{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:46:23Z","timestamp":1776149183651,"version":"3.50.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["25K18652"],"award-info":[{"award-number":["25K18652"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Effective sulbactam dosing regimens for treating Acinetobacter baumannii meningitis in pediatric patients, considering the degree of cerebrospinal fluid (CSF) inflammation and its consequent effect on drug penetration, have not been thoroughly studied. This study aimed to describe a cerebrospinal pharmacokinetic (PK) model of sulbactam and propose a dosing strategy in pediatric patients based on pharmacodynamic (PD) evaluation with stochastic simulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Publications were systematically extracted from MEDLINE for sulbactam CSF PK data collection. A cerebrospinal PK model was described using CSF samples and applied to estimate the probability of attaining the PK\/PD target (60% time above the minimum inhibitory concentration [T\u2009&amp;gt;\u2009MIC] in CSF). The cerebrospinal PK\/PD breakpoint was defined as the highest MIC at which the target attainment probability in CSF was \u226590% for each age group (infants [4\u00a0weeks to 11\u00a0months], children [1-6\u00a0years], and pediatrics [7-16\u00a0years]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>The study population included 21 pediatric patients aged 0.083-13.5\u00a0years. The CSF\/serum concentration ratio at the various sampling points ranged 0.002-0.695. Based on the result of covariate analysis, CSF protein and CSF glucose levels were incorporated into the CSF-to-serum partition coefficient. The visual predictive check of CSF concentrations indicated no major bias. Regarding the cerebrospinal PK\/PD evaluation, in infants and children groups with meningeal inflammation (eg, CSF protein\u2009&amp;gt;\u2009100\u00a0mg\/dL and CSF glucose\u2009&amp;lt;\u200940\u00a0mg\/dL) a sulbactam dose of 200\u00a0mg\/kg\/day (as sulbactam component) with 0.5-h infusion was required to achieve 90% probability of CSF target attainment (60% T\u2009&amp;gt;\u2009MIC) up to an MIC of 4\u00a0\u03bcg\/mL for A. baumanii.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified effective dosing regimens for A. baumannii meningitis in pediatric patients in consideration of the degree of inflammation in CSF. High-dose sulbactam regimens can be considered to optimize CSF target attainment for A. baumannii meningitis in pediatric patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpids\/piag017","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T12:14:28Z","timestamp":1773231268000},"source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal Pharmacokinetic and Pharmacodynamic Evaluation of Sulbactam: Dosing Considerations for\n                    <i>Acinetobacter baumannii<\/i>\n                    Meningitis in Pediatric Patients"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1174-0787","authenticated-orcid":false,"given":"Tetsushu","family":"Onita","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shimane University Hospital , 89-1 Enya, Izumo, Shimane 693-8501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuro","family":"Ikawa","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical and Health Sciences, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"2026041401521410100_ref1","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1093\/cid\/ciaf071","article-title":"The effectiveness of newer beta-lactams for the treatment of antimicrobial-resistant Gram-negative meningitis","volume":"80","author":"Hsu","year":"2025","journal-title":"Clin Infect Dis"},{"key":"2026041401521410100_ref2","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1128\/AAC.04808-14","article-title":"Molecular mechanisms of sulbactam antibacterial activity and resistance determinants in Acinetobacter baumannii","volume":"59","author":"Penwell","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2026041401521410100_ref3","doi-asserted-by":"publisher","first-page":"piaf004","DOI":"10.1093\/jpids\/piaf004","article-title":"Suggested dosing of select beta-lactam agents for the treatment of antimicrobial-resistant gram-negative infections in children","volume":"14","author":"Lockowitz","year":"2025","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2026041401521410100_ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/516284","article-title":"Pharmacokinetic\/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men","volume":"26","author":"Craig","year":"1998","journal-title":"Clin Infect Dis"},{"key":"2026041401521410100_ref5","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3390\/antibiotics14010092","article-title":"PK\/PD-guided