Prophylactic antibiotics in adults with acute brain injury who are invasively ventilated in the Intensive Care Unit: A systematic review and meta-analysis

Kathryn Hadley-Brown; Laura Hailstone; Roisin Devane; Tak Chan; Anthony Devaux; Joshua S Davis; Naomi Hammond; Qiang Li MBioStat; Edward Litton; John Myburgh; Alexis Poole; Joseph Alvin Santos; Ian Seppelt; Steven Y C Tong; Andrew Udy; Balasubramanian Venkatesh; Paul J Young; Anthony P Delaney

doi:10.1016/j.chest.2024.10.031

Prophylactic antibiotics in adults with acute brain injury who are invasively ventilated in the Intensive Care Unit: A systematic review and meta-analysis

Chest. 2024 Oct 25:S0012-3692(24)05420-5. doi: 10.1016/j.chest.2024.10.031. Online ahead of print.

Authors

Kathryn Hadley-Brown¹, Laura Hailstone², Roisin Devane³, Tak Chan¹, Anthony Devaux⁴, Joshua S Davis⁵, Naomi Hammond⁶, Qiang Li MBioStat⁴, Edward Litton³, John Myburgh⁴, Alexis Poole⁷, Joseph Alvin Santos⁴, Ian Seppelt⁸, Steven Y C Tong⁹, Andrew Udy¹⁰, Balasubramanian Venkatesh⁴, Paul J Young¹¹, Anthony P Delaney¹²

Affiliations

¹ Intensive Care Unit, Wellington Regional Hospital, Wellington South, New Zealand.
² Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, NSW, Australia.
³ Intensive Care Unit, Fiona Stanley Hospital, Murdoch, West Australia, Australia.
⁴ Critical Care Program, The George Institute for Global Health and UNSW, NSW, Australia.
⁵ Hunter Medical Research Institute, Infection Research Program, Newcastle, New South Wales, Australia.
⁶ Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, NSW, Australia; Critical Care Program, The George Institute for Global Health and UNSW, NSW, Australia.
⁷ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁸ Critical Care Program, The George Institute for Global Health and UNSW, NSW, Australia; Department of Intensive Care Medicine, Nepean Hospital, Penrith, NSW, Australia.
⁹ Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, Victoria, Australia; Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹⁰ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Intensive Care Unit, The Alfred Hospital, Prahan, Victoria, Australia.
¹¹ Intensive Care Unit, Wellington Regional Hospital, Wellington South, New Zealand; Medical Research Institute of New Zealand, Wellington, New Zealand.
¹² Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, NSW, Australia; Critical Care Program, The George Institute for Global Health and UNSW, NSW, Australia; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Electronic address: [email protected].

PMID: 39490972
DOI: 10.1016/j.chest.2024.10.031

Abstract

Background: Lower respiratory tract infections are common in patients receiving invasive mechanical ventilation in an Intensive Care Unit (ICU) after an acute brain injury and may have deleterious consequences.

Research question: In adults with acute brain injury receiving invasive mechanical ventilation in an ICU, is the administration of prophylactic parenteral antibiotics, compared to placebo or usual care, associated with reduced mortality?

Study design and methods: We conducted a systematic review and meta-analysis. We searched for randomised clinical trials (RCTs) in electronic databases, as well as unpublished trials. The primary outcome was hospital mortality, secondary outcomes included the incidence of ventilator associated pneumonia, ICU length of stay, and duration of mechanical ventilation. We used a random effects model to estimate the pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) for binary outcomes and the mean difference (MD) with 95% CI for continuous outcomes. Certainty of evidence was evaluated using GRADE methods.

Results: There were 1728 reports of studies screened, with 7 RCTs recruiting 835 participants included. No trials were adjudicated as having a high risk of bias. The pooled estimated risk ratio (RR) for mortality associated with the use of prophylactic antibiotics was 0.91 (95% CI 0.70 to 1.17, p=0.39, low certainty). The pooled estimated RR for ventilator associated pneumonia was 0.56 (95% CI 0.35 to 0.89, low certainty). The pooled estimated duration of mechanical ventilation for those allocated to prophylactic antibiotics compared to control (mean difference (MD) -2.0 days, 95% CI -6.1 to 2.1, very low certainty) and duration of ICU admission (MD -2.2 days, 95% CI -5.4 to 1.1 days, very low certainty) were similar.

Interpretation: Current evidence from randomised clinical trials does not provide definitive evidence regarding the effect of prophylactic antibiotics on mortality in patients receiving invasive mechanical ventilation in the ICU.

Keywords: Acute brain injury; meta-analysis; prophylaxis; ventilator-associated pneumonia.