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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
Abstract : 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.
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Submitted on : Friday, February 4, 2022 - 12:34:42 PM
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Tanya Babich, Pontus Naucler, John Karlsson Valik, Christian Giske, Natividad Benito, et al.. Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2021, 76 (8), pp.2172-2181. ⟨10.1093/jac/dkab134⟩. ⟨hal-03557469⟩



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