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Systemic Pharmacokinetics and Safety of High Doses of Nebulized Colistimethate Sodium in Critically Ill Patients With Hospital-Acquired and Ventilator-Associated Pneumonia

Systemic Pharmacokinetics and Safety of High Doses of Nebulized Colistimethate Sodium in Critically Ill Patients With Hospital-Acquired and Ventilator-Associated Pneumonia

Adela Benítez-Cano, Marta de Antonio-Cuscó, Sonia Luque, Luisa Sorlí, Jesús Carazo, Isabel Ramos, Silvia Bermejo, Nuria Campillo, Juan P Horcajada, Enric Samsó, Santiago Grau

J Antimicrob Chemother. 2019 Nov 1;74(11):3268-3273.

PMID: 31495877

Abstract:

Objectives:
To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).
Patients and methods:
Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.
Results:
Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12-0.33), 0.20 (0.11-0.24), 0.17 (0.12-0.23) and 0.17 (0.11-0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11-0.35), 0.24 (0.12-0.44), 0.24 (0.10-0.49) and 0.23 (0.11-0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed.
Conclusions:
In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP8068288-A	Colistimethate Sodium		8068-28-8	Price

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