Activity of ceftolozane-tazobactam against carbapenem- resistant, non-carbapenemase-producing pseudomonas aeruginosa and associated resistance mechanisms

Yu Mi Wi, Kerryl E. Greenwood-Quaintance, Audrey N. Schuetz, Kwan Soo Ko, Kyong Ran Peck, Jae Hoon Song, Robin Patel

Research output: Contribution to journalArticle

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Abstract

Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemaseproducing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168 -172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for blaIMP, blaVIM, blaSPM, blaGIM, blaSIM, and blaKPC by PCR. In the prior study, expression of oprD, ampC, and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 noncarbapenemase- producing CRPA isolates, overall susceptibility to C/T was 95.2%, compared to 71.4%, 42.9%, 23.8%, 21.4%, and 2.4% for C/A, ceftazidime, piperacillintazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased oprD and increased mexB expression (5.1% versus 25.6%, P0.025, and 4.3% versus 34.8%, P 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased oprD and increased ampC expression. C/T was active against 95.2% of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.

Original languageEnglish (US)
Article numbere01970
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Carbapenems
Pseudomonas aeruginosa
meropenem
Pseudomonas Infections
Polymerase Chain Reaction
tazobactam drug combination ceftolozane
Reverse Transcription
ceftazidime drug combination avibactam
Guidelines
Mutation

Keywords

  • Carbapenem resistant
  • Ceftolozane-tazobactam
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Activity of ceftolozane-tazobactam against carbapenem- resistant, non-carbapenemase-producing pseudomonas aeruginosa and associated resistance mechanisms. / Wi, Yu Mi; Greenwood-Quaintance, Kerryl E.; Schuetz, Audrey N.; Ko, Kwan Soo; Peck, Kyong Ran; Song, Jae Hoon; Patel, Robin.

In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 1, e01970, 01.01.2018.

Research output: Contribution to journalArticle

Wi, Yu Mi ; Greenwood-Quaintance, Kerryl E. ; Schuetz, Audrey N. ; Ko, Kwan Soo ; Peck, Kyong Ran ; Song, Jae Hoon ; Patel, Robin. / Activity of ceftolozane-tazobactam against carbapenem- resistant, non-carbapenemase-producing pseudomonas aeruginosa and associated resistance mechanisms. In: Antimicrobial Agents and Chemotherapy. 2018 ; Vol. 62, No. 1.
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abstract = "Although carbapenems are effective for treating serious multidrug-resistant Pseudomonas aeruginosa infections, carbapenem-resistant P. aeruginosa (CRPA) is now being reported worldwide. Ceftolozane-tazobactam (C/T) demonstrates activity against many multidrug-resistant isolates. We evaluated the activity of C/T and compared its activity to that of ceftazidime-avibactam (C/A) using a well-characterized collection of non-carbapenemase-producing CRPA isolates. Forty-two non-carbapenemaseproducing CRPA isolates from a previous study (J. Y. Lee and K. S. Ko, Int J Antimicrob Agents 40:168 -172, 2012, https://doi.org/10.1016/j.ijantimicag.2012.04.004) were included. All had been previously shown to be negative for blaIMP, blaVIM, blaSPM, blaGIM, blaSIM, and blaKPC by PCR. In the prior study, expression of oprD, ampC, and several efflux pump genes had been defined by quantitative reverse transcription-PCR. Here, antimicrobial susceptibility was determined by broth microdilution according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Time-kill curve assays were performed using three C/T- and C/A-susceptible CRPA isolates. Among 42 noncarbapenemase- producing CRPA isolates, overall susceptibility to C/T was 95.2{\%}, compared to 71.4{\%}, 42.9{\%}, 23.8{\%}, 21.4{\%}, and 2.4{\%} for C/A, ceftazidime, piperacillintazobactam, cefepime, and meropenem, respectively. The C/T resistance rate was significantly lower than that of C/A among isolates showing decreased oprD and increased mexB expression (5.1{\%} versus 25.6{\%}, P0.025, and 4.3{\%} versus 34.8{\%}, P 0.022, respectively). In time-kill curve studies, C/T was less bactericidal than C/A against an isolate with decreased oprD and increased ampC expression. C/T was active against 95.2{\%} of non-carbapenemase-producing CRPA clinical isolates. No apparent correlation of C/T MIC values with specific mutation-driven resistance mechanisms was noted.",
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