Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study

Author:

Vena Antonio12,Schenone Michela1,Corcione Silvia34ORCID,Giannella Maddalena56,Pascale Renato56,Giacobbe Daniele Roberto12ORCID,Muccio Marco1,Mornese Pinna Simone3,Pari Bianca3,Giovannenze Francesca7,Geremia Nicholas8,Mikulska Malgorzata12ORCID,Taddei Eleonora7,Sangiorgi Flavio9,Bavaro Davide Fiore101112,Scaglione Vincenzo13,Vassia Veronica1415ORCID,Merli Marco16,Bartoletti Michele1011,Viale Pierluigi56,De Rosa Francesco Giuseppe3ORCID,Bassetti Matteo12, ,Giuseppe Accurso,Fiore Bavaro Davide,Stefania Chiappetta,Domenico Faliero,Benedetta Fumarola,Nicholas Geremia,Francesca Giovannenze,Angelo Maccaro,Andrea Marino,Marco Merli,Gabriele Pagani,Alessia Sardanelli,Vincenzo Scaglione,Monica Tontodonati,Veronica Vassia

Affiliation:

1. Department of Health Sciences (DISSAL), University of Genoa , Genoa , Italy

2. Clinica Malattie Infettive, IRCCS San Martino polyclinic Hospital , Genoa , Italy

3. Department of Medical Sciences, Infectious Diseases, University of Turin , Turin , Italy

4. Department of Infectious Diseases, Tufts University School of Medicine , Boston, MA , USA

5. Infectious Diseases Unit, IRCCS—Sant'Orsola Polyclinic , Bologna , Italy

6. Department of Medical and Surgical Sciences, University of Bologna , Bologna , Italy

7. Department of Laboratory and Infectious Sciences, IRCCS A. Gemelli University polyclinic Foundation , Rome , Italy

8. Unit of Infectious Diseases, Department of Clinical Medicine, Dell'Angelo Hospital , Venice , Italy

9. Department of Security and Bioethics—Infectious Diseases Section, Catholic University of the Sacred Heart , Rome , Italy

10. Department of Biomedical Sciences, Humanitas University , Milan , Italy

11. Infectious Disease Unit, IRCCS Humanitas Research Hospital , Rozzano, Milan , Italy

12. Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area), University of Bari ‘Aldo Moro’ , Bari , Italy

13. Infectious and Tropical Diseases Unit, Padua University Hospital , Padua , Italy

14. Infectious and Tropical Disease Unit, Mauriziano Umberto I Hospital , Turin , Italy

15. Infectious and Tropical Disease Unit, Civile Hospital , Ivrea , Italy

16. Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda , Milan , Italy

Abstract

Abstract Objectives To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI). Methods This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021–2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses. Results Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12–0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25–2.14; P = 0.568). Conclusions AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings.

Funder

Pfizer

Shionogi and Tillotts Pharma

Publisher

Oxford University Press (OUP)

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