Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study
Tanya Babich
(1)
,
Pontus Naucler
(2)
,
John Karlsson Valik
(2)
,
Christian Giske
(2)
,
Natividad Benito
(3)
,
Ruben Cardona
(4)
,
Alba Rivera
(4)
,
Celine Pulcini
(5, 6)
,
Manal Abdel Fattah
(6)
,
Justine Haquin
(6)
,
Alasdair Macgowan
(7)
,
Sally Grier
(7)
,
Julie Gibbs
(7)
,
Bibiana Chazan
(8)
,
Anna Yanovskay
(8)
,
Ronen Ben Ami
(1, 9)
,
Michal Landes
(9)
,
Lior Nesher
(10)
,
Adi Zaidman-Shimshovitz
(10)
,
Kate Mccarthy
(11)
,
David Paterson
(11)
,
Evelina Tacconelli
(12)
,
Michael Buhl
(12)
,
Susanna Mauer
(12)
,
Jesus Rodriguez-Bano
(13)
,
Isabel Morales
(13)
,
Antonio Oliver
(14)
,
Enrique Ruiz de Gopegui
(14)
,
Angela Cano
(15)
,
Isabel Machuca
(15)
,
Monica Gozalo-Marguello
(16)
,
Luis Martinez Martinez
(16)
,
Eva Gonzalez-Barbera
(17)
,
Iris Gomez Alfaro
(17)
,
Miguel Salavert
(17)
,
Bojana Beovic
(18)
,
Andreja Saje
(18)
,
Manica Mueller-Premru
(18)
,
Leonardo Pagani
(19)
,
Virginie Vitrat
(20)
,
Diamantis Kofteridis
(21)
,
Maria Zacharioudaki
(21)
,
Sofia Maraki
(21)
,
Yulia Weissman
(1)
,
Mical Paul
(22)
,
Yaakov Dickstein
(22)
,
Leonard Leibovici
(23)
,
Dafna Yahav
(23)
1
TAU -
Tel Aviv University
2 Karolinska University Hospital [Stockholm]
3 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
4 Hospital de la Santa Creu i Sant Pau
5 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
6 Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
7 Southmead Hospital
8 Rappaport faculty of Medicine
9 Tel Aviv Sourasky Medical Center [Tel Aviv]
10 BGU - Ben-Gurion University of the Negev
11 USQ - University of Southern Queensland
12 Universitätsklinikum Tübingen - University Hospital of Tübingen
13 Universidad de Sevilla = University of Seville
14 Hospital Universitari Son Espases
15 Universidad de Córdoba = University of Córdoba [Córdoba]
16 Hospital Universitario Marqués de Valdecilla [Santander]
17 Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
18 University of Ljubljana
19 Bolzano Central Hospital = Ospedale Provinciale di Bolzano
20 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
21 University Hospital of Heraklion
22 Rambam Health Care Campus
23 Beilinson Hospital, Petach Tikva, Israel
2 Karolinska University Hospital [Stockholm]
3 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
4 Hospital de la Santa Creu i Sant Pau
5 APEMAC - Adaptation, mesure et évaluation en santé. Approches interdisciplinaires
6 Service des Maladies Infectieuses et Tropicales [CHRU Nancy]
7 Southmead Hospital
8 Rappaport faculty of Medicine
9 Tel Aviv Sourasky Medical Center [Tel Aviv]
10 BGU - Ben-Gurion University of the Negev
11 USQ - University of Southern Queensland
12 Universitätsklinikum Tübingen - University Hospital of Tübingen
13 Universidad de Sevilla = University of Seville
14 Hospital Universitari Son Espases
15 Universidad de Córdoba = University of Córdoba [Córdoba]
16 Hospital Universitario Marqués de Valdecilla [Santander]
17 Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
18 University of Ljubljana
19 Bolzano Central Hospital = Ospedale Provinciale di Bolzano
20 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
21 University Hospital of Heraklion
22 Rambam Health Care Campus
23 Beilinson Hospital, Petach Tikva, Israel
Natividad Benito
- Fonction : Auteur
- PersonId : 762350
- ORCID : 0000-0001-6410-013X
Jesus Rodriguez-Bano
- Fonction : Auteur
- PersonId : 786441
- ORCID : 0000-0001-6732-9001
Antonio Oliver
- Fonction : Auteur
- PersonId : 763700
- ORCID : 0000-0001-9327-1894
Eva Gonzalez-Barbera
- Fonction : Auteur
- PersonId : 796723
- ORCID : 0000-0003-1674-1391
Leonardo Pagani
- Fonction : Auteur
- PersonId : 781948
- ORCID : 0000-0002-2553-9147
Diamantis Kofteridis
- Fonction : Auteur
- PersonId : 797153
- ORCID : 0000-0001-7603-2592
Résumé
Abstract Background Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. Methods This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. Results Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. Conclusions In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.