Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients with Lower Respiratory Tract Infections Caused by Multidrug- And Extensively Drug-Resistant Pseudomonas aeruginosa Treated with Ceftolozane/Tazobactam

Olga Rodríguez-Núñez, Leonor Periañez-Parraga, Antonio Oliver, Jose M. Munita, Anna Boté, Oriol Gasch, Xavier Nuvials, Aurélien Dinh, Robert Shaw, Jose M. Lomas, Vicente Torres, Juanjo Castón, Rafael Araos, Lilian M. Abbo, Robert Rakita, Federico Pérez, Samuel L. Aitken, Cesar A. Arias, M. Luisa Martín-Pena, Asun ColomarM. Belén Núñez, Josep Mensa, José Antonio Martínez, Alex Soriano

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50%T > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible P. aeruginosa. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-P. aeruginosa considering the C/T MIC. Methods: This was a multicenter retrospective study of 90 patients with LRI caused by resistant P. aeruginosa who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality. Results: The median age (interquartile range) was 65 (51-74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5-4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with P. aeruginosa strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; P =. 041). Multivariate analysis identified septic shock (P <. 001), C/T MIC >2 mg/L (P =. 045), and increasing Charlson Comorbidity Index (P =. 019) as independent predictors of mortality. Conclusions: The effectiveness of C/T in P. aeruginosa LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.

Original languageEnglish (US)
Article numberofz416
JournalOpen Forum Infectious Diseases
Volume6
Issue number10
DOIs
StatePublished - Oct 1 2019

Keywords

  • Pseudomonas aeruginosa
  • ceftolozane/tazobactam
  • multidrug-resistant
  • pneumonia
  • tracheobronchitis

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

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    Rodríguez-Núñez, O., Periañez-Parraga, L., Oliver, A., Munita, J. M., Boté, A., Gasch, O., Nuvials, X., Dinh, A., Shaw, R., Lomas, J. M., Torres, V., Castón, J., Araos, R., Abbo, L. M., Rakita, R., Pérez, F., Aitken, S. L., Arias, C. A., Martín-Pena, M. L., ... Soriano, A. (2019). Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients with Lower Respiratory Tract Infections Caused by Multidrug- And Extensively Drug-Resistant Pseudomonas aeruginosa Treated with Ceftolozane/Tazobactam. Open Forum Infectious Diseases, 6(10), [ofz416]. https://doi.org/10.1093/ofid/ofz416