TY  - JOUR
A1  - Toy, Virginia Gail
A1  - Sutherland, Rupert
A1  - Townend, John
A1  - Allen, Michael J.
A1  - Becroft, Leeza
A1  - Boles, Austin
A1  - Boulton, Carolyn
A1  - Carpenter, Brett
A1  - Cooper, Alan
A1  - Cox, Simon C.
A1  - Daube, Christopher
A1  - Faulkner, D. R.
A1  - Halfpenny, Angela
A1  - Kato, Naoki
A1  - Keys, Stephen
A1  - Kirilova, Martina
A1  - Kometani, Yusuke
A1  - Little, Timothy
A1  - Mariani, Elisabetta
A1  - Melosh, Benjamin
A1  - Menzies, Catriona D.
A1  - Morales, Luiz
A1  - Morgan, Chance
A1  - Mori, Hiroshi
A1  - Niemeijer, Andre
A1  - Norris, Richard
A1  - Prior, David
A1  - Sauer, Katrina
A1  - Schleicher, Anja Maria
A1  - Shigematsu, Norio
A1  - Teagle, Damon A. H.
A1  - Tobin, Harold
A1  - Valdez, Robert
A1  - Williams, Jack
A1  - Yeo, Samantha
A1  - Baratin, Laura-May
A1  - Barth, Nicolas
A1  - Benson, Adrian
A1  - Boese, Carolin
A1  - Célérier, Bernard
A1  - Chamberlain, Calum J.
A1  - Conze, Ronald
A1  - Coussens, Jamie
A1  - Craw, Lisa
A1  - Doan, Mai-Linh
A1  - Eccles, Jennifer
A1  - Grieve, Jason
A1  - Grochowski, Julia
A1  - Gulley, Anton
A1  - Howarth, Jamie
A1  - Jacobs, Katrina
A1  - Janku-Capova, Lucie
A1  - Jeppson, Tamara
A1  - Langridge, Robert
A1  - Mallyon, Deirdre
A1  - Marx, Ray
A1  - Massiot, Cécile
A1  - Mathewson, Loren
A1  - Moore, Josephine
A1  - Nishikawa, Osamu
A1  - Pooley, Brent
A1  - Pyne, Alex
A1  - Savage, Martha K.
A1  - Schmitt, Doug
A1  - Taylor-Offord, Sam
A1  - Upton, Phaedra
A1  - Weaver, Konrad C.
A1  - Wiersberg, Thomas
A1  - Zimmer, Martin
T1  - Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand
JF  - New Zealand journal of geology and geophysics : an international journal of the geoscience of New Zealand, the Pacific Rim, and Antarctica ; NZJG
N2  - During the second phase of the Alpine Fault, Deep Fault Drilling Project (DFDP) in the Whataroa River, South Westland, New Zealand, bedrock was encountered in the DFDP-2B borehole from 238.5–893.2 m Measured Depth (MD). Continuous sampling and meso- to microscale characterisation of whole rock cuttings established that, in sequence, the borehole sampled amphibolite facies, Torlesse Composite Terrane-derived schists, protomylonites and mylonites, terminating 200–400 m above an Alpine Fault Principal Slip Zone (PSZ) with a maximum dip of 62°. The most diagnostic structural features of increasing PSZ proximity were the occurrence of shear bands and reduction in mean quartz grain sizes. A change in composition to greater mica:quartz + feldspar, most markedly below c. 700 m MD, is inferred to result from either heterogeneous sampling or a change in lithology related to alteration. Major oxide variations suggest the fault-proximal Alpine Fault alteration zone, as previously defined in DFDP-1 core, was not sampled.
KW  - Alpine Fault
KW  - New Zealand
KW  - scientific drilling
KW  - mylonite
KW  - cataclasite
Y1  - 2017
U6  - https://doi.org/10.1080/00288306.2017.1375533
SN  - 0028-8306
SN  - 1175-8791
VL  - 60
IS  - 4
SP  - 497
EP  - 518
PB  - Taylor & Francis
CY  - Abingdon
ER  - 
TY  - GEN
A1  - Ehmann, Lisa
A1  - Zoller, Michael
A1  - Minichmayr, Iris K.
A1  - Schmitt, Maximilian V.
