Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients

Athanassa, Zoe; Markantonis, Sophia L.; Fousteri, Marina-Zoe F.; Myrianthefs, Pavlos; Boutzouka, Eleni; Tsakris, Athanassios; Baltopoulos, George

doi:10.1007/s00134-012-2628-7

Cited by 116 publications

(108 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, recent studies revealed that nebulized colistin, as adjunctive therapy simultaneously administered with intravenous colistin, was significantly associated with improved rate of clinical cure and reduced duration of mechanical ventilation without noticeable adverse events in patients with VAP due to CRAB (8,9). The use of nebulized colistin in critically ill patients may be supported by previous reports suggesting that it effectively achieved high concentrations in the lungs, with minimal systemic exposure (10,11). However, there is a paucity of data to evaluate the efficacy of nebulized colistin as monotherapy for pneumonia of multidrugresistant gram-negative bacteria (12)(13)(14).…”

Section: Introductionmentioning

confidence: 73%

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Kim

Lee

et al. 2017

J. Thorac. Dis.

View full text Add to dashboard Cite

Background: Although there have been studies regarding the role of nebulized colistin as adjunctive therapy of ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB), a paucity of information on the efficacy of nebulized colistin as monotherapy is available. Methods:We retrospectively reviewed 219 patients with VAP caused by CRAB treated with either intravenous (n=93) or nebulized colistin (n=126), from March 2010 to November 2015. Factors related to clinical failure was assessed using propensity-score-matched analysis.Results: Of 219 patients, 39 patients from each group (n=78) were matched after covariate adjustment using propensity score. There were no significant differences in baseline characteristics as well as the rates of clinical failure between the propensity-score-matched groups [Odds ratio (OR), 0.48; 95% confidence interval (CI), 0.19-1.19; P=0.11], while a significantly lower rate of acute kidney injury (AKI) during colistin therapy (18% vs. 49%, P=0.004) was observed in nebulized colistin group. In addition, multivariable analysis revealed that nebulized colistin did not significantly alter the rate of clinical failure [adjusted odds ratio (aOR), 0.36; 95% CI, 0.12-1.09; P=0.070]. Instead, medical intensive care unit (ICU) admission (aOR, 7.14; 95% CI, 1.60-32.00; P=0.010), and septic shock (aOR, 3.93; 95% CI,; P=0.018) were independent risk factors for clinical failure.Conclusions: Our findings suggest that nebulized colistin-based therapy, even without concurrent administration of intravenous colistin, may be an effective and safe treatment option for VAP caused by CRAB.

show abstract

Section: Introductionmentioning

confidence: 73%

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Kim

Lee

et al. 2017

J. Thorac. Dis.

View full text Add to dashboard Cite

show abstract

“…Almost all modern PK studies on polymyxins are for colistin that is administered parenterally as its inactive prodrug CMS (77,82). In contrast, polymyxin B is available for direct parenteral administration, that is, as the antibacterial entity (83).…”

Section: Dosing Strategiesmentioning

confidence: 99%

Intravenous polymyxins: Revival with puzzle

Fei

et al. 2017

BST

View full text Add to dashboard Cite

“…PK studies reporting antibiotic concentrations in the lung compartments using nebulization are becoming increasingly reported. 45,46 Athanassa et al 45 evaluated 20 critically ill patients with ventilator-associated tracheobronchitis treated with nebulized colistin. After the first nebulization, the median ELF concentrations were 6.7 and 2.0 mg/L at 1 and 8 hours, respectively.…”

Section: Alternative Dosing Strategies: Nebulizationmentioning

confidence: 99%

“…concentrations can be achieved in the ELF with nebulization, 45 which suggests improved target site concentrations with nebulization. Luyt et al 46 similarly showed favorable amikacin concentrations in ELF in a study of 28 mechanically ventilated patients with gram-negative VAP.…”

Section: Alternative Dosing Strategies: Nebulizationmentioning

confidence: 99%

“…However, issues relating to appropriate dose selection in the context of pathogen susceptibility need to be considered. 45 Further, TDM to prevent any local or systemic unwanted effects 46 as well as use of a specially formulated antibiotic solutions for inhalation and delivery devices should be considered. 46 …”

Section: Alternative Dosing Strategies: Nebulizationmentioning

confidence: 99%

See 1 more Smart Citation

Defining Antibiotic Dosing in Lung Infections

Jamal

Abdul‐Aziz

Lipman

et al. 2013

Clinical Pulmonary Medicine

View full text Add to dashboard Cite

Defining optimal antibiotic dosing for treatment of lung infections is challenging because of the interrelationship between patient characteristics (eg, pathophysiological changes of lung during an infection, albumin level, renal function), antibiotic characteristics (eg, physicochemical properties, protein binding), and bacterial pathogen susceptibility. Measurement of antibiotic concentration in the lung compartments, such as epithelial lining fluid (ELF), is important to describe the drug exposure at site of infection. This article reviews published data on antibiotic penetration described by the ELF to plasma (ELF:plasma) ratios and the probability of pharmacokinetic/ pharmacodynamics (PK/PD) attainment at the target site with current dosing regimens to outline dosing strategies that could optimize the PK/PD indices. Antibiotic physicochemical properties could be used to predict the extent of penetration into the lung tissues. Lipophilic antibiotics penetrate well into the lung compartments; however, standard dosing regimens generally seem to be insufficient to achieve optimal PK/PD indices in the ELF, particularly during severe infections. Aggressive dosing regimens are required for antibiotics that poorly or moderately penetrate the lung tissues, whereas nebulization could be the alternative method to enhance antibiotic concentration at the target site. Special populations such as the critically ill, patients on renal replacement therapy, and those with renal impairment need dosing to be individualized, as these populations have high PK variability. Dosing based on free drug concentrations should be considered preferred, as these concentrations frequently reflect the antibiotic concentration at the target site. Therefore, the use of therapeutic drug monitoring should be considered necessary, whenever possible, to guide dosing in lung infection.

show abstract

Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients

Abstract: Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80 mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB.

Cited by 116 publications

References 29 publications

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Intravenous polymyxins: Revival with puzzle

Defining Antibiotic Dosing in Lung Infections

Contact Info

Product

Resources

About