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

2021 ◽  
Author(s):  
Taciéli Fagundes da Rosa ◽  
Catrine de Souza Machado ◽  
Marissa Bolson Serafin ◽  
Angelita Bottega ◽  
Silvana Silveira Coelho ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Culture Collection ◽  
Bacterial Strains ◽  
Gram Positive

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.

scholarly journals Design, Synthesis, and Antibacterial Evaluation of Novel Ocotillol Derivatives and Their Synergistic Effects with Conventional Antibiotics

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5969
Author(s):  
Doudou Zhang ◽  
Yucheng Cao ◽  
Kaiyi Wang ◽  
Zhuoyue Shi ◽  
Ruodong Wang ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Design Synthesis ◽  
Improper Use ◽  
Compound 21 ◽  
Conventional Antibiotics

The improper use of antibiotics has led to the development of bacterial resistance, resulting in fewer antibiotics for many bacterial infections. Especially, the drug resistance of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) is distinctly serious. This research designed and synthesized two series of 3-substituted ocotillol derivatives in order to improve their anti-HA-MRSA potency and synergistic antibacterial activity. Among the synthesized compounds, 20–31 showed minimum inhibitory concentration (MIC) values of 1–64 µg/mL in vitro against HA-MRSA 18–19, 18–20, and S. aureus ATCC29213. Compound 21 showed the best antibacterial activity, with an MIC of 1 μg/mL and had synergistic inhibitory effects. The fractional inhibitory concentration index (FICI) value was 0.375, when combined with chloramphenicol (CHL) or kanamycin (KAN). The structure–activity relationships (SARs) of ocotillol-type derivatives were also summarized. Compound 21 has the potential to be developed as a novel antibacterial agent or potentiator against HA-MRSA.

scholarly journals Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7400
Author(s):  
José B. de Araújo-Neto ◽  
Maria M. C. da Silva ◽  
Cícera D. de M. Oliveira-Tintino ◽  
Iêda M. Begnini ◽  
Ricardo A. Rebelo ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Antibiotic Activity ◽  
Bacterial Strains ◽  
Microdilution Method ◽  
Fluoroquinolone Antibiotics ◽  
Broth Microdilution Method ◽  
Resistant Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.

Bacterial Communications in Implant Infections: A Target for an Intelligence War

2007 ◽  
Vol 30 (9) ◽  
pp. 757-763 ◽  
Author(s):  
J.W. Costerton ◽  
L. Montanaro ◽  
C.r. Arciola
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Homoserine Lactone ◽  
Bacterial Virulence ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Sensing Systems

The status of population density is communicated among bacteria by specific secreted molecules, called pheromones or autoinducers, and the control mechanism is called “quorum-sensing”. Quorum-sensing systems regulate the expression of a panel of genes, allowing bacteria to adapt to modified environmental conditions at a high density of population. The two known different quorum systems are described as the LuxR-LuxI system in gram-negative bacteria, which uses an N-acyl-homoserine lactone (AHL) as signal, and the agr system in gram-positive bacteria, which uses a peptide-tiolactone as signal and the RNAIII as effector molecules. Both in gram-negative and in gram-positive bacteria, quorum-sensing systems regulate the expression of adhesion mechanisms (biofilm and adhesins) and virulence factors (toxins and exoenzymes) depending on population cell density. In gram-negative Pseudomonas aeruginosa, analogs of signaling molecules such as furanone analogs, are effective in attenuating bacterial virulence and controlling bacterial infections. In gram-positive Staphylococcus aureus, the quorum-sensing RNAIII-inhibiting peptide (RIP), tested in vitro and in animal infection models, has been proved to inhibit virulence and prevent infections. Attenuation of bacterial virulence by quorum-sensing inhibitors, rather than by bactericidal or bacteriostatic drugs, is a highly attractive concept because these antibacterial agents are less likely to induce the development of bacterial resistance.

scholarly journals Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 727
Author(s):  
Hang Thi Nguyen ◽  
Mahmud T. Morshed ◽  
Daniel Vuong ◽  
Andrew Crombie ◽  
Ernest Lacey ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Specific Treatment ◽  
Multidrug Resistant ◽  
Survival Times ◽  
Fungal Natural Products ◽  
Serious Bacterial Infections ◽  
Further Development ◽  
Reference Strains

Our recent focus on the “lost antibiotic” unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen Staphylococcus pseudintermedius, with minimum inhibitory concentration (MIC) ranging 0.5–1 μg/mL. When combined with sub-inhibitory concentrations of colistin, the benzguinols demonstrated synergy against Gram-negative reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MICs of 1–2 μg/mL in the presence of colistin), whereas the benzguinols alone had no activity. Administration of three intraperitoneal (IP) doses of 20 mg/kg benzguinol A or B to mice did not result in any obvious adverse clinical or pathological evidence of acute toxicity. Importantly, mice that received three 20 mg/kg IP doses of benzguinol A or B at 4 h intervals exhibited significantly reduced bacterial loads and longer survival times than vehicle-only treated mice in a bioluminescent S. aureus murine sepsis challenge model. We conclude that the benzguinols are potential candidates for further development for specific treatment of serious bacterial infections as both stand-alone antibiotics and in combination with existing antibiotic classes.

