In-vivo Antibacterial Activity Research Articles

Effect of Ducrosia anethifolia methanol extract against methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms on excision wound in diabetic mice.

Ducrosia anethifolia is an aromatic desert plant used in Saudi folk medicine to treat skin infections. It is widely found in Middle Eastern countries. A methanolic extract of the plant was prepared, and its phytoconstituents were determined using LC-MS. In-vitro and in-vivo antibacterial and antibiofilm activities of the methanolic extract were evaluated against multidrug-resistant bacteria. The cytotoxic effect was assessed using HaCaT cell lines in-vitro. Diabetic mice were used to study the in-vivo antibiofilm and wound healing activity using the excision wound method. More than 50 phytoconstituents were found in the extract after LC-MS analysis. The extract exhibited antibacterial activity against both the tested pathogens. The extract was free of irritant effects on mice skin, and no cytotoxicity was observed on HaCaT cells with an IC50 value of 1381 µg/ml. The ointment formulation of the extract increased the healing of diabetic wounds. The microbial load of both pathogens in the wounded tissue was also reduced after the treatment. The extract was more effective against methicillin-resistant Staphylococcus aureus (MRSA) than MDR-P. aeruginosa in both in vitro and in vivo experiments. Further, skin regeneration was also observed in histological studies. The results showed that D. anethifolia methanol extract supports wound healing in infected wounds in diabetic mice through antibacterial, antibiofilm, and wound healing activities.

QbD Based Formulation Development and Optimisation of Ozenoxacin Topical Nano-Emulgel and Efficacy Evaluation Using Impetigo Mice Model.

To formulate and optimize Ozenoxacin nano-emulsion using Quality by Design (QbD) concept by means of Box-Behnken Design (BBD) and converting it to a gel to form Ozenoxacin nano-emulgel followed by physico-chemical, in-vitro, ex-vivo and in-vivo evaluation. This study demonstrates the application of QbD methodology for the development and optimization of an effective topical nanoemulgel formulation for the treatment of Impetigo focusing on the selection of appropriate excipients, optimization of formulation and process variables, and characterization of critical quality attributes. BBD was used to study the effect of "% of oil, % of Smix and homogenization speed" on critical quality attributes "globule size and % entrapment efficiency" for the optimisation of Ozenoxacin Nano-emulsion. Ozenoxacin loaded nano-emulgel was characterized for "description, identification, pH, specific gravity, amplitude sweep, viscosity, assay, organic impurities, antimicrobial effectiveness testing, in-vitro release testing, ex-vivo permeation testing, skin retention and in-vivo anti-bacterial activity". In-vitro release and ex-vivo permeation, skin retention and in-vivo anti-bacterial activity were found to be significantly (p < 0.01) higher for the nano-emulgel formulation compared to the innovator formulation (OZANEX™). Antimicrobial effectiveness testing was performed and found that even at 70% label claim of benzoic acid is effective to inhibit microbial growth in the drug product. The systematic application of QbD principles facilitated the successful development and optimization of a Ozenoxacin Nano-Emulsion. Optimised Ozenoxacin Nano-Emulgel can be considered as an effective alternative and found to be stable at least for 6months at 40°C / 75% RH and 30°C / 75% RH.

In-vitro and in-vivo antibacterial activity of potential probiotic Lactobacillus paracasei against Staphylococcus aureus and Escherichia coli

Previous studies documented that Lactobacillus paracasei has obvious in vitro cholesterol-lowering abilities. In this study, initially, L. paracasei was tested in terms of antibacterial properties as well as antibiogram profile. Then, the safety of the mentioned strain was evaluated in rats. Evaluation of antibiotic susceptibility revealed that the L. paracasei strain had high antibiotic resistance to several antibiotics as well as a great ability to autoaggregation. After identification of the probiotic aptitude, six groups of six rats from both sexes were used (three groups of each sex). L. paracasei was administered to the experimental groups via drinking water for 28 days (1 × 108 and 1 × 109, respectively). The negative control group received only tap water during this period. Hematological indicators, serum liver enzyme activity including (alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST)) as well as serum creatinine and urea were evaluated at the end of 28 days. The blood and serum factors were not changed significantly during the 28 days. The only noticeable difference was the increase of blood urea in both sexes which was in a normal range. Furthermore, the evaluation of antagonistic properties revealed that L. paracasei had antibacterial aptitude against Escherichia coli and Staphylococcus aureus. In conclusion, this strain has good cholesterol-lowering and antibacterial properties and is a safe supplement in Wistar rats.

