In Vitro and In Vivo Antibacterial Activities of a Novel Quinolone Compound, OPS-2071, Against Clostridioides difficile

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The in vitro and in vivo antibacterial activities of OPS-2071 against Clostridioides difficile were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated C. difficile strains with a minimum inhibitory concentration of 0.125 μg/mL (MIC50) and 0.5 μg/mL (MIC90), making it more active than vancomycin on a concentration basis (MIC50: 2 μg/mL, MIC90: 4 μg/mL) and comparable to fidaxomicin (MIC50: 0.063 μg/mL, MIC90: 8 μg/mL). OPS-2071 showed equally potent antibacterial activity against both hypervirulent and non-hypervirulent strains, while a significant difference in susceptibility to fidaxomicin was observed. Spontaneous resistance to OPS-2071 and vancomycin was not observed, however, resistance to fidaxomicin was observed at 4× MIC concentration. The mutant prevention concentration of OPS-2071 was 16-fold lower than those of fidaxomicin and vancomycin, and the post-antibiotic effect of OPS-2071 was longer than those of fidaxomicin and vancomycin. Also, OPS-2071 showed low systemic exposure, with OPS-2071 having 2.9% oral bioavailability at 1 mg/kg in rats. Furthermore, OPS-2071 showed significant in vivo efficacy at 0.0313 mg/kg/day (50% effective doses), 39.0-fold and 52.1-fold lower than those of vancomycin and fidaxomicin, respectively, in a hamster model of C. difficile infection. OPS-2071 has the potential to become a new therapeutic option for treating C. difficile infection.

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Efficacy of a novel lantibiotic, CMB001, against MRSA

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab040 ◽

2021 ◽

Author(s):

Jerzy Karczewski ◽

Christine M Brown ◽

Yukari Maezato ◽

Stephen P Krasucki ◽

Stephen J Streatfield

Keyword(s):

Antibacterial Activity ◽

Pharmacokinetic Analysis ◽

Maximum Tolerable Dose ◽

In Vivo Efficacy ◽

Clostridioides Difficile ◽

Alternative Treatment Option ◽

Significant Damage ◽

Tolerable Dose

Abstract Objectives To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection. Methods Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection. Results CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin. Conclusions CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.

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IN VITRO ANTIBACTERIAL ACTIVITY OF ETHANOLIC EXTRACT OF SEEDPOD AND QUERCETIN OF NELUMBO NUCIFERA GAERTN

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i1.28915 ◽

2019 ◽

Vol 12 (1) ◽

pp. 164

Author(s):

Ruvanthika Pn ◽

Manikandan S

Keyword(s):

Antibacterial Activity ◽

Ethanolic Extract ◽

Antibacterial Activities ◽

Nelumbo Nucifera ◽

Diffusion Method ◽

Dependent Manner ◽

E Coli ◽

In Vitro Antibacterial Activity

Objective: The objective of the study was to evaluate whether ethanolic extracts of Nelumbo nucifera (EENN) seedpod and quercetin (active component of NN) possess antibacterial proprieties against Gram (-) bacteria such as Escherichia coli and Pseudomonas aeruginosa and Gram (+) bacteria such as Staphylococcus aureus. Methods: Antibacterial activities of EENN seedpod and quercetin were investigated using disc diffusion method, minimum inhibitory concentration against E. coli and P. aeruginosa and Gram (+) bacteria such as S. aureus. Results: The antibacterial activity of both EENN seedpod and quercetin was found to be increased in dose-dependent manner. The maximum zone of inhibition was exhibited by both EENN seedpod and quercetin against E. coli (14 mm and 15 mm) and P. aeruginosa (13 mm and 15 mm). Gram-negative bacteria were more susceptible to the EENN seedpod extract and quercetin than Gram-positive bacteria.Conclusion: The results of the present study suggested that the effect of EENN seedpod and quercetin against the tested bacteria in vitro may contribute to the in vivo activities of the EENN seedpod and quercetin.

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In Vivo Study of the Antibacterial Chitosan/Polyvinyl Alcohol Loaded with Silver Nanoparticle Hydrogel for Wound Healing Applications

International Journal of Polymer Science ◽

10.1155/2019/7382717 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Tan Dat Nguyen ◽

Thanh Truc Nguyen ◽

Khanh Loan Ly ◽

Anh Hien Tran ◽

Thi Thanh Ngoc Nguyen ◽

...

