Comparison between the in-vitro activity of new agents on Pseudomonas aeruginosa isolates from cystic fibrosis patients and other chronic infections

1984 ◽  
Vol 14 (1) ◽  
pp. 25-29 ◽  
Author(s):  
B. Gordts ◽  
C. Vandenborre ◽  
Ph. VanderAuwera ◽  
J. P. Butzler
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.


2006 ◽  
Vol 50 (2) ◽  
pp. 819-821 ◽  
Author(s):  
M. M. Traczewski ◽  
S. D. Brown

ABSTRACT The in vitro activities of doripenem, imipenem, levofloxacin, piperacillin, ceftazidime, aztreonam, tobramycin, and cefepime were determined for 160 isolates of Pseudomonas aeruginosa (82 from cystic fibrosis [CF] patients) and 34 isolates of Burkholderia cepacia. Doripenem MIC90s were lower than those of all other comparative agents against all isolates combined and against all P. aeruginosa isolates. Doripenem was as active as levofloxacin and 2- to 32-fold more active than the other comparative agents against B. cepacia.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S581-S582
Author(s):  
Patrick James Nolan ◽  
Tiffeny Smith ◽  
James D Finklea ◽  
Leah Cohen ◽  
Raksha Jain

Abstract Background Pseudomonas aeruginosa is a commonly isolated pathogen in adults with cystic fibrosis (CF). Antimicrobial resistance is an escalating problem due to chronic colonization and frequent antimicrobial exposure. Ceftolozane–tazobactam (C/T) and ceftazidime–avibactam (CZA) exhibit promising activity against antimicrobial-resistant organisms, including P. aeruginosa. In this study, we compared in vitro activity of C/T and CZA against P. aeruginosa isolated from respiratory cultures obtained from adult patients with CF. Methods This is a retrospective study of respiratory cultures positive for P. aeruginosa collected from adult CF patients between January 1, 2015 to November 30, 2018. The first isolate per patient per year that underwent susceptibility testing for C/T, CZA, and colistin were included in the study. All isolates underwent in-house susceptibility testing for 9 anti-pseudomonal agents according to the methodology established by the Clinical Laboratory Standards Institute (CLSI). Susceptibility testing of C/T, CZA, and colistin were performed by a reference lab. Isolates were classified into 3 drug-resistant categories using the following definition: multidrug-resistant (MDR) non-susceptible (NS) to ≥1 agent in ≥3 different antimicrobial classes, extensive drug-resistant (XDR) NS to 4 or 5 different classes, and pan drug-resistant (PDR) NS to all 6 classes except colistin. Results Forty-two P. aeruginosa respiratory isolates from 32 patients with CF were included. The overall susceptibility to C/T and CZA was 59.5% and 42.9%, respectively. Thirty-eight (90%) isolates were considered MDR with susceptibility of 55.3% to C/T and 44.7% to CZA. Among the 11 XDR isolates, susceptibility to C/T was 81.8% vs. CZA 72.7%. Susceptibility to C/T vs. CZA was also higher (37.5% vs. 25%) among the 24 PDR isolates. Conclusion Among P. aeruginosa isolated from CF respiratory cultures, C/T appears to have better in vitro activity compared with CZA, and remained true among isolates considered XDR and PDR. These results suggest using C/T while awaiting susceptibilities when standard anti-pseudomonal agents cannot be used. Future studies evaluating clinical outcomes for the treatment of pulmonary CF exacerbations are needed to assess the applicability of in vitro susceptibility data. Disclosures All authors: No reported disclosures.


2005 ◽  
Vol 49 (6) ◽  
pp. 2510-2511 ◽  
Author(s):  
Yunhua Chen ◽  
Elizabeth Garber ◽  
Qiuqu Zhao ◽  
Yigong Ge ◽  
Matthew A. Wikler ◽  
...  

ABSTRACT Doripenem 50% inhibitory concentrations (MIC50) and 90% inhibitory concentrations (MIC90) for multidrug-resistant strains of mucoid Pseudomonas aeruginosa (n = 200 strains), nonmucoid P. aeruginosa (n = 200), and Burkholderia cepacia complex (n = 200) isolated from patients with cystic fibrosis were 8 and 32, 8 and 64, and 8 and 32 μg/ml, respectively. Doripenem had somewhat better activity than established antimicrobial agents.


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