Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections

Clinical Effectiveness and Evolution of Resistance

Ghady Haidar, Nathan J. Philips, Ryan K. Shields, Daniel Snyder, Shaoji Cheng, Brian A. Potoski, Yohei Doi, Binghua Hao, Ellen G. Press, Vaughn S. Cooper, Cornelius J. Clancy, M. Hong Nguyen

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background. Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods. We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results. Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions. In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalClinical Infectious Diseases
Volume65
Issue number1
DOIs
Publication statusPublished - 01-07-2017
Externally publishedYes

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Pseudomonas Infections
Pseudomonas aeruginosa
Therapeutics
Intraabdominal Infections
tazobactam drug combination ceftolozane
Mutation
Mortality
Multiple Drug Resistance
Exanthema
Urinary Tract Infections
Respiratory Tract Infections
Real-Time Polymerase Chain Reaction
Pneumonia
Retrospective Studies
Genome

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Haidar, Ghady ; Philips, Nathan J. ; Shields, Ryan K. ; Snyder, Daniel ; Cheng, Shaoji ; Potoski, Brian A. ; Doi, Yohei ; Hao, Binghua ; Press, Ellen G. ; Cooper, Vaughn S. ; Clancy, Cornelius J. ; Nguyen, M. Hong. / Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections : Clinical Effectiveness and Evolution of Resistance. In: Clinical Infectious Diseases. 2017 ; Vol. 65, No. 1. pp. 110-120.
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title = "Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance",
abstract = "Background. Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods. We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results. Median age was 58 years; 9 patients (43{\%}) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86{\%}) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10{\%} (2/21) and 5{\%} (1/21), respectively; corresponding 90-day mortality rates were 48{\%} (10/21) and 19{\%} (4/21). The ceftolozane-tazobactam failure rate was 29{\%} (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14{\%}) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions. In this small study, ceftolozane-tazobactam was successful in treating 71{\%} of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.",
author = "Ghady Haidar and Philips, {Nathan J.} and Shields, {Ryan K.} and Daniel Snyder and Shaoji Cheng and Potoski, {Brian A.} and Yohei Doi and Binghua Hao and Press, {Ellen G.} and Cooper, {Vaughn S.} and Clancy, {Cornelius J.} and Nguyen, {M. Hong}",
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Haidar, G, Philips, NJ, Shields, RK, Snyder, D, Cheng, S, Potoski, BA, Doi, Y, Hao, B, Press, EG, Cooper, VS, Clancy, CJ & Nguyen, MH 2017, 'Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: Clinical Effectiveness and Evolution of Resistance', Clinical Infectious Diseases, vol. 65, no. 1, pp. 110-120. https://doi.org/10.1093/cid/cix182

Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections : Clinical Effectiveness and Evolution of Resistance. / Haidar, Ghady; Philips, Nathan J.; Shields, Ryan K.; Snyder, Daniel; Cheng, Shaoji; Potoski, Brian A.; Doi, Yohei; Hao, Binghua; Press, Ellen G.; Cooper, Vaughn S.; Clancy, Cornelius J.; Nguyen, M. Hong.

In: Clinical Infectious Diseases, Vol. 65, No. 1, 01.07.2017, p. 110-120.

Research output: Contribution to journalArticle

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T1 - Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections

T2 - Clinical Effectiveness and Evolution of Resistance

AU - Haidar, Ghady

AU - Philips, Nathan J.

AU - Shields, Ryan K.

AU - Snyder, Daniel

AU - Cheng, Shaoji

AU - Potoski, Brian A.

AU - Doi, Yohei

AU - Hao, Binghua

AU - Press, Ellen G.

AU - Cooper, Vaughn S.

AU - Clancy, Cornelius J.

AU - Nguyen, M. Hong

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N2 - Background. Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods. We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results. Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions. In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.

AB - Background. Data on the use of ceftolozane-tazobactam and emergence of ceftolozane-tazobactam resistance during multidrug resistant (MDR)-Pseudomonas aeruginosa infections are limited. Methods. We performed a retrospective study of 21 patients treated with ceftolozane-tazobactam for MDR-P. aeruginosa infections. Whole genome sequencing and quantitative real-time polymerase chain reaction were performed on longitudinal isolates. Results. Median age was 58 years; 9 patients (43%) were transplant recipients. Median simplified acute physiology score-II (SAPS-II) was 26. Eighteen (86%) patients were treated for respiratory tract infections; others were treated for bloodstream, complicated intraabdominal infections, or complicated urinary tract infections. Ceftolozane-tazobactam was discontinued in 1 patient (rash). Thirty-day all-cause and attributable mortality rates were 10% (2/21) and 5% (1/21), respectively; corresponding 90-day mortality rates were 48% (10/21) and 19% (4/21). The ceftolozane-tazobactam failure rate was 29% (6/21). SAPS-II score was the sole predictor of failure. Ceftolozane-tazobactam resistance emerged in 3 (14%) patients. Resistance was associated with de novo mutations, rather than acquisition of resistant nosocomial isolates. ampC overexpression and mutations were identified as potential resistance determinants. Conclusions. In this small study, ceftolozane-tazobactam was successful in treating 71% of patients with MDR-P. aeruginosa infections, most of whom had pneumonia. The emergence of ceftolozane-tazobactam resistance in 3 patients is worrisome and may be mediated in part by AmpC-related mechanisms. More research on treatment responses and resistance during various types of MDR-P. aeruginosa infections is needed to define ceftolozane-tazobactam's place in the armamentarium.

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