Pulmonary and Systemic Pharmacokinetics of Colistin Following a Single Dose of Nebulized Colistimethate in Mechanically Ventilated Neonates

Nakwan, Narongsak; Lertpichaluk, Pichaya; Chokephaibulkit, Kulkanya; Villani, Paola; Regazzi, Mario; Imberti, Roberto

doi:10.1097/inf.0000000000000775

Cited by 19 publications

(11 citation statements)

References 13 publications

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“…Serum biochemical parameters of samples were evaluated for alkaline phosphatase (ALP), aspartate transaminase (AST), urea nitrogen (UN), glucose (GLU), total protein [ 30 ], albumin (ALB), globulin (GLO), calcium (Ca), phosphate (P), using an automatic biochemical analyzer (7180ISE, Japan Hitachi High-Tech, Japan).…”

Section: Methodsmentioning

confidence: 99%

Effects of soybean meal fermented by L. plantarum, B. subtilis and S. cerevisieae on growth, immune function and intestinal morphology in weaned piglets

et al. 2017

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BackgroundThe present study compared the effects of soybean meal fermented by three different probiotics organisms with non-fermented soybean meal on growth performance, serum parameters, immune chemistry and intestinal morphology in weaned piglets.MethodsOne hundred and forty-four 35-day old crossbred (Duroc × Landrace × Yorkshire) piglets were randomly allocated into four different dietary treatments (n = 36 per group) containing 0, 5, 10 and 15% fermented soybean meal.ResultsThe piglets fed fermented soybean meal showed an increase (p < 0.05) in average daily weight gain and a reduction in feed consumption (p < 0.05).The piglets fed 10 and 15% fermented soybean meal showed the greatest growth improvement with higher levels of serum alkaline phosphatase and total serum proteins. Serum urea nitrogen in the experimental group was significantly lower than control whereas serum IgG, IgM and IgA levels were all significantly higher. Moreover, villus height in the duodenum, jejunum, and ileum was significantly higher (p < 0.05) and the crypt depth was significantly lower (p < 0.05). The levels of the autophagy factor LC3B in piglets showed a downward trend in the jejunum and ileum compared to control.ConclusionsFermented soybean meal could significantly improve the growth, immune function and intestinal health in weaned piglets, and the best effective benefits showed in 10% FSBM group.Electronic supplementary materialThe online version of this article (10.1186/s12934-017-0809-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Effects of soybean meal fermented by L. plantarum, B. subtilis and S. cerevisieae on growth, immune function and intestinal morphology in weaned piglets

et al. 2017

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“…Over the last decade, nebulization of colistin has become an alternative in treating MDR Gram-negative respiratory tract infections (10,11). Inhalation therapy of colistin reduces systemic exposure and thus minimizes potential systemic side effects such as nephrotoxicity (1,12). PK studies in rats (6)(7)(8) and cystic fibrosis patients (9) have clearly demonstrated that nebulization of CMS/colistin resulted in much higher drug exposure in the epithelial lining fluid (ELF) or sputum than by systemic administration.…”

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confidence: 99%

Pharmacokinetics/Pharmacodynamics of Pulmonary Delivery of Colistin against Pseudomonas aeruginosa in a Mouse Lung Infection Model

