{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T17:51:20Z","timestamp":1792950680150,"version":"4.5.0"},"reference-count":108,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Sepsis-associated acute kidney injury (SA-AKI) often requires renal replacement therapy (RRT), which markedly alters antimicrobial pharmacokinetics (PK) and pharmacodynamics (PD). Novel \u03b2-lactam\/\u03b2-lactamase inhibitor (BL\/BLI) combinations broaden options against multidrug-resistant Gram-negative bacteria, but dosing during RRT remains uncertain. This review summarizes PK\/PD features, extracorporeal clearance, and practical dosing considerations about ceftolozane\u2013tazobactam, ceftazidime\u2013avibactam, aztreonam\u2013avibactam, cefiderocol, meropenem\u2013vaborbactam, imipenem\u2013relebactam, and newer agents including sulbactam\u2013durlobactam, cefepime\u2013enmetazobactam, and cefepime\u2013taniborbactam. Pharmacokinetic data, RRT impact, PK\/PD targets, pediatric aspects, and clinical outcomes were extracted from experimental models, case reports, and clinical studies. Drug exposure varies with RRT modality, effluent flow, membrane properties, and patient-specific factors such as augmented renal clearance, hypoalbuminemia, and fluid overload. Standard renal-adjusted dosing often yields subtherapeutic concentrations in critically ill patients. Pediatric data remain scarce and largely limited to case reports. Optimal BL\/BLI use in septic patients with SA-AKI on RRT requires individualized dosing that accounts for PK\/PD variability and dialysis settings. Full-dose initiation during the first 24\u201348 h, followed by careful adjustment, appears prudent. Therapeutic drug monitoring should be used when available, and institution-specific protocols should be integrated into stewardship programs to improve efficacy and minimize resistance.<\/jats:p>","DOI":"10.3390\/antibiotics14111097","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"1097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["\u03b2-Lactam\/\u03b2-Lactamase Inhibitor Combinations in Sepsis-Associated Acute Kidney Injury and Renal Replacement Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1705-8770","authenticated-orcid":false,"given":"Antonio","family":"Lacquaniti","sequence":"first","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Internal Medicine, Papardo Hospital, 98158 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-9462","authenticated-orcid":false,"given":"Valentina","family":"Pistolesi","sequence":"additional","affiliation":[{"name":"Hemodialysis Unit, Department of Internal Medicine and Clinical Sciences, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-304X","authenticated-orcid":false,"given":"Antonella","family":"Smeriglio","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Santoro","sequence":"additional","affiliation":[{"name":"Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Iannetti","sequence":"additional","affiliation":[{"name":"Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0537-9943","authenticated-orcid":false,"given":"Giuseppe","family":"Lentini","sequence":"additional","affiliation":[{"name":"Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-4637","authenticated-orcid":false,"given":"Roberto","family":"Chimenz","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Chirico","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology and Dialysis Unit, University Hospital \u201cG. Martino\u201d, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-5224","authenticated-orcid":false,"given":"Domenico","family":"Trombetta","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4897-1602","authenticated-orcid":false,"given":"Santo","family":"Morabito","sequence":"additional","affiliation":[{"name":"Hemodialysis Unit, Department of Internal Medicine and Clinical Sciences, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Sapienza University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-5022","authenticated-orcid":false,"given":"Paolo","family":"Monardo","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, Department of Internal Medicine, Papardo Hospital, 98158 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"J. Am. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13054-020-02950-2","article-title":"Mortality in Sepsis and Septic Shock in Europe, North America and Australia between 2009 and 2019\u2014Results from a Systematic Review and Meta-Analysis","volume":"24","author":"Bauer","year":"2020","journal-title":"Crit. Care"},{"key":"ref_3","unstructured":"GBD 2019 Antimicrobial Resistance Collaborators (2022). Global Mortality Associated with 33 Bacterial Pathogens in 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet, 400, 2221\u20132248."