scholarly journals Antibacterial activity of some 1,2,3,4-tetrasubstituted pyrrole derivatives and molecular docking studies

2021 ◽  
Vol 4 (1) ◽  
pp. 1-9
Author(s):  
Dilek A Akbaşlar ◽  
Osman Gülnaz ◽  
Mehmet Abdullah Alagöz ◽  
E. Sultan Giray
Keyword(s):  
Antibacterial Activity ◽  
Molecular Docking ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Docking Studies ◽  
Diffusion Method ◽  
Gram Positive ◽  
Pyrrole Derivatives ◽  
Molecular Docking Studies

Pyrrole compounds are important classes of heterocycle compounds in the search for effective agents against multidrug-resistant bacterial infections. With an approach to reduce the growing bacterial resistance and to discover more active antibacterial agents with fewer side effects, the previously synthesized 1,2,3,4-tetrasubstituted pyrrole derivatives were screened for their in vitro antibacterial activity by disc diffusion method against some gram-positive and gram-negative bacteria, for the first time. The results indicated that compounds 4, 11, and 12 showed promising antibacterial activity against gram-positive S. aureus and B. cereus bacteria equal or more than standard as tetracycline. Molecular docking studies were employed both to explain the activity results of the more active compounds at the level of protein-ligand interactions and to compare the interactions of these compounds with the interactions of tetracycline. The relationship between structure and antibacterial activity was also discussed.

scholarly journals The Minimum Inhibitory Concentration of Antibiotics: Methods, Interpretation, Clinical Relevance

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 165
Author(s):  
Beata Kowalska-Krochmal ◽  
Ruth Dudek-Wicher
Keyword(s):  
Monte Carlo ◽  
Bacterial Infections ◽  
Statistical Estimation ◽  
Therapeutic Strategy ◽  
Inhibitory Concentration ◽  
Therapeutic Strategies ◽  
Bacterial Strains ◽  
Method Choice ◽  
Reliable Assessment

Inefficiency of medical therapies used in order to cure patients with bacterial infections requires not only to actively look for new therapeutic strategies but also to carefully select antibiotics based on variety of parameters, including microbiological. Minimal inhibitory concentration (MIC) defines in vitro levels of susceptibility or resistance of specific bacterial strains to applied antibiotic. Reliable assessment of MIC has a significant impact on the choice of a therapeutic strategy, which affects efficiency of an infection therapy. In order to obtain credible MIC, many elements must be considered, such as proper method choice, adherence to labeling rules, and competent interpretation of the results. In this paper, two methods have been discussed: dilution and gradient used for MIC estimation. Factors which affect MIC results along with the interpretation guidelines have been described. Furthermore, opportunities to utilize MIC in clinical practice, with pharmacokinetic /pharmacodynamic parameters taken into consideration, have been investigated. Due to problems related to PK determination in individual patients, statistical estimation of the possibility of achievement of the PK/PD index, based on the Monte Carlo, was discussed. In order to provide comprehensive insights, the possible limitations of MIC, which scientists are aware of, have been outlined.

scholarly journals Antibacterial Activity of Colloidal Silver against Gram-Negative and Gram-Positive Bacteria

Antibiotics ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 36 ◽  
Author(s):  
Andrea Vila Domínguez ◽  
Rafael Ayerbe Algaba ◽  
Andrea Miró Canturri ◽  
Ángel Rodríguez Villodres ◽  
Younes Smani
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Properties ◽  
Multidrug Resistant ◽  
Colloidal Silver ◽  
Ros Production ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Kill Curve

Due to the emergence of antimicrobial resistance, new alternative therapies are needed. Silver was used to treat bacterial infections since antiquity due to its known antimicrobial properties. Here, we aimed to evaluate the in vitro activity of colloidal silver (CS) against multidrug-resistant (MDR) Gram-negative and Gram-positive bacteria. A total of 270 strains (Acinetobacter baumannii (n = 45), Pseudomonas aeruginosa (n = 25), Escherichia coli (n = 79), Klebsiella pneumoniae (n = 58)], Staphylococcus aureus (n = 34), Staphylococcus epidermidis (n = 14), and Enterococcus species (n = 15)) were used. The minimal inhibitory concentration (MIC) of CS was determined for all strains by using microdilution assay, and time–kill curve assays of representative reference and MDR strains of these bacteria were performed. Membrane permeation and bacterial reactive oxygen species (ROS) production were determined in presence of CS. CS MIC90 was 4–8 mg/L for all strains. CS was bactericidal, during 24 h, at 1× and 2× MIC against Gram-negative bacteria, and at 2× MIC against Gram-positive bacteria, and it did not affect their membrane permeabilization. Furthermore, we found that CS significantly increased the ROS production in Gram-negative with respect to Gram-positive bacteria at 24 h of incubation. Altogether, these results suggest that CS could be an effective treatment for infections caused by MDR Gram-negative and Gram-positive bacteria.

