Murepavadin activity tested against contemporary (2016-17) clinical isolates of XDR Pseudomonas aeruginosa
| Autor: | Paul R. Rhomberg, Robert K. Flamm, Glenn E. Dale, Mariana Castanheira, Helio S. Sader |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Carbapenem medicine.drug_class 030106 microbiology Cephalosporin Microbial Sensitivity Tests Tazobactam Peptides Cyclic Microbiology 03 medical and health sciences Drug Resistance Multiple Bacterial medicine Tobramycin Humans Pharmacology (medical) Pseudomonas Infections Aspartate Aminotransferases Pharmacology business.industry Broth microdilution Anti-Bacterial Agents Penicillin Europe Infectious Diseases North America Pseudomonas aeruginosa Colistin Ceftolozane business medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 73(9) |
| ISSN: | 1460-2091 |
| Popis: | 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/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. 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. |
| Databáze: | OpenAIRE |
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