Feasibility of aerosolized colistin in the era of escalating drug-resistant Pseudomonas pneumonia: pressing need for validation clinical trials

Safdar, Amar

doi:10.1007/s00134-010-1883-8

Cited by 5 publications

(1 citation statement)

References 12 publications

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“…In some cases, drug combination may result in convergence of MPC and MIC but drug concentrations at the infection site may not be sufficient to even eradicate less resistant bacteria subpopulation. High-dose sulbactam regimens provide sufficient penetration into the lung tissues to achieve their target PD indices, whereas polymyxins and amikacin, due to their high molecular mass and hydrophilicity ( Safdar, 2010 ; Zhu et al, 2021 ), have low ELF penetration after an IV administration. Low tissue drug concentrations in the lung after an IV administration will lead to treatment failure ( Zhu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii

Zhu

Song²,

Zhang³

et al. 2022

Front. Microbiol.

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Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant Acinetobacter baumannii at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit in vitro synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of A. baumannii harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (fTMSW) and the fraction of time that the free drug concentration was above the MPC (fT>MPC) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant A. baumannii and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize fTMSW and fT>MPC from drug exposures in the blood. Mean fT>MPC were ≥ 60% and ≥ 80% for amikacin and polymyxin-B, whereas mean fTMSW was reduced to <30% and <15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting.

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Section: Discussionmentioning

confidence: 99%