scholarly journals Rosuvastatin as forthcoming antibiotic or as adjuvant additive agent: In vitro novel antibacterial study

2018 ◽  
Vol 10 (03) ◽  
pp. 271-275 ◽  
Author(s):  
Hayder M. Al-Kuraishy ◽  
Ali I. Al-Gareeb ◽  
Ali K. Al-Buhadily
Keyword(s):  
Antibacterial Activity ◽  
Pathogenic Bacteria ◽  
Inhibitory Concentration ◽  
Cholesterol Biosynthesis ◽  
Lipid Lowering ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli

ABSTRACT INTRODUCTION: Rosuvastatin is a lipid-lowering agent that inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase leading to a reduction of cholesterol biosynthesis. Many studies have shown an association between statins use and the reduction of sepsis. The aim of the present study was to evaluate the in vitro combined antibacterial activity of rosuvastatin and cefixime. MATERIALS AND METHODS: Five pathogenic bacteria isolates (Gram positive and Gram negative) were used for testing the antibacterial activity of rosuvastatin alone and in combination with cefixime. Results: Rosuvastatin mainly inhibited Klebsiella pneumoniae and Escherichia coli where it caused zones of inhibition of (17.9 ± 0.6 mm) and (16.9 ± 0.3 mm), respectively; however, it moderately inhibited the growth of Staphylococcus epidermidis (12.9 ± 0.2 mm) and Staphylococcus aureus (12.76 ± 0.2) and produced less inhibition for Pseudomonas aeruginosa growth where it led to a zone of inhibition equal to (9.1 ± 0.5 mm). Minimal inhibitory concentration (μg/mL) of rosuvastatin was high compared to cefixime. Fractional inhibitory concentration (FIC) of rosuvastatin was low for E. coli and K. pneumoniae compared to the other types of bacterial strains. Rosuvastatin exhibited additive effects with cefixime against E. coli and K. pneumoniae. ΣFIC index was 0.536 and 0.734 for E. coli and K. pneumoniae, respectively. Conclusions: Rosuvastatin has a significant antibacterial activity against both Gram-negative and Gram-positive bacteria with a potential additive effect when used in combination with cefixime.

scholarly journals Resveratrol enhances the antimicrobial effect of polymyxin B on Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Li Liu ◽  
Jingyi Yu ◽  
Xiaofei Shen ◽  
Xingwei Cao ◽  
Qing Zhan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Antimicrobial Effect ◽  
Polymyxin B ◽  
Multidrug Resistant ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Optimal Drug

Abstract Background Multidrug resistant (MDR) Gram-negative bacterial infections are a serious threat to human health due to the lack of effective treatments. In this study, we selected 50 Gram-negative bacterial strains, including 26 strains of Klebsiella pneumoniae and 24 strains of Escherichia coli, to explore whether resveratrol and polymyxin B have a synergistic killing effect. Results MIC values against polymyxin B were ≥ 4 μg/mL for 44 of the strains and were 2 μg/mL for the other 6 strains. MICs against polymyxin B in the isolates tested were significantly reduced by the addition of resveratrol. The degree of decline depended on the bacteria, ranging from 1/2 MIC to 1/512 MIC, and the higher the concentration of resveratrol, the greater the decrease. Checkerboard analysis indicated a synergistic effect between resveratrol and polymyxin B; the optimal drug concentration for different bacteria was different, that of resveratrol ranging from 32 μg/mL to 128 μg/mL. Subsequent time-kill experiments showed that a combination of polymyxin B and resveratrol was more effective in killing bacteria. Conclusions Our in vitro studies have shown that resveratrol can increase the sensitivity of MDR bacterial strains to polymyxin B, suggesting a potential new approach to the treatment of MDR infections.

scholarly journals Tigecycline: a review of the literature

2006 ◽  
Vol 7 (4) ◽  
pp. 211-222
Author(s):  
Mario Venditti ◽  
Maria Elena Pompeo ◽  
Flavia Fabi
Keyword(s):  
Antimicrobial Agent ◽  
Broad Spectrum ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Antibiotic Administration ◽  
Spectrum Activity

Tigecycline is a new first-in-class glycylcycline antimicrobial agent with expanded broad-spectrum activity. It was developed to overcome the two key resistance mechanisms, efflux pumps and ribosomal protection, that limit the use of tetracycline. The spectrum of activity extends to clinically relevant susceptible and multidrug resistant bacteria, as methicillin resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, vancomycin resistant Enterococci, Acinetobacter spp, Acinetobacter baumannii and Enterobacteriaceae, including extended-spectrum β-lactamase-producing strains (ESBLs). Tigecycline has been introduced into clinical practice as part of the effort to combat the growing problem of bacterial resistance to anti-infective therapy: tigecycline could replace some broad-spectrum agents for approved indications reducing the selective pressure provided by antibiotic administration. The expanded in vitro activity against a broad range of bacteria, including resistant pathogens, of tigecycline suggest that this novel antimicrobial agent should offer clinicians an option for the treatment of patients with serious bacterial infections.

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