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Time above the minimum inhibitory concentration of piperacillin/tazobactam as a predictor of outcome in Pseudomonas aeruginosa bacteraemia.

Tannous, Elias; Lipman, Shelly; Tonna, Antonella; Hector, Emma; Hussein, Ziad; Stein, Michal; Reisfeld, Sharon

Authors

Elias Tannous

Shelly Lipman

Antonella Tonna

Emma Hector

Ziad Hussein

Michal Stein

Sharon Reisfeld



Abstract

Pseudomonas aeruginosa bacteraemia is an infection associated with high mortality rate. Piperacillin + Tazobactam is a β-lactam β-lactamase inhibitor combination that is frequently used for the management of Pseudomonas aeruginosa . The pharmacokinetic-pharmacodynamic index associated with in-vitro maximal bacterial killing for Piperacillin + Tazobactam is the percentage of time at which the free fraction concentration is above the minimum inhibitory concentration (%fT > MIC). However, the precise %fT > MIC target associated with improved clinical outcomes is unknown. The aim of this study was to investigate the correlation between survival of patients with Pseudomonas aeruginosa bacteraemia and the threshold of Piperacillin + Tazobactam %fT > MIC. This retrospective study included all adult patients hospitalized over an 82 month period with Pseudomonas aeruginosa bacteraemia, and treated with Piperacillin + Tazobactam . Patients with a polymicrobial infection or those who died within 72 hours of culture, were excluded. The %fT > MIC of Piperacillin + Tazobactam associated with in-hospital survival was derived using Classification and Regression Tree analysis. After screening 270 patients, 78 were eligible for inclusion in the study; 18% died during hospitalization. Classification and Regression Tree analysis identified %fT > MIC > 60.68% as associated with improved survival, and this remained statistically significant after controlling for clinical covariates (OR= 7.74, 95% CI 1.32-45.2). In conclusion, the findings recommend dosing of Piperacillin + Tazobactam with the aim of achieving a pharmacodynamic target of at least 60% fT > MIC in these patients.

Journal Article Type Article
Journal Antimicrobial agents and chemotherapy
Print ISSN 0066-4804
Electronic ISSN 1098-6596
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Institution Citation TANNOUS, E., LIPMAN, S., TONNA, A., HECTOR, E., HUSSEIN, Z., STEIN, M., and REISFELD, S. (2020). Time above the minimum inhibitory concentration of piperacillin/tazobactam as a predictor of outcome in Pseudomonas aeruginosa bacteraemia. Antimicrobial agents and chemotherapy [online], Accepted Manuscripts. Available from: https://doi.org/10.1128/aac.02571-19
DOI https://doi.org/10.1128/aac.02571-19
Keywords Pseudomonas aeruginosa bacteraemia; Mortality; Infection; Piperacillin; Tazobactam; Bacteria Pharmacology; Infectious Diseases
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