{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:53:30Z","timestamp":1775714010941,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Meropenem is commonly used to treat severe postoperative infections. However, substantial pharmacokinetic variability among surgical patients makes dose optimization challenging. Population pharmacokinetic (PopPK) modeling integrated with pharmacokinetic\/pharmacodynamic (PK\/PD) simulations may help support individualized dosing in this setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult patients with severe postoperative infections receiving meropenem were prospectively enrolled for therapeutic drug monitoring. Plasma meropenem concentrations were determined using a validated high-performance liquid chromatography (HPLC) assay. A nonlinear mixed-effects modeling approach was used to characterize meropenem pharmacokinetics and to explore potential covariates. Monte Carlo simulations (MCS) were performed to estimate the probability of target attainment (PTA) across different renal function categories and minimum inhibitory concentrations (MICs), using PK\/PD targets of 40% fT &amp;gt; MIC, 100% fT &amp;gt; MIC, 50% fT &amp;gt; 4\u00d7MIC, and 100% fT &amp;gt; 4\u00d7MIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>44 patients with 135 concentration measurements were analyzed. Meropenem pharmacokinetics were described by a one-compartment model with linear elimination. The typical population clearance (CL) and apparent volume of distribution (Vc) were 6.472\u00a0L\/h and 26.69 L, respectively. Postoperative creatinine clearance (CRCL) was the only significant covariate affecting CL. Patients with augmented renal clearance or elevated MIC values may require intensified dosing strategies, whereas dose reduction is generally required in patients with renal impairment. For MIC \u22641\u00a0mg\/L, 500\u00a0mg every 8\u00a0h achieved adequate PTA across most renal strata. At MIC 4\u00a0mg\/L, intensified regimens (e.g., 1\u00a0g every 6\u20138\u00a0h or prolonged infusion) were required depending on renal function. At MIC 8\u00a0mg\/L, even high-dose regimens were insufficient to achieve stringent PK\/PD targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Postoperative renal function is a major determinant of meropenem exposure in patients with severe postoperative infections. PopPK-guided dosing combined with Monte Carlo simulation provides a practical framework for optimizing meropenem therapy and facilitating individualized antimicrobial treatment. Selecting dosing regimens according to renal function and MIC may improve the therapeutic effectiveness of meropenem in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1778552","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:21:24Z","timestamp":1775712084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetic modeling and Monte Carlo simulation to optimize meropenem dosing in patients with severe postoperative infections"],"prefix":"10.3389","volume":"17","author":[{"given":"Yang","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianke","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haibo","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyan","family":"Li","sequence":"additional","affiliation":[{"name":"General Intensive Care Unit, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangping","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]},{"name":"State Key Laboratory of Chemo\/Bio-Sensing and Chemometrics, School of Biomedical Sciences, Hunan University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, The Central Hospital of Xiangtan (The affiliated Hospital of Hunan University)","place":["Xiangtan, China"]},{"name":"State Key Laboratory of Chemo\/Bio-Sensing and Chemometrics, School of Biomedical Sciences, Hunan University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1097\/ftd.0000000000000675","article-title":"Meropenem, cefepime, and piperacillin protein binding in patient samples","volume":"42","author":"Al-Shaer","year":"2020","journal-title":"Ther. Drug Monit."},{"key":"B2","first-page":"497","article-title":"Elevated \u0392-Lactam concentrations associated with neurological deterioration in icu septic patients","volume":"81","author":"Beumier","year":"2015","journal-title":"Minerva Anestesiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0084522","DOI":"10.1128\/aac.00845-22","article-title":"Population pharmacokinetics\/pharmacodynamics and clinical outcomes of meropenem in critically ill patients","volume":"66","author":"Boonpeng","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e507","DOI":"10.1097\/pcc.0000000000003698","article-title":"Subtherapeutic meropenem antibiotic exposure in children with septic shock assessed by noncompartmental pharmacokinetic analysis in a prospective dataset","volume":"26","author":"Bradley","year":"2025","journal-title":"Pediatr. Crit. Care Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13054-018-1940-1","article-title":"Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study","volume":"22","author":"Braune","year":"2018","journal-title":"Crit. Care"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1007\/s40265-018-0966-7","article-title":"Meropenem\/vaborbactam: a review in complicated urinary tract infections","volume":"78","author":"Dhillon","year":"2018","journal-title":"Drugs"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0316523","DOI":"10.1128\/mbio.03165-23","article-title":"Molecular pharmacodynamics of meropenem for nosocomial pneumonia caused by Pseudomonas aeruginosa","volume":"15","author":"Farrington","year":"2024","journal-title":"mBio"},{"key":"B8","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.burns.2015.01.001","article-title":"Impact of the introduction of real-time therapeutic drug monitoring on empirical doses of carbapenems in critically ill burn patients","volume":"41","author":"Fournier","year":"2015","journal-title":"Burns"},{"key":"B9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2147\/idr.S343264","article-title":"Meropenem target attainment and population pharmacokinetics in critically ill septic patients with preserved or increased renal function","volume":"15","author":"Gijsen","year":"2022","journal-title":"Infect. Drug Resist"},{"key":"B10","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1001\/jamasurg.2024.0775","article-title":"Incisional wound irrigation for the prevention of surgical site infection: a systematic review and network meta-analysis","volume":"159","author":"Groenen","year":"2024","journal-title":"JAMA Surg."