strategies for appropriate antibiotic use in the era of antimicrobial resistance","volume":"14","author":"Onita","year":"2025","journal-title":"Antibiotics (Basel)"},{"key":"2026041401521410100_ref6","author":"Japanese Children's Body Size Table in 2000 for the Japanese Association for Human Auxology, Joint Committee for the Japanese Association for Human Auxologyand the Japanese Society for Pediatric Endocrinology"},{"key":"2026041401521410100_ref7","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.ijantimicag.2019.06.021","article-title":"Cerebrospinal pharmacokinetic and pharmacodynamic analysis of efficacy of meropenem in paediatric patients with bacterial meningitis","volume":"54","author":"Ohata","year":"2019","journal-title":"Int J Antimicrob Agents"},{"key":"2026041401521410100_ref8","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1002\/jcph.1800","article-title":"Prostatic pharmacokinetic\/pharmacodynamic evaluation of ampicillin-sulbactam for bacterial prostatitis and preoperative prophylaxis","volume":"61","author":"Onita","year":"2021","journal-title":"J Clin Pharmacol"},{"key":"2026041401521410100_ref9","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3390\/antibiotics12020303","article-title":"Pulmonary pharmacokinetic and pharmacodynamic evaluation of ampicillin\/sulbactam regimens for pneumonia caused by various bacteria, including Acinetobacter baumannii","volume":"12","author":"Onita","year":"2023","journal-title":"Antibiotics (Basel)"},{"key":"2026041401521410100_ref10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/jcph.6119","article-title":"Prostatic pharmacokinetic and pharmacodynamic analysis of ceftazidime: dosing strategy for bacterial prostatitis","volume":"65","author":"Onita","year":"2025","journal-title":"J Clin Pharmacol"},{"key":"2026041401521410100_ref11","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.3390\/antibiotics14101008","article-title":"Cerebrospinal pharmacokinetic modeling and pharmacodynamic simulation of high-dose cefazolin for meningitis caused by methicillin-susceptible Staphylococcus aureus","volume":"14","author":"Onita","year":"2025","journal-title":"Antibiotics."},{"key":"2026041401521410100_ref12","doi-asserted-by":"publisher","first-page":"piaf043","DOI":"10.1093\/jpids\/piaf043","article-title":"Population pharmacokinetic analysis and pharmacodynamic evaluation of sulbactam in pediatric patients: dosing suggestions for Acinetobacter baumannii infections","volume":"14","author":"Onita","year":"2025","journal-title":"J Pediatric Infect Dis Soc"},{"key":"2026041401521410100_ref13","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1093\/brain\/91.4.707","article-title":"Formation and absorption of cerebrospinal fluid in man","volume":"91","author":"Cutler","year":"1968","journal-title":"Brain"},{"key":"2026041401521410100_ref14","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.cmpb.2003.11.003","article-title":"Perl-speaks-NONMEM (PsN)\u2014a Perl module for NONMEM related programming","volume":"75","author":"Lindbom","year":"2004","journal-title":"Comput Methods Prog Biomed"},{"key":"2026041401521410100_ref15","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ijantimicag.2014.02.012","article-title":"Pharmacokinetic\/pharmacodynamic evaluation of sulbactam against Acinetobacter baumannii in in vitro and murine thigh and lung infection models","volume":"43","author":"Yokoyama","year":"2014","journal-title":"Int J Antimicrob Agents"},{"key":"2026041401521410100_ref16","volume-title":"M100: Performance Standards for Antimicrobial Susceptibility Testing","author":"Clinical and Laboratory Standards Institute"},{"key":"2026041401521410100_ref17","first-page":"579","article-title":"Pharmacokinetic and bacteriological studies on sulbactam\/ampicillin in the field of pediatrics","volume":"42","author":"Sato","year":"1989","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref18","first-page":"623","article-title":"Clinical and pharmacokinetic studies on intravenous administration of sulbactam\/ampicillin in pediatrics","volume":"42","author":"Sato","year":"1989","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref19","first-page":"651","article-title":"Pharmacokinetic and clinical studies on sulbactam\/ampicillin in the pediatric field","volume":"42","author":"Ito","year":"1989","journal-title":"Jpn J Antibiot"},{"key":"2026041401521410100_ref20","first-page":"687","article-title":"Laboratory and clinical studies of sulbactam\/ampicillin in pediatric field","volume":"42","author":"Nishimura","year":"1989","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref21","first-page":"733","article-title":"Clinical