{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:12:43Z","timestamp":1753877563168,"version":"3.41.2"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Pseudomonas aeruginosa is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP\/VABP). Novel \u03b2-lactam\/\u03b2-lactamase inhibitor (BL\/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL\/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index \u226535\u2005kg\/m2) and non\u2013morbidly obese (&amp;lt;35\u2005kg\/m2) and receiving BL\/BLI for P aeruginosa HABP\/VABP.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This retrospective study was based on a cohort of patients hospitalized at 2 urban academic medical centers in Detroit, Michigan, from August 2014 through February 2021 with P aeruginosa HABP\/VABP who were receiving BL\/BLI (ceftazidime\/avibactam, ceftolozane\/tazobactam, or meropenem\/vaborbactam) for \u226572 continuous hours. The primary endpoint was presumed treatment failure, defined as the presence of all-cause in-hospital mortality or the continuation of infectious symptoms. Analyses were adjusted for possible confounding with inverse probability of treatment weighting. Multivariable regression was used to identify predictors of treatment failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 285 patients with HABP (61.4%) and\/or VABP (56.1%) were enrolled (morbidly obese, n = 95; non\u2013morbidly obese, n = 190). The median Acute Physiology and Chronic Health Evaluation II score was 23 (IQR, 13\u201326), and 60% of patients were admitted to the intensive care unit at index culture collection. Patients who were morbidly obese demonstrated significantly greater odds of presumed treatment failure vs those who were non\u2013morbidly obese (58.9% vs 37.9%, respectively; adjusted odds ratio, 1.675 [95% CI, 1.465\u20131.979]). In multivariable analysis, morbid obesity (1.06; 95% CI, 1.02\u20131.79), prolonged time to BL\/BLI initiation (1.47; 95% CI, 1.28\u20132.66), renal dose\u2013adjusted BL\/BLI in the first 48 hours of therapy (1.12; 95% CI, 1.09\u20131.75), and continuous renal replacement therapy during BL\/BLI therapy (1.35; 95% CI, 1.06\u20131.68) were independently associated with increased odds of presumed treatment failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among hospitalized patients receiving BL\/BLI for P aeruginosa HABP\/VABP, those who were morbidly obese had significantly greater odds of presumed treatment failure when compared with those who were non\u2013morbidly obese.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofad454","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T14:01:53Z","timestamp":1692972113000},"source":"Crossref","is-referenced-by-count":3,"title":["Weighing the Odds: Novel \u03b2-Lactam\/\u03b2-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated <i>Pseudomonas aeruginosa<\/i> Pneumonia for Patients Who Are Morbidly Obese"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-8625","authenticated-orcid":false,"given":"Ashlan J","family":"Kunz Coyne","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"},{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Orzol","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"},{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5967-5211","authenticated-orcid":false,"given":"Michael P","family":"Veve","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"},{"name":"Department of Pharmacy, Henry Ford Hospital , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0081","authenticated-orcid":false,"given":"Michael J","family":"Rybak","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"},{"name":"Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University , Detroit, Michigan , USA"},{"name":"Department of Pharmacy Services, Detroit Receiving Hospital, Detroit Medical Center , Detroit, Michigan , USA"},{"name":"Division of Infectious Diseases, School of Medicine, Wayne State University , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"year":"2022","key":"2023091403594564500_ofad454-B1"},{"key":"2023091403594564500_ofad454-B2","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: a systematic analysis for the global burden of disease study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"2023091403594564500_ofad454-B3","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/oby.2005.49","article-title":"Obesity and the use of health care services","volume":"13","author":"Bertakis","year":"2005","journal-title":"Obes Res"},{"key":"2023091403594564500_ofad454-B4"},{"key":"2023091403594564500_ofad454-B5"},{"key":"2023091403594564500_ofad454-B6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/j.1467-789X.2008.00546.x","article-title":"Effect of body mass index on the outcome of infections: a systematic review","volume":"10","author":"Falagas","year":"2009","journal-title":"Obes Rev"},{"key":"2023091403594564500_ofad454-B7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ijo.2012.62","article-title":"Obesity and the risk and outcome of infection","volume":"37","author":"Huttunen","year":"2013","journal-title":"Int J Obes"},{"key":"2023091403594564500_ofad454-B8"},{"key":"2023091403594564500_ofad454-B9"},{"key":"2023091403594564500_ofad454-B10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/phar.2769","article-title":"Comprehensive guidance for antibiotic dosing in obese adults: 2022 