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1097\/01.CCM.0000217961.75225.E9","article-title":"Duration of Hypotension before Initiation of Effective Antimicrobial Therapy Is the Critical Determinant of Survival in Human Septic Shock","volume":"34","author":"Kumar","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13054-021-03883-0","article-title":"Time-to-Antibiotics and Clinical Outcomes in Patients with Sepsis and Septic Shock: A Prospective Nationwide Multicentre Cohort Study","volume":"26","author":"Im","year":"2022","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1097\/CCM.0000000000004863","article-title":"The Association between Antibiotic Delay Intervals and Hospital Mortality among Patients Treated in the Emergency Department for Suspected Sepsis","volume":"49","author":"Taylor","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1097\/CCM.0b013e31821e87ab","article-title":"Association between Timing of Antibiotic Administration and Mortality from Septic Shock in Patients Treated with a Quantitative Resuscitation Protocol","volume":"39","author":"Puskarich","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1093\/cid\/cix997","article-title":"Infectious Diseases Society of America (IDSA) Position Statement: Why IDSA Did Not Endorse the Surviving Sepsis Campaign Guidelines","volume":"66","author":"Force","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/cid\/ciaa059","article-title":"Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure","volume":"72","author":"Rhee","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1001\/jamainternmed.2016.5651","article-title":"Estimating National Trends in Inpatient Antibiotic Use among US Hospitals from 2006 to 2012","volume":"176","author":"Baggs","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_11","first-page":"48","article-title":"Dosing Errors of Empirical Antibiotics in Critically Ill Patients with Severe Sepsis or Septic Shock: A Prospective Observational Study","volume":"13","author":"Eissa","year":"2019","journal-title":"Int. J. Health Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1007\/s00134-014-3403-8","article-title":"Risk Factors for Target Non-attainment during Empirical Treatment with \u03b2-Lactam Antibiotics in Critically Ill Patients","volume":"40","author":"Lipman","year":"2014","journal-title":"Intensive Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ijantimicag.2013.06.021","article-title":"Can Changes in Renal Function Predict Variations in Beta-Lactam Concentrations in Septic Patients?","volume":"42","author":"Casu","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1093\/cid\/ciaa224","article-title":"The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study","volume":"72","author":"Roberts","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1097\/CCM.0b013e3181aab3d0","article-title":"Principles of Antibacterial Dosing in Continuous Renal Replacement Therapy","volume":"37","author":"Choi","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1128\/AAC.37.5.1065","article-title":"Development of a Population Pharmacokinetic Model and Optimal Sampling Strategies for Intravenous Ciprofloxacin","volume":"37","author":"Forrest","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2165\/00003088-200847030-00003","article-title":"Population Pharmacokinetics of Meropenem in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy","volume":"47","author":"Isla","year":"2008","journal-title":"Clin. Pharmacokinet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mahmoud, S.H., and Shen, C. (2017). Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9030036"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1378\/chest.11-1671","article-title":"Subtherapeutic Initial Beta-Lactam Concentrations in Select Critically Ill Patients: Association between Augmented Renal Clearance and Low Trough Drug Concentrations","volume":"142","author":"Udy","year":"2012","journal-title":"Chest"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.ijantimicag.2011.12.011","article-title":"Augmented Renal Clearance in Septic Patients and Implications for Vancomycin Optimisation","volume":"39","author":"Baptista","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1007\/s00134-007-0745-5","article-title":"Replacement of 24-h Creatinine Clearance by 2-h Creatinine Clearance in Intensive Care Unit Patients: A Single-Centre Study","volume":"33","year":"2007","journal-title":"Intensive Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial Therapeutic Drug Monitoring in Critically Ill Adult Patients: A Position Paper","volume":"46","author":"Alffenaar","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R206","DOI":"10.1186\/cc10441","article-title":"Antibiotics in Critically Ill Patients: A Systematic Review of the