IBS Therapeutic has Broad Spectrum Antimicrobial Activity

Author(s):  
Ashley L. Cunningham ◽  
Orhi Esarte Palomero ◽  
Bradley J. Voss ◽  
M. Stephen Trent ◽  
Bryan W. Davies

Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multi-drug resistant strains. Our results suggest otilonium bromide could act on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stéphane L. Benoit ◽  
Alan A. Schmalstig ◽  
John Glushka ◽  
Susan E. Maier ◽  
Arthur S. Edison ◽  
...  

Abstract The nickel (Ni)-specific chelator dimethylglyoxime (DMG) has been used for many years to detect, quantitate or decrease Ni levels in various environments. Addition of DMG at millimolar levels has a bacteriostatic effect on some enteric pathogens, including multidrug resistant (MDR) strains of Salmonella Typhimurium and Klebsiella pneumoniae. DMG inhibited activity of two Ni-containing enzymes, Salmonella hydrogenase and Klebsiella urease. Oral delivery of nontoxic levels of DMG to mice previously inoculated with S. Typhimurium led to a 50% survival rate, while 100% of infected mice in the no-DMG control group succumbed to salmonellosis. Pathogen colonization numbers from livers and spleens of mice were 10- fold reduced by DMG treatment of the Salmonella-infected mice. Using Nuclear Magnetic Resonance, we were able to detect DMG in the livers of DMG-(orally) treated mice. Inoculation of Galleria mellonella (wax moth) larvae with DMG prior to injection of either MDR K. pneumoniae or MDR S. Typhimurium led to 40% and 60% survival, respectively, compared to 100% mortality of larvae infected with either pathogen, but without prior DMG administration. Our results suggest that DMG-mediated Ni-chelation could provide a novel approach to combat enteric pathogens, including recalcitrant multi-drug resistant strains.


2021 ◽  
Vol 18 (4) ◽  
pp. 719-732
Author(s):  
Najwa Menwer Alharbi ◽  
Amjad Khalid Alharthi ◽  
Alsamadani Alsamadani ◽  
Raneem Ahmed Almihmadi ◽  
Bothaina Ali Alaidaroos

This study aimed to investigate a method to manage antimicrobial resistance (AMR) issues by exploring soil microorganisms that are capable of producing bioactive compounds. Eight different types of soil were selected from three locations to screen, isolate, and identify microorganisms that are capable of producing antimicrobial compounds. The multi-drug resistant strains are Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans were selected for primary and secondary screening using the crowded plate method and the agar well diffusion method. Inhibition zones were measured, and data were assessed using statistical tests to check for normality and differences between parametric variables and nonparametric data. This was followed by biochemical characterization, DNA isolation, and polymerase chain reaction (PCR). Molecular identification was performed using 16S rRNA amplification and sequencing. Here, 86 isolates containing bacteria and fungi were successfully extracted from soil samples. Further, 49 of 86 microbes showed possible antimicrobial activity, but only 12 isolates resulted in distinct inhibition zones with the selected multi-drug resistant strains. The following different taxa were identified: Firmicutes (nine strains), Proteobacteria (one strain), Actinobacteria (one strain), and Azotobacter (one strain). Species are represented in a phylogenetic tree, which was constructed using the unweighted pair-group method with arithmetic mean (UPGMA) method. The evolutionary distances were computed using the Maximum Composite Likelihood method. The identified microorganisms showed antimicrobial activity, confirming that soil microorganisms have great potential to address AMR issues.


2019 ◽  
pp. 56-62 ◽  
Author(s):  
Y. V. Korotkii ◽  
N. A. Vrynchanu ◽  
M. L. Dronova ◽  
Z. S. Suvorova ◽  
O. A. Smertenko

The emergence and spread of resistant strains of pathogens as well as reduction of the efficacy of current antimicrobial agents requires the development of novel antimicrobial compounds. The aim of the present study was synthesis and evaluation of antimicrobial activity of new arylaliphatic aminopropanols. The objects of the present study were 1-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts (compounds I–XIV). Compounds synthesis was carried out by heating of precursor epoxide and excessive amount of appropriate amines in isopropanole, followed by treatment with excess of alkyl halides. Methods of elemental analysis, IR- and PMR-spectroscopy were used for confirmation of chemical structure. Antimicrobial activity against Staphylococcus аureus АTCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa АТСС 27853 and Candida albicans NCTC 885/653 was determined by a broth dilution method and evaluated via minimum inhibitory concentration (MIC). Our investigation of antibacterial and antifungal activity of 1-[4-(1,1,3,3-tetra methylbutyl)phenoxy]-3-dialkylamino-2-propanol quaternary salts showed that compounds possess narrow spectrum, as well as broad spectrum action. Significant antimicrobial activity of the novel aryl aliphatic aminoalcohols indicates their potential usage as a component of new antimicrobial drugs.


