurotoxicity.
- Due to its significant toxicity profile, colistin should be reserved for infections with limited or no alternative treatment options, preferably with infectious disease consultation and as part of combination therapy to prevent resistance development.
Combination Therapy
- The use of combination therapy with colistin is still a topic of debate, with some studies suggesting a potential benefit in certain cases, while others show no advantage over monotherapy 1.
- The choice of combination therapy should be based on the specific infection, local antimicrobial susceptibility, and patient factors, such as renal and hepatic function, and comorbidities.
Pediatric Patients
- The optimal dosage of colistin in pediatric patients remains uncertain, with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) recommending a loading dose of 0.15 MU/kg of colistin, followed by a maintenance dose of 0.075 MU/kg every 12 h 1.
- However, recent studies suggest that this dosage may be inadequate in certain cases, such as when the MIC of the infecting pathogen is ≥ 1 mg/L or when the patient has augmented renal clearance or good renal function for their age.
From the FDA Drug Label
INDICATIONS AND USAGE Colistimethate for Injection, USP is indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. Colistimethate for Injection, USP has proven clinically effective in treatment of infections due to the following gram-negative organisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa
Colistin is indicated for the treatment of infections caused by sensitive strains of certain gram-negative bacilli, including:
- Pseudomonas aeruginosa
- Enterobacter aerogenes
- Escherichia coli
- Klebsiella pneumoniae 2
From the Research
Colistin Overview
- Colistin is an antibiotic used to treat infections caused by multi-drug-resistant gram-negative bacteria 3, 4, 5, 6
- It has been shown to be effective in treating infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa 3, 5
Efficacy of Colistin
- Studies have demonstrated that colistin is effective in treating multi-drug-resistant gram-negative infections, with clinical cure rates ranging from 42.7% to 92% 3, 4, 5
- The efficacy of colistin is influenced by the minimum inhibitory concentration (MIC) of the bacteria, with lower MIC values associated with higher cure rates 4
Safety and Toxicity of Colistin
- Colistin has been associated with nephrotoxicity and neurotoxicity, with reported incidence rates of 20% or lower for nephrotoxicity 7, 6
- Curcumin has been shown to alleviate colistin-induced nephrotoxicity and neurotoxicity in rats by attenuating oxidative stress, inflammation, and apoptosis 7