Antibiotic therapy for severe bacterial infections

Jean-François Timsit^{1

2

3}, Lowell Ling⁴, Etienne de Montmollin^{5

6

7}, Hendrik Bracht⁸, Andrew Conway-Morris^{9

10}, Liesbet De Bus^{11

12}, Marco Falcone^{13

14}, Patrick N A Harris^{15

16

17

18}, Flavia R Machado¹⁹, José-Artur Paiva^{20

21

22}, David L Paterson^{15

23}, Garyphallia Poulakou²⁴, Jason A Roberts^{15

17

25

26}, Claire Roger²⁶, Andrew F Shorr²⁷, Alexis Tabah^{15

28

29}, Jeffrey Lipman^{15

17

26

29

30}

Affiliations

¹ Université Paris-Cité, INSERM, IAME, U1137, Team MOCLID, Paris, France. Jean-francois.timsit@aphp.fr.
² APHP, Bichat Hospital, Medical and Infectious Diseases ICU, Paris, France. Jean-francois.timsit@aphp.fr.
³ OUTCOME REA Research Network, Drancy, France. Jean-francois.timsit@aphp.fr.
⁴ Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁵ Université Paris-Cité, INSERM, IAME, U1137, Team MOCLID, Paris, France.
⁶ APHP, Bichat Hospital, Medical and Infectious Diseases ICU, Paris, France.
⁷ OUTCOME REA Research Network, Drancy, France.
⁸ Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine, and Pain Therapy, University Hospital OWL, Campus Bielefeld-Bethel, Bielefeld, Germany.
⁹ Perioperative, Acute, Critical Care and Emergency Medicine Section, Department of Medicine, University of Cambridge, Cambridge, UK.
¹⁰ JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK.
¹¹ Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.
¹² Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
¹³ Infectious Diseases Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
¹⁴ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
¹⁵ The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.
¹⁶ Department of Infectious Disease, Royal Brisbane & Women's Hospital, Herston, Australia.
¹⁷ Herston Infectious Disease Institute, Metro North Hospitals and Health Service, Brisbane, Australia.
¹⁸ Pathology Queensland, Central Microbiology, Royal Brisbane & Women's Hospital, Herston, Australia.
¹⁹ Intensive Care Department, Hospital São Paulo, Escola Paulista de Medicina Universidade Federal de São Paulo, São Paulo, Brazil.
²⁰ Intensive Care Medicine Department, ULS São João, Porto, Portugal.
²¹ Faculty of Medicine, University of Porto, Porto, Portugal.
²² Infection and Sepsis I&D Group, Porto, Portugal.
²³ ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²⁴ Third Department of Internal Medicine and Laboratory, Medical School, "SOTIRIA" General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
²⁵ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
²⁶ Division of Anesthesia Critical Care and Emergency and Pain Medicine, UR UM 103, University of Montpellier, Nimes University Hospital, Nimes, France.
²⁷ Medstar Washington Hospital Center, Washington, DC, USA.
²⁸ Intensive Care Unit, Redcliffe Hospital, Metro North Hospital and Health Services, Redcliffe, Australia.
²⁹ Queensland University of Technology (QUT), Brisbane, Australia.
³⁰ Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Herston, Australia.

PMID: 40888899
DOI: 10.1007/s00134-025-08063-0

Review

Antibiotic therapy for severe bacterial infections

Jean-François Timsit et al. Intensive Care Med. 2025.

. 2025 Sep 1.

doi: 10.1007/s00134-025-08063-0. Online ahead of print.

Authors

Affiliations

¹ Université Paris-Cité, INSERM, IAME, U1137, Team MOCLID, Paris, France. Jean-francois.timsit@aphp.fr.
² APHP, Bichat Hospital, Medical and Infectious Diseases ICU, Paris, France. Jean-francois.timsit@aphp.fr.
³ OUTCOME REA Research Network, Drancy, France. Jean-francois.timsit@aphp.fr.
⁴ Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁵ Université Paris-Cité, INSERM, IAME, U1137, Team MOCLID, Paris, France.
⁶ APHP, Bichat Hospital, Medical and Infectious Diseases ICU, Paris, France.
⁷ OUTCOME REA Research Network, Drancy, France.
⁸ Department of Anesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine, and Pain Therapy, University Hospital OWL, Campus Bielefeld-Bethel, Bielefeld, Germany.
⁹ Perioperative, Acute, Critical Care and Emergency Medicine Section, Department of Medicine, University of Cambridge, Cambridge, UK.
¹⁰ JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK.
¹¹ Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.
¹² Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
¹³ Infectious Diseases Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
¹⁴ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
¹⁵ The University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.
¹⁶ Department of Infectious Disease, Royal Brisbane & Women's Hospital, Herston, Australia.
¹⁷ Herston Infectious Disease Institute, Metro North Hospitals and Health Service, Brisbane, Australia.
¹⁸ Pathology Queensland, Central Microbiology, Royal Brisbane & Women's Hospital, Herston, Australia.
¹⁹ Intensive Care Department, Hospital São Paulo, Escola Paulista de Medicina Universidade Federal de São Paulo, São Paulo, Brazil.
²⁰ Intensive Care Medicine Department, ULS São João, Porto, Portugal.
²¹ Faculty of Medicine, University of Porto, Porto, Portugal.
²² Infection and Sepsis I&D Group, Porto, Portugal.
²³ ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²⁴ Third Department of Internal Medicine and Laboratory, Medical School, "SOTIRIA" General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
²⁵ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
²⁶ Division of Anesthesia Critical Care and Emergency and Pain Medicine, UR UM 103, University of Montpellier, Nimes University Hospital, Nimes, France.
²⁷ Medstar Washington Hospital Center, Washington, DC, USA.
²⁸ Intensive Care Unit, Redcliffe Hospital, Metro North Hospital and Health Services, Redcliffe, Australia.
²⁹ Queensland University of Technology (QUT), Brisbane, Australia.
³⁰ Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, Herston, Australia.

