Murepavadin activity tested against contemporary (2016-17) clinical isolates of XDR Pseudomonas aeruginosa.
J Antimicrob Chemother
; 73(9): 2400-2404, 2018 09 01.
Article
em En
| MEDLINE
| ID: mdl-29901750
ABSTRACT
Background:
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.Objectives:
To evaluate the antimicrobial activity of murepavadin against XDR P. aeruginosa.Methods:
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/ß-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.Results:
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).Conclusions:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
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Farmacorresistência Bacteriana Múltipla
/
Antibacterianos
Limite:
Humans
País/Região como assunto:
America do norte
/
Europa
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos