PK/PD of fosfomycin iv

Fosfomycin is active in vitro against some multidrug Gram-negative bacteria and could be a component of a combination regimen for the treatment of these infections. The concentrations required for activity are, however, relatively high for non-fermenters. There are only a few available data on PK/PD characteristics and clinical outcomes of fosfomycin. Based on in vitro data and PK/PD modelling, a high dose and prolonged infusion combination strategy has been suggested. Clinically, doses of 4 g four times daily and up to 8 g three times daily have been reported, but appropriate dosage regimens in extensively resistant infections have not yet been established (P.A. Tambyah et al 2013)

PK/PD index

It is not clear which PK/PD index best predicts outcome. Both AUC/MIC and t>MIC have been used in PK/PD studies.

One presented at ICAAC 2012 defined the PK/PD target as 70% T>MIC. A 10,000-subject Monte Carlo simulation was performed to calculate the percentage of target attainment based on different dosing regimens (O. Asuphon et al, ICAAC 2012, abstract A-1279).

% probability of target attainment of fosfomycin (O. Asuphon et al, ICAAC 2012, abstract A-1279):

Fosfomycin PTA

OtherĀ  authors describe AUC/MIC as the most predictive PK/PD index.

Fosfomycin is a very small molecule and penetrates well across membranes.

V. Matzi et al 2010 studied the penetration of fosfomycin in the lung interstitial fluid:

Fosfomycin lung

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