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Sample records for bioadhesive controlled metronidazole

  1. Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum

    PubMed Central

    Eftaiha, Ala’a F.; Qinna, Nidal; Rashid, Iyad S.; Al Remawi, Mayyas M.; Al Shami, Munther R.; Arafat, Tawfiq A.; Badwan, Adnan A.

    2010-01-01

    Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole. PMID:20559494

  2. Development and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use

    PubMed Central

    Bhabani Shankar, Nayak; Prasant Kumar, Rout; Udaya Kumar, Nayak; Benoy Brata, Bhowmik

    2010-01-01

    The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and evaluated for particle size, shape, flow properties, wall thickness, drug encapsulation efficiency and in vitro release performance. The drug carrier interactions were investigated in solid state by FT-IR spectroscopy and scanning electron microscopy. The microcapsules with a narrow size range of 23-68 μm showed higher encapsulation efficiency. The selected microcapsule formulation, MC3 (Drug polymer ratio 1:4) was employed for gel formulation with a variety of carbopol polymers (carbopol-934, 940, 974 and 980) by mechanical stirring method in order to develop a sustained release microencapsulated metronidazole microcapsules-containing bioadhesive gel. The prepared bioadhesive gels were evaluated for pH, spreadability, extrudability, viscosity, vaginal irritation, in vitro drug release, bioadhesion, accelerated stability and in vitro drug release kinetic. In vitro experiments indicated a sustained release over 24 h and an acceptable bioadhesion quality for formulation F3. Hence, it can be concluded that the formulation F3 has potential to deliver metronidazole in a controlled and constant manner for prolong period over other formulations and can be adopted for a successful delivery of metronidazole for vaginal use. PMID:24363730

  3. [Metronidazole].

    PubMed

    Martinez, V; Caumes, E

    2001-09-01

    Metronidazole was first introduced for the treatment of trichomoniasis. Now, its therapeutics use has subsequently been expanded to include protozoal and anaerobic infections. Oral administration is recommended: rosacea, perioral dermatitis, Helicobacter pylori, Trichomonas vaginalis and Giardia lamblia infections and bacterial vaginosis. Metronidazole given orally is absorbed almost completely. Metronidazole has limited plasma protein binding but can reach very favourable tissue distribution, including central nervous system and placenta. This drug is extensively metabolised by the liver to form 5 oxydative metabolites. The majority of this drug and metabolites are excreted in urine and feces. The half-life is 6 to 10 hours. The recommended dose is 500 mg three time per day and an adaptation is necessary in renal insufficiency. Metronidazole is well tolerated when administered in dosages of less than 2 g per day. Some adverse reactions appear to be related to the high dosages and treatment duration. Drug interactions with alcohol, warfarin and phenytoin have been reported. Mutagenesis and cancerogenesis is only described in mouse. Resistance, both clinical and microbiological, has been described only rarely.

  4. Zwitterionic-based stainless steel with well-defined polysulfobetaine brushes for general bioadhesive control.

    PubMed

    Sin, Mei-Chan; Sun, Yi-Ming; Chang, Yung

    2014-01-22

    Stainless steels are widely used as orthopaedic and dental implant; however, bioadhesion in the case of thrombosis, inflammation, and infection is one of their major limitations. One way to tackle this problem is to graft the stainless steel surface with a zwitterionic polymer known for being anti-bioadhesive. Controlled atom transfer radical polymerization (ATRP) of zwitterionic poly(sulfobetaine methacrylate) (polySBMA) grafted from biomedical grade stainless steel surface was employed in this study. The interactions of polySBMA-grafted surfaces with biomacromolecules were demonstrated in vitro by the adhesion tests of plasma protein, blood cells, human MG63 osteoblast- and HT1080 fibroblast-like cells in biological complex media to evaluate their bioadhesive properties. Anti-microbial effects were also assessed for two most ordinary seen clinical bacteria, i.e., Escherichia coli and Staphylococcus epidermidis. Results showed that polySBMA-grafted surface exhibited evident bioadhesion resistance and conferring antibacterial efficacy. This work is also dedicated to deduce the effectiveness of polySBMA brushes' conformational structure on the prevention of bioadhesion. To this aim, the anti-bioadhesive effect of polySBMA brushes prepared by dopamine- and silane-surfaced immobilization method was evaluated. Results show that polySBMA grafted from immobilized polydopamine interfacial layers achieved better bioadhesion resistance, which could be causally related to their greater grafting coverage, flexible brush conformational structures, and greater hydration capabilities.

  5. Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers

    SciTech Connect

    Ch'ng, H.S.; Park, H.; Kelly, P.; Robinson, J.R.

    1985-04-01

    A series of cross-linked, swellable polymers was sythesized from monomers such as acrylic acid, methacrylic acid, and others with various cross-linking agents to produce a range of polymers differing in charge densities and hydrophobicity. The densities, rate, and extent of hydration of the polymers were determined. An increase in the number of hydrophobic groups in the polymer structure reduced hydration whereas the density of the polymer was unaffected. A sensitive in vitro method for measuring adhesion of polymer to tissue from the rabbit stomach was developed. Polymers of acrylic acid loosely cross-linked (0.3%, w/w) with three different agents, divinyl glycol, 2,5-dimethyl-1,5-hexadiene, and divinylbenzene, showed the same degree of bioadhesion while poly(methacrylic acid-divinylbenzene) showed reduced bioadhesion. The small percent of cross-linking agent, irrespective of physicochemical properties, did not contribute substantially to bioadhesion, whereas the starting monomer had a large effect. The effect of pH on the bioadhesion of poly(acrylic acid-divinyl glycol) was studied at constant temperature, ionic strength, and osmolality. The polymer showed maximum adhesion at pH 5 and 6 and a minimum at pH 7. Gastrointestinal transit studies of cross-linked polymers in rats were studied. Poly(acrylic acid-divinyl glycol) and poly(methacrylic acid-divinylbenzene) were shown to have substantially longer GI transit times than the control, Amberlite 200 resin beads. The delay in transit time was due to bioadhesion of the polymer to the mucin-epithelial cell surface which was clearly observable on animal autopsy. The acrylic acid polymer showed a longer GI transit time than the methacrylic acid polymer, and this in vivo GI transit result is consistent with in vitro bioadhesion test results.

  6. Topical Metronidazole for Odor Control in Pressure Ulcers.

    PubMed

    Lyvers, Elizabeth; Elliott, David P

    2015-09-01

    There are many remedies that have been recommended for the treatment of foul odor associated with pressure ulcers. This article seeks to review the literature surrounding the use of metronidazole as a safe and effective solution to an oftentimes stubborn and frustrating problem. Other tools used to control odor include bleach-based solutions and charcoal dressings. Metronidazole, with its antianaerobic properties, appears to have a useful role in therapy when applied topically to a pressure ulcer. Commercially available products include 0.75% and 1% creams, gels, lotions, and intravenous solutions. Of the 59 cases viewed throughout several publications, 56 reported nearly complete odor resolution in two to seven days when metronidazole was applied to the wound two or three times daily. Virtually no systemic adverse events have been reported in the literature, despite the risk for systemic absorption. A need remains to monitor for toxicities such as nausea, gastrointestinal distress, and neural toxicities from long-term use.

  7. Controlled synthesis of N,N,N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability.

    PubMed

    Pardeshi, Chandrakantsing V; Belgamwar, Veena S

    2016-01-01

    In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (δ=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces.

  8. Bioadhesive emulsions for control release of progesterone resistant to vaginal fluids clearance.

    PubMed

    Campaña-Seoane, Maria; Peleteiro, Aaron; Laguna, Reyes; Otero-Espinar, Francisco J

    2014-12-30

    The aim of this study is to propose that mucoadhesive vaginal emulsions can be able to resist the clearance effect of vaginal fluid and to have an effective control release of progesterone. With this goal, silicon derivative, cyclomethicone pentamer, was selected as the bioadhesive and water resistant material. In order to obtain a system which is insensitive to the dilution of aqueous fluids, water in silicone (W/S) emulsions were prepared and different proportions of cyclomethicone as well as 8% or 15% w/w of progesterone were employed. The rheological, mechanical and mucoadhesive properties of emulsions were characterized and the drug release was measured for each formulation. Mucoadhesive behavior was determined and the influence of simulated vaginal fluid (SVF) at bioadhesion was assessed using three commercial mucoadhesive vaginal gels (Crinone(®), K-Y jelly(®) and Zidoval(®)) as the bioadhesive references. All assayed emulsions have good rheological and mechanical properties and their consistence and viscosity increase when the proportion of the internal phase increases. Related to mucoadhesion, in the absence of SVF, W/S emulsions showed similar bioadhesive levels like the commercial formulations. However, in the presence of SVF, W/S emulsions are able to keep their mucoadhesive properties while the marketed references drastically lose their consistency and adherence to the vaginal mucosa. Drug release profiles from W/S emulsion show that progesterone is released with pseudo-order zero kinetics and a constant release rate is maintained for at least two weeks. The results of the in vivo studies developed in rats show that after a single vaginal administration, bioadhesive W/S emulsions increase the uterine tissue progesterone levels in young and postmenopausal rats. Moreover in postmenopausal rats, they provide high uterine levels of progesterone compared to the bioadhesive-marketed gel used as a reference. Therefore, W/S emulsions have an interesting

  9. Formulation Optimization of Hydrodynamically Balanced Oral Controlled Release Bioadhesive Tablets of Tramadol Hydrochloride

    PubMed Central

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 32 central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean ± SEM of −0.06% ± 0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables. PMID:21179349

  10. Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

    PubMed

    Sanchez, Sixto; Garcia, Patricia J; Thomas, Katherine K; Catlin, Mary; Holmes, King K

    2004-12-01

    We compared metronidazole 0.75% gel (containing 37.5 mg metronidazole per dose) with ovules containing metronidazole 500 mg and nystatin 100,000 U, for intravaginal treatment of bacterial vaginosis (BV). In a single-blinded trial, symptomatic women with BV by both Amsel and Nugent criteria were randomly assigned to gel or ovules, once nightly for 5 nights, and asked to return 3 times after treatment. Analyses were intent-to-treat. Of 151 women with BV by both criteria at enrollment, 138 (91%) returned at least once. Product limit estimates for persistence or recurrence of BV at 14, 42, and 104 days were 20% (95% CI 10%-29%), 38% (95% CI 25%-48%), and 52% (95% CI 37%-63%) after gel treatment, and 4% (95% CI 0%-9%), 17% (95% CI 7%-26%), and 33% (95% CI 21%-46%) after ovule treatment ( P = .01). Among women without BV at first follow-up, subsequent intercourse without condoms independently predicted subsequent recurrence ( P Metronidazole/nystatin ovules were significantly more effective than metronidazole gel. Unprotected sex predicted recurrence after initial improvement.

  11. Chitosan-polycarbophil interpolyelectrolyte complex as an excipient for bioadhesive matrix systems to control macromolecular drug delivery.

    PubMed

    Lu, Zhilei; Chen, Weiyang; Hamman, Josias H; Ni, Jian; Zhai, Xiaoling

    2008-01-01

    The in vitro performance of monolithic matrix systems containing the interpolyelectrolyte complex between chitosan and polycarbophil as excipient was evaluated in terms of their swelling, bioadhesive, and drug release properties. The different matrix systems showed excellent swelling properties without erosion, except for the formulation containing the highest quantity chitosan-polycarbophil complex that exhibited surface erosion in addition to swelling. All the different matrix systems exhibited significantly higher bioadhesive properties than the control group. Furthermore, they showed controlled insulin release without an initial burst release effect. However, only the matrix system that exhibited surface erosion in combination with swelling approached zero-order release.

  12. Novel PLA microspheres with hydrophilic and bioadhesive surfaces for the controlled delivery of fenretinide.

    PubMed

    Falconi, Mirella; Focaroli, Stefano; Teti, Gabriella; Salvatore, Viviana; Durante, Sandra; Nicolini, Benedetta; Orienti, Isabella

    2014-01-01

    Novel polylactide (PLA) microspheres endowed with hydrophilic and bioadhesive surfaces as injectable formulations for the controlled release of fenretinide were prepared, using a novel technique based on the co-precipitation of PLA with gelatin, at the interface of a liquid dispersion formed by the addition of N-methylpyrrolidone containing PLA and dextrin (DX), towards an aqueous solution of gelatin (G). The resulting PLA-G-DX microspheres were compared with others prepared by the same technique using polylactide-co-glycolide (PLGA), with or without DX, and with or without phosphatidylcholine. Of the different systems, the PLA-G-DX microspheres had the best morphological, dimensional and functional characteristics. They had the highest drug loading, and their drug release was the most efficient over time without any burst effect. Their in vitro anti-tumoural activity was strongly enhanced with respect to the pure fenretinide. This paralleled the increased drug concentration inside the cells due to their marked bioadhesion to the tumour cell membranes as indicated by scanning electron microscope images.

  13. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Latha, Subbiah; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan; Beniwal, Vijender Singh; Rao, Poduri Rama

    2009-05-01

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

  14. Simultaneous size control and surface functionalization of titania nanoparticles through bioadhesion-assisted bio-inspired mineralization

    NASA Astrophysics Data System (ADS)

    Shi, Jiafu; Yang, Dong; Jiang, Zhongyi; Jiang, Yanjun; Liang, Yanpeng; Zhu, Yuanyuan; Wang, Xiaoli; Wang, Huihui

    2012-09-01

    Simultaneous size control and surface functionalization of inorganic nanoparticles (NPs) are often desired for their efficient applications in (bio)catalysis, drug and/or DNA delivery, and photonics, etc. In this study, a novel strategy "bioadhesion-assisted bio-inspired mineralization (BABM)" was put forward to prepare titania nanoparticles (TiNPs) with tunable particle size and multiple surface functionality. Specifically, the initial formation and subsequent growth of TiNPs were enabled by arginine via bio-inspired mineralization, while the mineralization process was terminated through the addition of the pre-polymerized dopa (oligodopa). By adjusting the addition time of oligodopa, the size of TiNPs could be facilely tailored from ca. 30-350 nm; meanwhile, the surface of TiNPs could be functionalized by oligodopa through metal-catechol coordination interaction (a typical bioadhesion phenomenon). In other words, oligodopa coating could not only exquisitely control the size of TiNPs, but also render TiNPs surface multifunctional groups for secondary treatment such as conjugating proteins through amine-catechol adduct formation. Hopefully, this BABM approach will construct a versatile platform for green and facile synthesis of inorganic NPs, in particular transition metal oxide NPs.

  15. Adjustable bioadhesive control of PEGylated hyperbranch brushes on polystyrene microplate interface for the improved sensitivity of human blood typing.

    PubMed

    Chen, Yan-Wen; Chang, Yung; Lee, Rong-Ho; Li, Wen-Tyng; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Hsiue, Ging-Ho

    2014-08-05

    A PEGylated 96-well polystyrene (PS) microplate was first introduced for applications in high-throughput screening for selective blood typing to minimize the risks in blood transfusions. Herein, we present a hemocompatible PS 96-well microplate with adjustable PEGylated hyperbranch brush coverage prepared by ozone pretreated activation and thermally induced surface PEGylation. The grafting properties, hydration capacity, and blood compatibility of the PEGylated hyperbrush immobilized PS surfaces in human blood were illustrated by the combined chemical and physical properties of the surface, and the dependence of the specific absorption of human plasma fibrinogen onto the PEGylated surfaces on the grafting density was analyzed by monoclonal antibodies. The surface coverage of PEGylated brushes plays a major role in the bioadhesive properties of modified PS microplates, which in turn control the level of agglutination sensitivity in blood typing. The bioadhesive resistance toward proteins, platelets, and erythrocytes in human whole blood showed a correlation to the controlled hydration properties of the PEGylated hyperbrush-modified surfaces. Therefore, we suggested that the surface coverage of PEGylated hyperbrushes on PS surfaces can increase the sensitivity of cross-matching blood agglutination by up to 16-fold compared to that of the conventional 96-well virgin PS due to the regulated biorecognition of hematocrit and antibodies of the PEGylated hyperbrush-modified surfaces.

