Christina A Sutherland1, David P Nicolau2. 1. Center for Anti-Infective Research and Development, Hartford, Connecticut. 2. Center for Anti-Infective Research and Development, Hartford, Connecticut; Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut. Electronic address: david.nicolau@hhchealth.org.
Abstract
PURPOSE: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently isolated pathogens in the hospital setting, and antimicrobial resistance among these organisms is on the rise. In an attempt to meet the challenge of gram-negative resistance, new therapies, including ceftolozane/tazobactam (C/T), were recently approved by the Food and Drug Administration, and others are in late-stage development. The purpose of this study is to describe the in vitro potency of C/T and other parenteral antimicrobials against a geographically diverse population of E coli, K pneumoniae, and P aeruginosa collected in US hospitals. METHODS: In 2013 to 2014, 44 hospitals provided nonduplicate, nonurine isolates of E coli (n = 1306), K pneumoniae (n = 1205), and P aeruginosa (n = 1257) from adult inpatients. MICs for C/T and 11 other antimicrobials were determined with broth microdilution methods. FINDINGS: The carbapenems, C/T, and colistin displayed the highest percentage of susceptibility and lowest MIC90 against the Enterobacteriaceae, followed by piperacillin/tazobactam (TZP), cefepime, tobramycin, aztreonam, ceftriaxone, and ciprofloxacin. C/T displayed the greatest potency (MIC90 = 2 mg/L) and 97% susceptibility of all compounds against P aeruginosa. In addition, C/T was highly active against P aeruginosa that were nonsusceptible to the carbapenems or TZP or were multidrug resistant and extended-spectrum β-lactamase-producing Enterobacteriaceae. IMPLICATIONS: This national survey reported high levels of nonsusceptibility to antimicrobials among both Enterobacteriaceae and P aeruginosa. In contrast, many of these resistant pathogens were susceptible to C/T. These data highlight the enhanced potency of C/T and its potential utility for commonly encountered gram-negative nosocomial pathogens.
PURPOSE:Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently isolated pathogens in the hospital setting, and antimicrobial resistance among these organisms is on the rise. In an attempt to meet the challenge of gram-negative resistance, new therapies, including ceftolozane/tazobactam (C/T), were recently approved by the Food and Drug Administration, and others are in late-stage development. The purpose of this study is to describe the in vitro potency of C/T and other parenteral antimicrobials against a geographically diverse population of E coli, K pneumoniae, and P aeruginosa collected in US hospitals. METHODS: In 2013 to 2014, 44 hospitals provided nonduplicate, nonurine isolates of E coli (n = 1306), K pneumoniae (n = 1205), and P aeruginosa (n = 1257) from adult inpatients. MICs for C/T and 11 other antimicrobials were determined with broth microdilution methods. FINDINGS: The carbapenems, C/T, and colistin displayed the highest percentage of susceptibility and lowest MIC90 against the Enterobacteriaceae, followed by piperacillin/tazobactam (TZP), cefepime, tobramycin, aztreonam, ceftriaxone, and ciprofloxacin. C/T displayed the greatest potency (MIC90 = 2 mg/L) and 97% susceptibility of all compounds against P aeruginosa. In addition, C/T was highly active against P aeruginosa that were nonsusceptible to the carbapenems or TZP or were multidrug resistant and extended-spectrum β-lactamase-producing Enterobacteriaceae. IMPLICATIONS: This national survey reported high levels of nonsusceptibility to antimicrobials among both Enterobacteriaceae and P aeruginosa. In contrast, many of these resistant pathogens were susceptible to C/T. These data highlight the enhanced potency of C/T and its potential utility for commonly encountered gram-negative nosocomial pathogens.
Authors: Jose M Munita; Samuel L Aitken; William R Miller; Federico Perez; Rossana Rosa; Luis A Shimose; Paola N Lichtenberger; Lilian M Abbo; Rupali Jain; Masayuki Nigo; Audrey Wanger; Rafael Araos; Truc T Tran; Javier Adachi; Robert Rakita; Samuel Shelburne; Robert A Bonomo; Cesar A Arias Journal: Clin Infect Dis Date: 2017-07-01 Impact factor: 9.079
Authors: Adam L Bailey; Tom Armstrong; Hari-Prakash Dwivedi; Gerald A Denys; Janet Hindler; Shelley Campeau; Maria Traczewski; Romney Humphries; C A Burnham Journal: J Clin Microbiol Date: 2018-08-27 Impact factor: 5.948
Authors: Dafna Yahav; Christian G Giske; Alise Grāmatniece; Henrietta Abodakpi; Vincent H Tam; Leonard Leibovici Journal: Clin Microbiol Rev Date: 2020-11-11 Impact factor: 26.132
Authors: Deanna J Buehrle; Ryan K Shields; Liang Chen; Binghua Hao; Ellen G Press; Ammar Alkrouk; Brian A Potoski; Barry N Kreiswirth; Cornelius J Clancy; M Hong Nguyen Journal: Antimicrob Agents Chemother Date: 2016-04-22 Impact factor: 5.191