Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates
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Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates. / Amann, Lisa F.; Broeker, Astrid; Riedner, Maria; Rohde, Holger; Huang, Jiabin; Nordmann, Patrice; Decousser, Jean-Winoc; Wicha, Sebastian G.
In: DIAGN MICR INFEC DIS, Vol. 108, No. 2, 116153, 02.2024, p. 116153.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates
AU - Amann, Lisa F.
AU - Broeker, Astrid
AU - Riedner, Maria
AU - Rohde, Holger
AU - Huang, Jiabin
AU - Nordmann, Patrice
AU - Decousser, Jean-Winoc
AU - Wicha, Sebastian G.
PY - 2024/2
Y1 - 2024/2
N2 - The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.g., Gram-negatives. A pharmacometric model was built from tigecycline concentrations (100 – 600 mg daily doses) against clinical Klebsiella pneumoniae isolates (MIC 0.125 – 0.5 mg/L). Regrowth occurred at clinically used doses and stasis was only achieved with 100 mg q8h for the strain with the lowest studied MIC of 0.125 mg/L. Stasis at 24 h was related to fAUC/MIC of 38.5. Our study indicates that even intensified dosing regimens might prevent bloodstream infections only for MIC values ≤0.125 mg/L for tigecycline. This indicates an overly optimistic breakpoint of 1 mg/L for Enterobacterales, which are deemed to respond to the tigecycline high dose regimen (EUCAST Guidance Document on Tigecycline Dosing 2022).
AB - The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.g., Gram-negatives. A pharmacometric model was built from tigecycline concentrations (100 – 600 mg daily doses) against clinical Klebsiella pneumoniae isolates (MIC 0.125 – 0.5 mg/L). Regrowth occurred at clinically used doses and stasis was only achieved with 100 mg q8h for the strain with the lowest studied MIC of 0.125 mg/L. Stasis at 24 h was related to fAUC/MIC of 38.5. Our study indicates that even intensified dosing regimens might prevent bloodstream infections only for MIC values ≤0.125 mg/L for tigecycline. This indicates an overly optimistic breakpoint of 1 mg/L for Enterobacterales, which are deemed to respond to the tigecycline high dose regimen (EUCAST Guidance Document on Tigecycline Dosing 2022).
KW - Hollow fiber infection model
KW - Pharmacokinetic-Pharmacodynamic modelling
KW - genetic analysis of resistant subpopulations
U2 - 10.1016/j.diagmicrobio.2023.116153
DO - 10.1016/j.diagmicrobio.2023.116153
M3 - SCORING: Journal article
C2 - 38086168
VL - 108
SP - 116153
JO - DIAGN MICR INFEC DIS
JF - DIAGN MICR INFEC DIS
SN - 0732-8893
IS - 2
M1 - 116153
ER -
