Colistin inhaled for the treatment of ventilator-associated pneumonia
The review provides modern approaches to colistin dosage regimens for inhalation administration in the treatment of bacterial infections caused by multidrug-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonia.
Polymyxins, including colistin, are currently used as the last line of treatment for bacterial infections caused by multidrug-resistant strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumonia [1,2]. The MPC of polymyxin for most multidrug-resistant Gram-negative pathogens is 1 to 2 μg / ml, however, resistance to pathogens is already forming for polymyxin, and therefore the appointment of a combination therapy is recommended [3 ].
Colistimetate sodium is a prodrug which, in the human body, including lung tissue, is hydrolyzed to colistin [2,4]. The end-use products are either colistimethate sodium or colistin base. Note that the conversion of equivalent doses of medication varies by study. Thus, 1 mg of sodium colistimetate is equivalent to approximately 125,000 IU. Colistimetate sodium is equivalent to colistin base in a ratio of approximately 2.67: 1 mg [5]. In the United States, the intravenous form of colistin is administered by nebulizer because the U.S. Food and Drug Administration (FDA) has not approved a form of colistin for inhalation.
Several pharmacokinetic studies of colistin have been performed, indicating that penetration of the intravenous form of colistitis into lung tissue is limited. Inhalation of a form of aerosolized colistin using a nebulizer may increase the concentration of the drug in the pulmonary tract with minimal systemic absorption, however, the concentration at the site of infection may be reduced due to pneumonia [2]. Studies in children with cystic fibrosis have shown that doses of 30 mg and 75 mg every 12 hours are safe and effective in inhibiting P. aeruginosa [6]. Doses of 100 mg and 150 mg of colistin base every 12 hours have already been used to treat respiratory pneumonia (VAP) [7].
The pharmacokinetics of inhaled colistin have been determined in patients with ventilator-associated tracheobronchitis caused by P. aeruginosa, A. baumannii or K. pneumonia , sensitive only to polymyxin. Patients received 1 million IU sodium colistimetate (equivalent to 30 mg colistin base) by nebulizer every 8 hours for 7 days. Healing was achieved in 16 out of 20 patients, however, the concentration of colistin in the fluid lining the alveoli (IVA) decreased below BMD after 8 hours in 8 out of 20 patients [8].
Also at around the same time, the results of a study on the clinical efficacy of higher doses of colistin administered via a nebulizer in the treatment of PAV caused by P. were published. aeruginosa or A. baumannii. Patients from whom β-lactam-sensitive pathogens were isolated were included in the control group and received intravenous antibiotic therapy for 14 days. Patients with PAV caused by multidrug-resistant pathogens received colistimetate sodium at a dose of 5 million units (equivalent to 150 mg colistin base) inhaled by nebulizer every 8 hours for 7 to 19 days. In the nebulizer treatment group, 67% of patients experienced clinical recovery at the end of treatment, compared to 66% of patients in the control group. An increase in serum creatinine of more than 1.5 times compared to the initial level occurred in 8% of patients in the intravenous β-lactam group and in 12% of patients receiving inhaled colistin [9].
In conclusion, it should be noted that the optimal dosing regimen of colistin nebulizer in patients infected with multidrug-resistant pathogens has not yet been determined due to the lack of randomized controlled trials. However, the successful use of higher doses of the drug have been demonstrated without a significant increase in the risk of nephrotoxicity. A dose of 150 mg colistin every 8 hours is considered to be effective and safe for critically ill patients with respiratory pneumonia (VAP) caused by multidrug-resistant pathogens (usually P. aeruginosa and A. baumannii ).