PURIFICATION AND CHARACTERIZATION OF ANTI-BACTERIAL BACTERIOCIN ISOLATED FROM HOSPITAL ACQUIRED MULTI DRUG RESISTANT Staphylococcus aureus

Concerns for public health have been raised all over the world as a result of a significant increase in bacterial resistance to the antibiotics that are currently available. As a result, antimicrobial peptides (AMPs) have emerged as a promisingly novel class of infectious disease treatment options. The current study focuses on the isolation and purification of a bacteriocin from clinically Multi-Drug Resistant Staphylococcus aureus (HA MRSA_1) that was acquired in a hospital including characterization. The ribosomally synthesized peptides have significant potential as an anti-bacterial peptide, and it was demonstrated that the bacteriocin has strong antagonistic activity against many pathogenic organisms. Ammonium sulfate precipitation, dialysis, Gel filtration chromatography, RP-HPLC, and SDS-PAGE were the initial methods used to purify it. A combination of LCMS analysis and Mass matrix-assisted laser desorption/ionization-mass spectrometry (MALDI TOF/MS) was used. The physio-chemical characterization of purified bacteriocin was studied using FT-IR, and XRD. The LCMS analysis of the RP-HPLC-collected active component revealed the amino acid sequence of the purified peptide (bacteriocin). After being subjected to high-performance liquid chromatography, a peak was discovered with a retention time of 5.330 minutes. The amino acid of bacteriocin was identified by LCMS, and the query sequence shared a match with the Staphylococcus aureus protein. In-silico molecular docking study investigated the significant evidence for the role of bacteriocin identified from Multi-Drug Resistant Staphylococcus aureus as an anti-bacterial agent. In conclusion, the bacteriocin found in this study may be a promising agent that should be further investigated for it’s cytotoxicity and in-vivo anti-bacterial activity in the future.

In-Vitro and In-Vivo Tolerance and Therapeutic Investigations of Phyto-Fabricated Iron Oxide Nanoparticles against Selected Pathogens.

The Paeonia emodi (P. emodi)-mediated iron oxide nanoparticles (Fe2O3 NPs) were screened for in-vitro and in-vivo antibacterial activity against the Staphylococcus aureus (S. aureus) (ATCC #: 6538) and Escherichia coli (E. coli) (ATCC #:15224). The synthesized Fe2O3 NPs were characterized via nitrogen adsorption-desorption process, X-ray diffractometer (XRD), transmission and scanning electron microscopies (TEM and SEM), energy dispersive X-ray (EDX) and Fourier transform infrared (FTIR) spectroscopies. The SBET was found to be 94.65 m2/g with pore size of 2.99 nm, whereas the average crystallite and particles size are 23 and 27.64 nm, respectively. The 4 μg/mL is the MIC that inhibits the growth of E. coli, whereas those for S. aureus are below the detection limit (<1.76 μg/mL). The tolerance limit of the mice model was inspected by injecting different concentration of Fe2O3 NPs and bacteria suspensions. The 14 ppm suspension was the tolerated dose and the concentration above were proved lethal. The most severe infection was induced in mice with injection of 3 × 107 CFUs of both bacteria, while the inoculation of higher concentrations of bacterial suspensions resulted in the mice’s death. The histopathological and hematological studies reveals that the no/negligible infection was found in the mice exposed to the simultaneous inoculation of Fe2O3 NPs (14 ppm) and bacterial suspensions (3 × 107 CFUs).