update","volume":"43","author":"Meng","year":"2023","journal-title":"Pharmacotherapy"},{"key":"2023091403594564500_ofad454-B11","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ijantimicag.2016.01.009","article-title":"Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review","volume":"47","author":"Alobaid","year":"2016","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B12","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1097\/CCM.0000000000002287","article-title":"Repeated piperacillin-tazobactam plasma concentration measurements in severely obese versus nonobese critically ill septic patients and the risk of under- and overdosing","volume":"45","author":"Jung","year":"2017","journal-title":"Crit Care Med"},{"key":"2023091403594564500_ofad454-B13","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40121-022-00591-2","article-title":"Therapeutic strategies for emerging multidrug-resistant Pseudomonas aeruginosa","volume":"11","author":"Kunz Coyne","year":"2022","journal-title":"Infect Dis Ther"},{"key":"2023091403594564500_ofad454-B14","doi-asserted-by":"crossref","first-page":"e169","DOI":"10.1093\/cid\/ciaa1478","article-title":"Infectious Diseases Society of America guidance on the treatment of extended-spectrum \u03b2-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P aeruginosa)","volume":"72","author":"Tamma","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B15","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.ijantimicag.2018.03.004","article-title":"Ceftolozane\/tazobactam dose regimens in severely\/morbidly obese patients with complicated intra-abdominal infection or complicated urinary tract infection","volume":"52","author":"Xiao","year":"2018","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B16","doi-asserted-by":"crossref","first-page":"6898","DOI":"10.3390\/jcm11236898","article-title":"Pharmacokinetics, pharmacodynamics, and dosing considerations of novel \u03b2-lactams and \u03b2-lactam\/\u03b2-lactamase inhibitors in critically ill adult patients: focus on obesity, augmented renal clearance, renal replacement therapies, and extracorporeal membrane oxygenation","volume":"11","author":"Bakdach","year":"2022","journal-title":"J Clin Med"},{"key":"2023091403594564500_ofad454-B17","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ajic.2008.03.002","article-title":"CDC\/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting","volume":"36","author":"Horan","year":"2008","journal-title":"Am J Infect Control"},{"key":"2023091403594564500_ofad454-B18"},{"key":"2023091403594564500_ofad454-B19"},{"key":"2023091403594564500_ofad454-B20"},{"key":"2023091403594564500_ofad454-B21"},{"key":"2023091403594564500_ofad454-B22","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1093\/cid\/ciz528","article-title":"The Pitt bacteremia score predicts mortality in nonbacteremic infections","volume":"70","author":"Henderson","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B23","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)\u2014a metadata-driven methodology and workflow process for providing translational research informatics support","volume":"42","author":"Harris","year":"2009","journal-title":"J Biomed Inform"},{"key":"2023091403594564500_ofad454-B24","doi-asserted-by":"crossref","first-page":"3661","DOI":"10.1002\/sim.6607","article-title":"Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies","volume":"34","author":"Austin","year":"2015","journal-title":"Stat Med"},{"key":"2023091403594564500_ofad454-B25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/cid\/cix014","article-title":"Multicenter evaluation of ceftolozane\/tazobactam for serious infections caused by carbapenem-resistant Pseudomonas aeruginosa","volume":"65","author":"Munita","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/cid\/cix182","article-title":"Ceftolozane-tazobactam for the treatment of multidrug-resistant Pseudomonas aeruginosa infections: clinical effectiveness and evolution of resistance","volume":"65","author":"Haidar","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B27","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.ijantimicag.2018.11.001","article-title":"Ceftolozane\/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience","volume":"53","author":"Bassetti","year":"2019","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B28","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.ijantimicag.2017.04.001","article-title":"Use of ceftolozane\/tazobactam as salvage therapy for infections due to extensively drug-resistant Pseudomonas aeruginosa","volume":"49","author":"Dinh","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s15010-018-1133-5","article-title":"Ceftolozane\/tazobactam for the treatment of XDR Pseudomonas aeruginosa infections","volume":"46","author":"Escol\u00e0-Verg\u00e9","year":"2018","journal-title":"Infection"},{"key":"2023091403594564500_ofad454-B30","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/cid\/civ411","article-title":"Ceftolozane\/tazobactam therapy of respiratory infections due to multidrug-resistant Pseudomonas aeruginosa","volume":"61","author":"Gelfand","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B31"},{"key":"2023091403594564500_ofad454-B32","doi-asserted-by":"crossref","first-page":"106517","DOI":"10.1016\/j.ijantimicag.2021.106517","article-title":"Effectiveness of ceftazidime-avibactam for the treatment of infections due to Pseudomonas aeruginosa","volume":"59","author":"Corbella","year":"2022","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B33","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofz522","article-title":"Real-world experience with ceftazidime-avibactam for multidrug-resistant