Keyword(s):

Wound Healing ◽

Silver Nanoparticles ◽

Antibacterial Activity ◽

Polyvinyl Alcohol ◽

Healing Rate ◽

Antibacterial Effects ◽

Topical Gel ◽

Significant Difference

Silver nanoparticles have attracted great interests widely in medicine due to its great characteristics of antibacterial activity. In this research, the antibacterial activity and biocompatibility of a topical gel synthesized from polyvinyl alcohol, chitosan, and silver nanoparticles were studied. Hydrogels with different concentrations of silver nanoparticles (15 ppm, 30 ppm, and 60 ppm) were evaluated to compare their antibacterial activity, nanoparticles’ sizes, and in vivo behaviors. The resulted silver nanoparticles in the hydrogel were characterized by TEM showing the nanoparticles’ sizes less than 22 nm. The in vitro results prove that the antibacterial effects of all of the samples are satisfied. However, the in vivo results demonstrate the significant difference among different hydrogels in wound healing, where hydrogel with 30 ppm shows the best healing rate.

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Design, Synthesis, and Biological Activity of Novel Myricetin Derivatives Containing Amide, Thioether, and 1,3,4-Thiadiazole Moieties

Molecules ◽

10.3390/molecules23123132 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3132 ◽

Cited By ~ 5

Author(s):

Xianghui Ruan ◽

Cheng Zhang ◽

Shichun Jiang ◽

Tao Guo ◽

Rongjiao Xia ◽

...

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Antibacterial Activities ◽

Xanthomonas Oryzae ◽

Design Synthesis ◽

Antiviral Activities ◽

Potential Alternative ◽

Better Than

A series of myricetin derivatives containing amide, thioether, and 1,3,4-thiadiazole moieties were designed and synthesized, and their antiviral and antibacterial activities were assessed. The bioassays showed that all the title compounds exhibited potent in vitro antibacterial activities against Xanthomonas citri (Xac), Ralstonia solanacearum (Rs), and Xanthomonas oryzae pv. Oryzae (Xoo). In particular, the compounds 5a, 5f, 5g, 5h, 5i, and 5l, with EC50 values of 11.5–27.3 μg/mL, showed potent antibacterial activity against Xac that was better than the commercial bactericides Bismerthiazol (34.7 μg/mL) and Thiodiazole copper (41.1% μg/mL). Moreover, the in vivo antiviral activities against tobacco mosaic virus (TMV) of the target compounds were also tested. Among these compounds, the curative, protection, and inactivation activities of 5g were 49.9, 52.9, and 73.3%, respectively, which were better than that of the commercial antiviral Ribavirin (40.6, 51.1, and 71.1%, respectively). This study demonstrates that myricetin derivatives bearing amide, thioether, and 1,3,4-thiadiazole moieties can serve as potential alternative templates for the development of novel, highly efficient inhibitors against plant pathogenic bacteria and viruses.

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In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pyloriInfection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.9.2455-2459.2001 ◽

2001 ◽

Vol 45 (9) ◽

pp. 2455-2459 ◽

Cited By ~ 44

Author(s):

Tsuneo Kanamaru ◽

Yoshitaka Nakano ◽

Yukio Toyoda ◽

Ken-Ichiro Miyagawa ◽

Mayumi Tada ◽

...

Keyword(s):

Antibacterial Activity ◽

Anaerobic Bacteria ◽

Antibacterial Activities ◽

Mongolian Gerbils ◽

Growth Inhibitory ◽

Growth Inhibitory Activity ◽

H Pylori ◽

Aerobic And Anaerobic

ABSTRACT The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 μg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure ofH. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

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Effects of strontium ions with potential antibacterial activity on in vivo bone regeneration

10.21203/rs.3.rs-18054/v2 ◽

2020 ◽

Author(s):

Nafiseh Baheiraei ◽

Hossein Eyni ◽

Bita bakhshi ◽

Raziyeh Najafloo

Keyword(s):

