Matches in SemOpenAlex for { <https://semopenalex.org/work/W2800533652> ?p ?o ?g. }
- W2800533652 abstract "ABSTRACT Augmented renal clearance (ARC) in critically ill patients can result in suboptimal drug exposures and treatment failure. Combination dosage regimens accounting for ARC have never been optimized and evaluated against Pseudomonas aeruginosa by use of the hollow-fiber infection model (HFIM). Using a P. aeruginosa isolate from a critically ill patient and static-concentration time-kill experiments (SCTKs), we studied clinically relevant piperacillin and tobramycin concentrations, alone and in combinations, against two inocula (10 5.8 and 10 7.6 CFU/ml) over 72 h. We subsequently evaluated the effects of optimized piperacillin (4 g every 4 h [q4h], given as 0.5-h infusions) plus tobramycin (5 mg/kg of body weight q24h, 7 mg/kg q24h, or 10 mg/kg q48h, given as 0.5-h infusions) regimens on killing and regrowth in the HFIM, simulating a creatinine clearance of 250 ml/min. Mechanism-based modeling was performed in S-ADAPT. In SCTKs, piperacillin plus tobramycin (except combinations with 8 mg/liter tobramycin and against the low inoculum) achieved synergistic killing (≥2 log 10 versus the most active monotherapy at 48 h and 72 h) and prevented regrowth. Piperacillin monotherapy (4 g q4h) in the HFIM provided 2.4-log 10 initial killing followed by regrowth at 24 h and resistance emergence. Tobramycin monotherapies displayed rapid initial killing (≥5 log 10 at 13 h) followed by extensive regrowth. As predicted by mechanism-based modeling, the piperacillin plus tobramycin dosage regimens were synergistic and provided ≥5-log 10 killing with resistance suppression over 8 days in the HFIM. Optimized piperacillin-tobramycin regimens provided significant bacterial killing and suppressed resistance emergence. These regimens appear to be highly promising for effective and early treatment, even in the near-worst-case scenario of ARC." @default.
- W2800533652 created "2018-05-17" @default.
- W2800533652 creator A5005119582 @default.
- W2800533652 creator A5015076483 @default.
- W2800533652 creator A5030691636 @default.
- W2800533652 creator A5042046351 @default.
- W2800533652 creator A5048000157 @default.
- W2800533652 creator A5058674939 @default.
- W2800533652 creator A5066789024 @default.
- W2800533652 creator A5071624617 @default.
- W2800533652 creator A5073046394 @default.
- W2800533652 creator A5088573805 @default.
- W2800533652 creator A5089733754 @default.
- W2800533652 date "2018-05-01" @default.
- W2800533652 modified "2023-10-17" @default.
- W2800533652 title "Optimization and Evaluation of Piperacillin-Tobramycin Combination Dosage Regimens against Pseudomonas aeruginosa for Patients with Altered Pharmacokinetics via the Hollow-Fiber Infection Model and Mechanism-Based Modeling" @default.
- W2800533652 cites W1497148223 @default.
- W2800533652 cites W1514477675 @default.
- W2800533652 cites W1838411867 @default.
- W2800533652 cites W185587909 @default.
- W2800533652 cites W1884184374 @default.
- W2800533652 cites W1933654092 @default.
- W2800533652 cites W1965409354 @default.
- W2800533652 cites W1966483053 @default.
- W2800533652 cites W1969762322 @default.
- W2800533652 cites W1974788123 @default.
- W2800533652 cites W1981898530 @default.
- W2800533652 cites W1982240222 @default.
- W2800533652 cites W1992114884 @default.
- W2800533652 cites W1998853564 @default.
- W2800533652 cites W2006314650 @default.
- W2800533652 cites W2006333306 @default.
- W2800533652 cites W2010053384 @default.
- W2800533652 cites W2024240091 @default.
- W2800533652 cites W2039740101 @default.
- W2800533652 cites W2042237163 @default.
- W2800533652 cites W2047635738 @default.
- W2800533652 cites W2050947530 @default.
- W2800533652 cites W2055417751 @default.
- W2800533652 cites W2055656378 @default.
- W2800533652 cites W2057226149 @default.
- W2800533652 cites W2058213101 @default.
- W2800533652 cites W2069335597 @default.
- W2800533652 cites W2073122282 @default.
- W2800533652 cites W2073521181 @default.
- W2800533652 cites W2074904217 @default.
- W2800533652 cites W2078974283 @default.
- W2800533652 cites W2079691262 @default.
- W2800533652 cites W2082321986 @default.
- W2800533652 cites W2085958466 @default.
- W2800533652 cites W2091955762 @default.
- W2800533652 cites W2094476444 @default.
- W2800533652 cites W2101416655 @default.
- W2800533652 cites W2104337600 @default.
- W2800533652 cites W2112401566 @default.
- W2800533652 cites W2113717321 @default.
- W2800533652 cites W2124431328 @default.
- W2800533652 cites W2127628246 @default.
- W2800533652 cites W2135246681 @default.
- W2800533652 cites W2135919784 @default.
- W2800533652 cites W2136706836 @default.
- W2800533652 cites W2137091511 @default.
- W2800533652 cites W2140185070 @default.
- W2800533652 cites W2143682782 @default.
- W2800533652 cites W2144719434 @default.
- W2800533652 cites W2149772433 @default.
- W2800533652 cites W2150115265 @default.
- W2800533652 cites W2150760368 @default.
- W2800533652 cites W2153641174 @default.
- W2800533652 cites W2159469354 @default.
- W2800533652 cites W2161363527 @default.
- W2800533652 cites W2165158988 @default.
- W2800533652 cites W2165839757 @default.
- W2800533652 cites W2166840599 @default.
- W2800533652 cites W2167425482 @default.
- W2800533652 cites W2169951238 @default.
- W2800533652 cites W2175383952 @default.
- W2800533652 cites W2408088108 @default.
- W2800533652 cites W2515285744 @default.
- W2800533652 cites W2551981896 @default.
- W2800533652 cites W2568698844 @default.
- W2800533652 cites W2592339885 @default.
- W2800533652 cites W2623986689 @default.
- W2800533652 cites W2735588250 @default.
- W2800533652 cites W2753275068 @default.
- W2800533652 cites W2754594431 @default.
- W2800533652 cites W2769641369 @default.
- W2800533652 cites W4249764287 @default.
- W2800533652 cites W4294990605 @default.
- W2800533652 doi "https://doi.org/10.1128/aac.00078-18" @default.
- W2800533652 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5923168" @default.
- W2800533652 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29463528" @default.
- W2800533652 hasPublicationYear "2018" @default.
- W2800533652 type Work @default.
- W2800533652 sameAs 2800533652 @default.
- W2800533652 citedByCount "18" @default.
- W2800533652 countsByYear W28005336522018 @default.
- W2800533652 countsByYear W28005336522019 @default.
- W2800533652 countsByYear W28005336522020 @default.
- W2800533652 countsByYear W28005336522021 @default.