What is the role of Colistin (Polymyxin E) in treating multidrug-resistant (MDR) Pseudomonas aeruginosa pneumonia?

From the Guidelines

Colistin is a recommended treatment option for multidrug-resistant (MDR) Pseudomonas pneumonia, particularly when other antibiotics are ineffective, with a suggested dosing regimen of 9 MU of colistin methanesulfonate (CMS) initially followed by 4.5 MU CMS twice a day as the maintenance dose, as supported by the most recent guidelines 1.

Key Considerations

• The optimal dose of colistin is crucial for effective treatment, and the recommended regimen is based on pharmacodynamic studies in critically ill patients 1.
• Colistin may be considered in combination with one or more additional agents to which the pathogen displays in vitro susceptibility, especially when a susceptible second agent is not available 1.
• The use of colistin should be guided by susceptibility testing and expert opinion, given its potential toxicity profile and the need for careful monitoring of renal function and neurological status.

Treatment Approach

• For MDR Pseudomonas pneumonia, colistin can be used as a last-resort option when other antibiotics, such as carbapenems, aminoglycosides, and fluoroquinolones, are ineffective or not tolerated 1.
• The treatment duration typically ranges from 7-14 days, depending on the clinical response and the severity of the infection, with adjustments made based on individual patient factors and infection site 1.
• Close monitoring for nephrotoxicity and neurotoxicity is essential, with regular assessment of renal function, serum creatinine, and neurological status, to minimize the risk of adverse effects 1.

From the FDA Drug Label

Colistimethate for Injection, USP is indicated for the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli. It is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa. 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 Colistimethate sodium is a surface active agent which penetrates into and disrupts the bacterial cell membrane It has been shown to have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Aerobic gram-negative microorganisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa

Colistin can be used for the treatment of Pseudomonas pneumonia, including MDR (Multi-Drug Resistant) strains, as it has been shown to have bactericidal activity against Pseudomonas aeruginosa 2 2.

• The drug label indicates that Colistimethate for Injection, USP is effective against gram-negative organisms, including Pseudomonas aeruginosa.
• It is essential to note that susceptibility testing should be performed to confirm the effectiveness of Colistin against the specific strain of Pseudomonas causing the infection.

From the Research

Colistin for Pseudomonas Pneumonia MDR

• Colistin is a safe option for the treatment of multidrug-resistant Pseudomonas aeruginosa (MDRP) infections, with acceptable clinical outcomes 3.
• The clinical outcome was favorable in 65% of patients with pneumonia treated with colistin, and eradication was achieved in 34.8% of patients with available bacteriologic data 3.
• Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa 3.
• Nebulized colistin may be reasonably efficacious and safe for treatment of MDR pneumonia, with overall clinical and microbiological response rates of 57.1% and 85.7%, respectively 4.
• Colistin retained significant in vitro activity against MDR P. aeruginosa, had an acceptable safety profile, and should be considered as a treatment option in critically ill patients with infection caused by MDR gram-negative bacilli 5.

Combination Therapy

• Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested, but in vitro synergy has been reported for certain combinations 6.
• The combination of ceftazidime-avibactam with colistin, or tobramycin, was effective against colistin-nonsusceptible strains of P. aeruginosa, and this combination therapy could be an alternative antibiotic therapy for resistant P. aeruginosa strains 7.
• Synergistic interactions were achieved with ceftazidime/avibactam + colistin, ceftazidime/avibactam + tobramycin, and ceftazidime/avibactam + levofloxacin combinations, with no antagonism observed against studied P. aeruginosa strains 7.

Safety and Efficacy

• Nephrotoxicity occurred in 8.3% of patients treated with colistin, with associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use 3.
• Deterioration of renal function occurred in 30% of patients treated with intravenous colistin, all of whom had a history of renal insufficiency 5.
• Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%) 3.