Ceftazidime, Carbapenems, or Piperacillin-tazobactam as Single Definitive Therapy for Pseudomonas aeruginosa Bloodstream Infection: A Multisite Retrospective Study

Author:

Babich Tanya1,Naucler Pontus2,Valik John Karlsson2,Giske Christian G3,Benito Natividad4,Cardona Ruben5,Rivera Alba6,Pulcini Celine78,Abdel Fattah Manal8,Haquin Justine8,Macgowan Alasdair9,Grier Sally9,Gibbs Julie9,Chazan Bibiana10,Yanovskay Anna10,Ben Ami Ronen111,Landes Michal11,Nesher Lior12,Zaidman-Shimshovitz Adi12,McCarthy Kate13,Paterson David L13,Tacconelli Evelina14,Buhl Michael14,Mauer Susanna14,Rodriguez-Bano Jesus15,Morales Isabel15,Oliver Antonio16,Ruiz De Gopegui Enrique16,Cano Angela17,Machuca Isabel17,Gozalo-Marguello Monica18,Martinez Martinez Luis18,Gonzalez-Barbera Eva M19,Alfaro Iris Gomez19,Salavert Miguel20,Beovic Bojana21,Saje Andreja21,Mueller-Premru Manica22,Pagani Leonardo23,Vitrat Virginie24,Kofteridis Diamantis25,Zacharioudaki Maria25,Maraki Sofia25,Weissman Yulia1,Paul Mical26,Dickstein Yaakov26,Leibovici Leonard27,Yahav Dafna28

Affiliation:

1. Sackler Faculty of Medicine, Tel Aviv University, Israel

2. Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, and Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden

3. Department of Laboratory Medicine, Karolinska Institutet, and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden

4. Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

5. Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

6. Department of Microbiology, Hospital de la Santa Creu i Sant Pau—Institut d’Investigació Biomèdica Sant Pau, Barcelona, Spain

7. APEMAC, France

8. CHRU-Nancy, Infectious Diseases Department, Université de Lorraine, France

9. Department of Infection Sciences, Southmead Hospital, Bristol, United Kingdom

10. Infectious Diseases Unit, Emek Medical Center, Afula, Rappaport Faculty of Medicine, Technion, Haifa

11. Infectious Diseases Unit Sourasky Medical Center, Tel-Aviv

12. Infectious Disease Institute, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheba, Israel

13. UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia

14. Division of Infectious Diseases, Tübingen University Hospital, Germany

15. Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena/Departamento de Medicina, Universidad de Sevilla/Instituto de Biomedicina de Sevilla

16. Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Illes Balears (IdISBa), Palma de Mallorca

17. Infectious Diseases Unit, Maimonides Biomedical Research Institute of Cordoba, Reina Sofia University Hospital, University of Cordoba, University Hospital Marqués de Valdecilla–IDIVAL, Santander

18. Microbiology Service, University Hospital Marqués de Valdecilla–IDIVAL, Santander

19. Microbiology Department, La Fe University Hospital, Valencia

20. Infectious Diseases Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain

21. Department of Infectious Diseases, University Medical Centre, Faculty of Medicine, University of Ljubljana

22. Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia

23. Infectious Diseases Unit, Bolzano Central Hospital, Italy

24. Infectious Diseases Unit, Annecy-Genevois Hospital Center, Annecy, France

25. Infectious Disease Unit, Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece

26. Infectious Diseases Unit, Rambam Health Care Campus, Haifa

27. Medicine E, Petah-Tikva, Israel

28. Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

Abstract

Abstract Background The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. Methods A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. Results Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). Conclusions No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.

Funder

Stockholm County Council and Emil

Wera Cornell Foundation.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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