{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:27:14Z","timestamp":1793384834436,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Optimizing the entire therapeutic regimen in septic critically ill patients should be based not only on improving antibiotic use but also on optimizing the entire therapeutic regimen by considering possible drug\u2013drug or drug\u2013nutrient interactions. The aim of this narrative review is to provide a comprehensive overview on recent advances to optimize the therapeutic regimen in septic critically ill patients based on a pharmacokinetics and pharmacodynamic approach. Studies on recent advances on TDM-guided drug therapy optimization based on PK and\/or PD results were included. Studies on patients &lt;18 years old or with classical TDM-guided therapy were excluded. New approaches in TDM-guided therapy in septic critically ill patients based on PK and\/or PD parameters are presented for cefiderocol, carbapenems, combinations beta-lactams\/beta-lactamase inhibitors (piperacillin\/tazobactam, ceftolozane\/tazobactam, ceftazidime\/avibactam), plazomicin, oxazolidinones and polymyxins. Increased midazolam toxicity in combination with fluconazole, nephrotoxic synergism between furosemide and aminoglycosides, life-threatening hypoglycemia after fluoroquinolone and insulin, prolonged muscle weakness and\/or paralysis after neuromuscular blocking agents and high-dose corticosteroids combinations are of interest in critically ill patients. In the real-world practice, the use of probiotics with antibiotics is common; even data about the risk and benefits of probiotics are currently spares and inconclusive. According to current legislation, probiotic use does not require safety monitoring, but there are reports of endocarditis, meningitis, peritonitis, or pneumonia associated with probiotics in critically ill patients. In addition, probiotics are associated with risk of the spread of antimicrobial resistance. The TDM-guided method ensures a true optimization of antibiotic therapy, and particular efforts should be applied globally. In addition, multidrug and drug\u2013nutrient interactions in critically ill patients may increase the likelihood of adverse events and risk of death; therefore, the PK and PD particularities of the critically ill patient require a multidisciplinary approach in which knowledge of clinical pharmacology is essential.<\/jats:p>","DOI":"10.3390\/medicina59030478","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T02:28:17Z","timestamp":1677637697000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Optimization of Therapy and the Risk of Probiotic Use during Antibiotherapy in Septic Critically Ill Patients: A Narrative Review"],"prefix":"10.3390","volume":"59","author":[{"given":"Maria Ioana","family":"Onofrei","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, \u201cSf. Parascheva\u201d Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania"},{"name":"Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-0425","authenticated-orcid":false,"given":"Cristina Mihaela","family":"Ghiciuc","sequence":"additional","affiliation":[{"name":"Pharmacology, Clinical Pharmacology and Algeziology, Department of Morpho-Functional Sciences II, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina Mihaela","family":"Luca","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, \u201cSf. Parascheva\u201d Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania"},{"name":"Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraschiva","family":"Postolache","sequence":"additional","affiliation":[{"name":"Department of Medicine I\u2014Pulmonary Rehabilitation Clinic, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Sapaniuc","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, \u201cSf. Parascheva\u201d Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania"},{"name":"Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana","family":"Enache Leonte","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, \u201cSf. Parascheva\u201d Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania"},{"name":"Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin Manuel","family":"Rosu","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, \u201cSf. Parascheva\u201d Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania"},{"name":"Department of Infectious Diseases, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 16 Universitatii Street, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.21037\/jeccm.2018.11.08","article-title":"Multidrug resistant bacteria in critically ill patients: A step further antibiotic therapy","volume":"2","author":"Tosi","year":"2018","journal-title":"J. Emerg. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pasero, D., Cossu, A.P., and Terragni, P. (2021). Multi-Drug Resistance Bacterial Infections in Critically Ill Patients Admitted with COVID-19. 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