experience with sulbactam\/ampicillin in the pediatric field","volume":"42","author":"Sekiguchi","year":"1989","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref22","first-page":"1788","article-title":"Clinical experience on sulbactam\/cefoperazone in the pediatric field","volume":"37","author":"Honjo","year":"1984","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref23","first-page":"1821","article-title":"Clinical evaluation of sulbactam\/cefoperazone in the pediatric infections","volume":"37","author":"Meguro H","year":"1984","journal-title":"Jpn J Antibiot"},{"key":"2026041401521410100_ref24","first-page":"1880","article-title":"Laboratory and clinical studies of sulbactam\/cefoperazone in the pediatric field","volume":"37","author":"Nishimura","year":"1984","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref25","first-page":"1898","article-title":"Fundamental and clinical studies of sulbactam\/cefoperazone in the pediatric field","volume":"37","author":"Motohiro","year":"1984","journal-title":"Jpn J Antibiot."},{"key":"2026041401521410100_ref26","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1093\/jac\/dkaa208","article-title":"In vitro activity of sulbactam\/durlobactam against global isolates of carbapenem-resistant Acinetobacter baumannii","volume":"75","author":"Seifert","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2026041401521410100_ref27","doi-asserted-by":"publisher","first-page":"e02534","DOI":"10.1128\/AAC.02534-19","article-title":"In vitro activity of sulbactam durlobactam against Acinetobacter baumannii-calcoaceticus complex isolates collected globally in 2016 and 2017","volume":"64","author":"McLeod","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2026041401521410100_ref28","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1128\/AAC.31.11.1703","article-title":"Penetration of sulbactam and ampicillin into cerebrospinal fluid of infants and young children with meningitis","volume":"31","author":"Foulds","year":"1987","journal-title":"Antimicrob Agents Chemother"},{"key":"2026041401521410100_ref29","doi-asserted-by":"publisher","first-page":"S612","DOI":"10.1093\/clinids\/8.Supplement_5.S612","article-title":"Penetration of sulbactam into the cerebrospinal fluid of patients with bacterial meningitis receiving ampicillin therapy","volume":"8","author":"Stahl","year":"1986","journal-title":"Rev Infect Dis"},{"key":"2026041401521410100_ref30","doi-asserted-by":"publisher","first-page":"S620","DOI":"10.1093\/clinids\/8.Supplement_5.S620","article-title":"Sulbactam\/ampicillin vs. chloramphenicol\/ampicillin for the treatment of meningitis in infants and children","volume":"8","author":"Rodr\u00edguez","year":"1986","journal-title":"Rev Infect Dis"},{"key":"2026041401521410100_ref31","doi-asserted-by":"publisher","first-page":"S609","DOI":"10.1093\/clinids\/8.Supplement_5.S609","article-title":"Penetration of sulbactam into cerebrospinal fluid of patients with viral meningitis or without meningitis","volume":"8","author":"H\u00e4nninen","year":"1986","journal-title":"Rev Infect Dis"},{"key":"2026041401521410100_ref32","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s40262-017-0588-3","article-title":"Antibiotic distribution into cerebrospinal fluid: can dosing safely account for drug and disease factors in the treatment of ventriculostomy-associated infections?","volume":"57","author":"Kumta","year":"2018","journal-title":"Clin Pharmacokinet"},{"key":"2026041401521410100_ref33","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1097\/INF.0000000000004582","article-title":"Therapeutic drug monitoring of high-dose sulbactam in pediatric patients: preliminary data from a prospective observational pharmacokinetic study","volume":"44","author":"Charoenwong","year":"2025","journal-title":"Pediatr Infect Dis J"}],"container-title":["Journal of the Pediatric Infectious Diseases Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpids\/advance-article-pdf\/doi\/10.1093\/jpids\/piag017\/67298646\/piag017.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpids\/article-pdf\/15\/4\/piag017\/67298646\/piag017.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpids\/article-pdf\/15\/4\/piag017\/67298646\/piag017.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:52:22Z","timestamp":1776145942000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpids\/article\/doi\/10.1093\/jpids\/piag017\/8514077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,14]]}},"URL":"https:\/\/doi.org\/10.1093\/jpids\/piag017","relation":{},"ISSN":["2048-7207"],"issn-type":[{"value":"2048-7207","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,11]]},"article-number":"piag017"}}