Repurposing of escitalopram oxalate and clonazepam in combination with ciprofloxacin and sulfamethoxazole–trimethoprim for treatment of multidrug-resistant microorganisms and evaluation of the cleavage capacity of plasmid DNA

Abstract

Bacterial resistance has propelled one of the most serious public health problems in the world. In this sense, drug repurposing has emerged for faster identification of effective drugs. The aim of this study was to investigate the repurposing of escitalopram oxalate and clonazepam drugs individually and in combination with antibiotics ciprofloxacin and sulfamethoxazole-trimethoprim to treat multidrug-resistant microorganisms (MDR) and to evaluate the chemical nuclease capacity. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), fractional inhibitory concentration index (FICI) and tolerance level were determined against each microorganism tested. In vitro antibacterial activity was evaluated against forty-seven multidrug-resistant clinical isolates and eleven standard bacterial strains of the American Type Culture Collection (ATCC). Escitalopram oxalate was active mainly against Gram-positive and clonazepam against Gram-positive and Gram-negative bacteria. When associated with the two antibiotics mentioned, they had a significant synergistic effect. Clonazepam was able to cleave plasmid DNA and the mechanisms involved were oxidative and hydrolytic. These results allow us to suggest repurposing these non-antibiotic drugs to treat bacterial infections. However, further studies on the mechanism of action of these drugs should be performed, including to increase safety in use.

Clinical significance of microbiota changes under the influence of psychotropic drugs. An updated narrative review

“…Exposure of bacteria to fluoxetine and sertraline solutions for 30 days has also been shown to promote the development of antibiotic resistance (Gurpinar et al, 2022). This observation is supported by other studies showing that fluoxetine and amitriptyline may increase the prevalence of aminoglycoside (aph3iiiA), multidrug (mdtK, mdtP, mdtH, mdtG, acrA), and tetracycline (tetM) resistance genes in the rats model (da Rosa et al, 2021). Ketamine, whose mechanism of antidepressant action is not fully understood, also exhibits in vitro antibacterial activity against six different bacterial strains: S. aureus, S. epidermidis, E. faecalis, It is worth emphasizing that the culture of these organisms in this study was carried out using propofol -a compound that stimulates the growth of bacteria (Begec et al, 2013).…”

“…Similar observations apply to metabolic diseases, in which the microbiota does not seem to change its composition but the functions of the microbiome (Kaczmarczyk et al, 2022). Finally, it is worth noting that one study observed that gut barrier integrity and markers of inflammation (gut microbiota can affect both of these parameters) might be related to the response to treatment in MDD patients and the severity of symptoms (da Rosa et al, 2021). The observed changes, however, were of a correlation rather than a causeand-effect relationship (Łoniewski et al, 2021).…”

“…Escitalopram oxalate and clonazepam inhibited multidrug-resistant clinical isolates and standard bacterial strains from the American Type Culture Collection in an in vitro study, especially in combination with ciprofloxacin and sulfamethoxazoletrimethoprim. The mechanism of bacterial inhibition by clonazepam is the digestion of plasmid DNA (da Rosa et al, 2021). Exposure of bacteria to fluoxetine and sertraline solutions for 30 days has also been shown to promote the development of antibiotic resistance (Gurpinar et al, 2022).…”

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis

“…In addition, no adverse event was reported by daily administration of 600 mg escitalopram oxalate [ 17 ]. Another study reported that an antibiotic regimen containing escitalopram oxalate reveals synergistic inhibitory effects on growth of multidrug-resistant (MDR) bacteria [ 39 ]. Indeed, these findings may provide reasonable suggestions that escitalopram oxalate is a favorable option for inclusion in a regimen for HCC treatment.…”

Anti-infective properties of proton pump inhibitors: perspectives

“…Studies reporting the importance of drug repositioning for the treatment of infectious diseases are available, and among them we cite several classes, such as antidepressants (Bottega et al 2020;da Rosa et al , 2021Foletto et al 2020Foletto et al , 2021Machado et al 2020;Serafin et al 2020), antihypertensive (Hu et al 2018), antihistamines (Bruer et al 2019;El-Nakeeb et al 2011), anti-inflammatory (Chan et al 2017), alcohol-aversive agentes (Serafin et al 2020), benzodiazepines (da Rosa et al 2021, and statins (Rampelotto et al 2018). In this commentary, the class of proton pump inhibitors (PPIs) is emphasized.…”