{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:05:58Z","timestamp":1791450358210,"version":"4.3.3"},"reference-count":184,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"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>Introduction: Not enough data exist to inform the optimal duration and type of antimicrobial therapy against GN infections in critically ill patients. Methods: Narrative review based on a literature search through PubMed and Cochrane using the following keywords: \u201cmulti-drug resistant (MDR)\u201d, \u201cextensively drug resistant (XDR)\u201d, \u201cpan-drug-resistant (PDR)\u201d, \u201cdifficult-to-treat (DTR) Gram-negative infection,\u201d \u201cantibiotic duration therapy\u201d, \u201cantibiotic combination therapy\u201d \u201cantibiotic monotherapy\u201d \u201cGram-negative bacteremia\u201d, \u201cGram-negative pneumonia\u201d, and \u201cGram-negative intra-abdominal infection\u201d. Results: Current literature data suggest adopting longer (\u226510\u201314 days) courses of synergistic combination therapy due to the high global prevalence of ESBL-producing (45\u201350%), MDR (35%), XDR (15\u201320%), PDR (5.9\u20136.2%), and carbapenemases (CP)\/metallo-\u03b2-lactamases (MBL)-producing (12.5\u201320%) Gram-negative (GN) microorganisms (i.e., Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumanii). On the other hand, shorter courses (\u22645\u20137 days) of monotherapy should be limited to treating infections caused by GN with higher (\u22653 antibiotic classes) antibiotic susceptibility. A general approach should be based on (i) third or further generation cephalosporins \u00b1 quinolones\/aminoglycosides in the case of MDR-GN; (ii) carbapenems \u00b1 fosfomycin\/aminoglycosides for extended-spectrum \u03b2-lactamases (ESBLs); and (iii) the association of old drugs with new expanded-spectrum \u03b2-lactamase inhibitors for XDR, PDR, and CP microorganisms. Therapeutic drug monitoring (TDM) in combination with minimum inhibitory concentration (MIC), bactericidal vs. bacteriostatic antibiotics, and the presence of resistance risk predictors (linked to patient, antibiotic, and microorganism) should represent variables affecting the antimicrobial strategies for treating GN infections. Conclusions: Despite the strategies of therapy described in the results, clinicians must remember that all treatment decisions are dynamic, requiring frequent reassessments depending on both the clinical and microbiological responses of the patient.<\/jats:p>","DOI":"10.3390\/antibiotics12081262","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T10:00:15Z","timestamp":1690797615000},"page":"1262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-3278","authenticated-orcid":false,"given":"Alberto","family":"Corona","sequence":"first","affiliation":[{"name":"Accident, Emergency and ICU Department and Surgical Theatre, ASST Valcamonica, University of Brescia, 25043 Breno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Santis","sequence":"additional","affiliation":[{"name":"AUSL Romagna, Umberto I Hospital, 48022 Lugo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6583-8670","authenticated-orcid":false,"given":"Andrea","family":"Agarossi","sequence":"additional","affiliation":[{"name":"Accident, Emergency and ICU Department, ASST Santi Paolo Carlo, 20142 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Prete","sequence":"additional","affiliation":[{"name":"AUSL Romagna, Umberto I Hospital, 48022 Lugo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1512-6530","authenticated-orcid":false,"given":"Dario","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomina","family":"Tomasini","sequence":"additional","affiliation":[{"name":"Urgency and Emergency Surgery and Medicine Division ASST Valcamonica, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3755-8919","authenticated-orcid":false,"given":"Graziella","family":"Bonetti","sequence":"additional","affiliation":[{"name":"Clinical Pathology and Microbiology Laboratory, ASST Valcamonica, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Patroni","sequence":"additional","affiliation":[{"name":"Medical Directorate, Infection Control Unit, ASST Valcamonica, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-5871","authenticated-orcid":false,"given":"Nicola","family":"Latronico","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1097\/QCO.0000000000000491","article-title":"Optimal duration of antibiotic treatment in Gram-negative infections","volume":"31","year":"2018","journal-title":"Curr. 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