IU Indianapolis ScholarWorks :: Browsing by Subject "Anti-Bacterial Agents"

Browsing by Subject "Anti-Bacterial Agents"

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The ability of new intracanal medicaments to prevent the formation of multi-species biofilm on radicular dentin
(2017) Jacobs, Jordon C.; Spolnik, Kenneth J.; Ehrlich, Ygal; Gregory, Richard L.; Yassen, Ghaeth; Bringas, Josef
The residual antibacterial effects of antimicrobials used in endodontic regeneration against biofilm bacteria obtained from immature and mature teeth Jordon C. Jacobs DDS, Richard L Gregory PhD, Ygal Ehrlich DMD, Kenneth Spolnik DDS, MS, Josef S. Bringas DMD, DDS, MS, and Ghaeth Yassen BDS, MSD, PhD We explored the residual antibacterial properties of dentin pretreated with low concentrations of double antibiotic paste (DAP) against biofilm bacteria obtained from different clinical sources. Dentin blocks were sterilized and randomized into 4 treatment groups and 2 control groups (n=20). Blocks from treatment groups were pretreated with DAP (1 or 5 mg/ml) loaded into methylcellulose, calcium hydroxide (Ca(OH)2), or methylcellulose paste. After one week, the treatment pastes were removed and all blocks were immersed in PBS. The dentin blocks from treatment groups and one of the control groups were then inoculated with bacterial isolates obtained from immature or mature teeth with pulpal necrosis(n=10). The remaining control group received no bacteria and was used as a sterile control. Blocks were then incubated anaerobically for 3 weeks. Biofilm disruption assays were conducted for all samples. Two-way ANOVA and pair-wise comparisons were used for statistical analyses. The residual antibacterial effect of dentin pretreated with 5 mg/ml of DAP was significantly higher than all other groups regardless of the source of biofilm. Dentin pretreated with 1 mg/ml of DAP demonstrated significantly higher residual antibacterial effects in comparison to dentin pretreated with placebo paste and Ca(OH)2 only in bacterial isolates obtained from mature teeth with pulpal necrosis. Dentin pretreated with Ca(OH)2 did not demonstrate any residual antibacterial effects. Dentin pretreated with 1 or 5 mg/ml of DAP demonstrated significantly better residual antibacterial effects against biofilm bacteria obtained from mature teeth with pulpal necrosis in comparison to bacterial isolates obtained from immature teeth with pulpal necrosis.
The antibacterial effect of new intracanal medicaments against established mutlispecies biofilm
(2017) Troxel, Alex; Spolnik, Kenneth J.; Gregory, Richard; Ehrlich, Ygal; Bringas, Josef; Zunt, Susan L.; Yassen, Ghaeth
We investigated the antibacterial effect of low concentrations of double antibiotic paste (DAP) loaded into a methylcellulose system against bacterial biofilms obtained from mature and immature teeth with necrotic pulps. Standardized radicular dentin specimens were randomly divided into six experimental groups (n = 20). Group 1: 5mg/mL DAP treatment. Group 2: 1mg/mL DAP treatment. Group 3: Calcium hydroxide (Ca(OH)2) treatment. Group 4: Methylcellulose. Group 5: No treatment. Group 6: No bacteria or treatment. Clinical bacterial isolates were obtained from mature and immature teeth with necrotic pulps indicated for endodontic regeneration or routine endodontic treatment, respectively. Specimens in each group were inoculated with either bacterial isolates (n = 10) and incubated anaerobically for 3 weeks. Specimens were then treated for one week with the assigned group treatment. Treatments were rinsed with sterile saline and biofilms were detached and spiral plated using biofilm disruption assays. Wilcoxon Rank Sum tests followed by pair-wise comparisons were used for statistical analyses. Treatment of infected dentin with 1 mg/ml of DAP, 5 mg/mL of DAP, and Ca(OH)2 demonstrated significant and substantial antibiofilm effects in comparison to untreated control groups or groups treated with placebo paste. Furthermore, 1 mg/mL of DAP caused complete eradication of biofilm obtained from mature tooth with necrotic pulp. However, the same concentration was not able to completely eradicate biofilm obtained from the immature tooth with necrotic pulp. Low concentrations of DAP (1-5 mg/mL) loaded into a biocompatible methylcellulose system demonstrated significant antibacterial effects against biofilm obtained from both mature and immature teeth with necrotic pulps.
