@article{ToySutherlandTownendetal.2017, author = {Toy, Virginia Gail and Sutherland, Rupert and Townend, John and Allen, Michael J. and Becroft, Leeza and Boles, Austin and Boulton, Carolyn and Carpenter, Brett and Cooper, Alan and Cox, Simon C. and Daube, Christopher and Faulkner, D. R. and Halfpenny, Angela and Kato, Naoki and Keys, Stephen and Kirilova, Martina and Kometani, Yusuke and Little, Timothy and Mariani, Elisabetta and Melosh, Benjamin and Menzies, Catriona D. and Morales, Luiz and Morgan, Chance and Mori, Hiroshi and Niemeijer, Andre and Norris, Richard and Prior, David and Sauer, Katrina and Schleicher, Anja Maria and Shigematsu, Norio and Teagle, Damon A. H. and Tobin, Harold and Valdez, Robert and Williams, Jack and Yeo, Samantha and Baratin, Laura-May and Barth, Nicolas and Benson, Adrian and Boese, Carolin and C{\´e}l{\´e}rier, Bernard and Chamberlain, Calum J. and Conze, Ronald and Coussens, Jamie and Craw, Lisa and Doan, Mai-Linh and Eccles, Jennifer and Grieve, Jason and Grochowski, Julia and Gulley, Anton and Howarth, Jamie and Jacobs, Katrina and Janku-Capova, Lucie and Jeppson, Tamara and Langridge, Robert and Mallyon, Deirdre and Marx, Ray and Massiot, C{\´e}cile and Mathewson, Loren and Moore, Josephine and Nishikawa, Osamu and Pooley, Brent and Pyne, Alex and Savage, Martha K. and Schmitt, Doug and Taylor-Offord, Sam and Upton, Phaedra and Weaver, Konrad C. and Wiersberg, Thomas and Zimmer, Martin}, title = {Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand}, series = {New Zealand journal of geology and geophysics : an international journal of the geoscience of New Zealand, the Pacific Rim, and Antarctica ; NZJG}, volume = {60}, journal = {New Zealand journal of geology and geophysics : an international journal of the geoscience of New Zealand, the Pacific Rim, and Antarctica ; NZJG}, number = {4}, publisher = {Taylor \& Francis}, address = {Abingdon}, organization = {DFDP-2 Sci Team}, issn = {0028-8306}, doi = {10.1080/00288306.2017.1375533}, pages = {497 -- 518}, year = {2017}, abstract = {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.}, language = {en} } @misc{EhmannZollerMinichmayretal.2018, author = {Ehmann, Lisa and Zoller, Michael and Minichmayr, Iris K. and Schmitt, Maximilian V. and Hartung, Niklas and Huisinga, Wilhelm and Zander, Johannes and Kloft, Charlotte}, title = {Development of a tool to identify intensive care patients at risk of meropenem therapy failure}, series = {International Journal of Clinical Pharmacy}, volume = {40}, journal = {International Journal of Clinical Pharmacy}, number = {1}, publisher = {Springer}, address = {Dordrecht}, issn = {2210-7703}, pages = {317 -- 317}, year = {2018}, language = {en} } @article{BusseSimonPetroffetal.2022, author = {Busse, David and Simon, Philipp and Petroff, David and El-Najjar, Nahed and Schmitt, Lisa and Bindellini, Davide and Dietrich, Arne and Zeitlinger, Markus and Huisinga, Wilhelm and Michelet, Robin and Wrigge, Hermann and Kloft, Charlotte}, title = {High-dosage fosfomycin results in adequate plasma and target-site exposure in morbidly obese and nonobese nonhyperfiltration patients}, series = {Antimicrobial agents and chemotherapy}, volume = {66}, journal = {Antimicrobial agents and chemotherapy}, number = {6}, publisher = {American Society for Microbiology}, address = {Washington}, issn = {0066-4804}, doi = {10.1128/aac.02302-21}, pages = {12}, year = {2022}, abstract = {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.}, language = {en} } @article{EhmannZollerMinichmayretal.2017, author = {Ehmann, Lisa and Zoller, Michael and Minichmayr, Iris K. and Scharf, Christina and Maier, Barbara and Schmitt, Maximilian V. and Hartung, Niklas and Huisinga, Wilhelm and Vogeser, Michael and Frey, Lorenz and Zander, Johannes and Kloft, Charlotte}, title = {Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients}, series = {Critical care}, volume = {21}, journal = {Critical care}, publisher = {BioMed Central}, address = {London}, issn = {1466-609X}, doi = {10.1186/s13054-017-1829-4}, pages = {14}, year = {2017}, abstract = {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.}, language = {en} } @article{SchulzeMakuchWagnerKounavesetal.2018, author = {Schulze-Makuch, Dirk and Wagner, Dirk and Kounaves, Samuel P. and Mangelsdorf, Kai and Devine, Kevin G. and de Vera, Jean-Pierre and Schmitt-Kopplin, Philippe and Grossart, Hans-Peter and Parro, Victor and Kaupenjohann, Martin and Galy, Albert and Schneider, Beate and Airo, Alessandro and Froesler, Jan and Davila, Alfonso F. and Arens, Felix L. and Caceres, Luis and Cornejo, Francisco Solis and Carrizo, Daniel and Dartnell, Lewis and DiRuggiero, Jocelyne and Flury, Markus and Ganzert, Lars and Gessner, Mark O. and Grathwohl, Peter and Guan, Lisa and Heinz, Jacob and Hess, Matthias and Keppler, Frank and Maus, Deborah and McKay, Christopher P. and Meckenstock, Rainer U. and Montgomery, Wren and Oberlin, Elizabeth A. and Probst, Alexander J. and Saenz, Johan S. and Sattler, Tobias and Schirmack, Janosch and Sephton, Mark A. and Schloter, Michael and Uhl, Jenny and Valenzuela, Bernardita and Vestergaard, Gisle and Woermer, Lars and Zamorano, Pedro}, title = {Transitory microbial habitat in the hyperarid Atacama Desert}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {11}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1714341115}, pages = {2670 -- 2675}, year = {2018}, language = {en} }