Octahedral ruthenium and magnesium naringenin 5-alkoxide complexes: NMR analysis of diastereoisomers and in-vivo antibacterial activity against Xylella fastidiosa

Although many copper-based antimicrobial compounds have been developed to control pathogenic bacteria and fungi in plants and applied for crop protection, there is evidence that several plant pathogens have developed resistance to copper-based antimicrobial compounds, including some Xanthomonas species. Xylella is a bacterial genus belonging to the Xanthomonas family; and X. fastidiosa, which is responsible for citrus variegated chlorosis (CVC) in sweet orange, may develop resistance to one or more copper-based antimicrobials. Because of the time required for the development and approval of new antimicrobials for commercial use, the discovery of novel bactericidal compounds is essential before the development of resistance to the antimicrobials currently in use becomes widespread. Here, we explored the antimicrobial potential of two newly synthesized antimicrobials complexes and one natural compound against X. fastidiosa. Several nuclear magnetic resonance (NMR) assays with high resolution and sensitivity were developed to identify new diastereoisomers in the context of octahedral ruthenium - [Ru(narin)(phen)2]PF6-and magnesium naringenin 5-alkoxide - [Mg(narin)(phen)2]OAc - complexes, obtained in the present work. The NMR assays proved to be powerful tools for the identification of isomers in metal complexes. Moreover, a protocol for the in-vivo determination of the effects of these complexes against X. fastidiosa was developed. The main trunks of X. fastidiosa infected plants were injected with the two complexes as well as with the limonoid azadirachtin using a syringe; the number of bacterial cells in the plants following treatment was estimated via real-time quantitative PCR (qPCR). Importantly, the administration of both complexes and of azadirachtin drastically reduced the number of X. fastidiosa cells in vivo.

EVALUATION OF BIOLOGICAL ACTIVITY OF GREENLY SYNTHESIZED SILVER NANOPARTICLES USING ALOE VERA GEL EXTRACT AS ANTIBACTERIAL AGENT IN-VITRO AND IN-VIVO

The present study was carried out to synthesis silver nanoparticles by using Aloe Vera gel and evaluates antibacterial activity in vitro and in vivo. The synthesis and characterization of silver nanoparticles was confirmed by Ultra Violet Visible- spectrophotometer, X-ray diffraction, Fourier Transmission Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy. Reduction of the Ag+ to Ag0 during exposure to the Aloe Vera gel extract was followed by color change of the solution from colorless, yellow to dark brown within 24 hours. It is observed that surface Plasmon resonance peaks of the maximum absorbance of silver-nanoparticles occur at 425 nm, indicating that AgNPs were produced. Later on, using agar well diffusion and tube dilution method against pathogenic methicillin resistance staphylococcus aureus, (MRSA). Pseudomonas. aeruginosa and Escherichia coli, the antimicrobial properties of synthesised AgNPs were investigated. To confirm in-vivo antibacterial activity, after inducing complicated skin and soft tissue infection in mice by injecting S.aureus subcutaneously. 16µg/gm AgNPs were applied skin infected daily for three days. Silver nanoparticles were as succeeded to reduce the lesion volume in infected mice and reduce the acute inflammation symptoms as clindamycin, In conclusion, A new approach can be used to combat serious infections caused by MRSA by Aloe Vera AgNPs.

Potential efficacy of garlic lock therapy in combating biofilm and catheter-associated infections; experimental studies on an animal model with focus on toxicological aspects

BackgroundLife-threatening central venous catheter-related infections are primarily initiated by biofilm formation on the catheter surface. Antibiotic lock therapy is recommended for eradicating intraluminal biofilm. In the era of antibiotic resistance, antibiotics of natural origins provide an effective and cheap option for combating resistant strains. Garlic especially stole the spotlight because of its impressive antimicrobial effectiveness against such superbugs. AimIs to estimate the potential use of fresh garlic extract (FGE) as a lock agent against multi-drug resistant (MDR) bacteria. MethodsThe agar well diffusion and broth microdilution techniques were employed to test the antimicrobial activities of FGE against five MDR strains; E. coli, Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Serratia marscens (S. marscens) and Methicillin-resistant Staphylococcus aureus (MRSA). Then the protective and therapeutic efficiencies of FGE against bacterial biofilms were in-vitro evaluated; at concentrations of 100, 75, 50 and 25%; in tissue culture plate (TCP) and on the polyurethane (PU) sheets using the crystal violet (CV) assay and colony-forming unit (CFU), respectively. Scanning electron microscopy (SEM) was also used to confirm eradication of biofilms on PU sheets. Finally, systemic and deep tissue infections by P. aeruginosa and MRSA were induced in mice that were then treated by FGE at either 100 or 200 mg/kg for seven days. Where the antibacterial activity was assessed by tissue and blood culturing at the end of the treatment period. Biochemical, hematological and histological parameters were also investigated. ResultsFGE exhibited potent in-vitro and in-vivo antibacterial and antibiofilm activities against MDR strains. It not only didn’t exhibit toxicological effects at the hematological and the histological levels but also provided protective effects as demonstrated by the significant drop in the biochemical parameters. ConclusionFGE has the potential to be used as a prophylactic and/or therapeutic lock agent against biofilm-associated infections caused by MDR bacteria.

