scholarly journals In vitro activity of imipenem-relebactam against resistant phenotypes of Enterobacteriaceae and Pseudomonas aeruginosa isolated from intraabdominal and urinary tract infection samples – SMART Surveillance Europe 2015–2017

2020 ◽  
Vol 69 (2) ◽  
pp. 207-217 ◽  
Author(s):  
Sibylle H. Lob ◽  
James A. Karlowsky ◽  
Katherine Young ◽  
Mary R. Motyl ◽  
Stephen Hawser ◽  
...  
2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S417-S417
Author(s):  
Sailaja Puttagunta ◽  
Steven Aronin ◽  
Michael Huband ◽  
Robert K Flamm ◽  
Michael Dunne

Abstract Background Sulopenem is a thiopenem antibacterial with oral and parenteral formulations being developed for the treatment of urinary tract infection (UTI) or complicated intra-abdominal infection (cIAI). The activity of sulopenem aligns with the most urgent drug-resistant antimicrobial threats defined by the Centers for Disease Control (CDC), including ESBL-producing strains of Escherichia coli and Klebsiella species. We evaluated the in vitro antibacterial activity of sulopenem against clinical Enterobacteriaceae isolates from patients in North America with UTI or cIAI collected during 2016–2017. Methods Sulopenem and other antimicrobial agents were tested for in vitro activity against 1,008 recent (2016–2017) consecutive Enterobacteriaceae isolates collected through the SENTRY Antimicrobial Surveillance Program from patients in North America with UTI (906 isolates) or cIAI (102 isolates). Reference broth microdilution susceptibility testing was conducted using frozen-form panels produced by JMI Laboratories according to CLSI (M07, 2018) guidelines using cation-adjusted Mueller–Hinton broth. Quality control (QC) and interpretation of results were performed in accordance with CLSI M100 (2018) guidelines. Results Table 1. Activity of sulopenem and comparator antimicrobial agents against 1,008 Enterobacteriaceae North American isolates The sulopenem MIC50/90 values for Enterobacteriaceae were 0.03/0.25 µg/mL. For Escherichia coli, Klebsiella species and Proteus mirabilis, the MIC50/90 results were 0.03/0.03 µg/mL, 0.03/0.06 µg/mL, and 0.12/0.25 µg/mL, respectively. Conclusion Sulopenem demonstrated potent in vitro activity against organisms commonly implicated in UTI and cIAI. These data support the further clinical development of sulopenem for Gram-negative infections. Disclosures S. Puttagunta, Iterum Therapeutics: Employee and Shareholder, Salary. S. Aronin, Iterum Therapeutics: Employee and Shareholder, Salary. M. Huband, JMI Labs: Research Contractor, Grant recipient. R. K. Flamm, Allergan: Research Contractor, Research support. M. Dunne, Iterum Therapeutics: Employee and Shareholder, Salary.


Author(s):  
Rana M. Abdullah Al-Shwaikh ◽  
Abbas Falih Alornaaouti

       Current study obtained (75) isolate of Pseudomonas aeruginosa collected from different cases included : 28 isolates from otitis media, 23 isolates from burn infections, 10 isolates from wound infections, 8 isolates from urinary tract infections and 6 isolates from blood, during the period between 1/9/2014 to 1/11/2014        The result revealed that the tox A gene was present in 54 isolates (72%) of Pseudomonas aeruginosa. The gel electrophoresis showed that the molecular weight of tox A gene was 352 bp. The result shows 17 isolates (60.71%) from otitis media has tox A gene, 18 isolates (78.26%) from burn followed by 8 isolate (80%) from wound infection and 5 isolates (62.5%) from urinary tract infection , finally 6 isolates (100%) from blood have this gene.


Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.


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