  16. Systemic Metronidazole May Not Reduce Posthemorrhoidectomy Pain: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Wanis, Kerollos Nashat; Emmerton-Coughlin, Heather M; Coughlin, Shaun; Foley, Norine; Vinden, Christopher

    2017-04-01

    Hemorrhoidectomy is associated with significant postoperative pain. Oral metronidazole has been recommended as an adjunct to improve posthemorrhoidectomy analgesia. This study aimed to evaluate the impact of oral metronidazole on patient-reported pain following hemorrhoidectomy. We conducted a systematic search in the MEDLINE, EMBASE, ISI Web of Science, and Cochrane Central Register of Controlled Trials databases. Randomized controlled trials examining adults who underwent surgical hemorrhoidectomy were included. Participants in an active intervention group received oral metronidazole postoperatively, and those in a control group received placebo or usual care. Postoperative pain was assessed for at least 3 days postoperatively. A random-effects model was used. The primary outcome was pain during the first 2 postoperative weeks, measured on a visual analogue scale. The secondary outcome was time to return to normal activities. Patients who received oral metronidazole had significantly lower reported pain scores on postoperative day 1 (standardized mean difference, -0.87 ± 0.44; 95% CI, -1.73 to -0.015; p = 0.046; n = 4) and day 4 (standardized mean difference, -1.43 ± 0.71; 95% CI, -2.83 to -0.037; p = 0.044; n = 3). Metronidazole use was associated with a significantly shorter time to return to normal activities (standardized mean difference, -0.76 ± 0.34; 95% CI, -1.43 to -0.088, p = 0.027). The improvements disappeared in a sensitivity analysis excluding the largest trial with a high risk of bias, and no significance was observed during the remaining postoperative days. The meta-analysis was limited by lack of double blinding, absence of a placebo, and unclear or high risk of bias in a proportion of the included trials. Although a favorable adverse effect profile supports consideration of oral metronidazole to reduce posthemorrhoidectomy pain, pooled analysis reveals inconsistent results with no pain reduction on most postoperative days. The

  17. Development and in vitro evaluation of an acid buffering bioadhesive vaginal gel for mixed vaginal infections.

    PubMed

    Ahmad, Farhan Jalees; Alam, Mohd Aftab; Khan, Zeenat Iqbal; Khar, Roop Krishen; Ali, Mushir

    2008-12-01

    An acid buffering bioadhesive vaginal (ABBV) gel was developed for the treatment of mixed vaginal infections. Different bioadhesive polymers were evaluated on the basis of their bioadhesive strength, stability and drug release properties. Bioadhesion and release studies showed that guar gum, xanthan gum and hydroxypropyl methylcelullose K4M formed a good combination of bioadhesive polymers to develop the ABBV gel. Monosodium citrate was used as an acid buffering agent to provide acidic pH (4.4). The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as antibacterial) were used in the formulation along with Lactobacillus spores to treat mixed vaginal infections. The ex vivo retention study showed that the bioadhesive polymers hold the gel for 12-13 hours inside the vaginal tube. Results of the in vitro antimicrobial study indicated that the ABBV gel had better antimicrobial action than the commercial intravaginal drug delivery systems and retention was prolonged in an ex vivo retention experiment.

  18. Metronidazole Oral

    MedlinePlus

    Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, ... Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ...

  19. A microtensiometer for the analysis of bioadhesive microspheres.

    PubMed

    Chickering, D E; Harris, W P; Mathiowitz, E

    1995-01-01

    Bioadhesive polymer microspheres are potential vehicles for the delivery of bioactive agents to mucosal tissues. Bioadhesive delivery devices could improve drug absorption, enhance bioavailability, and increase patient compliance by minimizing dosing regimens. Identification of bioadhesive materials is the first phase in developing bioadhesive drug delivery systems. Additionally, quantification and analysis of the bioadhesive event are essential to successful development of a new generation of adhesive delivery systems. A unique, microbalance-based instrument was developed to analyze bioadhesive forces between polymer microspheres and mucosal tissue segments. A contact angle analyzer, with a custom-made physiologic tissue chamber, was linked to a computer via the serial port. Software was used to modify the microbalance operation to behave as a microtensiometer with a sensitivity of 0.1 microN. After mounting a microsphere and tissue segment in the balance and adjusting the experimental settings, the instrument performs a tensile experiment and automatically determines the following parameters: compressive deformation, peak compressive load, compressive work, yield point, deformation to yield, returned work, peak tensile load, deformation to peak tensile load, fracture strength, deformation to failure, and tensile work. Using this device the authors identified several bioadhesive materials ideally suited for orally-delivered, controlled-release systems. GI-transit studies in rats showed strong correlation between increased GI-residence time and strong bioadhesive interactions.

  20. Design strategies and applications of tissue bioadhesives.

    PubMed

    Mehdizadeh, Mohammadreza; Yang, Jian

    2013-03-01

    In the past two decades tissue adhesives and sealants have revolutionized bleeding control and wound healing. This paper focuses on existing tissue adhesive design, their structure, functioning mechanism, and their pros and cons in wound management. It also includes the latest advances in the development of new tissue adhesives as well as the emerging applications in regenerative medicine. We expect that this paper will provide insightful discussion on tissue bioadhesive design and lead to innovations for the development of the next generation of tissue bioadhesives and their related biomedical applications.

  1. Development and evaluation of acid-buffering bioadhesive vaginal tablet for mixed vaginal infections.

    PubMed

    Alam, Mohd Aftab; Ahmad, Farhan Jalees; Khan, Zeenat Iqbal; Khar, Roop Krishen; Ali, Mushir

    2007-12-14

    An acid-buffering bioadhesive vaginal tablet was developed for the treatment of genitourinary tract infections. From the bioadhesion experiment and release studies it was found that polycarbophil and sodium carboxymethylcellulose is a good combination for an acid-buffering bioadhesive vaginal tablet. Sodium monocitrate was used as a buffering agent to provide acidic pH (4.4), which is an attribute of a healthy vagina. The effervescent mixture (citric acid and sodium bicarbonate) along with a superdisintegrant (Ac-Di-sol) was used to enhance the swellability of the bioadhesive tablet. The drugs clotrimazole (antifungal) and metronidazole (antiprotozoal as well as an antibacterial) were used in the formulation along with Lactobacillus acidophilus spores to treat mixed vaginal infections. From the ex vivo retention study it was found that the bioadhesive polymers hold the tablet for more than 24 hours inside the vaginal tube. The hardness of the acid-buffering bioadhesive vaginal tablet was optimized, at 4 to 5 kg hardness the swelling was found to be good and the cumulative release profile of the developed tablet was matched with a marketed conventional tablet (Infa-V). The in vitro spreadability of the swelled tablet was comparable to the marketed gel. In the in vitro antimicrobial study it was found that the acid-buffering bioadhesive tablet produces better antimicrobial action than marketed intravaginal drug delivery systems (Infa-V, Candid-V and Canesten 1).

  2. Metronidazole Topical

    MedlinePlus

    ... a moisturizer (if your skin is dry) and cosmetics. Ask your doctor for advice on what cosmetics to use.Metronidazole gel for the vagina comes ... not swallow it. Do not apply dressings, bandages, cosmetics, lotions, or other skin medications to the area ...

  3. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery.

    PubMed

    Kaur, Gurpreet; Singh, Deepinder; Brar, Vivekjot

    2014-09-01

    In the present investigation, polysaccharide from the Okra fruits (Hibiscus esculentus) was extracted, characterized and explored for its mucoadhesive potential. Mucoadhesive films of okra polymer (OP) were prepared by solvent casting method based on 3(2) factorial design. For these studies, OP (2.0%, 2.5%, 3.0%, w/v) and glycerol (plasticizer) (0.25%, 0.50%, 0.75%, v/v) were taken as independent variables while tensile strength, mucoadhesive strength, contact angle, swelling index and residence time as dependent variables. The developed films were evaluated for their physicochemical, mechanical and electrical properties. The formulated films were found to be smooth, flexible, and displayed adequate mucoadhesive and tensile strength. Their near neutral pH and negative hemolytic studies indicated their non-irritability and biocompatible nature with biological tissues. The formulation comprising of 3% OP and 0.5% glycerol (F8) was found to exhibit optimum mechanical properties. Further, optimized film was loaded with zolmitriptan (model drug) to determine its drug release profiles. In vitro and ex vivo drug release studies demonstrated a controlled release of zolmitriptan over a period of 8h in simulated salivary fluid (SSF) pH 6.8, with the correlation coefficient values indicating its non-Fickian kinetics. Thus, OP can be used as a promising biomaterial for controlled drug delivery.

  4. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials.

    PubMed

    Johnson, Stuart; Louie, Thomas J; Gerding, Dale N; Cornely, Oliver A; Chasan-Taber, Scott; Fitts, David; Gelone, Steven P; Broom, Colin; Davidson, David M

    2014-08-01

    Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Metronidazole (Flagyl) and Arnica Montana in the prevention of post-surgical complications, a comparative placebo controlled clinical trial.

    PubMed

    Kaziro, G S

    1984-02-01

    A double blind trial, was designed, in which 118 patients undergoing the removal of impacted wisdom teeth were randomly divided into the following groups; 41 patients received Metronidazole, 39 patients received Arnica Montana, 38 patients received the placebo. Metronidazole was more effective in pain control than Arnica (p less than 0.001) and placebo (p less than 0.01). It prevented swelling better than Arnica (p less than 0.01) and placebo (p less than 0.05) and was more effective in promoting healing than Arnica (p less than 0.01) and placebo (p greater than 0.02). Arnica Montana appeared to give rise to greater pain than placebo (p less than 0.05) and caused more swelling than the placebo (p less than 0.01).

  6. Effect of metronidazole versus standard care on length of stay of patients admitted with severe infectious mononucleosis: a randomized controlled trial.

    PubMed

    Lennon, P; O'Neill, J P; Fenton, J E

    2014-07-01

    Metronidazole may be of use in the treatment of infectious mononucleosis (IM). Our aim is to show that metronidazole shortens hospital stay for patients with severe IM. A single-centre randomized controlled trial was undertaken in patients admitted with severe IM, who were with a similar group treated by the standard care. Patients were blinded to which treatment arm they were in. Forty-two of these patients were enrolled in the trial. The primary endpoint was the difference in length of stay. This was significantly less in the metronidazole group (3.67 days v 4.67) (p 0.032). This study demonstrates that metronidazole has a role to play in severe infectious mononucleosis.

  7. Design Strategies and Applications of Tissue Bioadhesives

    PubMed Central

    Mehdizadeh, Mohammadreza; Yang, Jian

    2013-01-01

    In the past two decades tissue adhesives and sealants have revolutionized hemostasis and wound management in traumatic and surgical injuries. Various biological-driven glues and synthetic adhesives are clinically utilized either as an adjunct to conventional hemostats and wound closure techniques, such as suturing, or as a replacement to them. The ability to effectively and promptly control bleeding, thus, reducing the risk of complications due to severe blood loss, in addition to convenience of use render medical adhesive a highly suitable tool for wound management. This review focuses on existing tissue adhesive systems, their structure, functioning mechanism, indicated and off-label applications, and limitations. It also includes the latest advances in the development of new tissue adhesives as well as the emerging applications in regenerative medicine. We expect that this review will provide insightful discussion on tissue bioadhesive design and lead to innovations for the development of the next generation of tissue bioadhesives and their related biomedical applications. PMID:23225776

  8. Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: statistical optimization and mechanistic evaluation.

    PubMed

    Kumari, Neeraj; Pathak, Kamla

    2012-01-01

    In situ gelling syringeable periodontal sol capable of dual controlled delivery of metronidazole benzoate and serratiopeptidase was designed based on 2(3) factorial design with drug, poloxamer 407 and aerosil as independent variables and sol gel transition characteristics, %CDR(48h) and palatability as responses. The sols had agreeable taste, were mucoadhesive, syringeable and inverted into gels at periodontal cavity temperature. F8 with optimal drug release was identified as the best formulation. The dispersion characteristics of poloxamer significantly affected the pharmacotechnical properties of the in situ gelling systems. Extra design checkpoint generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Thus a thermoreversible, in situ gelling and syringeable periodontal sol with acceptable taste characteristics that offered controlled release of metronidazole benzoate and serratiopeptidase was developed for application into the periodontal pocket. The developed optimized sol was satisfactory in terms of taste, syringeability, palatability and incorporation of serratiopeptidase as anti-inflammatory agent, has the potential of developing a therapeutically efficacious system for treatment of periodontal inflammatory anaerobic infections.

  9. [Topical treatment of peri-implantitis with metronidazole dental gel 25%. Clinical analysis and microbiological control].

    PubMed

    Stellini, E; Migliorato, A; Mazzoleni, S; Mottola, A; Lombardi, L; Favero, G A

    2000-01-01

    Aim of this research is to verify the efficacy of metronidazole dental gel 25%, used as a topical antibiotic for the treatment of peri-implantitis. The efficacy of the medicine in the starting phase of the disease (mucositis), as well as during peri-implantitis involving bone-bearing loss has been evaluated. Twenty patients were chosen as a sample for the study. After careful evaluation of the several protocols concerning peri-implantitis treatment, some diagnostic clinical parameters have been recorded for each patient and metronidazole dental gel 25% (Elyzol Cabon) has been administered in two applications at perimplants pocket (one after a week). For each patient 3 microbiological drawings were made for the evaluation of the bacterial population around the implant site. From the microbiological examination a decrease of Gram- and an increase of Gram+ which returned in almost all the patients to normal levels have been observed; moreover, in all the patients a gradual decrease of PMN, resolution index of the inflammatory process was obtained, confirmed also by a remarkable improvement of all the observed diagnostic parameters, except for the peri-implants bone radiotransparency which was unchanged. The research showed that the peri-implant diseases can be positively resolved by using the metronidazole dental gel 25% topical antibiotic. This drug led to a 60-70% decrease of Gram-, and 40-50% increase for Gram+, bringing these back to normal values in almost all the patients. Moreover, a good recovery of the peri-implants soft tissues has been observed.

  10. Lectin-mediated drug delivery: the second generation of bioadhesives.

    PubMed

    Lehr, C M

    2000-03-01

    This paper reviews some recent developments in the area of bioadhesive drug delivery systems. The area of bioadhesion in drug delivery had started some 20 years ago by using so-called mucoadhesive polymers. Many of these polymers were already used as excipients in pharmaceutical formulations. This has facilitated the development of the first bioadhesive drug products, which are now commercially available. A major disadvantage of the hitherto known mucoadhesives, however, is their non-specificity with respect to the substrate. In particular for gastro-intestinal applications, this may cause some premature inactivation and moreover limits the duration of mucoadhesive bonds to the relatively fast mucus turnover. Nevertheless, for some mucoadhesive polymers other interesting functionalities were discovered, such as their ability to modulate epithelial permeability and to inhibit proteolytic enzymes. In contrast to the mucoadhesive polymers, lectins and some other adhesion molecules specifically recognize receptor-like structures of the cell membrane and therefore bind directly to the epithelial cells themselves ("cytoadhesion") rather than to the mucus gel layer. Furthermore, when bioadhesion is receptor-mediated, it is not only restricted to mere binding, but may subsequently trigger the active transport of large molecules or nanoscalic drug carrier systems by vesicular transport processes (endo-/transcytosis). Rather than only acting as a platform for controlled release systems, the concept of lectin-mediated bioadhesion therefore bears the potential for the controlled delivery of macromolecular biopharmaceuticals at relevant biological barriers, such as the epithelia of the intestinal or respiratory tract.

  11. Bismuth, Metronidazole, and Tetracycline

    MedlinePlus

    Helidac® (as a kit containing Bismuth Subsalicylate, Metronidazole, Tetracycline) ... Bismuth, metronidazole, and tetracycline is used along with other ulcer medications to treat duodenal ulcers. It is in a ...

  12. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    Metronidazole (Flagyl®) In every pregnancy, a woman starts out with a 3-5% chance of having a ... risk. This sheet talks about whether exposure to metronidazole may increase the risk for birth defects over ...

  13. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    ... than 40 years, and is sold under the brand name Flagyl®. Can taking metronidazole during early pregnancy ... previously raised some concerns. Older studies suggested an association between metronidazole and an increase in various birth ...

  14. Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.

    PubMed

    Lan, Shih-Feng; Kehinde, Timilehin; Zhang, Xiangming; Khajotia, Sharukh; Schmidtke, David W; Starly, Binil

    2013-06-01

    Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  15. Metronidazole in prevention and treatment of bacteroides infections after appendicectomy.

    PubMed Central

    Willis, A T; Ferguson, I R; Jones, P H; Phillips, K D; Tearle, P V; Berry, R B; Fiddian, R V; Graham, D F; Harland, D H; Innes, D B; Mee, W M; Rothwell-Jackson, R L; Sutch, I; Kilbey, C; Edwards, D

    1976-01-01

    The frequency of non-clostridial anaerobic infection was studied in 95 patients who had undergone acute appendicectomy: 49 received prophylactic metronidazole and 46 received placebo. Anaerobic infection did not develop in any of the metronidazole-treated patients, but infections did develop in nine (19%) of the 46 controls. Metronidazole is conveniently administered by suppository to patients who cannot take oral drugs. Five patients with intra-abdominal infections caused by non-clostridial anaerobes were successfully treated with metronidazole. PMID:764935

  16. Bioadhesive-based dosage forms: the next generation.

    PubMed

    Lee, J W; Park, J H; Robinson, J R

    2000-07-01

    Prolonged contact time of a drug with a body tissue, through the use of a bioadhesive polymer, can significantly improve the performance of many drugs. These improvements range from better treatment of local pathologies to improved drug bioavailability and controlled release to enhanced patient compliance. There are abundant examples in the literature over the past 15 years of these improvements using first generation or "off-the-shelf" bioadhesive polymers. The present mini-review will remind us of the success achieved with these first-generation polymers and focus on proposals for the next-generation polymers and attendant benefits likely to occur with these improved polymeric systems.