Extracts of Hesperozygis ringens (Benth.) Epling: invitro and invivo antibacterial activity against fish pathogenic bacteria.

This study investigated the invitro antibacterial activity of Hesperozygis ringens (Benth.) Epling leaf extracts against fish pathogenic bacteria, as well as the invivo activity of the most active extract in silver catfish (Rhamdia quelen) experimentally infected with Aeromonas hydrophila. Moreover, the chemical composition of the extract used in the survival assay was evaluated. Only hexane extract (HEHR) showed invitro antibacterial activity (MIC and MBC ranging from 1600 to 3200μgml-1 ) against clinical isolates of A. hydrophila, Raoultella ornithinolytica and Citrobacter freundii, obtained from naturally infected silver catfish, and A. hydrophilaATCC 7966. The major compound of the volatile fraction of HEHR was determined as pulegone. HEHR promoted a 93·33% relative survival rate of silver catfish experimentally infected with A. hydrophila 7days after a single therapeutic bath at 30mgl-1 , while florfenicol at 4mgl-1 , which promoted a 60% relative survival rate. The antibacterial activity of H. ringens (Benth.) Epling leaf extracts seems to be related to phytochemicals of apolar character, since HEHR promoted better survival rate of infected animals than florfenicol. The HEHR has potential to be used in the control and treatment of bacterial infections in organic aquaculture.

Synthesis and antibacterial activities of novel pleuromutilin derivatives bearing an aminothiophenol moiety.

We synthesized a series of novel thioether pleuromutilin derivatives incorporating 2-aminothiophenol moieties into the C14 side chain via acylation reactions under mild conditions. We evaluated the in-vitro antibacterial activities of the derivatives against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300), Staphylococcus aureus (ATCC 29213) and Escherichia coli (ATCC 25922). The majority of the synthesized derivatives possessed moderate antibacterial activities. Compound 8 was found to be the most active antibacterial derivative against MRSA. We conducted docking experiments to understand the possible mode of interactions between compounds 8, 9b, 11a and 50S ribosomal subunit. The docking results proved that there is a reasonable correlation between the binding free energy and the antibacterial activity. Compound 8 was evaluated for its in-vivo antibacterial activity and showed higher efficacy than tiamulin against MRSA in mouse infection model.

Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation

The current research focuses on developing positively charged gelatin nanoparticles loaded with moxifloxacin for its effective ocular delivery and controlled release in corneal eye layer. We selected type A gelatin because of its biodegradable and non-toxic nature as the polymer of choice for fabricating the nanoparticles by a modified two step desolvation technique. The produced nanoparticles were positively charged (+24±0.12mV) with a narrow particle size of 175±1.11nm as measured by dynamic light scattering (DLS). The in-vitro drug release from the nanoformulations exhibited a burst effect in the first hour followed by a controlled release of the drug for the subsequent 12h. The Korsmeyer-Peppas model showed better linearity and the formulations displayed non-Fickian drug release pattern. The optimized formulation was assessed for its utility as an anti-bacterial agent and its effectiveness was tested on the corneal eye surface of rabbits. The in-vivo tolerance tests revealed that the drug loaded nano-formulations was non-irritant to the ocular tissues indicating its safety. The in-vivo anti-bacterial activity of the nanosuspension was more effective against S. aureus than the commercially market product, MoxiGram®. Microbiological efficacy assessed against B. subtilus using cup-plate method suggested that our fabricated nanosuspension possess better anti-microbial activity as compared to the commercial agent, MoxiGram® revealing promising potentials for the currently developed gelatin based nanoformualtions.