PMID: 40888899
DOI: 10.1007/s00134-025-08063-0

Abstract

Background: Early antibiotic therapy for patients with severe infections is essential to improve outcomes. Conversely, use of overly broad antibiotic therapy for susceptible pathogens or unnecessary antibiotics in patients without bacterial infections is associated with adverse life-threatening events and superinfections. Antibiotics-induced changes in the human microbiota alter both immune and metabolic systems. Uncontrolled antibiotic use encourages emergence of antibiotic-resistant organisms. Around 50% of ICU patients receiving antibiotic therapy do not have confirmed infections, whilst de-escalation and shortened treatment duration are infrequently performed. Mortality from serious infections remains high, highlighting the need for treatment optimisation.

Methods: Narrative review.

Objectives: To summarise the available evidence, emerging options, and unresolved controversies in optimising antibiotic therapy in severe infections.

Results: Local epidemiology, underlying illnesses, accessibility to health care systems, and diagnostic and therapeutic resources are important factors to consider. Rapid diagnostic tests combined with individualised decision-making improve the selection of antibiotic therapy. Rapid de-escalation to narrow-spectrum monotherapy and shortening of the duration of therapy should be the rule. Uncertainty still persists regarding the personalisation of therapy for difficult-to-treat resistant bacteria. Pharmacokinetic (PK) optimisation and prolonged or continuous beta-lactam use is safe and may improve outcomes. Therapeutic drug monitoring (TDM) should be used, especially when altered volume of distribution and/or drug clearance is suspected or where toxicity is likely. The impact of TDM combined with prompt dose adjustment is encouraged. Emerging technologies including rapid broad diagnostic tests and electronic antibiotic optimisation tools will further support collaboration between pharmacists, microbiologists, infectious diseases specialists, and intensivists for optimising antibiotic therapy and stewarding these precious resources.

Keywords: Antibiotic stewardship; Antibiotics; Critically ill; Pharmacokinetics; Rapid diagnostic tests; Sepsis.

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Conflict of interest statement

Declarations. Conflicts of interest: The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests. J-FT; received research grants from Pfizer, Merck, was speaker in conferences for Pfizer, Advanz, Biomerieux, Shionogi, Mundipharma, Qiagen, and participates to advisory boards organised by Menarini, Biomerieux, Merck, Advanz pharma all out of the submitted article. LL Non-financial research support from Biomerieux; received funding from Health and Medical Research Fund of the Health Bureau of Hong Kong SAR Government (No. 18190381) to support this work. EdM none; HB none; ACM speaking fees Biomerieux, Thermo-Fisher, Fischer and Paykel and Boston Scientific (paid to institution); ACM is supported by a Clinician Scientist Fellowship from the UK Medical Research Council (MR/V006118/1); LdB none; MF received research grants from Gilead and ViiV, and was speaker for conferences or advisory boards organised by Pfizer, Menarini, Infectiopharm, Thermo-Fisher; PNAH received research grants from Tamrisa, Microbio and Gilead, honoraria for speaking events from Pfizer, Biomerieux and Gilead and has served on advisory boards for Sandoz and OpGen and received travel support from Shionogi; FRM none; J-AP Talks or advisory boards for Pfizer, Merck-Sharp-Dohme, Gilead, AOP Orphan Pharmaceuticals, Cepheid; DLP received research funding from Shionogi, Merck, bioMérieux, BioVersys, Gilead and Pfizer, consulting fees from the AMR Action Fund, CARB-X, GARDP, Aurobac, Pfizer, Merck, Cepheid, bioMérieux, and Spero.; GP Grants/Research Support:Pfizer, MSD, Gilead, Menarini, PharmaMar, Fabentech, Bausch, Astra-Zeneca, Hellenic Institute for the Study of Sepsis, University College London/University of Minnesota; Scientific Advisory board: Pfizer, Astra-Zeneca, Gilead, MSD, Menarini, SOBI; CR received speaker’s fees from Shionogi, bioMerieux, AOP Orphan, Advanz Pharma, Fresenius, Pfizer and MSD. attended Scientific Advisory Board from bioMerieux, Advanz Pharma and Viatris; JAR Consultancies/Advisory Boards—Sandoz (2024); Wolters Kluwer (2024); Qpex (2022); Gilead (2022); Advanz Pharma (2022); Speaking Fees—Sandoz (2024); Pfizer (2023); MSD (2022); Gilead (2022); Industry Grants—Biomerieux (2024); Pfizer (2023); AFS Consultant to Merck, Pfizer and Eagle Pharmaceuticals; AT none; JL none. Ethical approval: Not needed.

References

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Antibiotic therapy for severe bacterial infections

Affiliations

Antibiotic therapy for severe bacterial infections

Authors

Affiliations

Abstract

Conflict of interest statement

References

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