Pharmacokinetics of Beta-Lactams","volume":"15","year":"2011","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6165","DOI":"10.1128\/AAC.00951-13","article-title":"Protein Binding of Beta-Lactam Antibiotics in Critically Ill Patients: Can We Successfully Predict Unbound Concentrations?","volume":"57","author":"Wong","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pereira, J.G., Fernandes, J., Duarte, A.R., and Fernandes, S.M. (2022). \u03b2-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121839"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4037\/aacnacc2017386","article-title":"Considerations for Medication Management and Anticoagulation during Continuous Renal Replacement Therapy","volume":"28","author":"Thompson","year":"2017","journal-title":"AACN Adv. Crit. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00583-19","DOI":"10.1128\/AAC.00583-19","article-title":"A Guide to Understanding Antimicrobial Drug Dosing in Critically Ill Patients on Renal Replacement Therapy","volume":"63","author":"Pistolesi","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bpa.2003.09.002","article-title":"Influence of Renal Replacement Therapy on Pharmacokinetics in Critically Ill Patients","volume":"18","author":"Bugge","year":"2004","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s40560-020-00504-w","article-title":"The Higher the Better? Defining the Optimal Beta-Lactam Target for Critically Ill Patients to Reach Infection Resolution and Improve Outcome","volume":"8","author":"Scharf","year":"2020","journal-title":"J. Intensive Care"},{"key":"ref_30","unstructured":"European Medicines Agency (2016). Guideline on the Use of Pharmacokinetics and Pharmacodynamics in the Development of Antimicrobial Medicinal Products, European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-use-pharmacokinetics-and-pharmacodynamics-development-antimicrobial-medicinal-products_en.pdf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2014.07.006","article-title":"The Effect of Pathophysiology on Pharmacokinetics in the Critically Ill Patient\u2014Concepts Appraised by the Example of Antimicrobial Agents","volume":"77","author":"Blot","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1186\/s13054-020-03272-z","article-title":"Failure of Target Attainment of Beta-Lactam Antibiotics in Critically Ill Patients and Associated Risk Factors: A Two-Centre Prospective Study (EXPAT)","volume":"24","author":"Abdulla","year":"2020","journal-title":"Crit. Care"},{"key":"ref_33","unstructured":"(2024, December 30). Zerbaxa\u00ae Ceftolozane and Tazobactam for Injection. Available online: https:\/\/www.merck.com\/product\/usa\/pi_circulars\/z\/zerbaxa\/zerbaxa_pi.pdf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/jac\/dkae058","article-title":"What Are the Optimal Pharmacokinetic\/Pharmacodynamic Targets for \u03b2-Lactamase Inhibitors? A Systematic Review","volume":"79","author":"Assefa","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13054-019-2378-9","article-title":"Optimisation of the Treatment with Beta-Lactam Antibiotics in Critically Ill Patients\u2014Guidelines from the French Society of Pharmacology and Therapeutics (Soci\u00e9t\u00e9 Fran\u00e7aise de Pharmacologie et Th\u00e9rapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Soci\u00e9t\u00e9 Fran\u00e7aise d\u2019Anesth\u00e9sie et R\u00e9animation-SFAR)","volume":"23","author":"Guilhaumou","year":"2019","journal-title":"Crit. Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40265-013-0168-2","article-title":"Ceftolozane\/Tazobactam: A Novel Cephalosporin\/Beta-Lactamase Inhibitor Combination with Activity against Multidrug-Resistant Gram-Negative Bacilli","volume":"74","author":"Zhanel","year":"2014","journal-title":"Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jcph.793","article-title":"Phase 1 Study Assessing the Pharmacokinetic Profile and Safety of Avibactam in Patients with Renal Impairment","volume":"57","author":"Merdjan","year":"2017","journal-title":"J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1128\/AAC.02151-13","article-title":"Impact of Renal Function on the Pharmacokinetics and Safety of Ceftolozane\u2013Tazobactam","volume":"58","author":"Wooley","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/hdi.13090","article-title":"Microbiologic Outcomes of Ceftazidime\u2013Avibactam Dosing in Patients with Sepsis Utilising Renal Replacement Therapies","volume":"27","author":"Abidi","year":"2023","journal-title":"Hemodial. