Tanya Babich1, Pontus Naucler2, John Karlsson Valik2, Christian G Giske3, Natividad Benito4, Ruben Cardona5, Alba Rivera6, Celine Pulcini7,8, Manal Abdel Fattah8, Justine Haquin8, Alasdair Macgowan9, Sally Grier9, Julie Gibbs9, Bibiana Chazan10, Anna Yanovskay10, Ronen Ben Ami1,11, Michal Landes11, Lior Nesher12, Adi Zaidman-Shimshovitz12, Kate McCarthy13, David L Paterson13, Evelina Tacconelli14, Michael Buhl14, Susanna Mauer14, Jesus Rodriguez-Bano15, Isabel Morales15, Antonio Oliver16, Enrique Ruiz De Gopegui16, Angela Cano17, Isabel Machuca17, Monica Gozalo-Marguello18, Luis Martinez Martinez18, Eva M Gonzalez-Barbera19, Iris Gomez Alfaro19, Miguel Salavert20, Bojana Beovic21, Andreja Saje21, Manica Mueller-Premru22, Leonardo Pagani23, Virginie Vitrat24, Diamantis Kofteridis25, Maria Zacharioudaki25, Sofia Maraki25, Yulia Weissman1, Mical Paul26, Yaakov Dickstein26, Leonard Leibovici27, Dafna Yahav28. 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
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.
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.
Authors: Johanna Ude; Vishwachi Tripathi; Julien M Buyck; Sandra Söderholm; Olivier Cunrath; Joseph Fanous; Beatrice Claudi; Adrian Egli; Christian Schleberger; Sebastian Hiller; Dirk Bumann Journal: Proc Natl Acad Sci U S A Date: 2021-08-03 Impact factor: 11.205