  17. Enhanced local anesthetic action of mepivacaine from the bioadhesive gels.

    PubMed

    Cho, Cheong-Weon; Choi, Jun-Shik; Shin, Sang-Chul

    2011-01-01

    Mepivacaine, an amide-type local anesthetic, has been used to relieve local pain. Among the many drug delivery systems, transdermal drug delivery has some advantages, as it provides controlled drug delivery for an extended period of time. To develop new gel formulations that have suitable bioadhesion, the bioadhesive force of hydroxypropyl methylcellulose (HPMC) was assessed using an auto-peeling tester. The effect of drug concentration on drug release from 2% HPMC gel was studied using synthetic cellulose membrane at 37±0.5°C. The drug concentrations tested were 0.5, 1, 1.5, 2, and 2.5%. The effect of temperature on drug release from the 2% drug gel was evaluated at 27, 32, 37 and 42°C. To increase the skin permeation of mepivacaine from HPMC gel, enhancers such as saturated and unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants were incorporated into the mepivacaine-HPMC gels. The enhancing effect of the enhancer on drug permeation was then examined in the modified Keshary-Chien cell. For the efficacy study, the anesthetic action of the formulated mepivacaine gel containing enhancer and vasoconstrictor was evaluated with the tail-flick analgesimeter. Among the various kinds of HPMC, HPMC-K100M gel showed the highest viscosity and bioadhesive force. As the viscosity of the HPMC gels increased, the bioadhesive forces increased. Increasing the drug concentration or temperature increased the drug release rate. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the greatest enhancement of permeation. Based on the area under the efficacy curve of the rat tail flick test curve, mepivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed prolonged and increased local anesthetic action compared to the control. For bioadhesive mepivacaine gels with enhanced local anesthetic action, mepivacaine gels containing penetration enhancer and vasoconstrictor could be developed with the

  18. Repercussions of intraalveolar placement of combination of 0.2% chlorhexidine & 10 Mg metronidazole gel on the occurrence of dry sockets- A randomized control trial

    PubMed Central

    Raval, Rushik; Bansal, Anupam; Kumawat, Vinod

    2017-01-01

    Background To evaluate the effects of intraalveolar placement of gel containing 0.2% chlorhexidine and 10gm of metronidazole on the incidence of alveolar osteitis. Material and Methods A total of 300 impacted third molars were extracted in 150 patients enrolled in this trial. In each subject a socket was randomly selected and packed to the crest of alveolar ridge with the gel. The contralateral socket was packed with placebo dressing. The occurrence of dry socket was assessed during 3rd and 5th postoperative days .The data was analysed using a meta analytical program. Study Design Double blind, prospective, placebo controlled trial. Results The combination of metronidazole + chlorhexidine gel significantly reduced dry socket incidence from 22.6% to 6.6% (P ≤ 0.001) [McNemar and chi-square tests]. Conclusions The decrease in incidence of adverse reactions and complications related to local application of metronidazole and chlorhexidine gel explains its clinical use, specifically in mandibular molar extractions where the chances of dry sockets are high. Key words:Chlorhexidine, dry socket, intra-alveolar, metronidazole, placebo. PMID:28210450

  19. Comparing the therapeutic effects of garlic tablet and oral metronidazole on bacterial vaginosis: a randomized controlled clinical trial.

    PubMed

    Mohammadzadeh, Farnaz; Dolatian, Mahrokh; Jorjani, Masoome; Alavi Majd, Hamid; Borumandnia, Nasrin

    2014-07-01

    Bacterial vaginosis (BV) is one of the most common gynecological infections during reproductive age. Although metronidazole is one of the most effective medications recommended as the first-line treatment, it has various side effects. Because of the side effects and contraindications of some chemical medicines, using herbs has been investigated in treating BV. The aim of this study was to compare the effect of garlic tablet (Garsin) and oral metronidazole in clinical treatment of the BV in women referred to Resalat Health Center, affiliated with Mazandaran University of Medical Sciences, in 2013. This randomized clinical trial was conducted on 120 married women aged 18 to 44 years who were diagnosed with BV by Amsel's clinical criteria and Gram staining. Enrolled women were randomly allocated to two groups of 60 patients and were treated with either garlic tablet or oral metronidazole for seven days. Amsel's criteria and Gram stain were assessed seven to ten days after beginning the treatment period and side effects were registered. Amsel's criteria were significantly decreased after treatment with garlic or metronidazole (70% and 48.3%, respectively; P < 0.001). Therapeutic effects of garlic on BV were similar to that of metronidazole (63.3% and 48.3%, respectively; P = 0.141). There were significant differences between the two treatment groups in terms of side effects; metronidazole was associated with more complications (P = 0.032). This study reveals that garlic could be a suitable alternative for metronidazole in treatment of BV in those interested in herbal medicines or those affected by side effects of metronidazole.

  20. Photocurable bioadhesive based on lactic acid.

    PubMed

    Marques, D S; Santos, J M C; Ferreira, P; Correia, T R; Correia, I J; Gil, M H; Baptista, C M S G

    2016-01-01

    Novel photocurable and low molecular weight oligomers based on l-lactic acid with proven interest to be used as bioadhesive were successfully manufactured. Preparation of lactic acid oligomers with methacrylic end functionalizations was carried out in the absence of catalyst or solvents by self-esterification in two reaction steps: telechelic lactic acid oligomerization with OH end groups and further functionalization with methacrylic anhydride. The final adhesive composition was achieved by the addition of a reported biocompatible photoinitiator (Irgacure® 2959). Preliminary in vitro biodegradability was investigated by hydrolytic degradation in PBS (pH=7.4) at 37 °C. The adhesion performance was evaluated using glued aminated substrates (gelatine pieces) subjected to pull-to-break test. Surface energy measured by contact angles is lower than the reported values of the skin and blood. The absence of cytoxicity was evaluated using human fibroblasts. A notable antimicrobial behaviour was observed using two bacterial models (Staphylococcus aureus and Escherichia coli). The cured material exhibited a strong thrombogenic character when placed in contact with blood, which can be predicted as a haemostatic effect for bleeding control. This novel material was subjected to an extensive characterization showing great potential for bioadhesive or other biomedical applications where biodegradable and biocompatible photocurable materials are required.

  1. Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

    PubMed Central

    Izadpanahi, Mohammad-Hossein; Majidi, Seyed Mahmood; Khorrami, Mohammad-Hatef; Mohammadi-Sichani, Mehrdad

    2017-01-01

    Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx). Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p = 0.017). Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx. PMID:28167960

  2. Metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma: A meta-analysis based on randomized controlled trials.

    PubMed

    Wei, Shengli; Xing, Yizhuo; Liu, Jixiang; Wang, Lin; Yang, Xiangli; Song, Fucun; Yang, Chunwei; Niu, Lin; Yang, Yang; Wu, Fei

    2015-10-01

    We performed this meta-analysis to assess the metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma. Two reviewers independently reviewed the databases of PubMed and CNKI. The prospective, randomized, controlled trials of metronidazole amino acidum natrium combined with radiation versus radiotherapy alone in the treatment of nasopharyngeal carcinoma were included in this meta-analysis. The objective response rate (RR) of 1-, 3-, and 5-year survival rates were pooled by statistical software. The publication bias was evaluated by Begg's funnel plot. Sixteen prospective, randomized, controlled trials were finally included in this meta-analysis. The quality assessment showed that the method's quality was relatively poor. The pooled results showed that the metronidazole amino acidum natrium combined with radiation can significantly improve the objective RR for the primary lesion (RR = 1.37, 95% confidence interval [CI]: 1.23-1.53, P < 0.05) and neck metastasis lesion (RR = 1.36, 95% CI: 1.25-1.49, P < 0.05). For survival analysis, the combined treatment can significantly improve the 1-year survival (RR = 1.57, 95% CI: 1.28-1.93, P < 0.05), 3-year survival (RR = 1.23, 95% CI: 1.06-1.41, P < 0.05), and 5-year survival rates (RR = 1.27, 95% CI: 1.05-1.53, P < 0.05). Metronidazole amino acidum natrium combined with radiation can improve the objective RR and long-term survival compared to radiation therapy alone in the treatment of nasopharyngeal carcinoma.

  3. Genotoxic effects of metronidazole.

    PubMed

    Elizondo, G; Gonsebatt, M E; Salazar, A M; Lares, I; Santiago, P; Herrera, J; Hong, E; Ostrosky-Wegman, P

    1996-09-13

    Metronidazole (MTZ) is an effective agent used in the treatment of parasitic infections. Its genotoxic effects have been shown in a variety of prokaryotic systems; however, negative results have been reported in human in vivo studies. Due to its wide spread use, a study was performed to evaluate the chromosomal aberration frequencies in peripheral blood lymphocyte cultures from 10 individuals, before and after metronidazole treatment. A significant increase in the percentage of cells with chromatid and isochromatid breaks was observed after metronidazole treatment (1500 mg per day for 10 days). The percentages of cells with aberrations did not correlate with the levels of MTZ found in plasma. Individual variability was observed with respect to both the induction of aberrations and the concentration of MTZ in plasma. They could represent differences at the metabolic level, since metronidazole is known to be biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown mutagenic activity.

  4. Bioadhesive potential of gliadin nanoparticulate systems.

    PubMed

    Arangoa, M A; Ponchel, G; Orecchioni, A M; Renedo, M J; Duchêne, D; Irache, J M

    2000-10-01

    The objective of this work was to prepare, characterise and evaluate the adhesive potential of gliadin nanoparticulate carriers. Firstly, lectin-nanoparticle conjugates were obtained by the carbodiimide (CDI) covalent binding of Dolichos biflorus lectin (DBA) to the surface of gliadin nanoparticles (NP) containing carbazole (as a model lipophilic drug). The DBA binding efficiency was favoured in mild acidic conditions. Similarly, a CDI concentration of about 0.63 mg/mg nanoparticles, acting during at least 1 h, provided binding efficiencies of about 50% bulk lectin. Under optimised experimental conditions, the DBA conjugates showed a size of around 500 nm and the amount of loaded carbazole and the DBA content were calculated to be around 15 and 23.5 microg/mg, respectively. The bioadhesive activity of NP and DBA conjugates was determined in samples of small and large rat intestinal mucosa. The amount of adsorbed NP was calculated to be around 8 and 4 g/m(2) in the small and large intestine, respectively. This high capacity to interact with the mucosa may be explained by gliadin composition. In fact, gliadin is rich in neutral and lipophilic residues. Neutral amino acids can promote hydrogen bonding interactions with the mucosa, while the lipophilic components can interact with the biological tissue by hydrophobic interactions. The bioadhesive activity of DBA conjugates was calculated to be about 2 g/m(2) in the small intestine and greater than 4 g/m(2) in the caecum and distal colon. These degrees of interaction were always significantly higher than those obtained with controls. Finally, DBA did not provide the specificity for interaction with Peyer's patches. In summary, gliadin nanoparticles show a high capacity of non-specific interaction with the intestine, whereas DBA binding to the surface of these carriers provided a greater specificity for colonic mucosa.

  5. Metronidazole-induced encephalopathy in a patient with liver cirrhosis

    PubMed Central

    Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul

    2011-01-01

    Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis. PMID:21757988

  6. Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

    PubMed

    Nishizawa, Toshihiro; Maekawa, Takama; Watanabe, Noriko; Harada, Naohiko; Hosoda, Yasuo; Yoshinaga, Masahiro; Yoshio, Toshiyuki; Ohta, Hajime; Inoue, Syuuji; Toyokawa, Tatsuya; Yamashita, Haruhiro; Saito, Hiroki; Kuwai, Toshio; Katayama, Shunsuke; Masuda, Eiji; Miyabayashi, Hideharu; Kimura, Toshio; Nishizawa, Yuko; Takahashi, Masahiko; Suzuki, Hidekazu

    2015-07-01

    Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

  7. Controlled study on thymol + eugenol vaginal douche versus econazole in vaginal candidiasis and metronidazole in bacterial vaginosis.

    PubMed

    Sosto, Francesco; Benvenuti, Claudio

    2011-01-01

    Bacterial vaginosis (BV) and vaginal candidiasis (VC) are usually managed with topical antibiotics. This study compared the efficacy of a thymol + eugenol vaginal douche (SD) (CAS nr. thymol: 89-83-8 and eugenol: 97-53-0), with econazole (CAS 27220-47-9) in VC and metronidazole (CAS 443-48-1) in BV, as suppository reference therapies. Thymol and eugenol are natural antibacterial and antimycotic active ingredients extracted from plants. A multicentre, parallel group, randomized study was performed, after stratification for diagnosis. Twenty-three Italian gynaecological units enrolled 459 patients (232 BV, 227 VC). The treatments applied were as follows: SD 1 douche/day (Saugella lavanda Attiva) for 1 week, 1 metronidazole vaginal suppository/night for 1 week and 1 econazole vaginal suppository/night for 3 days. Clinical evaluations were performed before and 1 week after treatment. A similar significant symptom reduction was observed with metronidazole and SD in BV and with econazole and SD in VC. SD was found to be an effective prescription drug in minor recurrent vaginal infectious episodes and its use can reduce the repeated exposure to antibiotics.

  8. Microscale Bioadhesive Hydrogel Arrays for Cell Engineering Applications.

    PubMed

    Patel, Ravi Ghanshyam; Purwada, Alberto; Cerchietti, Leandro; Inghirami, Giorgio; Melnick, Ari; Gaharwar, Akhilesh K; Singh, Ankur

    2014-09-01

    Bioengineered hydrogels have been explored in cell and tissue engineering applications to support cell growth and modulate its behavior. A rationally designed scaffold should allow for encapsulated cells to survive, adhere, proliferate, remodel the niche, and can be used for controlled delivery of biomolecules. Here we report a microarray of composite bioadhesive microgels with modular dimensions, tunable mechanical properties and bulk modified adhesive biomolecule composition. Composite bioadhesive microgels of maleimide functionalized polyethylene glycol (PEG-MAL) with interpenetrating network (IPN) of gelatin ionically cross-linked with silicate nanoparticles were engineered by integrating microfabrication with Michael-type addition chemistry and ionic gelation. By encapsulating clinically relevant anchorage-dependent cervical cancer cells and suspension leukemia cells as cell culture models in these composite microgels, we demonstrate enhanced cell spreading, survival, and metabolic activity compared to control gels. The composite bioadhesive hydrogels represent a platform that could be used to study independent effect of stiffness and adhesive ligand density on cell survival and function. We envision that such microarrays of cell adhesive microenvironments, which do not require harsh chemical and UV crosslinking conditions, will provide a more efficacious cell culture platform that can be used to study cell behavior and survival, function as building blocks to fabricate 3D tissue structures, cell delivery systems, and high throughput drug screening devices.

  9. Bioadhesive floating microsponges of cinnarizine as novel gastroretentive delivery: Capmul GMO bioadhesive coating versus acconon MC 8-2 EP/NF with intrinsic bioadhesive property.

    PubMed

    Raghuvanshi, Smita; Pathak, Kamla

    2016-01-01

    The study was aimed at the development of low-density gastroretentive bioadhesive microsponges of cinnarizine by two-pronged approach (i) coating with bioadhesive material and (ii) exploration of acconon MC 8-2 EP/NF as bioadhesive raw material for fabrication. Microsponges were prepared by quasi-emulsion solvent diffusion method using 3(2) factorial design. Capmul GMO was employed for bioadhesive coating. In parallel, potential of acconon for the fabrication of bioadhesive floating microsponges (A8) was assessed. Formulation with entrapment efficiency = 82.4 ± 3.4%, buoyancy = 82.3 ± 2.5%, and correlation of drug release (CDR8h) = 88.7% ± 2.9% was selected as optimized formulation (F8) and subjected to bioadhesive coating (BF8). The %CDR8h for A8 was similar to BF8 (87.2% ± 3.5%). Dynamic in vitro bioadhesion test revealed comparable bioadhesivity with BF8. The ex vivo permeation across gastric mucin displayed 63.16% for BF8 against 56.74% from A8; affirmed the bioadhesivity of both approaches. The study concluded with the development of novel bioadhesive floating microsponges of cinnarizine employing capmul GMO as bioadhesive coating material and confirmed the viability of acconon MC 8-2EP/NF as bioadhesive raw material for sustained targeted delivery of drug.