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/jac\/dkaa416","article-title":"Ceftolozane\/Tazobactam Exposure in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy: A PK\/PD Approach to Tailor Dosing","volume":"76","author":"Gatti","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1002\/phar.1744","article-title":"Ceftolozane\/Tazobactam Pharmacokinetics in a Critically Ill Adult Receiving Continuous Renal Replacement Therapy","volume":"36","author":"Bremmer","year":"2016","journal-title":"Pharmacotherapy"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"El Nekidy, W.S., Al Ali, M., Abidi, E., El Lababidi, R., Alrahmany, D., Ghazi, I.M., Mooty, M., Hijazi, F., Ghosn, M., and Mallat, J. (2024). Clinical Outcomes of Ceftazidime\u2013Avibactam versus Ceftolozane\u2013Tazobactam in Managing Pseudomonal Infections in Patients Undergoing Renal Replacement Therapy. Antibiotics, 13.","DOI":"10.3390\/antibiotics13080699"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1093\/jac\/dkx221","article-title":"Determination of Alternative Ceftolozane\/Tazobactam Dosing Regimens for Patients with Infections Due to Pseudomonas aeruginosa with MIC Values between 4 and 32 mg\/L","volume":"72","author":"Natesan","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Butrague\u00f1o-Laiseca, L., Troconiz, I.F., Grau, S., Campillo, N., Garc\u00eda, X., Padilla, B., Fern\u00e1ndez, S.N., and Santiago, M.J. (2020). Finding the Dose for Ceftolozane\u2013Tazobactam in Critically Ill Children with and without Acute Kidney Injury. Antibiotics, 9.","DOI":"10.3390\/antibiotics9120887"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s40265-013-0013-7","article-title":"Ceftazidime\u2013Avibactam: A Novel Cephalosporin\/\u03b2-Lactamase Inhibitor Combination","volume":"73","author":"Zhanel","year":"2013","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1378\/chest.10-2371","article-title":"Antibiotic Dosing in Multiple Organ Dysfunction Syndrome","volume":"139","author":"Ulldemolins","year":"2011","journal-title":"Chest"},{"key":"ref_47","unstructured":"Food and Drug Administration (2025, March 30). Highlights of Prescribing Information. Ceftazidime\u2013Avibactam Package Insert. Allergen. AVYCAZ Safely and Effectively, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/206494s000lbl.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00464-17","DOI":"10.1128\/AAC.00464-17","article-title":"Pharmacokinetics and Dialytic Clearance of Ceftazidime\u2013Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration","volume":"61","author":"Wenzler","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1002\/phar.2338","article-title":"Steady-State Ceftazidime\u2013Avibactam Serum Concentrations and Dosing Recommendations in a Critically Ill Patient Being Treated for Pseudomonas aeruginosa Pneumonia and Undergoing Continuous Venovenous Hemodiafiltration","volume":"39","author":"Soukup","year":"2019","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e02497-17","DOI":"10.1128\/AAC.02497-17","article-title":"Pneumonia and Renal Replacement Therapy Are Risk Factors for Ceftazidime\u2013Avibactam Treatment Failures and Resistance among Patients with Carbapenem-Resistant Enterobacteriaceae Infections","volume":"62","author":"Shields","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e02097-16","DOI":"10.1128\/AAC.02097-16","article-title":"Emergence of Ceftazidime\u2013Avibactam Resistance Due to Plasmid-Borne blaKPC-3 Mutations during Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections","volume":"61","author":"Shields","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.2147\/IDR.S320056","article-title":"Carbapenem-Resistant Klebsiella pneumoniae Osteomyelitis Treated with Ceftazidime\u2013Avibactam in an Infant: A Case Report","volume":"14","author":"Ji","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.2147\/IDR.S369368","article-title":"Ceftazidime\u2013Avibactam as Salvage Therapy in Paediatric Liver Transplantation Patients with Infections Caused by Carbapenem-Resistant Enterobacterales","volume":"15","author":"Wang","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1097\/INF.0000000000003716","article-title":"Ceftolozane\/Tazobactam and Ceftazidime\/Avibactam: An Italian Multi-Centre Retrospective Analysis of Safety and Efficacy in Children with Haematologic Malignancies and Multi-Drug Resistant Gram-Negative Bacteria Infections","volume":"41","author":"Perruccio","year":"2022","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.2147\/IDR.S426326","article-title":"Use of Ceftazidime\u2013Avibactam for Suspected or Confirmed Carbapenem-Resistant Organisms in Children: A Retrospective Study","volume":"16","author":"Meng","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Araujo da Silva, A.R., and Quijada, R. (2024). Use of Ceftazidime\u2013Avibactam in Children Admitted to Paediatric Intensive Care Units. Children, 11.","DOI":"10.21203\/rs.3.rs-3979740\/v1"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Li, D., Yu, H., Huang, X., Long, S., and Zhang, J. (2023). In Vitro Activity of Ceftazidime\u2013Avibactam, Imipenem\u2013Relebactam, Aztreonam\u2013Avibactam, and Comparators toward Carbapenem-Resistant and Hypervirulent Isolates. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.02806-23"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ran, X., Chen, X., Wang, C., Wang, H., Xie, W., and Jing, C. (2025). Carbapenem-Resistant Klebsiella pneumoniae Infections in Chinese Children: In Vitro Activities of Ceftazidime\u2013Avibactam and Aztreonam\u2013Avibactam against Carbapenemase-Producing Strains in a Two-Centre Study. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1545999"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11663","DOI":"10.1073\/pnas.1205073109","article-title":"Avibactam Is a Covalent, Reversible, Non-\u03b2-Lactam \u03b2-Lactamase Inhibitor","volume":"109","author":"Ehmann","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S1473-3099(24)00499-7","article-title":"Aztreonam\u2013Avibactam versus Meropenem for the Treatment of Serious Infections Caused by Gram-Negative Bacteria (REVISIT): A Descriptive, Multinational, Open-Label, Phase 3, Randomised Trial","volume":"25","author":"Carmeli","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40261-015-0347-x","article-title":"A Randomised, Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Ceftazidime\u2013Avibactam in Healthy Chinese Subjects","volume":"36","author":"Li","year":"2016","journal-title":"Clin. Drug Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"154301","DOI":"10.1016\/j.jcrc.2023.154301","article-title":"A Descriptive Pharmacokinetic\/Pharmacodynamic Analysis of Continuous Infusion Ceftazidime\u2013Avibactam for Treating DTR Gram-Negative Infections in a Case Series of Critically Ill Patients Undergoing Continuous Veno-Venous Haemodiafiltration (CVVHDF)","volume":"76","author":"Gatti","year":"2023","journal-title":"J. Crit. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e0093522","DOI":"10.1128\/aac.00935-22","article-title":"Safety of Ceftazidime\u2013Avibactam in Combination with Aztreonam (COMBINE) in a Phase I, Open-Label Study in Healthy Adult Volunteers","volume":"66","author":"Lodise","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1093\/jac\/dkz497","article-title":"Pharmacokinetics and Safety of Aztreonam\/Avibactam for the Treatment of Complicated Intra-Abdominal Infections in Hospitalised Adults: Results from the REJUVENATE Study","volume":"75","author":"Cornely","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13613-023-01153-6","article-title":"Rationale and Evidence for the Use of New Beta-Lactam\/Beta-Lactamase Inhibitor Combinations and Cefiderocol in Critically Ill Patients","volume":"13","author":"Barbier","year":"2023","journal-title":"Ann. Intensive Care"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"106776","DOI":"10.1016\/j.ijantimicag.2023.106776","article-title":"Activity of Aztreonam\/Avibactam Against Metallo-\u03b2-Lactamase-Producing Enterobacterales from the UK: Impact of Penicillin-Binding Protein-3 Inserts and CMY-42 \u03b2-Lactamase in Escherichia coli","volume":"61","author":"Livermore","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e02446-17","DOI":"10.1128\/AAC.02446-17","article-title":"Avibactam Pharmacokinetic\/Pharmacodynamic Targets","volume":"62","author":"Nichols","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00228-023-03609-x","article-title":"Dose Selection for Aztreonam\u2013Avibactam, Including Adjustments for Renal Impairment, for Phase IIa and Phase III Evaluation","volume":"80","author":"Das","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.2147\/IDR.S273989","article-title":"In Vitro Activity of Ceftazidime\u2013Avibactam and Aztreonam\u2013Avibactam Against Carbapenem-Resistant Isolates Collected from Three Secondary Hospitals in Southwest China Between 2018 and 2019","volume":"13","author":"Zou","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ilham, D., Souad, L., Asmae, L., Kawtar, N., Mohammed, T., and Nabila, S. (2023). Prevalence, Antibiotic Resistance Profile, MBLs Encoding Genes, and Biofilm Formation Among Clinical Carbapenem-Resistant Enterobacterales Isolated from Patients in Mohammed VI University Hospital Centre, Morocco. Lett. Appl. Microbiol., 76.","DOI":"10.1093\/lambio\/ovad107"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s40121-020-00286-6","article-title":"Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms","volume":"9","author":"Wu","year":"2020","journal-title":"Infect. Dis. