Multidrug-resistant Pseudomonas aeruginosa from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam

Stan D. Atkin, Shadaan Abid, Michael Foster, Moumita Bose, Ashley Keller, Rita Hollaway, Helio S. Sader, David E Greenberg, James D Finklea, Mariana Castanheira, Raksha Jain

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: Ceftazidime–avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital-and ventilator-acquired pneumonia. The use of ceftazidime–avibactam to treat Pseudomonas aeruginosa respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime–avibactam susceptibility of multidrug-resistant (MDR) P. aeruginosa sputum isolates from adults with CF. Methods: Sputum was collected from individuals with CF, aged ≥18 years, known to be colonized with MDR P. aeruginosa, and tested for susceptibility to 11 different antipseudomonal antimicrobial agents. Isolates were included in the analysis if they were resistant to both ceftazidime and at least one agent in ≥3 different antimicrobial categories routinely used to treat P. aeruginosa. Subject demographics and clinical characteristics were collected. Ceftazidime–avibactam-resistant isolates were screened for the presence of β-lactam-resistant mechanisms. Results: Thirty-two P. aeruginosa isolates were analyzed, of which 23 isolates were sensitive to ceftazidime–avibactam (71.9%). Ten of the isolates were mucoid and 22 isolates were non-mucoid, both demonstrating >70% susceptibility to ceftazidime–avibactam. The most notable difference in the subjects with resistant strains was an older age and lower body mass index (BMI). Ceftazidime–avibactam-resistant strains showed elevated AmpC expression in >60% of the strains and loss of OprD detection in >70% of the strains. Conclusion: Ceftazidime–avibactam demonstrated a significant in vitro activity against highly resistant P. aeruginosa sputum isolates from individuals with CF. Further evaluation of the cause of resistance and clinical impact of ceftazidime–avibactam in CF patients with MDR P. aeruginosa is warranted.

Original languageEnglish (US)
Pages (from-to)1499-1510
Number of pages12
JournalInfection and Drug Resistance
Volume11
DOIs
StatePublished - Jan 1 2018

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Sputum
Cystic Fibrosis
Pseudomonas aeruginosa
Lactams
Ceftazidime
Cephalosporins
Mechanical Ventilators
Anti-Infective Agents
Respiratory Tract Infections
Pneumonia
Body Mass Index
Demography

Keywords

  • Avibactam
  • Ceftazidime
  • Cystic fibrosis
  • Multidrug-resistant
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Multidrug-resistant Pseudomonas aeruginosa from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam. / Atkin, Stan D.; Abid, Shadaan; Foster, Michael; Bose, Moumita; Keller, Ashley; Hollaway, Rita; Sader, Helio S.; Greenberg, David E; Finklea, James D; Castanheira, Mariana; Jain, Raksha.

In: Infection and Drug Resistance, Vol. 11, 01.01.2018, p. 1499-1510.

Research output: Contribution to journalArticle

Atkin, Stan D. ; Abid, Shadaan ; Foster, Michael ; Bose, Moumita ; Keller, Ashley ; Hollaway, Rita ; Sader, Helio S. ; Greenberg, David E ; Finklea, James D ; Castanheira, Mariana ; Jain, Raksha. / Multidrug-resistant Pseudomonas aeruginosa from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam. In: Infection and Drug Resistance. 2018 ; Vol. 11. pp. 1499-1510.
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abstract = "Purpose: Ceftazidime–avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital-and ventilator-acquired pneumonia. The use of ceftazidime–avibactam to treat Pseudomonas aeruginosa respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime–avibactam susceptibility of multidrug-resistant (MDR) P. aeruginosa sputum isolates from adults with CF. Methods: Sputum was collected from individuals with CF, aged ≥18 years, known to be colonized with MDR P. aeruginosa, and tested for susceptibility to 11 different antipseudomonal antimicrobial agents. Isolates were included in the analysis if they were resistant to both ceftazidime and at least one agent in ≥3 different antimicrobial categories routinely used to treat P. aeruginosa. Subject demographics and clinical characteristics were collected. Ceftazidime–avibactam-resistant isolates were screened for the presence of β-lactam-resistant mechanisms. Results: Thirty-two P. aeruginosa isolates were analyzed, of which 23 isolates were sensitive to ceftazidime–avibactam (71.9{\%}). Ten of the isolates were mucoid and 22 isolates were non-mucoid, both demonstrating >70{\%} susceptibility to ceftazidime–avibactam. The most notable difference in the subjects with resistant strains was an older age and lower body mass index (BMI). Ceftazidime–avibactam-resistant strains showed elevated AmpC expression in >60{\%} of the strains and loss of OprD detection in >70{\%} of the strains. Conclusion: Ceftazidime–avibactam demonstrated a significant in vitro activity against highly resistant P. aeruginosa sputum isolates from individuals with CF. Further evaluation of the cause of resistance and clinical impact of ceftazidime–avibactam in CF patients with MDR P. aeruginosa is warranted.",
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author = "Atkin, {Stan D.} and Shadaan Abid and Michael Foster and Moumita Bose and Ashley Keller and Rita Hollaway and Sader, {Helio S.} and Greenberg, {David E} and Finklea, {James D} and Mariana Castanheira and Raksha Jain",
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T1 - Multidrug-resistant Pseudomonas aeruginosa from sputum of patients with cystic fibrosis demonstrates a high rate of susceptibility to ceftazidime–avibactam

