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 Colomar; M. Belén Núñez; Josep Mensa; José Antonio Martínez; Alex Soriano

doi:10.1093/ofid/ofz416

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Article number	ofz416
Journal	Open Forum Infectious Diseases
Volume	6
Issue number	10
DOIs	https://doi.org/10.1093/ofid/ofz416
State	Published - Oct 1 2019

Keywords

Pseudomonas aeruginosa
ceftolozane/tazobactam
multidrug-resistant
pneumonia
tracheobronchitis

ASJC Scopus subject areas

Oncology
Infectious Diseases

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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), Article ofz416. https://doi.org/10.1093/ofid/ofz416

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. / Rodríguez-Núñez, Olga; Periañez-Parraga, Leonor; Oliver, Antonio et al.
In: Open Forum Infectious Diseases, Vol. 6, No. 10, ofz416, 01.10.2019.

Research output: Contribution to journal › Article › peer-review

Rodríguez-Núñez, O, Periañez-Parraga, L, Oliver, A, Munita, JM, Boté, A, Gasch, O, Nuvials, X, Dinh, A, Shaw, R, Lomas, JM, Torres, V, Castón, J, Araos, R, Abbo, LM, Rakita, R, Pérez, F, Aitken, SL, Arias, CA, Martín-Pena, ML, Colomar, A, Núñez, MB, Mensa, J, Martínez, JA & 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, vol. 6, no. 10, ofz416. https://doi.org/10.1093/ofid/ofz416

Rodríguez-Núñez O, Periañez-Parraga L, Oliver A, Munita JM, Boté A, Gasch O et al. 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. 2019 Oct 1;6(10):ofz416. doi: 10.1093/ofid/ofz416

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title = "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",

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.",

keywords = "Pseudomonas aeruginosa, ceftolozane/tazobactam, multidrug-resistant, pneumonia, tracheobronchitis",

author = "Olga Rodr{\'i}guez-N{\'u}{\~n}ez and Leonor Peria{\~n}ez-Parraga and Antonio Oliver and Munita, {Jose M.} and Anna Bot{\'e} and Oriol Gasch and Xavier Nuvials and Aur{\'e}lien Dinh and Robert Shaw and Lomas, {Jose M.} and Vicente Torres and Juanjo Cast{\'o}n and Rafael Araos and Abbo, {Lilian M.} and Robert Rakita and Federico P{\'e}rez and Aitken, {Samuel L.} and Arias, {Cesar A.} and Mart{\'i}n-Pena, {M. Luisa} and Asun Colomar and N{\'u}{\~n}ez, {M. Bel{\'e}n} and Josep Mensa and Mart{\'i}nez, {Jos{\'e} Antonio} and Alex Soriano",

note = "Publisher Copyright: {\textcopyright} 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.",

year = "2019",

month = oct,

day = "1",

doi = "10.1093/ofid/ofz416",

language = "English (US)",

volume = "6",

journal = "Open Forum Infectious Diseases",

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TY - JOUR

T1 - 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

AU - Rodríguez-Núñez, Olga

AU - Periañez-Parraga, Leonor

AU - Oliver, Antonio

AU - Munita, Jose M.

AU - Boté, Anna

AU - Gasch, Oriol

AU - Nuvials, Xavier

AU - Dinh, Aurélien

AU - Shaw, Robert

AU - Lomas, Jose M.

AU - Torres, Vicente

AU - Castón, Juanjo

AU - Araos, Rafael

AU - Abbo, Lilian M.

AU - Rakita, Robert

AU - Pérez, Federico

AU - Aitken, Samuel L.

AU - Arias, Cesar A.

AU - Martín-Pena, M. Luisa

AU - Colomar, Asun

AU - Núñez, M. Belén

AU - Mensa, Josep

AU - Martínez, José Antonio

AU - Soriano, Alex

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Pseudomonas aeruginosa

KW - ceftolozane/tazobactam

KW - multidrug-resistant

KW - pneumonia

KW - tracheobronchitis

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JO - Open Forum Infectious Diseases

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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

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