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e02031-18","DOI":"10.1128\/AAC.02031-18","article-title":"In Vivo Pharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models","volume":"63","author":"Nakamura","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/jcph.841","article-title":"Cefiderocol, a Siderophore Cephalosporin for Gram-Negative Bacterial Infections: Pharmacokinetics and Safety in Subjects with Renal Impairment","volume":"57","author":"Katsube","year":"2017","journal-title":"J. Clin. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"S552","DOI":"10.1093\/cid\/ciz828","article-title":"Pharmacokinetic and Pharmacodynamic Profiles of Cefiderocol, a Novel Siderophore Cephalosporin","volume":"69","author":"Katsube","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mornese Pinna, S., Corcione, S., De Nicol\u00f2, A., Montrucchio, G., Scabini, S., Vita, D., De Benedetto, I., Lupia, T., Mula, J., and Di Perri, G. (2022). Pharmacokinetics of Cefiderocol in Critically Ill Patients Receiving Renal Replacement Therapy: A Case Series. Antibiotics, 11.","DOI":"10.3390\/antibiotics11121830"},{"key":"ref_76","unstructured":"Shionogi Inc (2021). Fetroja: Cefiderocol for Injection for Intravenous Use, Prescribing Information."},{"key":"ref_77","unstructured":"(2024, December 30). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/fetcroja-epar-product-information_en.pdf."},{"key":"ref_78","first-page":"S330","article-title":"Prediction of Cefiderocol Pharmacokinetics and Probability of Target Attainment in Paediatric Subjects for Proposing Dose Regimens","volume":"6","author":"Katsube","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1093\/jac\/dkab280","article-title":"Intrapulmonary Pharmacokinetic Profile of Cefiderocol in Mechanically Ventilated Patients with Pneumonia","volume":"76","author":"Katsube","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1177\/03913988251322702","article-title":"Impact of Continuous Renal Replacement Therapy and CytoSorb on Cefiderocol Pharmacokinetics: \u201cOne Size Does Not Fit All\u201d","volume":"48","author":"Bottari","year":"2025","journal-title":"Int. J. Artif. Organs"},{"key":"ref_81","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":"ref_82","doi-asserted-by":"crossref","first-page":"e01659-18","DOI":"10.1128\/AAC.01659-18","article-title":"Pharmacokinetics\/Pharmacodynamics of Vaborbactam, a Novel \u03b2-Lactamase Inhibitor, in Combination with Meropenem","volume":"63","author":"Griffith","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6326","DOI":"10.1128\/AAC.00568-16","article-title":"Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the \u03b2-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects","volume":"60","author":"Griffith","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e02103-17","DOI":"10.1128\/AAC.02103-17","article-title":"Single-Dose Pharmacokinetics and Safety of Meropenem\u2013Vaborbactam in Subjects with Chronic Renal Impairment","volume":"62","author":"Rubino","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1093\/jac\/dkz103","article-title":"In Vivo Pharmacokinetic Analysis of Meropenem\/Vaborbactam During Continuous Venovenous Haemodialysis","volume":"74","author":"Kufel","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e01306-18","DOI":"10.1128\/AAC.01306-18","article-title":"Ex Vivo Characterisation of Effects of Renal Replacement Therapy Modalities and Settings on Pharmacokinetics of Meropenem and Vaborbactam","volume":"62","author":"Sime","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e02606-20","DOI":"10.1128\/AAC.02606-20","article-title":"Population Pharmacokinetics of Meropenem and Vaborbactam Based on Data from Noninfected Subjects and Infected Patients","volume":"65","author":"Trang","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e00108-25","DOI":"10.1128\/aac.00108-25","article-title":"Population Pharmacokinetics of Meropenem\u2013Vaborbactam in Acutely Ill Hospitalised Patients with Various Degrees of Renal Dysfunction Including Continuous Renal Replacement Therapy","volume":"69","author":"Reed","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1111\/bcp.16145","article-title":"Dose Rationale for the Use of Meropenem\/Vaborbactam Combination in Paediatric Patients with Gram-Negative Bacterial Infections","volume":"90","author":"Fornari","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"ofaa054","DOI":"10.1093\/ofid\/ofaa054","article-title":"Evaluation of Renal Safety Between Imipenem\/Relebactam and Colistin Plus Imipenem in Patients with Imipenem-Nonsusceptible Bacterial Infections in the Randomised, Phase III RESTORE-IMI 1 Study","volume":"7","author":"Brown","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1093\/jac\/dkae079","article-title":"Imipenem\/Relebactam Pharmacokinetics in Critically Ill Patients Supported on Extracorporeal Membrane Oxygenation","volume":"79","author":"Fratoni","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/cid\/ciz530","article-title":"RESTORE-IMI 1: A Multicentre, Randomised, Double-Blind Trial Comparing Efficacy and Safety of Imipenem\/Relebactam vs Colistin Plus Imipenem in Patients with Imipenem-Nonsusceptible Bacterial Infections","volume":"70","author":"Motsch","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_93","unstructured":"Merck & Co., Inc (2025, March 30). Recarbrio: Package Insert. Available online: https:\/\/www.merckconnect.com\/recarbrio\/dosing-administration."