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A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic\/pharmacodynamic (PK\/PD) targets for efficacy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Twenty-five septic ICU patients (19\u00a0m, 6f) aged 32\u201386\u00a0years with the mean APACHE II score of 20.2 (range 11\u201333), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (<jats:italic>n<\/jats:italic>\u2009=\u200918), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CL<jats:sub>cr<\/jats:sub>) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Eleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (<jats:italic>n<\/jats:italic>\u2009=\u200914, 11 with pneumonia), the FO patients had a lower meropenem clearance (CL<jats:sub>me<\/jats:sub> 8.5\u2009\u00b1\u20093.2 vs 11.5\u2009\u00b1\u20093.5 L\/h), higher volume of distribution (V<jats:sub>1<\/jats:sub> 14.9\u2009\u00b1\u20093.5 vs 13.5\u2009\u00b1\u20094.1 L) and longer half-life (t<jats:sub>1\/2<\/jats:sub> 1.4\u2009\u00b1\u20090.63 vs 0.92\u2009\u00b1\u20090.54\u00a0h) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Over three days, the CFB of the FO patients decreased (11.7\u2009\u00b1\u20093.3 vs 6.7\u2009\u00b1\u20094.3 L, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and the PK parameters reached the values comparable with NoFO patients (CL<jats:sub>me<\/jats:sub> 12.4\u2009\u00b1\u20093.8 vs 11.5\u2009\u00b1\u20092.0 L\/h, V<jats:sub>1<\/jats:sub> 13.7\u2009\u00b1\u20092.0 vs 14.0\u2009\u00b1\u20095.1 L, t<jats:sub>1\/2<\/jats:sub> 0.81\u2009\u00b1\u20090.23 vs 0.87\u2009\u00b1\u20090.40\u00a0h). The CL<jats:sub>cr<\/jats:sub> and Cockroft\u2013Gault CL<jats:sub>cr<\/jats:sub> were stable in time and comparable. The correlation with CL<jats:sub>me<\/jats:sub> was weak to moderate (CL<jats:sub>cr<\/jats:sub>, day 3 CGCL<jats:sub>cr<\/jats:sub>) or absent (day 1 and 2 CGCL<jats:sub>cr<\/jats:sub>). Dosing with 2\u00a0g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2\u00a0mg\/L). The proportion of pre-dose concentrations exceeding the MIC 8\u00a0mg\/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1\u20133 <jats:italic>f<\/jats:italic> C<jats:sub>min<\/jats:sub>\u2009&gt;\u2009MIC: 67 vs 27%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; day 1%<jats:italic>f<\/jats:italic> T\u2009&gt;\u2009MIC: 79\u2009\u00b1\u200917 vs 58\u2009\u00b1\u200917, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CL<jats:sub>me<\/jats:sub> and creatinine clearance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13054-021-03680-9","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T09:03:03Z","timestamp":1626512583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Impact of cumulative fluid balance on the pharmacokinetics of extended infusion meropenem in critically ill patients with sepsis"],"prefix":"10.1186","volume":"25","author":[{"given":"Renata \u010cern\u00e1","family":"Pa\u0159\u00edzkov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u0159ina","family":"Mart\u00ednkov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Havel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"\u0160afr\u00e1nek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan","family":"Ka\u0161ka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Astapenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Bezou\u0161ka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9052-6318","authenticated-orcid":false,"given":"Jaroslav","family":"Chl\u00e1dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladim\u00edr","family":"\u010cern\u00fd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,17]]},"reference":[{"key":"3680_CR1","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.1086\/590064","volume":"47","author":"DP Nicolau","year":"2008","unstructured":"Nicolau DP. 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