  10. Bioadhesive floating microsponges of cinnarizine as novel gastroretentive delivery: Capmul GMO bioadhesive coating versus acconon MC 8-2 EP/NF with intrinsic bioadhesive property

    PubMed Central

    Raghuvanshi, Smita; Pathak, Kamla

    2016-01-01

    Introduction: The study was aimed at the development of low-density gastroretentive bioadhesive microsponges of cinnarizine by two-pronged approach (i) coating with bioadhesive material and (ii) exploration of acconon MC 8-2 EP/NF as bioadhesive raw material for fabrication. Materials and Methods: Microsponges were prepared by quasi-emulsion solvent diffusion method using 32 factorial design. Capmul GMO was employed for bioadhesive coating. In parallel, potential of acconon for the fabrication of bioadhesive floating microsponges (A8) was assessed. Results: Formulation with entrapment efficiency = 82.4 ± 3.4%, buoyancy = 82.3 ± 2.5%, and correlation of drug release (CDR8h) = 88.7% ± 2.9% was selected as optimized formulation (F8) and subjected to bioadhesive coating (BF8). The %CDR8h for A8 was similar to BF8 (87.2% ± 3.5%). Dynamic in vitro bioadhesion test revealed comparable bioadhesivity with BF8. The ex vivo permeation across gastric mucin displayed 63.16% for BF8 against 56.74% from A8; affirmed the bioadhesivity of both approaches. Conclusion: The study concluded with the development of novel bioadhesive floating microsponges of cinnarizine employing capmul GMO as bioadhesive coating material and confirmed the viability of acconon MC 8-2EP/NF as bioadhesive raw material for sustained targeted delivery of drug. PMID:28123987

  11. Inkjet printing of bioadhesives.

    PubMed

    Doraiswamy, Anand; Dunaway, Timothy M; Wilker, Jonathan J; Narayan, Roger J

    2009-04-01

    Over the past century, synthetic adhesives have largely displaced their natural counterparts in medical applications. However, rising concerns over the environmental and toxicological effects of the solvents, monomers, and additives used in synthetic adhesives have recently led the scientific community to seek natural substitutes. Marine mussel adhesive protein is a formaldehyde-free natural adhesive that demonstrates excellent adhesion to several classes of materials, including glasses, metals, metal oxides, and polymers. In this study, we have demonstrated computer aided design (CAD) patterning of various biological adhesives using piezoelectric inkjet technology. A MEMS-based piezoelectric actuator was used to control the flow of the mussel adhesive protein solution through the ink jet nozzles. Fourier transform infrared spectroscopy (FTIR), microscopy, and adhesion studies were performed to examine the chemical, structural, and functional properties of these patterns, respectively. FTIR revealed the piezoelectric inkjet technology technique to be nondestructive. Atomic force microscopy was used to determine the extent of chelation caused by Fe(III). The adhesive strength in these materials was correlated with the extent of chelation by Fe(III). Piezoelectric inkjet printing of naturally-derived biological adhesives may overcome several problems associated with conventional tissue bonding materials. This technique may significantly improve wound repair in next generation eye repair, fracture fixation, wound closure, and drug delivery devices.

  12. Bioadhesive Mini-Tablets for Vaginal Drug Delivery

    PubMed Central

    Hiorth, Marianne; Nilsen, Susanne; Tho, Ingunn

    2014-01-01

    Different non-ionic cellulose ethers (methyl cellulose, MC; hydroxyethyl cellulose, HEC; hydroxypropyl cellulose, HPC; hydroxypropylmethyl cellulose, HPMC) and microcrystalline cellulose (MCC) were investigated as matrix formers for preparation of mini-tablets targeting vaginal drug delivery. Hexyl aminolevulinat hydrochloridum (HAL) was used as a model drug. The mini-tablets were characterized with respect to their mechanical strength, bioadhesion towards cow vaginal tissue in two independent tests (rotating cylinder test, detachment test using texture analyzer), and dissolution rate in two media mimicking the pH levels of fertile, healthy and post-menopausal women (vaginal fluid simulant pH 4.5, phosphate buffer pH 6.8). Mini-tablets with a matrix of either HPMC or HPC were found to possess adequate mechanical strength, superior bioadhesive behavior towards vaginal tissue, and pH independent controlled release of the model drug, suggesting that both systems would be suited for the treatment of women regardless of age, i.e., respective of their vaginal pH levels. Bioadhesive mini-tablets offer a potential for improved residence time in the vaginal cavity targeting contact with mucosal tissue and prolonged release of the drug. PMID:25166286

  13. Optical spectroscopy of marine bioadhesive interfaces.

    PubMed

    Barlow, Daniel E; Wahl, Kathryn J

    2012-01-01

    Marine organisms have evolved extraordinarily effective adhesives that cure underwater and resist degradation. These underwater adhesives differ dramatically in structure and function and are composed of multiple proteins assembled into functional composites. The processes by which these bioadhesives cure--conformational changes, dehydration, polymerization, and cross-linking--are challenging to quantify because they occur not only underwater but also in a buried interface between the substrate and the organism. In this review, we highlight interfacial optical spectroscopy approaches that can reveal the biochemical processes and structure of marine bioadhesives, with particular emphasis on macrofoulers such as barnacles and mussels.

  14. Injectable bioadhesive hydrogels with innate antibacterial properties

    NASA Astrophysics Data System (ADS)

    Giano, Michael C.; Ibrahim, Zuhaib; Medina, Scott H.; Sarhane, Karim A.; Christensen, Joani M.; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P.

    2014-06-01

    Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~\

  15. Optical Spectroscopy of Marine Bioadhesive Interfaces

    NASA Astrophysics Data System (ADS)

    Barlow, Daniel E.; Wahl, Kathryn J.

    2012-07-01

    Marine organisms have evolved extraordinarily effective adhesives that cure underwater and resist degradation. These underwater adhesives differ dramatically in structure and function and are composed of multiple proteins assembled into functional composites. The processes by which these bioadhesives cure—conformational changes, dehydration, polymerization, and cross-linking—are challenging to quantify because they occur not only underwater but also in a buried interface between the substrate and the organism. In this review, we highlight interfacial optical spectroscopy approaches that can reveal the biochemical processes and structure of marine bioadhesives, with particular emphasis on macrofoulers such as barnacles and mussels.

  16. Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system.

    PubMed

    Jelvehgari, Mitra; Montazam, Hassan

    2011-06-01

    Rosacea is a chronic multifactorial vascular skin disorder that affects about 10 percent of the general population. Metronidazole is an effective antibiotic in the treatment of moderate-to severe rosacea. Metronidazole is a suitable drug in cases of resistance to tetracycline or erythromycin, but it has also been shown that oral metronidazole may increase the side effects (e.g., peripheral neuropathy). Oral metronidazole should not be used for more than three months, and hence topical metronidazole gel is the best therapeutic choice in rosacea (especially during pregnancy). This study examined the mechanical (adhesiveness, cohesiveness, extrudability, spreadability, homogeneity) and rheological (viscosity), skin irritant and drug release properties of different metronidazole gel formulations that contain anionic emulsifying wax, glycerin and lactic acid in different proportions. The release studies were conducted using Franz diffusion cells and Silastic membrane as a barrier. The results indicated that gel compressibility, hardness, and adhesiveness, are the factors that influence the ease of gel removal from the container, ease of gel application onto the mucosal membrane, and gel bioadhesion. The findings showed that there exists a strong negative correlation between the spreadability of a formulation and its cohesiveness, the spreadability of a formulation is inversely proportional to its cohesiveness. However, sorbitol solution (70%) concentration was not significantly correlated with drug release. In addition, drug release was significantly reduced as the concentration of anionic emulsifying wax increased and the concentration of lactic acid decreased. The maximum metronidazole release was achieved at a pH of 4-6. Data obtained from in vitro release studies were fitted to various kinetic models and high correlation was obtained in the Higuchi and first order models. The results showed that all the gel formulations showed good extrudability, viscosity

  17. Comparative Evaluation of Sustained Release Collagen Device Containing 5% Metronidazole (Metrogene) along With and Without Scaling and Root Planing at Regular Intervals with Treatment of Chronic Periodontitis: A Case Control Study.

    PubMed

    Paul, Tony P; Emmatty, Rishi; Pulikkottil, Joseph J; Rahman, Aslam Abdul; Kumar, S Arun; George, Neethu

    2015-06-01

    A short-term study was undertaken with an objective to demonstrate the therapeutic benefit resulting from the use of Metronidazole sponges combined with and without mechanical debridement to mechanical treatment alone in the treatment of periodontal pockets in chronic periodontitis. The study compared the plaque index, gingival index, sulcus bleeding index and probing pocket depth in twenty control sites that received superficial scaling and root planing without the local drug delivery with experimental site A (20 sites that received local drug delivery (5% metronidazole) without superficial scaling and root planing) and experimental site B (20 sites received superficial scaling, root planing and local drug delivery (5% metronidazole) at "0" day, 15(th) day and 30(th) day. There was a significant reduction in plaque index, gingival index, sulcus bleeding index and probing pocket depth in both experimental sites A and B at different intervals from the baseline. From the above conclusions, it can be suggested that a single subgingival application of 5% metronidazole in a collagen carrier can be effective, when associated with debridement in the treatment of adult periodontitis.

  18. Injectable bioadhesive hydrogels with innate antibacterial properties.

    PubMed

    Giano, Michael C; Ibrahim, Zuhaib; Medina, Scott H; Sarhane, Karim A; Christensen, Joani M; Yamada, Yuji; Brandacher, Gerald; Schneider, Joel P

    2014-06-24

    Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5 wt% oxidized dextran and 6.9 wt% polyethylenimine sets within seconds forming a mechanically rigid (~1,700 Pa) gel offering a maximum adhesive stress of ~2.8 kPa. A murine infection model showed that the adhesive is capable of killing Streptococcus pyogenes introduced subcutaneously at the bioadhesive's surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound-filling applications.

  19. Comparison of adjunctive azithromycin and amoxicillin/metronidazole for patients with chronic periodontitis: preliminary randomized control trial.

    PubMed

    Saleh, A; Rincon, J; Tan, A; Firth, M

    2016-12-01

    There are insufficient guidelines for the use of adjunctive systemic antibiotics for patients with periodontal disease. The aim of this study was to compare clinical outcomes for patients with moderate-advanced chronic periodontitis treated with: scaling and root planing (SRP), SRP with amoxicillin and metronidazole (A+M), SRP with Azithromycin (Az). Thirty-seven non-smokers with generalized moderate to advanced chronic periodontitis were divided into three treatment groups: SRP, A+M and Az. Patients received the medications after the last SRP session and were reviewed three months later. Changes in clinical parameters were compared between the groups. Separate analyses were executed for: 'all sites', 'molar sites', 'sites with different PPD severities' and 'number of sites with shallow, moderate and deep PPD'. The three groups exhibited improvements in most clinical parameters. At three months, A+M showed a higher reduction in PPD compared to Az in the 'all sites analysis'. Molars exhibited better reduction in BOP and PPD with A+M than SRP. Pocket depth of the 4-6 mm category reduced more in the A+M than SRP. A+M experienced a higher increase in the number of sites with PPD 1-3 mm than Az. Adjunctive systemic antibiotics in the initial phase of treatment may result in improved clinical outcomes. © 2016 Australian Dental Association.

  20. The use of metronidazole during pregnancy: a review of evidence.

    PubMed

    Sheehy, Odile; Santos, Fabiano; Ferreira, Ema; Berard, Anick

    2015-01-01

    To review the available evidence concerning the relationship between the exposure to metronidazole during pregnancy and the risk of preterm delivery and birth defects. Studies investigating the association between gestational use of oral metronidazole on human subjects and the risk of preterm birth or/and birth defects were systematically retrieved from MEDLINE and EMBASE databases. We selected studies published in English or French between 1964 and 2012. Where effect estimates were not reported, crude ORs along with 95% confidence intervals were calculated. We selected 17 studies investigating the association between exposure to oral metronidazole and the risk of preterm birth, from which 12 were randomized clinical trials. In addition, we identified 13 studies devoted to the relationship between metronidazole and birth defects, from which 10 were cohort studies, 1 was a case-control study and 2 were meta-analysis. During pregnancy, treating bacterial vaginosis and trichomoniasis with metronidazole is effective and offers no teratogen risk. Benefit of metronidazole in the reduction of preterm birth was demonstrated for the combination of this medication with other antibiotics. Additional information is needed when metronidazole is used in association with other agents.

  1. Metronidazole with Lactacyd vaginal gel in bacterial vaginosis.

    PubMed

    Decena, Ditas Cristina D; Co, Jennifer T; Manalastas, Ricardo M; Palaypayon, Evelyn P; Padolina, Christia S; Sison, Judith M; Dancel, Louella A; Lelis, Marievi A

    2006-04-01

    To assess the efficacy and tolerability of lactic acid (Lactacyd vaginal gel; LVG) when given as an adjunct to metronidazole in the treatment of bacterial vaginosis (BV) among Filipino patients. A multicenter, open-labeled, controlled, randomized, three-arm comparative study on 90 women aged 18 years or over with clinically and microbiologically proven BV. The lactobacilli colony count significantly increased over time in all three arms. At day 14, growth of lactobacilli was significantly higher among patients in the lactic acid gel and combination treatment arms. Significant reduction of malodorous vaginal discharge (whiff test) and lowest recurrence of BV were noted in the metronidazole plus lactic acid gel arm. Regarding disappearance of signs of BV, there was significant decrease in the pH level and frequency of clue cell positive patients across time but was not significantly different across treatment groups. Only one patient (3%, 1/60) among those who received lactic acid gel complained of increased curd-like discharge. Six patients (10%, 6/60) who received metronidazole complained of epigastric pain/discomfort, dizziness and dyspnea. Lactic acid gel (LVG) is safe and as efficacious as metronidazole in the treatment of BV. There is evidence that LVG when combined with metronidazole is superior to metronidazole alone in promoting lactobacilli colonization. LVG as an adjunct to metronidazole, having the least number of recurrent BV, appears to result in better long-term treatment effect on bacterial vaginosis.

  2. Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal Bioadhesive Gel

    PubMed Central

    Chatterjee, A; Bhowmik, B B; Thakur, Y S

    2011-01-01

    Inexpensive and female-controlled pre-exposure prophylaxis strategies to prevent mucosal transmission of the virus, is urgently needed with the rising prevalence of human immunodeficiency virus (HIV-1 and HIV2) infections in women. Zidovudine-loaded bioadhesive vaginal gel may become one of the very useful strategies, as it can be used not only for controlled release but also for enhancing bioavailability. Drug delivery through vaginal gel is a promising area for continued research with the aim of achieving controlled release with enhanced bioavailability over longer periods of time. The aim of the study was to develop a newer prolong releasing Zidovudine (AZT) bioadhesive vaginal gel to treat HIV infections with increased patient convenience. AZT-loaded bioadhesive vaginal gel was prepared successfully by using cold mechanical method. F3 formulation containing carbopol–HPMC (1:3) was selected and evaluated in order to achieve objectives of this study. In vitro drug release study of F3 showed in 24 h drug released following case I Fickian (n ≤ 0.5) transport mechanism, and in vivo drug release was found much better (Tmax), (Cmax), and bioavailability (F) comparison with oral pour drug solution. It was also showed good extrudability, spreadability, and bioadhesive strength. A generalized protocol, for the further research, in this area will surely expected to yield significant outcome with improved drug delivery system. PMID:21731351

  3. Single and dual crosslinked oxidized methacrylated alginate/PEG hydrogels for bioadhesive applications.

    PubMed

    Jeon, Oju; Samorezov, Julia E; Alsberg, Eben

    2014-01-01

    A degradable, cytocompatible bioadhesive can facilitate surgical procedures and minimize patient pain and post-surgical complications. In this study a bioadhesive hydrogel system based on oxidized methacrylated alginate/8-arm poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive characteristics of the crosslinked OMA/PEG hydrogels evaluated. Here we demonstrate that the swelling behavior, degradation profiles, and storage moduli of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells. In addition, the adhesion strength of these hydrogels, controllable by varying the alginate oxidation level and measured using a porcine skin model, is superior to commercially available fibrin glue. This OMA/PEG hydrogel system with controllable biodegradation and mechanical properties and adhesion strength may be a promising bioadhesive for clinical use in biomedical applications, such as drug delivery, wound closure and healing, biomedical device implantation, and tissue engineering.

  4. Dual-crosslinked oxidized, methacrylated alginate/PEG hydrogels for bioadhesive applications

    PubMed Central

    Jeon, Oju; Samorezov, Julia E.; Alsberg, Eben

    2013-01-01

    A degradable, cytocompatible bioadhesive can facilitate surgical procedures and minimize patient pain and postsurgical complications. In this study, a bioadhesive hydrogel system based on oxidized, methacrylated alginate/8-arm poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive characteristics of the crosslinked OMA/PEG hydrogels are evaluated. Here, we demonstrate that the swelling behavior, degradation profiles, and storage moduli of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when cultured with human bone marrow-derived mesenchymal stem cells. In addition, the adhesion strength of these hydrogels, controllable by varying the alginate oxidation level and measured using a porcine skin model, is superior to commercially available fibrin glue. This OMA/PEG hydrogel system with controllable biodegradation and mechanical properties and adhesion strength may be a promising bioadhesive for clinical use in biomedical applications, such as drug delivery, wound closure and healing, biomedical device implantation, and tissue engineering. PMID:24035886

  5. Tuning model drug release and soft-tissue bioadhesion of polyester films by plasma post-treatment.

    PubMed

    Mogal, Vishal T; Yin, Chaw Su; O'Rorke, Richard; Boujday, Souhir; Méthivier, Christophe; Venkatraman, Subbu S; Steele, Terry W J

    2014-04-23

    Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils".

  6. Efficacy of Oral Metronidazole with Vaginal Clindamycin or Vaginal Probiotic for Bacterial Vaginosis: Randomised Placebo-Controlled Double-Blind Trial

    PubMed Central

    Bradshaw, Catriona S.; Pirotta, Marie; De Guingand, Deborah; Hocking, Jane S.; Morton, Anna N.; Garland, Suzanne M.; Fehler, Glenda; Morrow, Andrea; Walker, Sandra; Vodstrcil, Lenka A.; Fairley, Christopher K.

