What are the uses of Colistin (Polymyxin E)?

From the Guidelines

Colistin should be used as a last-resort antibiotic for treating serious infections caused by multidrug-resistant Gram-negative bacteria, particularly when other antibiotics have failed, due to its potential for nephrotoxicity and neurotoxicity. The use of colistin is primarily recommended for infections caused by carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii 1. For systemic infections, colistimethate sodium is typically administered intravenously at a dose of 9 MU of colistin methanesulfonate (CMS) initially followed by 4.5 MU CMS twice a day as the maintenance dose, as supported by pharmacodynamic studies in critically ill patients and international consensus guidelines 1. The optimal dosage of colistin in pediatric patients remains uncertain, but a recent population pharmacokinetic study suggests that the recommended dose by the U.S. FDA and EMA may be inadequate in cases where 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 1. There is controversy on whether colistin-based combination therapy is superior to monotherapy for treatment of infections due to CR-GNB, but the panel suggests that colistin may be considered in combination with one or more additional agents to which the pathogen displays in vitro susceptibility 1. A randomized controlled trial concluded that the combination of colistin and meropenem was not superior to colistin monotherapy, with a 14-day mortality for Pseudomonas or other CR-GNBs of 25% vs 31%, p = 1.0 1. However, another study demonstrated that polymyxin B combination therapy for treatment of DTR-PA had a lower mortality rate compared to monotherapy even when the combined antimicrobial agent lacked in vitro activity 1. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines suggest that combination therapy for CRAB has been suggested based on in vitro studies showing synergistic interactions between polymyxins and meropenem, imipenem, doripenem, but the effects of a specific combination regimen cannot be assessed from observational studies 1. The RCT, including a considerable sample of patients with severe, high-risk, infections caused by CRAB, contribute to high-certainty evidence against carbapenem-polymyxin combination therapies for CRAB infections 1. Other combinations, such as colistin-vancomycin and colistin-fosfomycin, have been tested in single studies, but the bulk of the data seem to show no advantage to combination therapy (very-low-certainty evidence) 1. Double covering therapy might be considered, provided that the CRAB is susceptible to more than one antibiotic, but very-low-certainty evidence exists for double covering combination therapy for CRAB 1. In summary, colistin should be used with caution and as a last-resort antibiotic, and the decision to use combination therapy should be based on the specific clinical scenario and the susceptibility of the infecting pathogen.

Some key points to consider when using colistin include:

• The potential for nephrotoxicity and neurotoxicity, which requires close monitoring of kidney function throughout therapy
• The optimal dosage of colistin in pediatric patients remains uncertain
• The use of colistin in combination with other antibiotics may be considered, but the effects of a specific combination regimen cannot be assessed from observational studies
• The decision to use combination therapy should be based on the specific clinical scenario and the susceptibility of the infecting pathogen.

Overall, the use of colistin should be guided by the principles of antimicrobial stewardship, and the decision to use this antibiotic should be made on a case-by-case basis, taking into account the potential benefits and risks of treatment 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION The dose of Colistimethate for Injection, USP should be 2. 5 to 5 mg/kg per day of colistin base in 2 to 4 divided doses for patients with normal renal function, depending on the severity of the infection. The uses of colistin are for treating infections, with the dosage depending on the severity of the infection and renal function.

• The drug can be administered through intravenous or intramuscular routes.
• The dosage for adults and pediatric patients is 2.5 to 5 mg/kg per day of colistin base, divided into 2 to 4 doses. 2

From the Research

Uses of Colistin

• Colistin is a polypeptide antibiotic used to treat multidrug-resistant gram-negative bacterial infections 3, 4, 5.
• It can be administered through various routes, including orally, topically, by inhalational route, intramuscularly, intrathecally, and intravenously 3.
• Colistin is effective against gram-negative organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii 3, 4, 5.
• It is used to treat ventilator-associated pneumonia (VAP) and bacteremia caused by multidrug-resistant bacteria 3.
• Inhaled colistin is used to treat pneumonia/VAP due to multidrug-resistant gram-negative organisms and is also used prophylactically in patients with cystic fibrosis 3.
• Colistin can be used as salvage therapy in the treatment of life-threatening infections due to multidrug-resistant Pseudomonas aeruginosa blood-stream infections (BSI) 4.
• Colistin-based combination therapy has been shown to have a microbiological benefit and no higher risk of nephrotoxicity compared to monotherapy in the treatment of Acinetobacter baumannii infection 6.

Clinical Applications

• Colistin has been used to treat various types of infections, including pneumonia, bacteremia, and urinary tract infections 5.
• It has been shown to have acceptable effectiveness and considerably less toxicity than previously reported 5.
• Colistin resistance in Escherichia coli has been found to confer protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic 7.
• The use of colistin in combination with other antibiotics has been explored, with some studies showing in vitro synergy and potential benefits in preventing or limiting the risk of induced resistance in multidrug-resistant strains 4.