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Jang, S.M., Infante, S., and Abdi Pour, A. (2020). Drug Dosing Considerations in Critically Ill Patients Receiving Continuous Renal Replacement Therapy. Pharmacy, 8.","DOI":"10.3390\/pharmacy8010018"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1177\/1060028019865873","article-title":"Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Haemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update","volume":"54","author":"Hoff","year":"2020","journal-title":"Ann. Pharmacother."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Jang, S.M., Yessayan, L., Dean, M., Costello, G., Katwaru, R., and Mueller, B.A. (2021). Imipenem\/Relebactam Ex Vivo Clearance During Continuous Renal Replacement Therapy. Antibiotics, 10.","DOI":"10.3390\/antibiotics10101184"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"piae134","DOI":"10.1093\/jpids\/piae134","article-title":"Antimicrobial Activity of Imipenem\/Relebactam and Comparator Agents Against Gram-Negative Isolates Collected from Paediatric Patients: SMART 2018\u20132022 Global Surveillance","volume":"14","author":"DeRyke","year":"2025","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1093\/jpids\/piaa056","article-title":"In Vitro Activity of Imipenem\/Relebactam Against Gram-Negative Bacilli from Paediatric Patients\u2014Study for Monitoring Antimicrobial Resistance Trends (SMART) Global Surveillance Program 2015\u20132017","volume":"10","author":"Karlowsky","year":"2021","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1007\/s00134-023-07138-0","article-title":"Sepsis-Associated Acute Kidney Injury in the Intensive Care Unit: Incidence, Patient Characteristics, Timing, Trajectory, Treatment, and Associated Outcomes. A Multicentre, Observational Study","volume":"49","author":"White","year":"2023","journal-title":"Intensive Care Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"S194","DOI":"10.1093\/cid\/ciad095","article-title":"Durlobactam, a Broad-Spectrum Serine \u03b2-Lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species","volume":"76","author":"McLeod","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","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":"ref_102","doi-asserted-by":"crossref","first-page":"e00794-19","DOI":"10.1128\/AAC.00794-19","article-title":"Pharmacokinetics, Safety, and Tolerability of Intravenous Durlobactam and Sulbactam in Subjects with Renal Impairment and Healthy Matched Control Subjects","volume":"63","author":"Preston","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e0167423","DOI":"10.1128\/aac.01674-23","article-title":"Ex Vivo Assessment of Sulbactam\u2013Durlobactam Clearance During Continuous Renal Replacement Therapy to Guide Dosing Recommendations","volume":"69","author":"Abouelhassan","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/phar.70027","article-title":"Pharmacokinetic and Pharmacodynamic Evaluation of Sulbactam\u2013Durlobactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration Infected with Carbapenem-Resistant Acinetobacter baumannii\u2013calcoaceticus Complex","volume":"45","author":"Kufel","year":"2025","journal-title":"Pharmacotherapy"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1001\/jama.2022.17034","article-title":"Effect of Cefepime\/Enmetazobactam vs Piperacillin\/Tazobactam on Clinical Cure and Microbiological Eradication in Patients with Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomised Clinical Trial","volume":"328","author":"Kaye","year":"2022","journal-title":"JAMA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s40265-024-02035-2","article-title":"Cefepime\/Enmetazobactam: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e00926-21","DOI":"10.1128\/AAC.00926-21","article-title":"Sigmoid Emax Modelling to Define the Fixed Concentration of Enmetazobactam for MIC Testing in Combination with Cefepime","volume":"65","author":"Knechtle","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e0006125","DOI":"10.1128\/aac.00061-25","article-title":"Ex Vivo Assessment and Simulation to Guide Cefepime\u2013Taniborbactam Dosing Recommendations for Patients Receiving Continuous Renal Replacement Therapy","volume":"69","author":"Fouad","year":"2025","journal-title":"Antimicrob. 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