Synthesis, Antimicrobial Evaluation of 4-[(arylimino) methyl-5-(4-[(aryl) methylidene] amino) Phenyl)-4H-1, 2, 4-triazole-3-thiol Derivatives

The synthesis of 4-[(arylimino) methyl-5-(4-[(aryl) methylidene] amino) phenyl)-4H-1, 2, 4-triazole-3-thiol were achieved in multi step synthesis, in first step, 4-amino benzoic acid was esterifies to ethyl-4-amino benzoate I; which was further refluxed with hydrazine hydrate 99% to obtain 4-aminobenzoic acid hydrazide II. Compound II was agitated with ethanolic KOH and CS2 to produce inorganic salt potassium-4-aminophenyl-dithiocarbazate III; later compound III was refluxed with hydrazine hydrate 99% to produce 4-amino-5-(4-aminophenyl)-4H-1,2,4-triazole-3-thiol IV. In final step; compound IV were treated with aromatic aldehydes to produce title compounds 4-[(arylimino) methyl-5-(4-[(aryl) methylidene] amino) phenyl)-4H-1, 2, 4-triazole-3-thiol Va-n. All the title compounds were identified by FT-IR, 1H-NMR, GC-mass spectroscopy data, and elemental analysis; have been screened for in-vivo antibacterial activity against organisms like E.coli. K. pneumonia, S. aureus, and B. subtilis as well as in-vitro antifungal activity against A. niger and C. albicans. In-vivo antimicrobial evaluation reveals that the most potent broad spectrum compounds Va, Ve, Vf, Vg, Vi, Vj and Vm were found to be significant agents in comparison with standard Norfloxacin and Fluconazole.

ANTIBACTERIAL AND BIOCHEMICAL EFFECTS OF ETHANOL LEAF EXTRACT OF SENNA HIRSUTA MILL USING ANIMAL MODEL-MICE

This study was carried out to investigate the in-vitro and in-vivo antibacterial and biochemical activities of 50, 100 and 200mg.mL-1 concentrations of ethanol leaf extract of Senna hirsuta (hairy senna) against seven human pathogenic bacteria species namely: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Enterococcus faecium, Bacillus cereus and Salmonella typhi. The in-vitro bioassay revealed the leaf extracts of valuable antibacterial activity where zones of inhibition ranging from 12.1mm to 39.1mm were observed on the test bacteria species. Among the test bacteria, K. pneumoniae was the most inhibited and S. typhi the least inhibited. On mice infection with the bacteria species for three days, decrease in weight of mice was observed. The in-vivo therapeutic use of the extracts in mice infected with the bacteria pathogens resulted to weight gain of the mice and other physiological changes that indicated health improvement of the mice and was also of hepatoprotective potential. The in-vivo antioxidant assay exhibited satisfactory therapeutic effects where improvement in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) status of mice was observed on comparing results of the positive and negative controls.

Antibacterial activity of ethanolic extract of Sweet Basil (Ocimumbasilicum L.) leaves against Escherichia coli in experimentally infected Rats

The present study was carried out to investigate the antibacterial activity of Ocimumbasilicum (OB)ethanolic extract in-vivo by inducing diarrhea in rats which was caused by oral administration of pathogenic Escherichea coli. The experiment that performed in this present study included study in-vivo antibacterial activity of the extract after inducing infectious diarrhea with oral pathogenic E. coli in five rats groups (eight rats of each). Two doses of O.B extract 100, 200 mg/kg. BW was used to treat this infection for fourteen days orally which compared with group E that treated with Trimethoprim/sulfa at dose 6.85mg/kg BW. The yielding percentage of Ocimumbasilicum 95% ethyl alcohol leaves extract was 13%. Phytochemicals analysis indicated the presence of alkaloids, phenols, tannins, saponins, flavonoids, steroids and terpenoids, while glycosides were absent, but Alkaloid, phenols, saponins and tannins were seemed to be found in high levels in the crude extract. Biochemical analysis of serum albumin showed different results; Albumin values returned to normal values during treatment with Ocimumbasilicum leaves extract dose of 200 mg/kg BW and Trimethoprim/sulfa at dose 6.85mg/kg BW also these two kinds of therapy returned intestinal secretory nearly to normal levels after treatment for seven days in comparison with other groups, while a dose of 100 mg/kg BW of OB extract showed a little decrease in albumin concentrations after 7 days of treatment. From the results obtained, it could be concluded that ethanolic extract of O.B leaves at dose 200 mg/kg BW was more effective and safe in comparison with antibacterial agent and other O.B dose, this antidiarrheal activity of O.Bethanolic extract may be due to its constituents of secondary metabolites that are responsible for the antibacterial activity with different mechanisms of action.