Lin

Zhou

Cheah

et al. 2017

Antimicrob Agents Chemother

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Colistin is often administered by inhalation and/or the parenteral route for the treatment of respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa. However, limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to guide the optimization of dosage regimens of inhaled colistin. In the present study, PK of colistin in epithelial lining fluid (ELF) and plasma was determined following intratracheal delivery of a single dose of colistin solution in neutropenic lung-infected mice. The antimicrobial efficacy of intratracheal delivery of colistin against three P. aeruginosa strains (ATCC 27853, PAO1, and FADDI-PA022; MIC of 1 mg/liter for all strains) was examined in a neutropenic mouse lung infection model. Dose fractionation studies were conducted over 2.64 to 23.8 mg/kg of body weight/day. The inhibitory sigmoid model was employed to determine the PK/PD index that best described the antimicrobial efficacy of pulmonary delivery of colistin. In both ELF and plasma, the ratio of the area under the unbound concentration-time profile to MIC (fAUC/MIC) was the PK/PD index that best described the antimicrobial effect in mouse lung infection (R 2 ϭ 0.60 to 0.84 for ELF and 0.64 to 0.83 for plasma). The fAUC/MIC targets required to achieve stasis against the three strains were 684 to 1,050 in ELF and 2.15 to 3.29 in plasma. The histopathological data showed that pulmonary delivery of colistin reduced infection-caused pulmonary inflammation and preserved the integrity of the lung epithelium, although colistin introduced mild pulmonary inflammation in healthy mice. This study showed pulmonary delivery of colistin provides antimicrobial effects against MDR P. aeruginosa lung infections superior to those of parenteral administrations. For the first time, our results provide important preclinical PK/PD information for optimization of inhaled colistin therapy.

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“…Only recently has the importance of aerosolized polymyxins for the treatment of respiratory tract infections started attracting significant interest (17)(18)(19)(20)(21)(22)(23)(24). The majority of current preclinical and clinical PK/PD data for aerosolized polymyxins focus on CMS/colistin (12,19,21,22,(25)(26)(27), although aerosolized polymyxin B has also been used in the clinic (28).…”

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confidence: 99%

Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic-Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model

Lin

Zhou

Onufrak

et al. 2017

Antimicrob Agents Chemother

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Pulmonary administration of polymyxins is increasingly used for the treatment of respiratory tract infections caused by multidrug-resistant Gram-negative bacteria, such as those in patients with cystic fibrosis. However, there is a lack of pharmacokinetics (PK), pharmacodynamics (PD), and toxicity data of aerosolized polymyxin B to inform rational dosage selection. The PK and PD of polymyxin B following pulmonary and intravenous dosing were examined in neutropenic infected mice, and the data were analyzed by a population PK model. Dose fractionation study was performed for total daily doses between 2.06 and 24.8 mg base/kg of weight against Pseudomonas aeruginosa ATCC 27853, PAO1, and FADDI-PA022 (MIC of 1 mg/liter for all three strains). Histopathological examination of the lung was undertaken at 24 h posttreatment in both healthy and neutropenic infected mice. A two-compartment PK model was required for both epithelial lining fluid (ELF) and plasma drug exposure. The model consisted of central and peripheral compartments and was described by bidirectional first-order distribution clearance. The ratio of the area under the curve to the MIC (AUC/MIC) was the most predictive PK/PD index to describe the antimicrobial efficacy of aerosolized polymyxin B in treating lung infections in mice (R 2 of 0.70 to 0.88 for ELF and 0.70 to 0.87 for plasma). The AUC/MIC targets associated with bacteriostasis against the three P. aeruginosa strains were 1,326 to 1,506 in ELF and 3.14 to 4.03 in plasma. Histopathological results showed that polymyxin B aerosols significantly reduced lung inflammation and preserved lung epithelial integrity. This study highlights the advantageous PK/PD characteristics of pulmonary delivery of polymyxin B over intravenous administration in achieving high drug exposure in ELF.

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Pulmonary and Systemic Pharmacokinetics of Colistin Following a Single Dose of Nebulized Colistimethate in Mechanically Ventilated Neonates

Cited by 19 publications

References 13 publications

Effects of soybean meal fermented by L. plantarum, B. subtilis and S. cerevisieae on growth, immune function and intestinal morphology in weaned piglets

Effects of soybean meal fermented by L. plantarum, B. subtilis and S. cerevisieae on growth, immune function and intestinal morphology in weaned piglets

Pharmacokinetics/Pharmacodynamics of Pulmonary Delivery of Colistin against Pseudomonas aeruginosa in a Mouse Lung Infection Model

Aerosolized Polymyxin B for Treatment of Respiratory Tract Infections: Determination of Pharmacokinetic-Pharmacodynamic Indices for Aerosolized Polymyxin B against Pseudomonas aeruginosa in a Mouse Lung Infection Model

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