Ceftazidime, carbapenems, or piperacillin-tazobactam as single definitive therapy for Pseudomonas aeruginosa bloodstream infection - a multi-site retrospective study

Tanya Babich, Pontus Naucler, John Karlsson Valik, Christian G Giske, Natividad Benito, Ruben Cardona, Alba Rivera, Celine Pulcini, Manal Abdel Fattah, Justine Haquin, Alasdair Macgowan, Sally Grier, Julie Gibbs, Bibiana Chazan, Anna Yanovskay, Ronen Ben Ami, Michal Landes, Lior Nesher, Adi Zaidman-Shimshovitz, Kate McCarthy, David L Paterson, Evelina Tacconelli, Michael Buhl, Susanna Mauer, Jesus Rodriguez- Bano, Isabel Morales, Antonio Oliver, Enrique Ruiz de Gopegui, Angela Cano, Isabel Machuca, Monica Gozalo-Marguello, Luis Martinez Martinez, Eva M Gonzalez-Barbera, Iris Gomez Alfaro, Miguel Salavert, Bojana Beovic, Andreja Saje, Manica Mueller-Premru, Leonardo Pagani, Virginie Vitrat, Diamantis Kofteridis, Maria Zacharioudaki, Sofia Maraki, Yulia Weissman, Mical Paul, Yaakov Dickstein, Leonard Leibovici, Dafna Yahav
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America 2019 July 17

BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Though beta-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 hospitalized patients with P . aeruginosa bacteremia treated with beta-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate analyses, including propensity adjusted analysis, were conducted introducing monotherapy type as an independent variable.

RESULTS: We included 767 patients. Thirty-day mortality was 37/213 (17.4%) in the ceftazidime group; 42/210 (20%) in the carbapenem group, and 55/344 (16%) in the piperacillin-tazobactam group. 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 frequently with carbapenems (36/206, 17.5% versus ceftazidime 25/201, 12.4% and piperacillin-tazobactam 28/332, 8.4%, p=0.007).

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.


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