Antibacterial Activity of &amp;beta;-Cyclodextrin and 2-Hydroxypropyl-&amp;beta;-Cyclodextrin Trimethoprim Complexes

Problem statement: Cyclodextrin complexation has previously been shown to improve the solubility and dissolution properties of trimethoprim; however, no report provides an account of the effect cyclodextrin complexation has on the antibacterial activity of this agent. Approach: β-cyclodextrin and 2-hydroxypropyl β-cyclodextrin inclusion complexes of trimethoprim were prepared and confirmed by differential scanning calorimetry and proton nuclear magnetic resonance. The in-vitro antibacterial activity, in terms of minimum inhibitory concentrations, of cyclodextrin-drug complexes were compared to uncomplexed free trimethoprim by a broth-microdilution method against several sensitive and resistant Gram-positive and Gram-negative bacteria. The effect of complexation on the apparent permeability coefficients was also determined using a Caco-2 permeability assay to account for potential alterations in bioavailability that could influence in-vivo antibacterial activity. Results: Inclusion complexation of trimethoprim with both unsubstituted and hydroxylated versions of β-cyclodextrin produced a reduction in the MIC80 required to inhibit the growth of S. aureus ATCC 29213, S. pneumoniae ATCC 4961, S. epidermidis ATCC 14990 and E. coli ATCC 25922 (p>0.05). The effect was limited to bacteria normally susceptible to trimethoprim. Neither complex negatively affected the antibacterial activity of trimethoprim. Hydroxypropyl-β-cyclodextrin and β-cyclodextrin inclusion complexes significantly (p<0.01) increased the apparent intestinal permeability of trimethoprim by 39.8 and 56.1%, respectively. Considering the effect cyclodextrin inclusion complexation has on the antibacterial activity of trimethoprim, the improved intestinal permeability of these complexes has the potential to improve the in-vivo antibacterial activity of the agent by enhancing the steady-state concentration of the drug when dosed orally. Conclusion: These results would suggest that physical complexation with either of these cyclodextrins would provide a feasible strategy to improve the pharmaceutical and pharmacokinetic properties of trimethoprim.

In-vitro and in-vivo antibacterial activity evaluation of a polyurethane matrix.

Various in-vitro and in-vivo methods for evaluation of the duration of antibacterial activity were compared using a controlled-release polyurethane matrix developed for the prevention of surface bacterial adhesion and growth. Cefadroxil was incorporated into this polyurethane matrix by a solvent casting method before the matrix was coated with polyurethane in tetrahydrofuran solution. The release of cefadroxil from the matrix into distilled water at 37 degrees C was measured by HPLC. The morphological change of matrices before and after release studies was investigated by scanning electron microscopy (SEM). The duration of antimicrobial activity of the matrix against Escherichia coli and Staphylococcus aureus was evaluated by measuring the diameters of the inhibition zone and the optical density of the broth. The matrices were also implanted subcutaneously in rats and the duration of the antibacterial activity was determined by measuring the inhibition zone. The results showed that duration of antibacterial activity of the polyurethane matrix was successfully determined in-vitro by these methods, and the results differed from the conventional in-vitro release study. It was also possible to determine the duration of action of the matrix in-vivo by implanting the matrix in rats, and then measuring the antibacterial activity of the matrix at predetermined time intervals. While a good correlation was observed between the in-vitro and in-vivo methods used in this study to evaluate the duration of the antibacterial activity of the polymeric matrix, the conventional in-vitro release study did not coincide with these results.