The antibacterial effects of radiopaque double antibiotic pastes against clinical bacterial isolates from mature and immature teeth with necrotic pulps
(2018) Ibrahim, Carolin Francis; Spolnik, Kenneth J.; Ehrlich, Ygal; Gregory, Richard L.; Zunt, Susan; Bringas, Josef; Yassen, Ghaeth
Low concentrations (1-10mg/mL) of double antibiotic paste (DAP) have demonstrated antibacterial properties in regenerative endodontics. The aim of this study was to evaluate if DAP made radiopaque (RoDAP) with barium sulfate has antibacterial effects against bacterial isolates from a mature and immature tooth with necrotic pulp. Clinical bacterial isolates were obtained from the canals of mature and immature teeth with necrotic pulps during root canal therapy or a regenerative procedure, respectively. Bacterial isolates were grown anaerobically for three weeks on 4x4mm dentin specimens prepared from extracted human teeth (n=48 per biofilm type). The dentin specimens were allocated into six groups and treated as follows: 1mg/mL RoDAP, 10mg/mL RoDAP, calcium hydroxide (UltraCal), placebo (barium sulfate in methylcellulose), no treatment, and no bacteria or treatment (sterile control). After one week of treatment the biofilm was detached and biofilm disruption assays were conducted to determine the bacterial numbers (CFUs/mL). The data was analyzed using Wilcoxon Rank Sum tests followed by pairwise comparisons. 1 and 10 mg/mL RoDAP as well as calcium hydroxide demonstrated significant antibacterial effects against the tested bacterial isolates. The placebo paste did not demonstrate any significant antibacterial effects. No significant difference in antibacterial effects was found against isolates from both mature and immature teeth regardless of the type of treatment. Both 1 and 10 mg/mL RoDAP demonstrated significant antibacterial effects against bacterial isolates from mature and immature teeth with necrotic pulps. RoDAP can be beneficial clinically since its adequate placement within the canal system can be confirmed radiographically.
The antibacterial stability of a new radiopaque double antibiotic paste
(2018-06) Epkey, Kathryn Eileen; Spolnik, Kenneth J.; Ehrlich, Ygal; Gregory, Richard L.; Zunt, Susan; Bringas, Josef; Yassen, Ghaeth
We evaluated the antibacterial stability (shelf life) of a new radiopaque double antibiotic paste (RoDAP) loaded in a methylcellulose system with 30% w/v barium sulfate against biofilm collected from an immature tooth with necrotic pulp. Uniform radicular dentin specimens were infected with bacterial biofilm obtained from an immature tooth with a necrotic pulp and incubated anaerobically for three weeks. These samples were randomly divided into 6 experimental groups (n=7) and treated for 1 week at three time points of aged radiopaque DAP: 0 months, 3 months, and 6 months. Group 1: 1mg/mL RoDAP treatment. Group 2: 10 mg/mL RoDAP treatment. Group 3: Calcium hydroxide (Ca(OH)2) treatment. Group 4: Methylcellulose with barium sulfate. Group 5: No treatment. Group 6: No bacteria or treatment. The samples were rinsed with sterile saline to detach biofilms and then spiral plated using a biofilm disruption assay. Statistical analyses were performed using Wilcoxon rank-sum tests and Wilcoxon signed rank tests with fixed effects for treatment, time, and the treatment-by-time interaction. Treatment of infected dentin with 1 mg/mL RoDAP, 10 mg/mL RoDAP, and Ca(OH)2 demonstrated significant and substantial antibiofilm effects in comparison to untreated control groups or groups treated with placebo paste after 0, 3, and 6 months of aging. Calcium hydroxide, however, showed slightly less antibiofilm activity after 6 months of aging when compared to 0 months and 3 months of aging. This difference was statistically significant (p > 0.05). In conclusion, both concentrations of RoDAP maintained full antibacterial efficacy after 6 months of aging, while calcium hydroxide lost some antibacterial activity after a shelf life of 6 months.
Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes
(American Society for Microbiology, 2015-12) Arivett, Brock A.; Fiester, Steven E.; Ohneck, Emily J.; Penwell, William F.; Kaufman, Cynthia M.; Relich, Ryan F.; Actis, Luis A.; Department of Pathology & Laboratory Medicine, IU School of Medicine
A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.
Azithromycin efficacy in asymptomatic rectal chlamydial infection in MSM: A more definitive answer soon?
(Wolters Kluwer, 2017-07) Batteiger, Byron E.; Medicine, School of Medicine
Bimix antimicrobial scaffolds for regenerative endodontics
(Elsevier, 2014-11) Palasuk, Jadesada; Kamocki, Krzysztof; Hippenmeyer, Lauren; Platt, Jeffrey A.; Spolnik, Kenneth J.; Gregory, Richard L.; Bottino, Marco C.; Department of Restorative Dentistry, IU School of Dentistry
INTRODUCTION: Eliminating and/or inhibiting bacterial growth within the root canal system has been shown to play a key role in the regenerative outcome. The aim of this study was to synthesize and determine in vitro both the antimicrobial effectiveness and cytocompatibility of bimix antibiotic-containing polydioxanone-based polymer scaffolds. METHODS: Antibiotic-containing (metronidazole [MET] and ciprofloxacin [CIP]) polymer solutions (distinct antibiotic weight ratios) were spun into fibers as a potential mimic to the double antibiotic paste (DAP, a MET/CIP mixture). Fiber morphology, chemical characteristics, and tensile strength were evaluated by scanning electron microscopy, Fourier transform infrared spectroscopy, and tensile testing, respectively. Antimicrobial efficacy was tested over time (aliquot collection) against Enterococcus faecalis (Ef), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn). Similarly, cytotoxicity was evaluated in human dental pulp stem cells. Data were statistically analyzed (P < .05). RESULTS: Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed that electrospinning was able to produce antibiotic-containing fibers with a diameter mostly in the nanoscale. The tensile strength of 1:1MET/CIP scaffolds was significantly (P < .05) higher than pure polydioxanone (control). Meanwhile, all other groups presented similar strength as the control. Aliquots obtained from antibiotic-containing scaffolds inhibited the growth of Ef, Pg, and Fn, except pure MET, which did not show an inhibitory action toward Pg or Fn. Antibiotic-containing aliquots promoted slight human dental pulp stem cell viability reduction, but none of them were considered to be cytotoxic. CONCLUSIONS: Our data suggest that the incorporation of multiple antibiotics within a nanofibrous scaffold holds great potential toward the development of a drug delivery system for regenerative endodontics.
