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1.
Microorganisms ; 10(5)2022 May 10.
Article in English | MEDLINE | ID: mdl-35630446

ABSTRACT

Pseudomonas aeruginosa is a dominant cause of respiratory infection in individuals with cystic fibrosis (CF), leading to significant morbidity and mortality. Detection of P. aeruginosa is conducted by culture of respiratory samples but this process may occasionally be compromised due to overgrowth by other bacteria and fungi. We aimed to evaluate a novel chromogenic medium, Pseudomonas aeruginosa chromogenic agar (PACA), for culture of P. aeruginosa from respiratory samples, from patients with CF. A total of 198 respiratory samples were cultured onto PACA and three other media: CHROMID® P. aeruginosa, CHROMagar™ Pseudomonas and MacConkey agar. P. aeruginosa was recovered from 66 samples (33%), using a combination of all media. After 72 h incubation, the sensitivity of the four chromogenic media was as follows: 91% for PACA and CHROMagar™ Pseudomonas, 85% for CHROMID® P. aeruginosa and 83% for MacConkey agar. For the three chromogenic media, the positive predictive value after 72 h was as follows: 95% for PACA, 56% for CHROMagar™ Pseudomonas and 86% for CHROMID® P. aeruginosa. PACA proved to be a highly effective culture medium for the isolation and specific detection of P. aeruginosa from respiratory samples.

2.
J Med Chem ; 59(6): 2780-93, 2016 Mar 24.
Article in English | MEDLINE | ID: mdl-26907951

ABSTRACT

Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the C5 aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.


Subject(s)
Adamantane/analogs & derivatives , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Drug Resistance, Multiple, Bacterial/drug effects , Ethylenediamines/chemical synthesis , Ethylenediamines/pharmacology , Mycobacterium tuberculosis/drug effects , Piperazines/chemical synthesis , Piperazines/pharmacology , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Adamantane/chemical synthesis , Adamantane/pharmacology , Carrier Proteins/drug effects , Cell Line , Cell Survival/drug effects , Computational Biology , Drug Design , Humans , Microbial Sensitivity Tests , Models, Molecular , Mycobacterium/drug effects , Pharmaceutical Preparations/metabolism , Structure-Activity Relationship
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