CW-270033, a Novel Pyrrolidinyl-thio Carbapenem, Has Potent Antimicrobial Activity in Vitro and in Vivo

CW-270033, an injectable carbapenem, is a novel, synthesized pyrrolidinyl-thio carbapenem. In the present study, the in-vitro and in-vivo antibacterial activities of CW-270033 against wild-type strains and clinical isolates were compared with those of imipenem and meropenem. CW-270033 was more active than imipenem against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) clinical isolates, but was slightly less active than meropenem. Against the Gram-positive clinical isolates methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), CW-270033 was slightly more active than meropenem, but was less active than imipenem. CW-270033 displayed potent in-vivo activity against E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus SMITH in the mouse systemic infection model; the efficacy of CW-270033 in this model was 2--7 fold higher than that of meropenem. This activity was comparable to the in-vitro activity of CW-270033. An intravenous injection of CW-270033 showed that the half-life of CW-270033 in serum in mice was about 20 min, which was about two times that of meropenem. CW-270033 was also found to be resistant to hydrolysis by the mouse renal dehydropeptidase I (DHP-I) enzyme.

In-vitro and in-vivo antibacterial activities of CS-834, a new oral carbapenem

We investigated the in vitro activity of voriconazole compared to those of fluconazole and itraconazole against 566 clinical isolates of Cryptococcus neoformans from Africa (164) and the United States (402). Isolates were obtained from cerebrospinal fluid (362), blood (139), and miscellaneous sites (65). Voriconazole (MIC at which 90% of the isolates are inhibited [MIC90], 0.12 to 0.25 microg/ml) was more active than either itraconazole (MIC90, 0.5 microg/ml) or fluconazole (MIC90, 8.0 to 16 microg/ml) against both African and U. S. isolates. Isolates inhibited by >/=16 microg of fluconazole per ml were almost all (99%) inhibited by </=1 microg of voriconazole per ml. These results suggest that voriconazole may be useful in the treatment of cryptococcosis.

Antibacterial properties of BO-2727, a new carbapenem antibiotic.

BO-2727 is a new injectable carbapenem antibiotic with broad-spectrum, potent antibacterial activity. The in-vitro and in-vivo antibacterial activities of BO-2727 were compared with those of meropenem, imipenem and biapenem. BO-2727 was four- to eight-fold more active in vitro than meropenem, imipenem and biapenem against methicillin-resistant Staphylococcus aureus, inhibiting more than 90% of clinical isolates at a concentration of 12.5 mg/L. BO-2727 also showed superior activity against Pseudomonas aeruginosa, and was two- to four-fold more active than imipenem against imipenem-resistant strains. The antimicrobial activity of BO-2727 was influenced by the pH of the medium and inoculum size, in the same way as meropenem and imipenem. In time-killing kinetic studies, BO-2727 showed dose-dependent bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa. In a morphological study, BO-2727 induced spherical forms in E. coli and bulging forms in P. aeruginosa. The affinity of BO-2727 for E. coli (PBP 2) was about twice that of imipenem. BO-2727 also had high affinities for P. aeruginosa penicillin-binding protein (PBPs) 2 and 3. The prophylactic efficacy of BO-2727 against Gram-positive and Gram-negative bacterial systemic infections was similar to that of imipenem and biapenem.

In-vitro and in-vivo antibacterial activity of plaunotol, a cytoprotective antiulcer agent, against Helicobacter pylori.

Recently, some antiulcer agents have been reported to have antibacterial activity against Helicobacter pylori, which is highly associated with gastritis and peptic ulcers. In-vitro and in-vivo activity of plaunotol, a cytoprotective antiulcer agent, against H. pylori was investigated. Antibacterial activity of plaunotol against a standard strain (NCTC 11637) and 14 clinical isolates was compared with those of other cytoprotective antiulcer agents: benexate, sofalcone, teprenone, cetraxate, and gefarnate, by an agar dilution method. The MIC50 and MIC90 of plaunotol against 15 strains were 6.25 and 12.5 mg/L, respectively, making it the most potent of the cytoprotective antiulcer agents. The bactericidal effect of plaunotol was investigated using an in-vitro killing assay. Plaunotol at concentrations of more than 6 mg/L induced a rapid reduction of culture turbidity, with an extensive loss of viability, within 30 min. Observation by scanning electron microscopy revealed that plaunotol caused autolysis and treated cells were deformed. In-vivo activity of plaunotol against H. pylori was examined in a nude mouse gastritis model. Plaunotol significantly decreased the number of H. pylori in the stomach of nude mice. In addition, the antiulcer agent enhanced the antibacterial activity of amoxycillin or clarithromycin in the infection model.