AU - Atkin, Stan D.

AU - Abid, Shadaan

AU - Foster, Michael

AU - Bose, Moumita

AU - Keller, Ashley

AU - Hollaway, Rita

AU - Sader, Helio S.

AU - Greenberg, David E

AU - Finklea, James D

AU - Castanheira, Mariana

AU - Jain, Raksha

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: Ceftazidime–avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital-and ventilator-acquired pneumonia. The use of ceftazidime–avibactam to treat Pseudomonas aeruginosa respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime–avibactam susceptibility of multidrug-resistant (MDR) P. aeruginosa sputum isolates from adults with CF. Methods: Sputum was collected from individuals with CF, aged ≥18 years, known to be colonized with MDR P. aeruginosa, and tested for susceptibility to 11 different antipseudomonal antimicrobial agents. Isolates were included in the analysis if they were resistant to both ceftazidime and at least one agent in ≥3 different antimicrobial categories routinely used to treat P. aeruginosa. Subject demographics and clinical characteristics were collected. Ceftazidime–avibactam-resistant isolates were screened for the presence of β-lactam-resistant mechanisms. Results: Thirty-two P. aeruginosa isolates were analyzed, of which 23 isolates were sensitive to ceftazidime–avibactam (71.9%). Ten of the isolates were mucoid and 22 isolates were non-mucoid, both demonstrating >70% susceptibility to ceftazidime–avibactam. The most notable difference in the subjects with resistant strains was an older age and lower body mass index (BMI). Ceftazidime–avibactam-resistant strains showed elevated AmpC expression in >60% of the strains and loss of OprD detection in >70% of the strains. Conclusion: Ceftazidime–avibactam demonstrated a significant in vitro activity against highly resistant P. aeruginosa sputum isolates from individuals with CF. Further evaluation of the cause of resistance and clinical impact of ceftazidime–avibactam in CF patients with MDR P. aeruginosa is warranted.

AB - Purpose: Ceftazidime–avibactam is a novel antimicrobial combining a third-generation cephalosporin with a non-β-lactam β-lactamase inhibitor that was recently approved to treat Gram-negative hospital-and ventilator-acquired pneumonia. The use of ceftazidime–avibactam to treat Pseudomonas aeruginosa respiratory infections in patients with cystic fibrosis (CF) has not been evaluated. In this study, we assessed the ceftazidime–avibactam susceptibility of multidrug-resistant (MDR) P. aeruginosa sputum isolates from adults with CF. Methods: Sputum was collected from individuals with CF, aged ≥18 years, known to be colonized with MDR P. aeruginosa, and tested for susceptibility to 11 different antipseudomonal antimicrobial agents. Isolates were included in the analysis if they were resistant to both ceftazidime and at least one agent in ≥3 different antimicrobial categories routinely used to treat P. aeruginosa. Subject demographics and clinical characteristics were collected. Ceftazidime–avibactam-resistant isolates were screened for the presence of β-lactam-resistant mechanisms. Results: Thirty-two P. aeruginosa isolates were analyzed, of which 23 isolates were sensitive to ceftazidime–avibactam (71.9%). Ten of the isolates were mucoid and 22 isolates were non-mucoid, both demonstrating >70% susceptibility to ceftazidime–avibactam. The most notable difference in the subjects with resistant strains was an older age and lower body mass index (BMI). Ceftazidime–avibactam-resistant strains showed elevated AmpC expression in >60% of the strains and loss of OprD detection in >70% of the strains. Conclusion: Ceftazidime–avibactam demonstrated a significant in vitro activity against highly resistant P. aeruginosa sputum isolates from individuals with CF. Further evaluation of the cause of resistance and clinical impact of ceftazidime–avibactam in CF patients with MDR P. aeruginosa is warranted.

KW - Avibactam

KW - Ceftazidime

KW - Cystic fibrosis

KW - Multidrug-resistant

KW - Pseudomonas aeruginosa

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