Antibacterial Activity ◽

Bone Formation ◽

Bone Regeneration ◽

Bone Repair ◽

Early Stage ◽

Antibacterial Activities ◽

Calvarial Bone ◽

Alizarin Red

Abstract Background: Bioactive glasses (BGs) have attracted added attention in the structure of the scaffolds for bone repair applications. Different metal ions could be doped in BGs to induce specific biological responses. Among these ions, strontium (Sr) is considered as an effective and safe doping element with promising effects on bone formation and regeneration.Methods: In this experiment, we evaluated the antibacterial activities of the gelatin-BG (Gel-BG) and Gel-BG/Sr scaffolds in vitro. The osteogenic properties of the prepared scaffolds were also assessed in rabbit calvarial bone defects for 12 weeks. Alizarin Red, Hematoxylin & Eosin (H&E) and Masson’s Trichrome staining were performed to assess bone regeneration and the obtained results were compared with those without Sr. Also, histomorphometric data were obtained to evaluate the new bone, residual graft, and connective tissue.Results: Both scaffolds showed in vivo bone formation during 12 weeks with the newly formed bone area in Gel-BG/Sr scaffold was higher than that in Gel-BG scaffolds after the whole period. Based on the histological results, Gel-BG/Sr exhibited acceleration of early-stage bone formation in vivo. The results of antibacterial investigation showed that although both Gel-BG/Sr and Gel-BG effectively inhibited the growth of Escherichia coli (E. coli) but, only Gel-BG/Sr structure could lead to a 3 log reduction in Staphylococcus aureus (S. aureus). Conclusions: Our results confirmed that Sr doped BG is a favorable candidate for bone tissue engineering with superior antibacterial activity and bone regeneration capacity compared with similar counterparts having no Sr ion.

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Antibacterial Activity of Two Chemomechanical Caries Removal Gels on Carious Dentin of Primary Teeth: An in vitro Study

The Journal of Contemporary Dental Practice ◽

10.5005/jp-journals-10024-1976 ◽

2016 ◽

Vol 17 (12) ◽

pp. 1027-1032 ◽

Cited By ~ 1

Author(s):

Hesham S Khalil ◽

Shabnam Gulzar ◽

Ruchi Arora ◽

Altaf H Shah ◽

Bhupendra Bhardwaj ◽

...

Keyword(s):

Antibacterial Activity ◽

Primary Teeth ◽

In Vitro Study ◽

Antibacterial Activities ◽

Viable Count ◽

Primary Molar ◽

Significant Difference ◽

Molar Teeth ◽

Caries Removal

ABSTRACT Introduction Chemomechanical caries removal (CMCR) is an effective method of caries removal especially for primary teeth as they cause less discomfort when compared with conventional caries removal. The most significant thing about caries removal is the elimination of cariogenic bacteria. This study compares the antibacterial activity of two CMCR gels. Materials and methods A total of 40 primary molar teeth with carious dentin were split along the long axis in a laboratory. Total viable count (TVC) was taken for the teeth before splitting as a measure of colony-forming units per milliliter (CFU/mL). Each half was treated with either Carisolv or Carie-Care CMCR gels. Clean dentin samples were evaluated for Streptococcus mutans (SM) and Lactobacillus acidophilus (LB) after removal of carious tissue using the caries removal gels using serial dilutions and incubating on specific agar plates. Results The results showed significant reduction in mean TVC after use of both the CMCR gels. Both gels reduced the CFU/mL of SM and LB to a significant level (p < 0.05). However, there was no significant difference between the antibacterial activities of the two CMCR gels. Conclusion The CMCR gels (Carisolv and Carie-Care) significantly reduced the residual TVC as well as SM and LB in carious primary dentin. Both CMCR gels had a similar antibacterial activity on the carious dentin of primary teeth. Clinical significance The CMCR gels tested have a significant antibacterial activity and can be effectively used for elimination of caries-causing bacteria in primary teeth. How to cite this article Gulzar S, Arora R, Shah AH, Bhardwaj B, Abusalim G, Khalil HS, Wyne AH. Antibacterial Activity of Two Chemomechanical Caries Removal Gels on Carious Dentin of Primary Teeth: An in vitro Study. J Contemp Dent Pract 2016;17(12):1027-1032.

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Effects of strontium ions with potential antibacterial activity on in vivo bone regeneration

10.21203/rs.3.rs-18054/v1 ◽

2020 ◽

Author(s):

Nafiseh Baheiraei ◽

Hossein Eyni ◽

Bita bakhshi ◽

Raziyeh Najafloo

Keyword(s):