A biophysical study of the antibiotic beauvericin
(1978) Braden, Bradford Carl
Development and validation of a high-throughput cell-based screen to identify activators of a bacterial two-component signal transduction system
(ACC, 2015-07) van Rensburg, Julia J.; Fortney, Kate R.; Chen, Lan; Krieger, Andrew J.; Lima, Bruno P.; Wolfe, Alan J.; Katz, Barry P.; Zhang, Zhong-Yin; Spinola, Stanley M.; Department of Microbiology and Immunology, IU School of Medicine
CpxRA is a two-component signal transduction system (2CSTS) found in many drug-resistant Gram-negative bacteria. In response to periplasmic stress, CpxA autophosphorylates and donates a phosphoryl group to its cognate response regulator, CpxR. Phosphorylated CpxR (CpxR-P) upregulates genes involved in membrane repair and downregulates multiple genes that encode virulence factors, which are trafficked across the cell membrane. Mutants that constitutively activate CpxRA in Salmonella enterica serovar Typhimurium and Haemophilus ducreyi are avirulent in mice and humans, respectively. Thus, the activation of CpxRA has high potential as a novel antimicrobial/antivirulence strategy. Using a series of Escherichia coli strains containing a CpxR-P-responsive lacZ reporter and deletions in genes encoding CpxRA system components, we developed and validated a novel cell-based high-throughput screen (HTS) for CpxRA activators. A screen of 36,000 compounds yielded one hit compound that increased reporter activity in wild-type cells. This is the first report of a compound that activates, rather than inhibits, a 2CSTS. The activity profile of the compound against CpxRA pathway mutants in the presence of glucose suggested that the compound inhibits CpxA phosphatase activity. We confirmed that the compound induced the accumulation of CpxR-P in treated cells. Although the hit compound contained a nitro group, a derivative lacking this group retained activity in serum and had lower cytotoxicity than that of the initial hit. This HTS is amenable for the screening of larger libraries to find compounds that activate CpxRA by other mechanisms, and it could be adapted to find activators of other two-component systems.
Development of a Double Antibiotic Electrospun scaffold for Root Canal Disinfection
(2015) Kutanovski, Christopher D.; Bottino, Marco C.; Spolnik, Kenneth J.; Ehrlich, Ygal; Gregory, Richard L.; Zunt, Susan L.
Objective: This study synthesized electrospun polymer-based scaffolds containing ciprofloxacin (CIP) and doxycycline (DOX), as a scaffold mimic of Double Antibiotic Paste (DAP) and determined, in vitro, its mechanical properties, chemical composition, and antimicrobial effectiveness against multiple endodontic bacterium. Methods: Polydioxanone sutures (PDS) were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP), mixed with CIP/DOX (i.e., 50%), and electrospun under optimized conditions into fibrous scaffolds. Tensile testing was used to evaluate the mechanical properties. Antimicrobial efficacy was determined over time using aliquots collected at 1, 4, 7, 14 day and agar diffusion assays. Two-Way Anova. Significance P < 0.05. Results: Tensile strength (MPa) of the CIP/DOX scaffold did not show significant difference from the control (pure PDS). Elongation at break (%) did show a significant difference between CIP/DOX scaffolds and the control group. Young’s modulus of elasticity (MPa) showed a significant difference between CIP/DOX scaffolds and the control. CIP-containing scaffolds did not inhibit Gram-negative (F. nucleatum and P. gingivalis) bacteria as effectively when compared to Gram-positive bacteria (E. faecalis and S. gordina). DOX-containing scaffolds showed less inhibition against Gram-positive (E. faecalis and S. gordina) bacteria then Gram-negative bacteria (F. nucleatum and P. gingivalis). In combination, CIP/DOX scaffolds showed significant inhibition against G(-) and G(+) bacteria. Conclusion: Electrospun double antibiotic scaffold demonstrated increased antimicrobial efficacy proving the potential for future clinical use to disinfect the RCS in permanent immature necrotic teeth to aid in regenerative treatment and or in persistent infections.

Browsing by Subject "Anti-Bacterial Agents"

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