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Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme.
J Antimicrob Chemother. 2018 09 01; 73(9):2519-2523.JA

Abstract

Objectives

This analysis evaluated the clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates pooled from the adult Phase III clinical trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP).

Methods

Baseline isolates from five Phase III randomized controlled trials of ceftazidime/avibactam versus predominantly carbapenem comparators in patients with cIAI (RECLAIM 1 and 2; NCT01499290 and RECLAIM 3; NCT01726023), cUTI (RECAPTURE 1 and 2; NCT01595438 and NCT01599806), NP including VAP (REPROVE; NCT01808092) and cIAI or cUTI caused by ceftazidime-non-susceptible Gram-negative pathogens (REPRISE; NCT01644643) were tested for MDR status and susceptibility to ceftazidime/avibactam and carbapenem-based comparators using CLSI broth microdilution methodology. Microbiological and clinical responses for patients with ≥1 MDR Enterobacteriaceae or P. aeruginosa isolate were assessed at the test-of-cure (TOC) visit.

Results

In the pooled microbiologically modified ITT population, 1051 patients with MDR Enterobacteriaceae and 95 patients with MDR P. aeruginosa isolates were identified. Favourable microbiological response rates at TOC for all MDR Enterobacteriaceae and MDR P. aeruginosa were 78.4% and 57.1%, respectively, for ceftazidime/avibactam and 71.6% and 53.8%, respectively, for comparators. The proportions of patients with ≥1 MDR isolate who were clinically cured at TOC were similar in the ceftazidime/avibactam (85.4%) and comparator (87.9%) arms.

Conclusions

Ceftazidime/avibactam demonstrated similar clinical efficacy to predominantly carbapenem comparators against MDR Enterobacteriaceae and P. aeruginosa, and may be a suitable alternative to carbapenem-based therapies for cIAI, cUTI and NP/VAP caused by MDR Gram-negative pathogens.

Authors+Show Affiliations

AstraZeneca Pharmaceuticals, 35 Gatehouse Drive, Waltham, MA 02451, USA.AstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.AstraZeneca, 1800 Concord Pike, Wilmington, DE 19803, USA.AstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.AstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.AstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.AstraZeneca, 199 Liangjing Road, Shanghai 201203, China.AstraZeneca, 199 Liangjing Road, Shanghai 201203, China.AstraZeneca, 1800 Concord Pike, Wilmington, DE 19803, USA.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29912399

Citation

Stone, Gregory G., et al. "Clinical Activity of Ceftazidime/avibactam Against MDR Enterobacteriaceae and Pseudomonas Aeruginosa: Pooled Data From the Ceftazidime/avibactam Phase III Clinical Trial Programme." The Journal of Antimicrobial Chemotherapy, vol. 73, no. 9, 2018, pp. 2519-2523.
Stone GG, Newell P, Gasink LB, et al. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018;73(9):2519-2523.
Stone, G. G., Newell, P., Gasink, L. B., Broadhurst, H., Wardman, A., Yates, K., Chen, Z., Song, J., & Chow, J. W. (2018). Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. The Journal of Antimicrobial Chemotherapy, 73(9), 2519-2523. https://doi.org/10.1093/jac/dky204
Stone GG, et al. Clinical Activity of Ceftazidime/avibactam Against MDR Enterobacteriaceae and Pseudomonas Aeruginosa: Pooled Data From the Ceftazidime/avibactam Phase III Clinical Trial Programme. J Antimicrob Chemother. 2018 09 1;73(9):2519-2523. PubMed PMID: 29912399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. AU - Stone,Gregory G, AU - Newell,Paul, AU - Gasink,Leanne B, AU - Broadhurst,Helen, AU - Wardman,Angela, AU - Yates,Katrina, AU - Chen,Zhangjing, AU - Song,Jie, AU - Chow,Joseph W, PY - 2017/12/22/received PY - 2018/05/02/accepted PY - 2018/6/19/pubmed PY - 2019/10/9/medline PY - 2018/6/19/entrez SP - 2519 EP - 2523 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 73 IS - 9 N2 - Objectives: This analysis evaluated the clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa isolates pooled from the adult Phase III clinical trials in patients with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI) or nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP). Methods: Baseline isolates from five Phase III randomized controlled trials of ceftazidime/avibactam versus predominantly carbapenem comparators in patients with cIAI (RECLAIM 1 and 2; NCT01499290 and RECLAIM 3; NCT01726023), cUTI (RECAPTURE 1 and 2; NCT01595438 and NCT01599806), NP including VAP (REPROVE; NCT01808092) and cIAI or cUTI caused by ceftazidime-non-susceptible Gram-negative pathogens (REPRISE; NCT01644643) were tested for MDR status and susceptibility to ceftazidime/avibactam and carbapenem-based comparators using CLSI broth microdilution methodology. Microbiological and clinical responses for patients with ≥1 MDR Enterobacteriaceae or P. aeruginosa isolate were assessed at the test-of-cure (TOC) visit. Results: In the pooled microbiologically modified ITT population, 1051 patients with MDR Enterobacteriaceae and 95 patients with MDR P. aeruginosa isolates were identified. Favourable microbiological response rates at TOC for all MDR Enterobacteriaceae and MDR P. aeruginosa were 78.4% and 57.1%, respectively, for ceftazidime/avibactam and 71.6% and 53.8%, respectively, for comparators. The proportions of patients with ≥1 MDR isolate who were clinically cured at TOC were similar in the ceftazidime/avibactam (85.4%) and comparator (87.9%) arms. Conclusions: Ceftazidime/avibactam demonstrated similar clinical efficacy to predominantly carbapenem comparators against MDR Enterobacteriaceae and P. aeruginosa, and may be a suitable alternative to carbapenem-based therapies for cIAI, cUTI and NP/VAP caused by MDR Gram-negative pathogens. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/29912399/Clinical_activity_of_ceftazidime/avibactam_against_MDR_Enterobacteriaceae_and_Pseudomonas_aeruginosa:_pooled_data_from_the_ceftazidime/avibactam_Phase_III_clinical_trial_programme_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dky204 DB - PRIME DP - Unbound Medicine ER -