    2012-01-01

    Background To determine if oral metronidazole (MTZ-400mg bid) with 2% vaginal clindamycin-cream (Clind) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob) reduces 6-month bacterial vaginosis (BV) recurrence. Methods Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1∶1∶1) conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS) = 7–10 or ≥3 Amsel's criteria and NS = 4–10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7–10) on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups. Results 450 18–50 year old females were randomized and 408 (91%), equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9%) participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351). One-month BV recurrence (NS 7–10) rates were 3.6% (5/140), 6.8% (9/133) and 9.6% (13/135) in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR) for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15–1.22) and 0.75 (95% CI 0.32–1.76) in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0–32.7%) with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70–1.70) and 1.03(95% CI = 0.65–1

  7. Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial.

    PubMed

    Bradshaw, Catriona S; Pirotta, Marie; De Guingand, Deborah; Hocking, Jane S; Morton, Anna N; Garland, Suzanne M; Fehler, Glenda; Morrow, Andrea; Walker, Sandra; Vodstrcil, Lenka A; Fairley, Christopher K

    2012-01-01

    To determine if oral metronidazole (MTZ-400 mg bid) with 2% vaginal clindamycin-cream (Clind) or a Lactobacillus acidophilus vaginal-probiotic containing oestriol (Prob) reduces 6-month bacterial vaginosis (BV) recurrence. Double-blind placebo-controlled parallel-group single-site study with balanced randomization (1:1:1) conducted at Melbourne Sexual Health Centre, Australia. Participants with symptomatic BV [Nugent Score (NS) = 7-10 or ≥3 Amsel's criteria and NS = 4-10], were randomly allocated to MTZ-Clind, MTZ-Prob or MTZ-Placebo and assessed at 1,2,3 and 6 months. MTZ and Clind were administered for 7 days and Prob and Placebo for 12 days. Primary outcome was BV recurrence (NS of 7-10) on self-collected vaginal-swabs over 6-months. Cumulative BV recurrence rates were compared between groups by Chi-squared statistics. Kaplan-Meier, log rank and Cox regression analyses were used to compare time until and risk of BV recurrence between groups. 450 18-50 year old females were randomized and 408 (91%), equally distributed between groups, provided ≥1 NS post-randomization and were included in analyses; 42 (9%) participants with no post-randomization data were excluded. Six-month retention rates were 78% (n = 351). One-month BV recurrence (NS 7-10) rates were 3.6% (5/140), 6.8% (9/133) and 9.6% (13/135) in the MTZ-Clind, MTZ-Prob and MTZ-Placebo groups respectively, p = 0.13. Hazard ratios (HR) for BV recurrence at one-month, adjusted for adherence to vaginal therapy, were 0.43 (95%CI 0.15-1.22) and 0.75 (95% CI 0.32-1.76) in the MTZ-Clind and MTZ-Prob groups compared to MTZ-Plac respectively. Cumulative 6-month BV recurrence was 28.2%; (95%CI 24.0-32.7%) with no difference between groups, p = 0.82; HRs for 6-month BV recurrence for MTZ-Clind and MTZ-Prob compared to MTZ-Plac, adjusted for adherence to vaginal therapy were 1.09(95% CI = 0.70-1.70) and 1.03(95% CI = 0.65-1.63), respectively. No serious adverse events occurred. Combining

  8. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  9. Metronidazole in conjunction with penicillin neither prevents recurrence nor enhances recovery from peritonsillar abscess when compared with penicillin alone: a prospective, double-blind, randomized, placebo-controlled trial.

    PubMed

    Wikstén, Johanna E; Pitkäranta, Anne; Blomgren, Karin

    2016-06-01

    The objectives of this study were to evaluate the efficacy of metronidazole in conjunction with penicillin in preventing the recurrence of peritonsillar abscess (PTA) and to learn whether metronidazole enhances the recovery from PTA when compared with penicillin alone. In this prospective, double-blind, randomized, placebo-controlled trial, 200 adult outpatients with PTA at our ear, nose and throat emergency department received either penicillin (1 000 000IU) × 3 and metronidazole (400 mg) × 3 for 10 and 7 days orally (combination group, N = 100) or penicillin and placebo (penicillin group, N = 100) after incision and drainage of the PTA. Afterwards they received a symptom questionnaire via e-mail daily for 2 weeks, then weekly for 6 weeks. The primary outcome was efficacy of metronidazole in conjunction with penicillin in preventing PTA recurrence in 56 days; the secondary outcome was ability of metronidazole plus penicillin to enhance recovery from PTA in 28 days. All healthcare contacts were registered during follow-up. Registered on www.clinicaltrials.gov with the identifier NCT01255670. Of the 200 patients, 20 returned to hospital with recurrent symptoms, 10 in each group (P = 1.00). In the combination group, the mean (SD) duration of throat-related symptoms was 5.6 (5.0) days and in the penicillin group it was 5.3 (2.7) days, values for fever were 1.5 (0.9) and 1.6 (1.0) days, respectively, and those for poor overall physical condition were 4.0 (3.9) and 4.5 (4.9) days; there were no significant differences between groups. The adverse effects nausea and diarrhoea lasted longer in the combination group (P = 0.01). For healthy adult PTA patients treated with incision and drainage, metronidazole neither prevents recurrence nor enhances recovery when combined with penicillin compared with penicillin alone, but instead leads to increased adverse effects. © The Author 2016. Published by Oxford University Press on behalf of the British

  10. Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: systemic antibiosis (metronidazole plus clindamycin), dermatosurgical approach, and high-dose isotretinoin.

    PubMed

    Tchernev, Georgi

    2011-05-01

    Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as 'acne necrotica miliaris' or 'Proprionibacterium' folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus), Yeasts (Malassezia species) and mites (Demodex folliculorum). The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.

  11. From sticky stuff to sweet receptors--achievements, limits and novel approaches to bioadhesion.

    PubMed

    Lehr, C M

    1996-01-01

    About 10 years ago, the concept of bioadhesion was introduced into the pharmaceutical literature and has since stimulated much research and development both in academia and in industry. The first generation of bioadhesive drug delivery systems (BBDS) were based on so-called mucoadhesive polymers, i.e. natural or synthetic macromolecules, often already well accepted and used as pharmaceutical excipients for other purposes, which show the remarkable ability to 'stick' to humid or wet mucosal tissue surfaces. While these novel dosage forms were mainly expected to allow for a possible prolongation, better localization or intensified contact to mucosal tissue surfaces, it had to be realized that these goals were often not so easily accomplished, at least not by means of such relatively straightforward technology. However, although not always convincing as a 'pharmaceutical glue', some of the mucoadhesive polymers were found to display other, possibly even more important biological activities, namely to inhibit proteolytic enzymes and/or to modulate the permeability of usually tight epithelial tissue barriers. Such features were found to be particularly useful in the context of peptide and protein drug delivery. But still, the interest in realizing 'true' bioadhesion continues: instead of mucoadhesive polymers, plant or bacterial lectins, i.e. adhesion molecules which specifically bind to sugar moieties of the epithelial cell membrane, are now widely being investigated as drug delivery adjuvants. These second-generation bioadhesives not only provide for cellular binding, but also for subsequent endo- and transcytosis. This makes the novel, specifically bioadhesive molecules particularly interesting for the controlled delivery of DNA/RNA molecules in the context of antisense or gene therapy.

  12. Formulation development of gastroretentive tablets of lamivudine using the floating-bioadhesive potential of optimized polymer blends.

    PubMed

    Singh, Bhupinder; Garg, Babita; Chaturvedi, Subhash Chand; Arora, Sharry; Mandsaurwale, Rachana; Kapil, Rishi; Singh, Baljinder

    2012-05-01

    The current studies entail successful formulation of optimized gastroretentive tablets of lamivudine using the floating-bioadhesive potential of carbomers and cellulosic polymers, and their subsequent in-vitro and in-vivo evaluation in animals and humans. Effervescent floating-bioadhesive hydrophilic matrices were prepared and evaluated for in-vitro drug release, floatation and ex-vivo bioadhesive strength. The optimal composition of polymer blends was systematically chosen using central composite design and overlay plots. Pharmacokinetic studies were carried out in rabbits, and various levels of in-vitro/in-vivo correlation (IVIVC) were established. In-vivo gamma scintigraphic studies were performed in human volunteers using (99m) Tc to evaluate formulation retention in the gastric milieu. The optimized formulation exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug-release control and pharmacokinetic extension of plasma levels. The successful establishment of various levels of IVIVC substantiated the judicious choice of in-vitro dissolution media for simulating the in-vivo conditions. In-vivo gamma scintigraphic studies ratified the gastroretentive characteristics of the optimized formulation with a retention time of 5 h or more. Besides unravelling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system with improved bioavailability potential exhibiting excellent swelling, floating and bioadhesive characteristics. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  13. Metronidazole neurotoxicosis in two cats.

    PubMed

    Caylor, K B; Cassimatis, M K

    2001-01-01

    Two cats were presented for neurological dysfunction from suspected metronidazole toxicity. One cat was receiving 111 mg/kg body weight per day of metronidazole for 9 weeks. After 9 weeks, the dose was increased to 222 mg/kg body weight per day, and 2 days later the cat began to experience progressive neurological signs that culminated in generalized seizures. The second cat was receiving metronidazole at a total dose of 58 mg/kg body weight per day for 6 months. This cat experienced acute onset of ataxia and alteration in mentation. Laboratory evaluations in both cases were without significant findings. The neurological signs in both cats resolved within days of initiating supportive therapy and withdrawal of the drug. This report describes the two cases and discusses the etiology of metronidazole neurotoxicosis.

  14. Conjugation of metronidazole with dextran: a potential pharmaceutical strategy to control colonic distribution of the anti-amebic drug susceptible to metabolism by colonic microbes

    PubMed Central

    Kim, Wooseong; Yang, Yejin; Kim, Dohoon; Jeong, Seongkeun; Yoo, Jin-Wook; Yoon, Jeong-Hyun; Jung, Yunjin

    2017-01-01

    Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8, respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ with a degree of substitution of 17 was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but it released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-d,l-glycine. These prodrugs were eliminated very rapidly, and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ (as MTDZ conjugated to [depolymerized] dextran) to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism. PMID:28243064

  15. Conjugation of metronidazole with dextran: a potential pharmaceutical strategy to control colonic distribution of the anti-amebic drug susceptible to metabolism by colonic microbes.

    PubMed

    Kim, Wooseong; Yang, Yejin; Kim, Dohoon; Jeong, Seongkeun; Yoo, Jin-Wook; Yoon, Jeong-Hyun; Jung, Yunjin

    2017-01-01

    Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTDZ conjugated to dextran via a succinate linker (Dex-SA-MTDZ), was designed. Upon treatment with dextranase for 8 h, the degree of Dex-SA-MTDZ depolymerization (%) with a degree of substitution (mg of MTDZ bound in 100 mg of Dex-SA-MTDZ) of 7, 17, and 30 was 72, 38, and 8, respectively, while that of dextran was 85. Depolymerization of Dex-SA-MTDZ was found to be necessary for the release of MTDZ, because dextranase pretreatment ensures that de-esterification occurs between MTDZ and the dextran backbone. In parallel, Dex-SA-MTDZ with a degree of substitution of 17 was found not to release MTDZ upon incubation with the contents of the small intestine and stomach of rats, but it released MTDZ when incubated with rat cecal contents (including microbial dextranases). Moreover, Dex-SA-MTDZ exhibited prolonged release of MTDZ, which contrasts with drug release by small molecular colon-specific prodrugs, MTDZ sulfate and N-nicotinoyl-2-{2-(2-methyl-5-nitroimidazol-1-yl)ethyloxy}-d,l-glycine. These prodrugs were eliminated very rapidly, and no MTDZ was detected in the cecal contents. Consistent with these in vitro results, we found that oral gavage of Dex-SA-MTDZ delivered MTDZ (as MTDZ conjugated to [depolymerized] dextran) to the distal colon. However, upon oral gavage of the small molecular prodrugs, no prodrugs were detected in the distal colon. Collectively, these data suggest that dextran conjugation is a potential pharmaceutical strategy to control the colonic distribution of drugs susceptible to colonic microbial metabolism.

  16. Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases.

    PubMed

    El-Kamel, Amal Hassan; Ashri, Lubna Y; Alsarra, Ibrahim A

    2007-09-14

    The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. Mucoadhesive micromatricial chitosan/poly(epsilon-caprolactone) (CH/PCL) films and chitosan films were prepared. Thermal behavior, morphology, and particle size measurements were used to evaluate the prepared films. The effect of different molar masses of CH and different ratios of medium Mwt molar mass chitosan (MCH):PCL on water absorption, in vitro bioadhesion, mechanical properties, and in vitro drug release was examined. In vivo performance of the selected formulation was also evaluated. Differential scanning calorimetry examination revealed that MET existed mainly in amorphous form. Under microscopic examination, PCL microparticles were homogeneously dispersed in the films. The use of different molar masses of CH and different ratios of (MCH):PCL affected the size of the entrapped particles. Addition of PCL significantly decreased percentage water uptake and bioadhesion force compared with pure CH film. With regard to mechanical properties, the 2-layered film containing 1:0.625 MCH:PCL had the best tensile properties. At fixed CH:PCL ratio (1:1.25), the slowest drug release was obtained from films containing high molar mass CH. On the other hand, the 2-layered film that consisted of 1:0.625 MCH:PCL had the slowest MET release. In vivo evaluation of the selected film revealed that metronidazole concentration in saliva over 6 hours ranged from 5 to 15 microg/mL, which was within and higher than the reported range of minimum inhibitory concentration for metronidazole. A significant in vitro/in vivo correlation under the adopted experimental conditions was obtained.

  17. Optimization of Metronidazole Emulgel

    PubMed Central

    Rao, Monica; Sukre, Girish; Aghav, Sheetal; Kumar, Manmeet

    2013-01-01

    The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 23 factorial design and could provide an effective treatment against topical infections. PMID:26555982

  18. [Perioperative metronidazole-prophylaxis for cesarian section (author's transl].

    PubMed

    Gerstner, G; Kofler, E; Huber, J

    1980-12-01

    A prospective, randomized clinical trial was conducted in 103 patients undergoing cesarian section to assess the efficacy of prophylactic, intravenously administered Metronidazole on the infectious morbidity. A group of 53 patients with perioperative Metronidazol-prophylaxis was compared to a similar controll-group without prophylaxis. Bacteriologic swabs were taken from the cervix pre- and postoperatively, using anaerobic transport media. Prophylactic Metronidazole reduced postoperative fever of more than 38 degrees C on two subsequent days from 60% in the controll-group to 30,2% in the Metronidazole-group (p less than 0,01) wound infections were reduced from 18% without to 5,7% with prophylaxis (p less than 0,05) and Endometritis from 30% without to 13,2% with prophylaxis (p less than 0,05). An additional antibiotic therapy was necessary in 44% of the cases in the controllgroup, compared to 24,5% of the cases in the Metronidazolegroup (p less than 0,05). The mean duration of hospitalisation was reduced from 12,1 +/- 3,2 days in the controll-group to 11,2 +/- 2,1 in the Metronidazole-group (p less than 0,01). Anaerobic bacteria were isolated from the servical swabs in 60% preoperatively, with a still increasing incidence to 72% postoperatively, compared to 7% in the Metronidazole-group. Our results suggest, that prophylactic, intravenously administered Metronidazol reduces the infectious morbidity following cesarian section due to the reduction of the anaerobic flora at the female genital-tract.

  19. Formulation and Characterization of Cetylpyridinium Chloride Bioadhesive Tablets

    PubMed Central

    Akbari, Jafar; Saeedi, Majid; Morteza-Semnani, Katayoun; Kelidari, Hamidreza; Lashkari, Maryam

    2014-01-01

    Purpose: Bioadhesive polymers play an important role in biomedical and drug delivery applications. The aim of this study is to develop a sustained- release tablet for local application of Cetylpyridinium Chloride (CPC). This delivery system would supply the drug at an effective level for a long period of time, and thereby overcome the problem of the short retention time of CPC and could be used for buccal delivery as a topical anti-infective agent. Methods: CPC bioadhesive tablets were directly prepared using 7 mm flat-faced punches on a hydraulic press. The materials for each tablet were weighted, introduced into the die and compacted at constant compression pressure. The dissolution tests were performed to the rotation paddle method and the bioadhesive strength of the tablets were measured. Results: The results showed that as the concentration of polymer increased, the drug release rate was decreased. Also the type and ratio of polymers altered the release kinetic of Cetylpyridinium Chloride from investigated tablets. The bioadhesion strength increased with increasing the concentration of polymer and maximum bioadhesion strength was observed with HPMC K100M. Conclusion: The selected formulation of CPC bioadhesive tablet can be used as a suitable preparation for continuous release of CPC with appropriate bioadhesion strength. PMID:25436196

  20. A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis

    PubMed Central

    Masoudi, Mansoureh; Rafieian Kopaei, Mahmoud; Miraj, Sepideh

    2017-01-01

    Objective: Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. Materials and Methods: This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel’s criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. Results: There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Conclusion: Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment. PMID:28348968

  1. A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis.

    PubMed

    Masoudi, Mansoureh; Rafieian Kopaei, Mahmoud; Miraj, Sepideh

    2017-01-01

    Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel's criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment.

