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Murepavadin activity tested against contemporary (2016-17) clinical isolates of XDR Pseudomonas aeruginosa.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); Sep2018, Vol. 73 Issue 9, p2400-2404, 5p
- Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>Murepavadin (POL7080) represents the first member of a novel class of outer membrane protein-targeting antibiotics. Murepavadin acts by binding to LPS transport protein D and is being developed for the treatment of hospital-acquired and ventilator-associated pneumonia caused by Pseudomonas aeruginosa.<bold>Objectives: </bold>To evaluate the antimicrobial activity of murepavadin against XDR P. aeruginosa.<bold>Methods: </bold>A total of 785 clinical isolates of XDR P. aeruginosa were collected in 2016-17 through the SENTRY Antimicrobial Surveillance Program from 34 medical centres in 21 European nations (n = 353) and 75 medical centres in North America (n = 432). Isolates were categorized as XDR when susceptible (CLSI) to ≤2 of the following antimicrobial classes: antipseudomonal cephalosporins, carbapenems, broad-spectrum penicillin/β-lactamase inhibitor combinations, fluoroquinolones, aminoglycosides and polymyxins. Susceptibility testing was performed by the reference broth microdilution method and EUCAST and CLSI interpretative criteria were applied.<bold>Results: </bold>Murepavadin (MIC50/90, 0.12/0.25 mg/L) inhibited 96.7% of isolates at ≤0.5 mg/L and was 8-fold more active than colistin (MIC50/90, 1/2 mg/L). Only seven isolates (0.9%) exhibited murepavadin MIC values >4 mg/L. Colistin (MIC50/90, 1/2 mg/L; 93.6% susceptible) was the most active comparator, followed by ceftolozane/tazobactam (MIC50/90, 2/>32 mg/L; 70.6% susceptible) and tobramycin (MIC50/90, 8/>8 mg/L; 47.5% susceptible). Murepavadin remained active against isolates that were non-susceptible to colistin (n = 50; MIC50/90, 0.25/0.25 mg/L), ceftolozane/tazobactam (n = 231; MIC50/90, 0.12/0.25 mg/L) and/or tobramycin (n = 412; MIC50/90, 0.12/0.25 mg/L).<bold>Conclusions: </bold>Murepavadin exhibited potent activity against a large collection of clinical XDR P. aeruginosa isolates from Europe and North America, including isolates that were non-susceptible to colistin, ceftolozane/tazobactam and/or tobramycin. [ABSTRACT FROM AUTHOR]
- Subjects :
- PSEUDOMONAS aeruginosa
MEMBRANE proteins
ANTIBIOTICS
CARRIER proteins
MEDICAL care
ASPARTATE aminotransferase
COMPARATIVE studies
DRUG resistance in microorganisms
RESEARCH methodology
MEDICAL cooperation
MICROBIAL sensitivity tests
PEPTIDES
PSEUDOMONAS
PSEUDOMONAS diseases
RESEARCH
EVALUATION research
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 73
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 131384573
- Full Text :
- https://doi.org/10.1093/jac/dky227