},{"key":"B11","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1089\/sur.2024.137","article-title":"The surgical infection society guidelines on the management of intra-abdominal infection: 2024 update","volume":"25","author":"Huston","year":"2024","journal-title":"Surg. Infect. (Larchmt)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2891","DOI":"10.1093\/jac\/dkx209","article-title":"Too much of a good thing: a retrospective study of \u0392-Lactam concentration-toxicity relationships","volume":"72","author":"Imani","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1128\/aac.04166-14","article-title":"Population pharmacokinetics and monte carlo dosing simulations of meropenem during the early phase of severe sepsis and septic shock in critically ill patients in intensive care units","volume":"59","author":"Jaruratanasirikul","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ijsu.2020.07.066","article-title":"Evaluation of different surgical dressings in reducing postoperative surgical site infection of a closed wound: a network meta-analysis","volume":"82","author":"Jiang","year":"2020","journal-title":"Int. J. Surg."},{"key":"B16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1080\/1120009x.2025.2465129","article-title":"Real-world effectiveness and safety of meropenem-vaborbactam in the treatment of carbapenem-resistant Enterobacterales (cre) infections: a systematic review and meta-analysis","volume":"37","author":"Jin","year":"2025","journal-title":"J. Chemother."},{"key":"B17","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1002\/phar.2092","article-title":"Meropenem and vaborbactam: stepping up the battle against carbapenem-resistant enterobacteriaceae","volume":"38","author":"Jorgensen","year":"2018","journal-title":"Pharmacotherapy"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1016\/j.xphs.2022.01.015","article-title":"Population pharmacokinetics analysis and dosing simulations of meropenem in critically ill patients with pulmonary infection","volume":"111","author":"Lan","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1093\/jac\/dky406","article-title":"Fosfomycin in severe infections due to genetically distinct pan-drug-resistant gram-negative microorganisms: synergy with meropenem","volume":"74","author":"Lauro Vieira","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"107697","DOI":"10.1016\/j.ijantimicag.2025.107697","article-title":"Enhancing meropenem therapy in critical care: a retrospective study of Pk\/Pd target attainment and therapeutic drug monitoring","volume":"67","author":"Liao","year":"2026","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/bmjqs-2025-019493","article-title":"Retrospective validation study of a large language model approach to screening for intraabdominal surgical site infections for quality and safety reporting","author":"Logan","year":"2025","journal-title":"BMJ Qual. Saf."},{"key":"B21","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.alit.2023.02.008","article-title":"Meropenem allergy testing performed at the bedside of hospitalized patients labelled with a penicillin allergy","volume":"72","author":"Mar\u00edn","year":"2023","journal-title":"Allergol. Int."},{"key":"B22","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1272\/jnms.JNMS.2020_87-403","article-title":"Postoperative infection after colorectal surgery: subanalysis of data from the 2015 Japan postoperative infectious Complications survey","volume":"87","author":"Maruyama","year":"2020","journal-title":"J. Nippon. Med. Sch."},{"key":"B23","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1136\/ejhpharm-2022-003535","article-title":"Meropenem population pharmacokinetics and model-based dosing optimisation in patients with serious bacterial infection","volume":"31","author":"Mur\u00ednov\u00e1","year":"2024","journal-title":"Eur. J. Hosp. Pharm."},{"key":"B24","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s13318-021-00709-w","article-title":"Population pharmacokinetics and pharmacodynamics of meropenem in critically ill patients: how to achieve best dosage regimen according to the clinical situation","volume":"46","author":"O'Jeanson","year":"2021","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1080\/14787210.2019.1673731","article-title":"Use of meropenem in treating carbapenem-resistant enterobacteriaceae infections","volume":"17","author":"Pascale","year":"2019","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1137975","DOI":"10.3389\/fphar.2023.1137975","article-title":"Individualized antibiotic dosage regimens for patients with augmented renal clearance","volume":"14","author":"Shi","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"106968","DOI":"10.1016\/j.ijantimicag.2023.106968","article-title":"Meropenem-vaborbactam restoration of first-line drug efficacy and comparison of meropenem-vaborbactam-moxifloxacin versus bpal Mdr-Tb regimen","volume":"62","author":"Singh","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B28","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1111\/jcpt.13369","article-title":"Meropenem use and therapeutic drug monitoring in clinical practice: a literature review","volume":"46","author":"Steffens","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"ciae403","DOI":"10.1093\/cid\/ciae403","article-title":"Infectious diseases society of America 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections","author":"Tamma","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.spinee.2019.09.013","article-title":"Prophylactic postoperative measures to minimize surgical site infections in spine surgery: Systematic review and evidence summary","volume":"20","author":"Tan","year":"2020","journal-title":"Spine J."},{"key":"B31","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1177\/08968608231167237","article-title":"Population pharmacokinetics of meropenem in patients undergoing automated peritoneal dialysis","volume":"43","author":"Ullah","year":"2023","journal-title":"Perit. Dial. Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s00228-016-2172-4","article-title":"Population pharmacokinetics of meropenem in elderly patients: dosing simulations based on renal function","volume":"73","author":"Usman","year":"2017","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0045124","DOI":"10.1128\/aac.00451-24","article-title":"Meropenem pharmacokinetics in cerebrospinal fluid: comparing intermittent and continuous infusion strategies in critically ill Patients-a prospective cohort study","volume":"68","author":"Wicha","year":"2024","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1778552\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:21:25Z","timestamp":1775712085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1778552\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":33,"alternative-id":["10.3389\/fphar.2026.1778552"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1778552","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"article-number":"1778552"}}