A1  - Hartung, Niklas
A1  - Huisinga, Wilhelm
A1  - Zander, Johannes
A1  - Kloft, Charlotte
T1  - Development of a tool to identify intensive care patients at risk of meropenem therapy failure
T2  - International Journal of Clinical Pharmacy
Y1  - 2018
SN  - 2210-7703
SN  - 2210-7711
VL  - 40
IS  - 1
SP  - 317
EP  - 317
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Busse, David
A1  - Simon, Philipp
A1  - Petroff, David
A1  - El-Najjar, Nahed
A1  - Schmitt, Lisa
A1  - Bindellini, Davide
A1  - Dietrich, Arne
A1  - Zeitlinger, Markus
A1  - Huisinga, Wilhelm
A1  - Michelet, Robin
A1  - Wrigge, Hermann
A1  - Kloft, Charlotte
T1  - High-dosage fosfomycin results in adequate plasma and target-site exposure in morbidly obese and nonobese nonhyperfiltration patients
JF  - Antimicrobial agents and chemotherapy
N2  - The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an %fT(>= MIC) (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC(0-24h)/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m(2)) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC <= 16 mg/L), intermittent "high-dosage" intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of,130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement beta-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status.
KW  - population pharmacokinetics
KW  - pharmacodynamics
KW  - fosfomycin
KW  - obesity
KW  - adipose tissue
KW  - interstitial space fluid
KW  - microdialysis
KW  - anti-infective
KW  - probability of target attainment
Y1  - 2022
U6  - https://doi.org/10.1128/aac.02302-21
SN  - 0066-4804
SN  - 1098-6596
VL  - 66
IS  - 6
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Ehmann, Lisa
A1  - Zoller, Michael
A1  - Minichmayr, Iris K.
A1  - Scharf, Christina
A1  - Maier, Barbara
A1  - Schmitt, Maximilian V.
A1  - Hartung, Niklas
A1  - Huisinga, Wilhelm
A1  - Vogeser, Michael
A1  - Frey, Lorenz
A1  - Zander, Johannes
A1  - Kloft, Charlotte
T1  - Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients
BT  - a prospective observational study
JF  - Critical care
N2  - Background: Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. Methods: A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100% T->MIC, 50% T->4xMIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Results: Large inter-and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100% T->MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50% T->4xMIC. A hyperbolic relationship between CLCRCG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C-8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). Conclusions: The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy-and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed.
KW  - beta-Lactam
KW  - Intensive care
KW  - Pharmacokinetics/Pharmacodynamics
KW  - Target attainment
KW  - Renal function
KW  - Risk assessment tool
KW  - Continuous renal replacement therapy
Y1  - 2017
U6  - https://doi.org/10.1186/s13054-017-1829-4
SN  - 1466-609X
SN  - 1364-8535
VL  - 21
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Schulze-Makuch, Dirk
A1  - Wagner, Dirk
A1  - Kounaves, Samuel P.
A1  - Mangelsdorf, Kai
A1  - Devine, Kevin G.
A1  - de Vera, Jean-Pierre
A1  - Schmitt-Kopplin, Philippe
A1  - Grossart, Hans-Peter
A1  - Parro, Victor
A1  - Kaupenjohann, Martin
A1  - Galy, Albert
A1  - Schneider, Beate
A1  - Airo, Alessandro
A1  - Froesler, Jan
A1  - Davila, Alfonso F.
A1  - Arens, Felix L.
A1  - Caceres, Luis
A1  - Cornejo, Francisco Solis
A1  - Carrizo, Daniel
A1  - Dartnell, Lewis
A1  - DiRuggiero, Jocelyne
A1  - Flury, Markus
A1  - Ganzert, Lars
A1  - Gessner, Mark O.
A1  - Grathwohl, Peter
A1  - Guan, Lisa
A1  - Heinz, Jacob
A1  - Hess, Matthias
A1  - Keppler, Frank
A1  - Maus, Deborah
A1  - McKay, Christopher P.
A1  - Meckenstock, Rainer U.
A1  - Montgomery, Wren
A1  - Oberlin, Elizabeth A.
A1  - Probst, Alexander J.
A1  - Saenz, Johan S.
A1  - Sattler, Tobias
A1  - Schirmack, Janosch
A1  - Sephton, Mark A.
A1  - Schloter, Michael
A1  - Uhl, Jenny
A1  - Valenzuela, Bernardita
A1  - Vestergaard, Gisle
A1  - Woermer, Lars
A1  - Zamorano, Pedro
T1  - Transitory microbial habitat in the hyperarid Atacama Desert
JF  - Proceedings of the National Academy of Sciences of the United States of America
KW  - habitat
KW  - aridity
KW  - microbial activity
KW  - biomarker
KW  - Mars
Y1  - 2018
U6  - https://doi.org/10.1073/pnas.1714341115
SN  - 0027-8424
VL  - 115
IS  - 11
SP  - 2670
EP  - 2675
PB  - National Acad. of Sciences
CY  - Washington
ER  -