New β-Lactam Antibiotics and Ceragenins – A Study to Assess Their Potential in Treatment of Infections Caused by Multidrug-Resistant Strains of Pseudomonas aeruginosa

Abstract

Background The increasing number of infections caused by antibiotic resistant strains of Pseudomonas aeruginosa posed a very serious challenge for clinical practice. This standing is driving scientists to develop new antibiotics against these microorganisms. Methods In this study, we measured the MIC/MBC values and estimated the ability of tested molecules to prevent bacterial biofilm formation to explore the effectiveness of β-lactam antibiotics ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, and ceragenins CSA-13, CSA-44, and CSA-131 against 150 clinical isolates of Pseudomonas aeruginosa that were divided into five groups, based on their antibiotic resistance profiles to beta-lactams. Selected strains of microorganisms from each group were also subjected to prolonged incubations (20 passages) with ceragenins to probe the development of resistance towards those molecules. Cytotoxicity of tested ceragenins was evaluated using human red blood cell (RBCs) hemolysis and microscopy observations of human lung epithelial A549 cells after ceragenin treatment. Poloxamer 407 (pluronic F-127) at concentrations ranging from 0.5% to 5% was tested as a potential drug delivery substrate to reduce ceragenin toxicity. Results Collected data proved that ceragenins at low concentrations are highly active against clinical strains of Pseudomonas aeruginosa regardless of their resistance mechanisms to conventional antibiotics. Ceragenins also show low potential for resistance development, high antibiofilm activity, and controlled toxicity when used together with poloxamer 407. Conclusion This data strongly supports the need for further study directed to develop this group of molecules as new antibiotics to fighting infections caused by antibiotic resistant strains of Pseudomonas aeruginosa .

Three-Year Evaluation of Pseudomonas aeruginosa Bacteremia in Patients Admitted to a University-Affiliated Hospital, Mashhad, Iran

“…At the same time, all the 34 isolates were sensitive to colistin. These results are in line with the previous evidence and suggest that P. aeruginosa has become resistant to antibiotics (both MDR and XDR), especially to betalactams (7,22). The significant effect of appropriate initial empirical antibiotics in bacteremia with P. aeruginosa on patient mortality has been previously emphasized, especially in immunocompromised patients, like those with cancer or neutropenia (6,23,24).…”

Pseudomonas aeruginosa Infections in Cancer Patients

“…The susceptibility patterns differ between geographical region and between hospital settings and depend on local epidemiology, antibiotic policy, patient profiles and the composition of examined strain collection [68]. In our last study [69], we assessed the activity of ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam and colistin against 150 P. aeruginosa strains isolated from oncological patients. Our collection consisted mainly of strains exhibiting various mechanisms of resistance to carbapenems, including MBL producers.…”

In Vitro Synergistic Inhibitory Activity of Natural Alkaloid Berberine Combined with Azithromycin against Alginate Production by Pseudomonas aeruginosa PAO1

“…Given the predominant role of biofilm in multidrug-resistant P. aeruginosa , the development of novel therapeutic strategies targeting biofilm is of the highest priority. Scientists have conducted many beneficial trials to evaluate the potential of artificial compounds [ 38 ], organic extracts [ 39 ], or modified compounds [ 40 ] from herbs, to combat such resistant strains. However, there is still a long journey to clinical application.…”