  2. Comparison of sequential intravenous/oral ciprofloxacin plus metronidazole with intravenous ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections.

    PubMed

    Wacha, Hannes; Warren, Brian; Bassaris, Harry; Nikolaidis, Paul

    2006-08-01

    Intra-abdominal infections are a substantial clinical problem and an important cause of morbidity and death in the hospital. Optimal treatment requires both source control and antibiotic therapy. Sequential intravenous (IV) to oral therapy may improve patient convenience and reduce total health care costs. In this randomized, double-blind trial, the efficacy of sequential IV-to-oral ciprofloxacin plus metronidazole was compared with ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal infections. The trial enrolled 531 patients, who began with IV therapy. Patients who improved clinically were switched to oral therapy on day three or later. The clinical and bacteriological responses four to six weeks after the end of therapy and the safety of the two regimens were assessed. To maintain blinding, the patients received placebo IV in the ciprofloxacin group or placebo orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of efficacy. All patients were included in the safety analysis. Of the patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to oral therapy. The clinical success rates were 98.9% and 96.9%, respectively, which were statistically equivalent. The clinical success rates for all patients, including those on continuous IV therapy, were 90.6% and 87.9%. Source control was achieved in more than 90% of the patients. The bacteriological eradication rates were similar in the two groups. Bacterial complications (e.g., surgical site infections, abscesses) were encountered more often in the ceftriaxone plus metronidazole group. Sequential ciprofloxacin plus metronidazole IV-to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole. The switch to oral therapy with ciprofloxacin plus metronidazole was as

  3. Metronidazole for the treatment of Tritrichomonas foetus in bulls.

    PubMed

    Love, David; Fajt, Virginia R; Hairgrove, Thomas; Jones, Meredyth; Thompson, James A

    2017-04-14

    Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Results from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovine Tritrichomonas foetus. The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior to treatment was negative for Tritrichomonas foetus culture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treat Tritrichomonas foetus in bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls. The study demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in vivo with metronidazole. The current status of metronidazole

  4. A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole.

    PubMed

    Ferrari, Priscileila Colerato; dos Santos Grossklauss, Dany Bruno Borella; Alvarez, Matheus; Paixão, Fabiano Carlos; Andreis, Uilian; Crispim, Alexandre Giordano; de Castro, Ana Dóris; Evangelista, Raul Cesar; de Arruda Miranda, José Ricardo

    2014-08-01

    Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets. The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery. Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release. The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%. The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

  5. Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.

    PubMed

    Charlton, S T; Davis, S S; Illum, L

    2007-04-02

    There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.

  6. The ability of retention, drug release and rheological properties of nanogel bioadhesives based on cellulose derivatives.

    PubMed

    Keshavarz, M; Kaffashi, B

    2014-12-01

    The rheological and drug release behavior of biopolymer nanocomposite gels based on the cellulose derivatives, formulated as the bioadhesive drug delivery platforms, were investigated. The bioadhesive gel is composed of the microcrystalline cellulose, sodium carboxymethyl cellulose and phosphate buffered saline (pH = 7.4 at 20 °C) as the dissolution and release medium. The reinforcing nanofillers such as MMT-clay, fumed porous silica and porous starch were used as additives in the nanogel bioadhesive. The constant steady state viscosities of this nanogels upon incorporation of various nanofillers into the systems is the sign of structural stability. Hence, this system is suitable for use in the controlled drug delivery systems in contact with the biological tissues. Based on the rheological measurements, the shear flow properties (i.e. zero shear viscosity and yield stress) were influenced by the concentration of polymers and nanoparticles. The results indicate that the nonlinear rheological data are fitted properly by the Giesekus model. Furthermore, the results showed that the nonlinear viscoelastic parameters (λ and α) are highly affected by the biogel and nanoparticles concentrations. Finally, the drug release was measured, and the results indicated that the biopolymer-clay nanocomposites have appropriate release pattern as the release is better controlled compared to the other nanogel formulations.

  7. Glioblastoma multiforme: treatment by large dose fraction irradiation and metronidazole

    SciTech Connect

    Kapp, D.S.; Wagner, F.C.; Lawrence, R.

    1982-03-01

    In an attempt to overcome the possible radioresistance of glioblastoma multiforme related to the large shoulder on the in vitro survival curves and to sensitize hypoxic tumor cells, a treatment protocol was instituted at Yale University Medical Center and affiliated hospitals, using large dose fraction irradiation therapy in conjunction with the hypoxic cell sensitizer metronidazole. Nineteen patients with biopsy-confirmed, previously untreated, cerebral grade IV glioblastoma multiforme were, following surgery, irradiated once a week at 600 rad per fraction, 3.5 to 4 hours after ingestion of metronidazole, 6 gm/m/sup 2/. A total of 7 treatments were employed, with all patients maintained on antiseizure medications and corticosteroids. Metronidazole levels were determined prior to each treatment and patients were followed closely clinically and with serial computerized tomography (CT) scans. The treatment was well tolerated, in general, with no untoward side effects related to the high dose fraction irradiation. The majority of the patients experienced varying degrees of gastrointestinal upset lasting up to several hours following metronidazole administration. Three patients died of pulmonary emboli. One patient experienced moderately severe ototoxicity. A median survival of 9.4 months was obtained for all 19 patients, suggestive of a prolongation of survival compared to historical controls treated with conventionally fractionated radiation or with unconventional radiation fractionation schemes and metronidazole or misonidazole.

  8. BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial.

    PubMed

    Zeron Mullins, Melinda; Trouton, Konia M

    2015-07-26

    Bacterial vaginosis is associated with increased transmission of sexually transmitted infections, preterm labor, post-surgical infections, and endometritis. Current treatment for symptomatic bacterial vaginosis includes antibiotics, such as metronidazole, which are 70-80 % effective at one month after treatment and result in high recurrence rates and secondary candida infections. Intravaginal boric acid has been used for over a hundred years to treat vaginal infections, such as bacterial vaginosis. Boric acid is inexpensive, accessible, and has shown to be an effective treatment for other infections, such as vaginal candidiasis. To date, there has been no clinical trial evaluation of boric acid effectiveness to treat bacterial vaginosis. The BASIC (Boric Acid, Alternate Solution for Intravaginal Colonization) trial is a randomized, double-blinded, multicenter study. The study will enroll a minimum of 240 women of 16-50 years of age who are symptomatic with bacterial vaginosis. Eligible participants will have Amsel and Nugent scores confirming bacterial vaginosis. Women who are pregnant or menopausal or have other active co-infections will be excluded. Consenting participants who meet exclusion and inclusion criteria will be randomly assigned to one of three treatment groups: boric acid, metronidazole, or an inert placebo. Self-administration of treatment intravaginally for 10 days will be followed by clinical assessment at 7 and 30 days (days 17 and 40, respectively) after the end of the treatment phase. Primary outcome is a non-inferiority, per-protocol comparison of the effectiveness of boric acid with that of metronidazole at day 17, as measured by the Nugent score in 16-50 year olds. Secondary outcomes include: non-inferiority, intention-to-treat comparison of effectiveness of boric acid with that of metronidazole at day 17, analysis for both per-protocol and intention-to-treat at day 40, and safety considerations, including adverse effects requiring patient

  9. Evaluation of bioadhesive glipizide spheres and compacts from spheres prepared by extruder/marumerizer technique.

    PubMed

    Garcia, J; Ghaly, E S

    2001-08-01

    The objective of this study was to attempt to deliver glipizide from spheres and compacts containing the natural polymer Carrageenan (Gelcarin, GP 812) and prepared by extruder/marumerizer technique. A second objective was to evaluate the mucoadhesive strength of the bioadhesive spheres onto the mucus membrane of rabbit. The effects of polymer, drug level, and type of spheronizing material were evaluated. All sphere formulations were compacted into tablets using a rotary Manesty B-3B machine equipped with 12/32 flat face tooling. Results show drug release from spheres and compacts decreased as the level of Carrageenan was increased. However as the level of drug was increased drug release also increased. Spheres containing Avicel PH-101 gave higher drug release than spheres of the same composition but prepared with Avicel RC-581. In general, the drug release from tablets was higher than its corresponding spheres and drug release from spheres and tablets containing Carrageenan was higher than control spheres and tablets of the same composition but without Carrageenan. Tablet formulations compacted from spheres containing Avicel RC-581 gave higher release rate constants than tablet formulations of the same composition but prepared with Avicel PH-101. The bioadhesion study showed that mucoadhesion strength between spheres and mucus membrane of the rabbit depends on the levels of polymer, drug, and type of spheronizing material. Developed bioadhesive spheres and tablets increase the solubility of glipizide which may increase its bioavailability and also increased the adherence of the bioadhesive systems to the mucous membrane so that once daily dose can be administered.

  10. Floating-bioadhesive gastroretentive Caesalpinia pulcherrima-based beads of amoxicillin trihydrate for Helicobacter pylori eradication.

    PubMed

    Thombre, Nilima A; Gide, Paraag S

    2016-01-01

    An oral dosage form containing floating bioadhesive gastroretentive microspheres forms a stomach-specific drug delivery system for the treatment of Helicobacter pylori. To prepare and evaluate controlled release floating bioadhesive gastroretentive chitosan-coated amoxicillin trihydrate-loaded Caesalpinia pulcherrima galactomannan (CPG)-alginate beads (CCA-CPG-A), for H. pylori eradication. CCA-CPG-A beads were prepared by ionotropic gelation, using 2(3) factorial design with quantity of drug, combination of CPG with sodium alginate and concentration of calcium chloride as variables. Beads facilitated mucoadhesion to gastric mucosa with floating nature caused by chitosan coating for wide distribution throughout GIT. Developed beads were evaluated for characteristics like beads size-morphology, entrapment efficiency, DSC, XRD, FTIR, swelling ratio, in vitro mucoadhesion, in vitro drug release, in vitro floating and in vitro H. pylori growth inhibition studies. CCA-CPG-A beads were studied in Wistar rats for in vivo gastric mucoadhesion, in vivo H. pylori growth inhibition studies using PCR amplification of isolated DNA, rapid urease test. Developed beads possess drug release of 79-92%, entrapment efficiency of 65-89%, mucoadhesion of 61-89%. In vivo mucoadhesion study showed more than 85% mucoadhesion of beads even after 7th hour. In vitro-in vivo growth inhibition study showed complete eradication of H. pylori. CPG-alginate and chitosan in beads interacts with gastric mucosubstrate surface for prolonged gastric residence with floating bioadhesion mechanism for H. pylori eradication in rats. Floating bioadhesive CCA-CPG-A beads offer a promising drug delivery system for H. pylori eradication at lower dose, reduced adverse effect and enhance bioavailability.

  11. A sunblock based on bioadhesive nanoparticles.

    PubMed

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael; Saltzman, W Mark

    2015-12-01

    The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

  12. A sunblock based on bioadhesive nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael; Saltzman, W. Mark

    2015-12-01

    The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

  13. A Sunblock Based On Bioadhesive Nanoparticles

    PubMed Central

    Deng, Yang; Ediriwickrema, Asiri; Yang, Fan; Lewis, Julia; Girardi, Michael

    2015-01-01

    The majority of commercial sunblock preparations utilize organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO) - a model UV filter - in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water-resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared to a commercial sunscreen formulation. PMID:26413985

  14. Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL

    PubMed Central

    Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

    2011-01-01

    The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO3) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO3 and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO3 and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism. PMID:22171304

  15. Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive gel.

    PubMed

    Boulmedarat, Laïla; Piel, Géraldine; Bochot, Amélie; Lesieur, Sylviane; Delattre, Luc; Fattal, Elias

    2005-06-01

    The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. A hydrophilic model molecule, inulin, was encapsulated within positively charged and PEG-ylated liposomes and its release was measured in the presence of Me(beta)CD after vesicle dispersion within the bioadhesive Carbopol 974P gel. Freeze-fracture electron microscopy (FFEM) was used to follow liposome morphological changes when dispersed within the hydrogel. Liposome-Me(beta)CD interactions were investigated by turbidity monitoring during continuous addition of Me(beta)CD to liposomes and by FFEM. Inulin diffusion within the gel was influenced by Carbopol 974P concentration since no gel erosion occurred. When dispersed within the gel, positively charged liposomes displayed a higher stability than PEG-ylated vesicles. In the presence of Me(beta)CD, higher amounts of free inulin were released from liposomes, especially in Carbopol-free system. Me(beta)CD appeared to diffuse towards lipid vesicles and permeabilized their bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome turbidity monitoring have shown that Me(beta)CD behaved as a detergent behavior, resulting in lipid vesicle solubilization. is able to mediate, within a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing further application of this delivery system for mucosal administration.

  16. Effect of bioadhesion on initial in vitro buoyancy of effervescent floating matrix tablets of ciprofloxacin HCL.

    PubMed

    Negi, Jeetendra Singh; Trivedi, Abhinav; Khanduri, Praveen; Negi, Vandana; Kasliwal, Nikhil

    2011-04-01

    The purpose of this study was to investigate effect of bioadhesion on the initial in vitro buoyancy behaviour of effervescent matrix tablets of ciprofloxacin HCl (CIPRO). Tablets were prepared by direct compression using HPMC K4M and Carbopol 971P as hydrophilic-controlled release polymers, sodium bicarbonate (NaHCO(3)) as gas-generating agent, polyplasdone XL, Explotab and Ac-Di-Sol as swelling agents. Tablets were evaluated for normal and modified initial in vitro floating behavior, floating duration, swelling behavior and in vitro drug release studies. A modified buoyancy lag time for tablets was determined in order to include the effect of bioadhesion on initial buoyancy. The initial buoyancy was found depended on bioadhesion ability of tablets. The lowest modified buoyancy lag time of 20 seconds was obtained for Formulation F7 having both NaHCO(3) and polyplasdone XL. The floating duration was also found dependent on concentration of NaHCO(3) and swelling agents. The drug release of F7 was also sustained up to 12-hr duration with anomalous drug transport mechanism.

  17. Microparticles containing propolis and metronidazole: in vitro characterization, release study and antimicrobial activity against periodontal pathogens.

    PubMed

    de Souza Ferreira, Sabrina Barbosa; de Assis Dias, Bruno Rafael; Obregón, Clarissa Silva; Gomes, Carla Carolina; de Araújo Pereira, Raphaela Regina; Ribeiro Godoy, Janine Silva; Estivalet Svidzinski, Terezinha Inez; Bruschi, Marcos Luciano

    2014-03-01

    Ethylcellulose microparticles containing metronidazole and propolis extractive solution were prepared and evaluated in vitro against periodontal pathogens. Scanning electron microscopy, particle size analysis, drug entrapment efficiency and drug release of microparticles were determined. The antimicrobial activity of microparticles was evaluated against microorganisms of periodontal importance (Enterococcus faecalis, Streptococcus pyogenes, Streptococcus mutans, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli). It was obtained particles with regular morphology, mean diameter of 1.23 µm, and entrapment efficiency for propolis and metronidazole were 91.41% and 22.23%, respectively. In vitro release studies of propolis and metronidazole from microparticles showed prolonged drug release and controlled by Fickian diffusion. Both propolis and metronidazole displayed activity against the tested strains. Moreover, the results showed that the strains of E. faecalis, S. pyogenes and S. mutans were more susceptible to the propolis and E. faecalis to the metronidazole. It was also observed that the amount of metronidazole to inhibit the microorganism strains in the physical mixture with propolis was smaller than in the metronidazole alone, suggesting potentiation effect between propolis and metronidazole. These microparticles would be useful for developing intermediary or eventual dosage form to be administered into the periodontal pocket more easily and safely.

  18. Muco-bioadhesive containing ginger officinale extract in the management of recurrent aphthous stomatitis: A randomized clinical study

    PubMed Central

    Haghpanah, Parya; Moghadamnia, Ali Akbar; Zarghami, Amin; Motallebnejad, Mina

    2015-01-01

    Background: Recurrent aphthous stomatitis (RAS) is the most common oral mucosal lesions in the general population. Various treatment modalities have been used; but no specific therapy proved to be definitive. Ginger Officinale (ginger) indicated to have anti-inflammatory properties in herbal medicine. Thus, this study aimed to evaluate the efficacy of ginger containing bioadhesive in the treatment of aphthous ulcers. Methods: In this randomized double-blind placebo-controlled trial, 15 patients were enrolled. The clinical efficacy of the mucoadhessive on pain, inflammatory zone and ulcer's diameter in the test period was compared with that of the base treatment and no treatment periods during 10 days of study. Results: Significant reduction in pain was observed on day 5 between placebo (using base bioadhesives) and without treatment periods at the first phase of the study (4.53 vs. 3.27; P=0.038. ( Reduction in inflamed halo diameters was significant on day 1 between without treatment and ginger containing bioadhesives )46.73 vs 28.67; P=0.044). Other variables such as the diameter of ulcers did not indicate any significant differences in both periods. Conclusion: This study indicated that ginger bioadhesive is capable to relieve pain of RAS. However, its efficacy on ulcer diameter, inflamed halo and healing time was not significantly different compared to the results of the placebo received period. PMID:26221489

  19. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration.