gram-negative bacterial infections","volume":"6","author":"Jorgensen","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2023091403594564500_ofad454-B34","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab371","article-title":"Real-world, multicenter experience with meropenem-vaborbactam for gram-negative bacterial infections including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa","volume":"8","author":"Alosaimy","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2023091403594564500_ofad454-B35","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S1473-3099(19)30403-7","article-title":"Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): a randomised, controlled, double-blind, phase 3, non-inferiority trial","volume":"19","author":"Kollef","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2023091403594564500_ofad454-B36","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofz149","article-title":"Randomized trial of ceftazidime-avibactam vs meropenem for treatment of hospital-acquired and ventilator-associated bacterial pneumonia (REPROVE): analyses per US FDA-specified end points","volume":"6","author":"Torres","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2023091403594564500_ofad454-B37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s40121-018-0214-1","article-title":"Effect and safety of meropenem\u2013vaborbactam versus best-available therapy in patients with carbapenem-resistant Enterobacteriaceae infections: the TANGO II randomized clinical trial","volume":"7","author":"Wunderink","year":"2018","journal-title":"Infect Dis Ther"},{"key":"2023091403594564500_ofad454-B38","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/cid\/civ097","article-title":"Ceftolozane\/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI)","volume":"60","author":"Solomkin","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2023091403594564500_ofad454-B39","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(14)62220-0","article-title":"Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI)","volume":"385","author":"Wagenlehner","year":"2015","journal-title":"Lancet"},{"key":"2023091403594564500_ofad454-B40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s13054-019-2434-5","article-title":"Optimizing ceftolozane-tazobactam dosage in critically ill patients during continuous venovenous hemodiafiltration","volume":"23","author":"Aguilar","year":"2019","journal-title":"Crit Care"},{"key":"2023091403594564500_ofad454-B41"},{"key":"2023091403594564500_ofad454-B42","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ijantimicag.2016.06.005","article-title":"Treatment of multidrug-resistant Pseudomonas aeruginosa with ceftolozane\/tazobactam in a critically ill patient receiving continuous venovenous haemodiafiltration","volume":"48","author":"Kuti","year":"2016","journal-title":"Int J Antimicrob Agents"},{"key":"2023091403594564500_ofad454-B43","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1038\/nutd.2014.15","article-title":"Broad-spectrum \u03b2-lactams in obese non-critically ill patients","volume":"4","author":"Hites","year":"2014","journal-title":"Nutr Diabetes"},{"key":"2023091403594564500_ofad454-B44","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1128\/AAC.01083-12","article-title":"Case-control study of drug monitoring of \u03b2-lactams in obese critically ill patients","volume":"57","author":"Hites","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"2023091403594564500_ofad454-B45","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/bcp.15586","article-title":"Clinical efficacy of renal dosing adjustments of ceftazidime-avibactam in patients affected by carbapenem-resistant gram-negative infections: a systematic review and meta-analysis of observational studies","volume":"89","author":"Gatti","year":"2023","journal-title":"Br J Clin Pharmacol"},{"key":"2023091403594564500_ofad454-B46","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/jcph.812","article-title":"Population pharmacokinetics and pharmacodynamics of meropenem in nonobese, obese, and morbidly obese patients","volume":"57","author":"Chung","year":"2017","journal-title":"J Clin Pharmacol"},{"key":"2023091403594564500_ofad454-B47","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1128\/AAC.00531-16","article-title":"Effect of obesity on the population pharmacokinetics of meropenem in critically ill patients","volume":"60","author":"Alobaid","year":"2016","journal-title":"Antimicrob Agents Chemother"},{"key":"2023091403594564500_ofad454-B48"},{"key":"2023091403594564500_ofad454-B49","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.3390\/jcm10194382","article-title":"The impact of morbid obesity on the health outcomes of hospital inpatients: an observational study","volume":"10","author":"Fusco","year":"2021","journal-title":"J Clin Med"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofad454\/51276598\/ofad454.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/9\/ofad454\/51546676\/ofad454.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/9\/ofad454\/51546676\/ofad454.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T04:13:43Z","timestamp":1694664823000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofad454\/7252628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,28]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofad454","relation":{},"ISSN":["2328-8957"],"issn-type":[{"type":"electronic","value":"2328-8957"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,8,28]]},"article-number":"ofad454"}}