2020 ◽  
Vol 22 (2) ◽  
pp. 128-136
Author(s):  
Dmitry V. Tapalskiy ◽  
T.A. Petrovskaya ◽  
A.I. Kozlova ◽  
Mikhail V. Edelstein

Objective. To reveal antibiotics being capable of potentiating the antimicrobial activity of colistin against multidrug- and extensively drug-resistant strains of Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods. The minimum inhibitory concentrations (MIC) of colistin alone and in combination with fixed concentrations of antibiotics of different groups were determined for 272 multidrug- and extensively drug-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa. Bactericidal activity of colistin, carbapenems, clarithromycin and their combinations were also determined at fixed PK/PD breakpoint concentrations of antibiotics. Results. Potentiation of colistin antibacterial activity in the presence of fixed concentration of rifampicin (0.5 mg/L) was observed as a 4–16-fold MIC decrease for K. pneumoniae and A. baumannii. In the presence of fixed concentrations of azithromycin (2 mg/L) or clarithromycin (1 mg/L), the colistin MICs decreased 64–512 times for K. pneumoniae, 4–32 times for A. baumannii, 16–64 times for P. aeruginosa. Two- or more-fold reduction of MIC of colistin in the presence of 1 mg/L clarithromycin was observed for 85.2% of K. pneumoniae, 86.3% of A. baumannii and 60.2% of P. aeruginosa strains. In the presence of 1 mg/L clarithromycin and 8 mg/L meropenem, the potentiation effect was enhanced and was observed for an even larger percent of isolates: 96.1% K. pneumoniae, 98.0% A. baumannii and 61.3% P. aeruginosa. Colistin-based combinations with clarithromycin-meropenem and clarithromycin-doripenem were bactericidal against most isolates of A. baumannii and P. aeruginosa (91.4–100%), and against colistin-sensitive K. pneumoniae (95.3%) and colistin-resistant K. pneumoniae (79.1%). Conclusions. The ability of macrolides to significantly potentiate the colistin antimicrobial activity against both colistin-sensitive and colistin-resistant strains of K. pneumoniae, A. baumannii and P. aeruginosa was shown. This potentiation effect was enhanced in the presence of carbapenems. The most potent bactericidal activity was revealed with dual and triple combinations of colistin-clarithromycin and colistinclarithromycin-carbapenems.


Author(s):  
Christine A. Pybus ◽  
Christina Felder-Scott ◽  
Victor Obuekwe ◽  
David E. Greenberg

Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multi-drug resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to seven commonly used antibiotics in well-characterized multi-drug resistant pathogens, then determined their efficacy in the biofilm setting. MIC90 values were consistently lower for cefiderocol in all strains tested compared to other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, tobramycin, clarithromycin). Cefiderocol treatment displayed a superior reduction in Pseudomonas aeruginosa biofilm (93%, p<0.0001) compared to other antibiotics (49-82%). Cefiderocol was generally as effective or superior in reducing biofilm in other pathogens depending on the pathogen-antibiotic combination. There was a trend towards greater biofilm reduction when the antibiotic dose was increased or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.


2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201 ◽  
Author(s):  
Jung-Eun Kim ◽  
Goo Yoon ◽  
Jung-Hyun Shim ◽  
Seung-Sik Cho

The aim of this study was to evaluate the antibacterial activity of the licochalcones A (1) and E (2) against drug resistant strains of clinical origin. The results indicate that the licochalcones had a broad inhibitory activity against tested bacteria. Compared to vancomycin and teicoplanin, these compounds provided weaker activity against non-MDR Staphylococcus aureus and Enterococcus but broader activity against MRSA and VRE strains. The results provide promising baseline information for the potential use of 1 and 2 from Glycyrrhiza inflata in the treatment of drug resistant bacterial infections.


2011 ◽  
Vol 7 (4) ◽  
pp. 522-526 ◽  
Author(s):  
S. Manikandan ◽  
S. Ganesapand ◽  
Manoj Singh ◽  
N. Sangeetha ◽  
A.K. Kumaraguru

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