    PubMed

    Perioli, Luana; Ambrogi, Valeria; Pagano, Cinzia; Scuota, Stefania; Rossi, Carlo

    2009-07-30

    Topical administration of the antibacterial metronidazole (MET) represents the most common therapy in the treatment of bacterial vaginosis (BV). The formulations generally available for BV therapy are creams, gels, vaginal lavages and vaginal suppositories. In this study, a new dosage form, containing MET, was developed with the aim to realize vaginal mucoadhesive tablets by including bioadhesive polymers as chitosan (FG90C), polyvinylpyrrolidone (PVPK90) and polycarbophil (PCPAA1), blended in different ratios. All formulations were characterized by studies of DSC, friability, hardness, hydration, mucoadhesion, in vitro release and antibacterial activity. All polymer mixtures employed were used to prepare tablets with the compactness and hardness so as allow the application on vaginal mucosa. FG90C performances improved in particular when mixed to PVPK90 (1:1 ratio). This kind of delivery system is suitable for formulating MET for topical application representing a good alternative to traditional dosage forms for vaginal topical administration.

  20. Tunable bioadhesive copolymer hydrogels of thermoresponsive poly(N-isopropyl acrylamide) containing zwitterionic polysulfobetaine.

    PubMed

    Chang, Yung; Yandi, Wetra; Chen, Wen-Yih; Shih, Yu-Ju; Yang, Chang-Chung; Chang, Yu; Ling, Qing-Dong; Higuchi, Akon

    2010-04-12

    This work describes a novel tunable bioadhesive hydrogel of thermoresponsive N-isopropylacrylamide (NIPAAm) containing zwitterionic sulfobetaine methacrylate (SBMA). This novel hydrogel highly regulates general bioadhesive foulants through the adsorption of plasma proteins, the adhesion of human platelets and cells, and the attachment of bacteria. In this investigation, nonionic hydrogels of polyNIPAAm, zwitterionic hydrogels of polySBMA, and three copolymeric hydrogels of NIPAAm and SBMA (poly(NIPAAm-co-SBMA)) were prepared. The copolymeric hydrogels exhibited controllable temperature-dependent swelling behaviors and showed stimuli-responsive phase characteristics in the presence of salts. The interactions of these hydrogels with biomolecules and microorganisms were demonstrated by protein adsorption, cell adhesion, and bacterial attachment, which allowed us to evaluate their bioadhesive properties. An enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies was used to measure different plasma protein adsorptions on the prepared hydrogel surfaces. At a physiological temperature, the high content of the nonionic polyNIPAAm in poly(NIPAAm-co-SBMA) hydrogel exhibits a high protein adsorption due to the interfacial exposure of polyNIPAAm-rich hydrophobic domains. A relatively high content of polySBMA in poly(NIPAAm-co-SBMA) hydrogel exhibits reduced amounts of protein adsorption due to the interfacial hydration of polySBMA-rich hydrophilic segments. The attachment of platelets and the spreading of cells were only observed on polyNIPAAm-rich hydrogel surfaces. Interestingly, the incorporation of zwitterionic SBMA units into the polyNIPAAm gels was found to accelerate the hydration of the cell-cultured surfaces and resulted in more rapid cell detachment. Such copolymer gel surface was shown to be potentially useful for triggered cell detachment. In addition, the interactions of hydrogels with bacteria were also evaluated. The polySBMA-rich hydrogels

  1. Metronidazole. A therapeutic review and update.

    PubMed

    Freeman, C D; Klutman, N E; Lamp, K C

    1997-11-01

    The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable

  2. An investigation and characterization on alginate hydogel dressing loaded with metronidazole prepared by combined inotropic gelation and freeze-thawing cycles for controlled release.

    PubMed

    Sarheed, Omar; Rasool, Bazigha K Abdul; Abu-Gharbieh, Eman; Aziz, Uday Sajad

    2015-06-01

    The purpose of this study was to investigate the effect of combined Ca(2+) cross-linking and freeze-thawing cycle method on metronidazole (model drug) drug release and prepare a wound film dressing with improved swelling property. The hydrogel films were prepared with sodium alginate (SA) using the freeze-thawing method alone or in combination with ionotropic gelation with CaCl2. The gel properties such as morphology, swelling, film thickness, and content uniformity and in vitro dissolution profiles using Franz diffusion cell were investigated. The cross-linking process was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. In vitro protein adsorption test, in vivo wound-healing test, and histopathology were also performed. The hydrogel (F2) composed of 6% sodium alginate and 1% metronidazole prepared by combined Ca(2+) cross-linking and freeze-thawing cycles showed good swelling. This will help to provide moist environment at the wound site. With the in vivo wound-healing and histological studies, F2 was found to improve the wound-healing effect compared with the hydrogel without the drug, and the conventional product.

  3. Controlled synthesis of uniform BiVO4 microcolumns and advanced visible-light-driven photocatalytic activity for the degradation of metronidazole-contained wastewater.

    PubMed

    Yu, Chongfei; Dong, Shuying; Feng, Jinglan; Sun, Jingyu; Hu, Limin; Li, Yukun; Sun, Jianhui

    2014-02-01

    Well-defined, uniform bismuth vanadate (BiVO4) microcolumns were synthesized through a refined hydrothermal route. During the fabrication process, a detailed orthogonal design on the synthetic conditions was performed, aiming to optimize the experimental parameters to produce BiVO4 materials (BiVO4 (Opt.)) with the most prominent visible-light-driven photocatalytic efficiency, where the catalytic activities of the synthesized materials were evaluated via the decolorization of methylene blue under visible light irradiation. The BiVO4 (Opt.) were then targetedly produced according to the determined optimal conditions and well characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet and visible diffuse-reflectance spectroscopy and photoluminescence spectroscopy. Compared with the commercial P25-TiO2 photocatalysts, the as-synthesized BiVO4 (Opt.) displayed superior visible-light-driven photocatalytic activities for the degradation of metronidazole-contained wastewater with the presence of H2O2. The degradation efficiency of metronidazole reached up to 70 % within 180 min, leading to a brief speculation on the possibly major steps of the visible-light-driven photocatalytic process. The current study provides a distinctive route to design novel shaped BiVO4 architectures with advanced photocatalytic capacities for the treatment of organic pollutants in the aqueous environment.

  4. Clindamycin vaginal cream vs oral metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Arredondo, J L; Higuera, F; Hidalgo, H; Narcio, L; Casanova, G; Beltran, M; Sanchez, C J

    1992-01-01

    This study was designed to compare the safety/efficacy of the treatment of 2% clindamycin vaginal cream and oral metronidazole in 184 women with bacterial vaginosis. This was a randomized, prospective, multicenter, double-blind, controlled study. Patients were randomized to either Clindamycin phosphate vaginal cream 2%, 5 gm intravaginally at bedtime, and placebo oral metronidazole capsules taken twice daily, or oral metronidazole capsules, 500 mg, taken twice daily, and placebo clindamycin vaginal cream, 5 gm to be administered intravaginally at bedtime. All treatments were for 7 days. Patients were seen for followup at 4-13 days and 20-43 days after completion of protocol therapy. 2 investigators in Mexico City enrolled a total of 184 patients (91 clindamycin and 93 metronidazole). 1 patient never received drugs after enrollment, leaving 183 valuable for safety. A total of 114 were valuable for efficacy. Protocol regimens were comparable in efficacy (p=0.22) and the percentage of cure/improvement was 87% in the clindamycin group compared to 79% in the metronidazole group. No relapse was observed in the clindamycin group, as opposed to 7% in the metronidazole group. The clindamycin group had a failure of 13% while this was 15% in the metronidazole group. Both treatments were well-tolerated. Most of the events were either vulvovaginal irritation upon application of the study drug, or the development of vaginitis/cervicitis. The 1 event classified as serious in this study (metronidazole group) was generalized rash which, in the opinion of the investigator, was related to the study drug. There were 4 nongenital tract side effects (1 gastrointestinal, 2 dermatologic, and 1 allergy) all in the metronidazole group. The authors can conclude that clindamycin 2% vaginal cream is at least as effective as orally administered metronidazole for the treatment of bacterial vaginosis in nonpregnant women.

  5. Metronidazole and the immune system.

    PubMed

    Shakir, L; Javeed, A; Ashraf, M; Riaz, A

    2011-06-01

    Metronidazole (MTZ) is a nitroimidazole antibiotic used mainly for the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. Distinct from its antibiotic, amoebicidal, and antiprotozoal effects, MTZ displays immunopharmacological behaviour. This review outlines multiple effects of MTZ on different aspects of immunity, including innate and acquired immunity, and also highlights the immunopharmacological behaviour of MTZ in terms of its relevance to inflammation, delayed type hypersensitivity (DTH) and graft versus host disease (GVHD).

  6. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

    PubMed Central

    Jaipal, A.; Pandey, M.M.; Charde, S.Y.; Raut, P.P.; Prasanth, K.V.; Prasad, R.G.

    2014-01-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 32 factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported. PMID:26106280

  7. Topical metronidazole can reduce pain after surgery and pain on defecation in postoperative hemorrhoidectomy.

    PubMed

    Ala, Shahram; Saeedi, Majid; Eshghi, Fariborz; Mirzabeygi, Parastou

    2008-02-01

    Topical metronidazole (10 percent) has been previously demonstrated to decrease postoperative pain after hemorrhoidectomy. The aim of this study was to evaluate the effect of topical metronidazole (10 percent) in reducing postoperative and after-defecation pain of hemorrhoidectomy. A double-blind, randomized trial was conducted to compare posthemorrhoidectomy pain with use of topical metronidazole (10 percent) vs. placebo carrier, applied to surgical site. Forty-seven patients were randomly allocated to receive metronidazole (n=25) or placebo (n=22). Pain was assessed using a visual analog scale preoperatively and on postoperative hours 6 and 12 and at days 1, 2, 7, and 14. The use of narcotic, additional analgesics, and complications were recorded. (Pain scores were calculated and compared with baseline values and control group (t test, SPSS ver.10). Patients in the topical metronidazole group had significantly less postoperative pain than those in the placebo group up to day 14 (P metronidazole group, after-defecation pain was ranked significantly lower at day 2 (P=0.016) and patients required fewer additional analgesics postoperatively on days 2 and 7 (P metronidazole significantly reduce posthemorrhoidectomy discomfort, and postoperative defecation pain is reduced compared with that of the placebo control group.

  8. Development of Injectable Citrate-Based Bioadhesive Bone Implants

    PubMed Central

    Xie, Denghui; Guo, Jinshan; Mehdizadeh, Mohammadreza; Tran, Richard T.; Chen, Ruisong; Sun, Dawei; Qian, Guoying; Jin, Dadi; Bai, Xiaochun; Yang, Jian

    2014-01-01

    Injectable bone implants have been widely used in bone tissue repairs including the treatment of comminuted bone fractures (CBF). However, most injectable bone implants are not suitable for the treatment of CBF due to their weak tissue adhesion strengths and minimal osteoinduction. Citrate has been recently reported to promote bone formation through enhanced bioceramic integration and osteoinductivity. Herein, a novel injectable citrate-based mussel-inspired bioadhesive hydroxyapatite (iCMBA/HA) bone substitute was developed for CBF treatment. iCMBA/HA can be set within 2–4 minutes and the as-prepared (wet) iCMBA/HA possess low swelling ratios, compressive mechanical strengths of up to 3.2±0.27 MPa, complete degradation in 30 days, suitable biocompatibility, and osteoinductivity. This is also the first time to demonstrate that citrate supplementation in osteogenic medium and citrate released from iCMBA/HA degradation can promote the mineralization of osteoblastic committed human mesenchymal stem cells (hMSCs). In vivo evaluation of iCMBA/HA in a rabbit comminuted radial fracture model showed significantly increased bone formation with markedly enhanced three-point bending strength compared to the negative control. Neovascularization and bone ingrowth as well as highly organized bone formation were also observed showing the potential of iCMBA/HA in treating CBF. PMID:25580247

  9. Treatment of trichomoniasis with metronidazole rectal suppositories

    PubMed Central

    Panja, S K

    1982-01-01

    Since a single dose of metronidazole in suppository form is very effective in the prevention of postoperative Gram-negative anaerobic infections, 84 patients with vaginal trichomoniasis were treated with metronidazole suppositories (two 1-g suppositories in a single dose). The cure rate in this series was 94%. PMID:7104657

  10. Toxic metronidazole-induced MRI changes.

    PubMed

    Horlen, C K; Seifert, C F; Malouf, C S

    2000-11-01

    To report a case of changes documented by magnetic resonance imaging (MRI) of the head probably due to accumulation of metronidazole in a patient with liver dysfunction. A 34-year-old Hispanic man with cirrhosis and hepatitis C being treated with metronidazole for Bacteroides fragilis meningitis and bacteremia developed ataxia, disorientation, and peripheral neuropathy. An MRI at the time meningitis was diagnosed was negative. After the patient received > 60 g of metronidazole, an MRI revealed increased signal intensity below, behind, and lateral to the fourth ventricle. Concomitant metronidazole serum concentration was toxic at 35.1 micrograms/mL. This is the second reported case of metronidazole-induced MRI changes. Metronidazole is known to accumulate in patients with liver dysfunction and can cause peripheral neuropathy and central nervous system (CNS) dysfunction; these effects may take up to two years to completely resolve. Metronidazole dosages should be reduced in patients with liver dysfunction to prevent the accumulation of metronidazole, which can lead to CNS dysfunction and peripheral neuropathy.

  11. [Is combining metronidazole and alcohol really hazardous?].

    PubMed

    Fjeld, Hilde; Raknes, Guttorm

    2014-09-16

    It is common practice to warn against intake of alcohol (ethanol) when taking metronidazole because of the risk of an effect similar to disulfiram (Antabuse). In this article we investigate whether such a warning has any real basis. KNOWLEDGE BASE: The article is based on a review of relevant literature retrieved through a search in PubMed. A search was also made in the WHO's database on adverse effects. No in-vitro studies, animal models, reports of adverse effects or clinical studies provide any convincing evidence of a disulfiram-like interaction between ethanol and metronidazole. The warning against simultaneous use of alcohol and metronidazole appear to be based on laboratory experiments and individual case histories in which the reported reactions are equally likely to have been caused by ethanol alone or by adverse effects of metronidazole. Recent research does not confirm a clinically relevant interaction between ethanol and metronidazole.

  12. The aerobic activity of metronidazole against anaerobic bacteria.

    PubMed

    Dione, Niokhor; Khelaifia, Saber; Lagier, Jean-Christophe; Raoult, Didier

    2015-05-01

    Recently, the aerobic growth of strictly anaerobic bacteria was demonstrated using antioxidants. Metronidazole is frequently used to treat infections caused by anaerobic bacteria; however, to date its antibacterial activity was only tested in anaerobic conditions. Here we aerobically tested using antioxidants the in vitro activities of metronidazole, gentamicin, doxycycline and imipenem against 10 common anaerobic and aerobic bacteria. In vitro susceptibility testing was performed by the disk diffusion method, and minimum inhibitory concentrations (MICs) were determined by Etest. Aerobic culture of the bacteria was performed at 37°C using Schaedler agar medium supplemented with 1mg/mL ascorbic acid and 0.1mg/mL glutathione; the pH was adjusted to 7.2 by 10M KOH. Growth of anaerobic bacteria cultured aerobically using antioxidants was inhibited by metronidazole after 72h of incubation at 37°C, with a mean inhibition diameter of 37.76mm and an MIC of 1μg/mL; however, strains remained non-sensitive to gentamicin. No growth inhibition of aerobic bacteria was observed after 24h of incubation at 37°C with metronidazole; however, inhibition was observed with doxycycline and imipenem used as controls. These results indicate that bacterial sensitivity to metronidazole is not related to the oxygen tension but is a result of the sensitivity of the micro-organism. In future, both culture and antibiotic susceptibility testing of strictly anaerobic bacteria will be performed in an aerobic atmosphere using antioxidants in clinical microbiology laboratories. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  13. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis.

    PubMed

    Schwebke, Jane R; Marrazzo, Jeanne; Beelen, Andrew P; Sobel, Jack D

    2015-07-01

    Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative "whiff test," and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV.

  14. A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis

    PubMed Central

    Schwebke, Jane R.; Marrazzo, Jeanne; Beelen, Andrew P.; Sobel, Jack D.

    2015-01-01

    Background Bacterial vaginosis (BV), a prevalent infection in women of reproductive age, is associated with increased risk of upper genital tract and sexually transmitted infections, and complications in pregnancy. Currently approved treatments include metronidazole, which requires once or twice daily intravaginal administration for 5 days or twice daily oral administration for 7 days. This phase 3 study determined the safety and efficacy of single-dose metronidazole vaginal gel (MVG) 1.3%. Methods In this double-blind, vehicle-controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical cure (normal discharge, negative “whiff test,” and <20% clue cells) at day 21. Secondary measures included therapeutic cure (both clinical and bacteriological; day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to resolution of symptoms (day 7). Results A total of 487 participants were included in the primary analysis. Clinical and therapeutic cure rates (day 21) were higher in participants treated with MVG 1.3% compared with vehicle gel (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively). Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3% group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively). The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6) than vehicle group (not reached). No serious adverse events were reported, and incidence was similar across treatment groups. Conclusions Single-dose MVG 1.3% was safe and superior to vehicle gel in producing cure among women with BV. PMID:26222750

  15. Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).