Antibacterial Activity ◽

Bone Formation ◽

Bone Regeneration ◽

Bone Repair ◽

Early Stage ◽

Antibacterial Activities ◽

Calvarial Bone ◽

Alizarin Red

Abstract Background Bioactive glasses (BGs) have attracted added attention in the structure of the scaffolds for bone repair applications. Different metal ions could be doped in BGs to induce specific biological responses. Among these ions, strontium (Sr) is considered as an effective and safe doping element with promising effects on bone formation and regeneration. Methods In this experiment, we evaluated the antibacterial activities of the gelatin-BG (Gel-BG) and Gel-BG/Sr scaffolds in vitro. The osteogenic properties of the prepared scaffolds were also assessed in rabbit calvarial bone defects for 12 weeks. Alizarin Red, Hematoxylin & Eosin (H&E) and Masson’s Trichrome staining were performed to assess bone regeneration and the obtained results were compared with those without Sr. Also, histomorphometric data were obtained to evaluate the new bone, residual graft, and connective tissue. Results Both scaffolds showed in vivo bone formation during 12 weeks with the newly formed bone area in Gel-BG/Sr scaffold was higher than that in Gel-BG scaffolds after the whole period. Based on the histological results, Gel-BG/Sr exhibited acceleration of early-stage bone formation in vivo. The results of antibacterial investigation showed that although both Gel-BG/Sr and Gel-BG effectively inhibited the growth of Escherichia coli (E. coli) but, only Gel-BG/Sr structure could lead to a 3 log reduction in Staphylococcus aureus (S. aureus). Conclusions: Our results confirmed that Sr doped BG is a favorable candidate for bone tissue engineering with superior antibacterial activity and bone regeneration capacity compared with similar counterparts having no Sr ion.

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IN VITRO ANTIBACTERIAL ACTIVITY OF THE ETHANOLIC EXTRACT OF JALOH (SALIX TETRASPERMA ROXB.) LEAVES AGAINST STAPHYLOCOCCUS AUREUS AND PSEUDOMONAS AERUGINOSA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s1.26580 ◽

2018 ◽

Vol 11 (13) ◽

pp. 107

Author(s):

Fitrah Wahyuni ◽

Urip Harahap ◽

Masfria Masfria

Keyword(s):

Staphylococcus Aureus ◽

Pseudomonas Aeruginosa ◽

Antibacterial Activity ◽

Ethanolic Extract ◽

Antibacterial Activities ◽

Regression Curve ◽

Significant Difference ◽

In Vitro Antibacterial Activity ◽

Weak Antibacterial Activity

Objective: This study aims to determine antibacterial activity of ethanolic extract of jaloh (Salix tetrasperma Roxb.) leaves against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA).Methods: Extract was obtained by maceration method of jaloh (S. tetrasperma Roxb.) leaves dried powder with 96% ethanol as solvent. The antibacterial activities of extract were tested by Kirby–Bauer method against SA and PA. Data were analyzed statistically using Kruskal–Wallis test for significant difference level p<0.05.Results: Based on the regression test, the equation of regression curve of extract antibacterial activity on SA and PA, respectively, was y=350.456x-229.579 and y=331.866x-272.069. The minimum inhibitory concentrations (MICs) of SA and PA from the equation of regression curve, respectively, were 4.5193 and 6.6039 mg/mL.Conclusion: Based on the MIC value, ethanolic jaloh leaves extract had a weak antibacterial activity against SA and PA.

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Repurposing auranofin as a Clostridioides difficile therapeutic

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz430 ◽

2019 ◽

Cited By ~ 3

Author(s):

Melanie L Hutton ◽

Havva Pehlivanoglu ◽

Callum J Vidor ◽

Meagan L James ◽

Melanie J Thomson ◽

...

Keyword(s):

Therapeutic Option ◽

Survival Rates ◽

Treatment Strategies ◽

Toxin Production ◽

Spore Production ◽

Clostridioides Difficile ◽

New Treatment ◽

Gut Damage

Abstract Background Clostridioides difficile (previously Clostridium difficile) is the leading cause of nosocomial, antibiotic-associated diarrhoea worldwide. Currently, the gold standard of treatment for C. difficile infection (CDI) is vancomycin or metronidazole, although these antibiotics also perturb the protective resident microbiota, often resulting in disease relapse. Thus, an urgent need remains for the development of new treatment strategies. Auranofin is an FDA-approved oral antirheumatic drug that was previously shown to inhibit C. difficile vegetative cell growth, toxin production and spore production in vitro. Objectives To determine the efficacy of auranofin as a CDI therapeutic by examining the effect of treatment on toxin and spore production in vitro and in vivo, and on disease outcomes in mice. Methods C. difficile cultures were treated with auranofin and examined for effects on sporulation and toxin production by sporulation assay and ELISA, respectively. Mice were pretreated with auranofin prior to infection with C. difficile and monitored for physiological conditions, survival and gut damage compared with control animals. Faeces from mice were analysed to determine whether auranofin reduces sporulation and toxin production in vivo. Results Auranofin significantly reduces sporulation and toxin production under in vitro conditions and in infected mice in vivo. Mice treated with auranofin lost less weight, displayed a significant increase in survival rates and had significantly less toxin-mediated damage in their colon and caecum compared with control mice. Conclusions Auranofin shows promise as a prospective therapeutic option for C. difficile infections.

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