    PubMed

    Pal, Dibyarupa; Banerjee, Sulagna; Cui, Jike; Schwartz, Aaron; Ghosh, Sudip K; Samuelson, John

    2009-02-01

    Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.

  16. Use of Novel Surfaces to Reduce Bioadhesion on Infrastructure

    DTIC Science & Technology

    2010-06-01

    ratio affects bioadhesion • Sharklet® technology: Navy • Greater than 80% reduction in Ulva spore and barnacle adhesion • Not investigated for...mix, degas to remove bubbles photolithography Pour on Si wafer mold Peel off PDMSe Engineer Research and Development Center Methods: superhydrophobic

  17. Novel bioadhesive polymers as intra-articular agents: Chondroitin sulfate-cysteine conjugates.

    PubMed

    Suchaoin, Wongsakorn; Bonengel, Sonja; Griessinger, Julia Anita; Pereira de Sousa, Irene; Hussain, Shah; Huck, Christian W; Bernkop-Schnürch, Andreas

    2016-04-01

    The aim of this study was to generate and characterize a chondroitin sulfate-cysteine conjugate (CS-cys) as a novel bioadhesive agent for intra-articular use. Mucoadhesive properties of synthesized CS-cys were investigated by rheological measurement of polymer-mucus mixture and rotating cylinder method, while bioadhesive features of CS-cys on porcine articular cartilage were evaluated via tensile studies. Thiolation was achieved by attachment of l-cysteine to CS via amide bond formation mediated by carbodiimide as a coupling reagent. The conjugate exhibited 421.17±35.14 μmol free thiol groups per gram polymer. The reduced CS-cys displayed 675.09±39.67 μmol free thiol groups per gram polymer after disulfide bonds reduction using tris(2-carboxyethyl)phosphine hydrochloride. The increase in dynamic viscosity of thiolated CS due to oxidative disulfide bond formation was demonstrated using capillary viscometer. The combination of CS-cys and mucus led to 4.57-fold increase in dynamic viscosity in comparison with mucus control. Furthermore, adhesion time to porcine mucosa of CS-cys-based test disk was enhanced by 2.48-fold compared to unmodified CS as measured by rotating cylinder method suggesting the interaction between thiomers and mucus gel layer via disulfide bonds formation. Tensile studies of thiolated CS on porcine articular cartilage showed 5.37- and 1.76-fold increase in the total work of adhesion and the maximum detachment force, respectively, in comparison with unmodified CS indicating bioadhesive features of CS-cys. Cytotoxicity of CS-cys was assessed in Caco-2 cells and rat primary articular chondrocytes using MTT and LDH release assay, thereby showing the safety of CS-cys at a concentration of 0.25% (w/v) in Caco-2 cells. Furthermore, 0.1% of CS-cys was found non-toxic to rat primary articular chondrocytes. According to these results, CS-cys provides improved bioadhesive properties that might be useful as an intra-articular agent for treatment of

  18. Possible nephotoxic interaction of lithium and metronidazole

    SciTech Connect

    Teicher, M.H.; Altesman, R.I.; Cole, J.O.; Schatzberg, A.F.

    1987-06-26

    Several classes of drugs can promote renal retention of lithium and, occasionally, can induce lithium intoxication. The antimicrobial agent metronidazole hydrochloride (Flagyl I.V.) was also implicated in producing such a reaction in one woman. The authors describe two patients who experienced toxic reactions to lithium following brief use of metronidazole. However, in these two patients, in contrast to the previous case, the degree of acute intoxication was less severe and treatment with metronidazole was completed without apparent suspicion, but persistent signs of renal damage later emerged.

  19. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis.

    PubMed

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-16

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection.

  20. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis

    PubMed Central

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-01

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection. PMID:25596288

  1. PNIPAM grafted surfaces through ATRP and RAFT polymerization: Chemistry and bioadhesion.

    PubMed

    Conzatti, G; Cavalie, S; Combes, C; Torrisani, J; Carrere, N; Tourrette, A

    2017-03-01

    Biomaterials surface design is critical for the control of materials and biological system interactions. Being regulated by a layer of molecular dimensions, bioadhesion could be effectively tailored by polymer surface grafting. Basically, this surface modification can be controlled by radical polymerization, which is a useful tool for this purpose. The aim of this review is to provide a comprehensive overview of the role of surface characteristics on bioadhesion properties. We place a particular focus on biomaterials functionalized with a brush surface, on presentation of grafting techniques for "grafting to" and "grafting from" strategies and on brush characterization methods. Since atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) polymerization are the most frequently used grafting techniques, their main characteristics will be explained. Through the example of poly(N-isopropylacrylamide) (PNIPAM) which is a widely used polymer allowing tuneable cell adhesion, smart surfaces involving PNIPAM will be presented with their main modern applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Design and evaluation of bioadhesive in-situ nasal gel of ketorolac tromethamine.

    PubMed

    Chelladurai, Sankar; Mishra, Madhusmita; Mishra, Brahmeshwar

    2008-11-01

    The present study was aimed at developing safe and effective bioadhesive gelling systems of ketorolac tromethamine, a potent non-narcotic analgesic with moderate anti-inflammatory activity for nasal systemic delivery. Chitosan and pectin based gelling systems were prepared with variables like polymer concentration and type. These systems were characterized in terms of their physical properties, in vitro bioadhesion, in vitro drug release and long-term stability. The anti-inflammatory activity and mucosal irritancy of selected gels were also evaluated in rats and these results were compared with per oral, intraperitoneal and nasal solution administration of ketorolac tromethamine. All the prepared formulations gelled immediately at the nasal mucosal pH and showed longer contact time. Addition of hydroxypropyl methylcellulose (HPMC) in both chitosan and pectin based gelling systems increased the viscosity and gel strength. All the formulated gels exhibited pseudoplastic rheology and diffusion-controlled drug release. The results from stability studies revealed that the prepared thermogels showed marginal decrease in viscosity but at the same time, no significant difference in drug content, and in vitro release characteristics were observed before and after accelerated studies. The developed gelling systems produced only mild to negligible irritant effect to nasal mucosae as compared to control group.

  3. Development of Bioadhesive Chitosan Superporous Hydrogel Composite Particles Based Intestinal Drug Delivery System

    PubMed Central

    Modhia, Ishan; Mehta, Anant; Patel, Rupal; Patel, Chhagan

    2013-01-01

    Bioadhesive superporous hydrogel composite (SPHC) particles were developed for an intestinal delivery of metoprolol succinate and characterized for density, porosity, swelling, morphology, and bioadhesion studies. Chitosan and HPMC were used as bioadhesive and release retardant polymers, respectively. A 32 full factorial design was applied to optimize the concentration of chitosan and HPMC. The drug loaded bioadhesive SPHC particles were filled in capsule, and the capsule was coated with cellulose acetate phthalate and evaluated for drug content, in vitro drug release, and stability studies. To ascertain the drug release kinetics, the drug release profiles were fitted for mathematical models. The prepared system remains bioadhesive up to eight hours in intestine and showed Hixson-Crowell release with anomalous nonfickian type of drug transport. The application of SPHC polymer particles as a biomaterial carrier opens a new insight into bioadhesive drug delivery system and could be a future platform for other molecules for intestinal delivery. PMID:23984380

  4. Nasal administration of an angiotensin antagonist in the rat model: effect of bioadhesive formulations on the distribution of drugs to the systemic and central nervous systems.

    PubMed

    Charlton, S T; Davis, S S; Illum, L

    2007-06-29

    The effect of bioadhesive formulations on the direct transport of an angiotensin antagonist drug ((14)C-GR138950) from the nasal cavity to the central nervous system was evaluated in a rat model. Three different bioadhesive polymer formulations (3% pectin LM-5, 1.0% pectin LM-12 and 0.5% chitosan G210) containing the drug were administered nasally to rats by inserting a dosing cannula 7mm into the nasal cavity after which the plasma and brain tissue levels were measured. It was found that the polymer formulations provided significantly higher plasma levels and significantly lower brain tissue levels of drug than a control, in the form of a simple drug solution. Changing the depth of insertion of the cannula from 7 to 15mm, in order to reach the olfactory region in the nasal cavity significantly decreased plasma levels and significantly increased brain tissue levels of drug for the two formulations studied (1.0% pectin LM-12 and a simple drug solution). There was no significant difference between the drug availability for the bioadhesive formulation and the control in the brain when the longer cannula was used for administration. It is suggested that the conventional rat model is not suitable for evaluation of the effects of bioadhesive formulations in nose-to-brain delivery.

  5. Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant Tuberculosis

    PubMed Central

    Carroll, Matthew W.; Jeon, Doosoo; Mountz, James M.; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E.; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C.; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y.; Dodd, Lori E.; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae

    2013-01-01

    Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens. PMID

  6. Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

    PubMed

    Carroll, Matthew W; Jeon, Doosoo; Mountz, James M; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y; Dodd, Lori E; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae; Barry, Clifton E; Cho, Sang-Nae

    2013-08-01

    Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

  7. Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Pathak, Meenakshi; Turner, Mark; Palmer, Cheryn; Coombes, Allan G A

    2014-09-01

    Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Electrochemical Determination of Metronidazole in Tablet Samples Using Carbon Paste Electrode

    PubMed Central

    Nikodimos, Yosef

    2016-01-01

    Cyclic voltammetric investigation of metronidazole at carbon paste electrode revealed an irreversible reduction peak centered at about −0.4 V. Observed peak potential shift with pH in the range 2.0 to 8.5 indicated the involvement of protons during the reduction of metronidazole, whereas the peak potential shift with scan rate in the range 10–250 mV/s confirmed the irreversibility of the reduction reaction. A better correlation coefficient for the dependence of peak current on the scan rate than on the square root of scan rate indicated an adsorption controlled kinetics. Under the optimized method and solution parameters, an excellent linearity between the reductive peak current and the concentration of metronidazole was observed in the concentration range 1.0 × 10−6 to 5.0 × 10−4 M with a correlation coefficient, method detection limit (based on s = 3σ), and limit of quantification of 0.999, 2.97 × 10−7 M and 9.91 × 10−7 M, respectively. Good recovery results for spiked metronidazole in tablet samples and selective determination of metronidazole in tablet formulations in the presence of selected potential interferents such as rabeprazole, omeprazole, and tinidazole confirmed the potential applicability of the developed method for the determination of metronidazole in real samples like pharmaceutical tablets. PMID:27119041

  9. Nanoscale engineering of extracellular matrix-mimetic bioadhesive surfaces and implants for tissue engineering.

    PubMed

    Shekaran, Asha; Garcia, Andres J

    2011-03-01

    The goal of tissue engineering is to restore tissue function using biomimetic scaffolds which direct desired cell fates such as attachment, proliferation and differentiation. Cell behavior in vivo is determined by a complex interaction of cells with extracellular biosignals, many of which exist on a nanoscale. Therefore, recent efforts in tissue engineering biomaterial development have focused on incorporating extracellular matrix- (ECM) derived peptides or proteins into biomaterials in order to mimic natural ECM. Concurrent advances in nanotechnology have also made it possible to manipulate protein and peptide presentation on surfaces on a nanoscale level. This review discusses protein and peptide nanopatterning techniques and examples of how nanoscale engineering of bioadhesive materials may enhance outcomes for regenerative medicine. Synergy between ECM-mimetic tissue engineering and nanotechnology fields can be found in three major strategies: (1) Mimicking nanoscale orientation of ECM peptide domains to maintain native bioactivity, (2) Presenting adhesive peptides at unnaturally high densities, and (3) Engineering multivalent ECM-derived peptide constructs. Combining bioadhesion and nanopatterning technologies to allow nanoscale control of adhesive motifs on the cell-material interface may result in exciting advances in tissue engineering. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine. 2010 Elsevier B.V. All rights reserved.

  10. Concentrations and in vivo antibacterial activity of spiramycin and metronidazole in patients with periodontitis treated with high-dose metronidazole and the spiramycin/metronidazole combination.

    PubMed

    Poulet, Pierre-Pascal; Duffaut, Danielle; Barthet, Pierre; Brumpt, Ivan

    2005-03-01

    Previous studies have shown that metronidazole, alone or in combination with spiramycin (250 mg/1 500 000 units, three times/day), is an effective treatment for active periodontitis, although the dose of metronidazole currently used (750 mg/day) could provide concentrations in gingival crevice fluid that are too low for the MICs of the involved pathogens. This study tested the in vivo antibacterial efficacy of the currently used metronidazole dose (as contained in the fixed spiramycin/metronidazole combination) in patients with an active periodontitis, and of a high dose (1500 mg/day) of metronidazole alone. We measured the MICs of spiramycin and metronidazole for the recovered pathogens and the gingival crevice fluid antibiotic concentrations of both antibiotics, and attempted to correlate them with bacterial eradication. The concentrations of metronidazole consistently exceeded the MICs for the pathogens isolated in the corresponding sites, even at the usual metronidazole (250 mg three times/day) dose. All the bacterial species were eradicated during treatment and at follow-up, although Fusobacterium spp. eradicated during treatment reappeared in a majority of the cases at follow-up, 30 days after treatment, in both groups. The results of antibiotic therapy with metronidazole or the spiramycin/metronidazole combination are consistent with their in vitro antibacterial activity and with the local antibiotic concentrations; they suggest that the currently used metronidazole dose (250 mg, three times/day) alone or as part of the spiramycin/metronidazole combination, could be sufficient for the treatment of active periodontitis.

  11. Delivery of Vaccines by Biodegradable Polymeric Microcapsules with Bioadhesion Properties.

    DTIC Science & Technology

    1997-05-01

    Urease in Acid Protection for the Gastric Colonizing Bacteria Helicobacter Pylori and Helicobacter Felis," Sp. Nov., Microb. Ecol. Health Dis., 4, 121...SUBJECT TERMS D!,W QL iD ’ 15. NUMBER OF PAGES 35 Oral vaccines, bioadhesives, poly(lactic-co-glycolic) acid 16. PRICE CODE mucosal immunoloqy 17. SECURITY...Introduction Microspheres and microcapsules made of poly (D,L-lactic-co-glycolic acid ) (PLGA) have been investigated as vaccine delivery systems [Eldridge

  12. [Extraction and application of Perna viridis foot protein as bioadhesive].

    PubMed

    Jiang, Zhen; Liu, Jiapeng; Jin, Lihua; Zhang, Qiqing

    2010-12-01

    Mussel adhesive proteins have attracted increasing interests for their potential use as environmentally friendly bioadhesives in medicine and aqueous conditions. In this study, surface coating analysis, quartz crystal microbalance (QCM), cell and bone tissue adhesion and cytotoxicity assay were used to study the properties of the Perna viridis foot proteins (Pvfp) extract as bioadhesive. The results of coating ability on various materials and QCM analysis revealed that Pvfp extract has comparable or superior adsorbtion ability to that of Cell-Tak (the naturally extracted MAP mixture from Mytilus edulis, and has been commercialized), and also, the cell adhesion ability of Pvfp extract was stronger than that of Cell-Tak and poly-L-lysine. No cytotoxicity was detected using human HeLa and 293T cells. Furthermore, broken bones of mouse could be stuck together by use of Pvfp extract. In bulk-scale adhesion tests, Pvfp extract showed much greater tensile strength than did fibrin glue for conglutinating poly (vinl chloride) sticks and for binding together pig's femur segments. These results suggested that Pvfp extract be an efficient cell and tissue adhesive in biotechnological application and it might be a potential bioadhesive in medical practice.

  13. Metronidazole for the treatment of vaginal infections.

    PubMed

    Sobel, Ryan; Sobel, Jack D

    2015-05-01

    Metronidazole , undoubtedly the most widely known and used member of the nitroimidazole drug class, remains not only first line therapy for bacterial vaginosis (BV) and trichomoniasis, but serves as drug of first choice. Available and used both orally and topically with high efficacy rates, especially for trichomoniasis, nevertheless numerous unanswered questions remain regarding mechanism of action. Given the extraordinary global frequency of vaginitis due to BV and trichomoniasis, especially the high recurrence rate observed in BV, it is timely to critically examine the therapeutic role of metronidazole in management decisions. Search methodology used PUBMED literature review. In spite of many years of successful use, multiple questions exist regarding optimal dose and duration of therapy especially in the management of BV. Antimicrobial drug resistance remains uncommon in spite of extensive use. The use of metronidazole for vaginitis is reviewed in this article together with challenges to improving its more effective administration. Currently metronidazole or the family of nitroimidazoles, represent the drugs of first choice for trichomonas vaginitis and first line therapy for BV. Drug resistance for both entities remains uncommon; however, in contrast to trichomoniasis where relapse is rare, high recurrence rates are common in women with BV. Metronidazole appears to allow persistence of vaginal microbiome microorganisms which translate into frequent relapses. In the absence of new therapeutic alternatives, strategies are being developed to enhance drug cure rates.

  14. Montmorillonite nanodevices for the colon metronidazole delivery.

    PubMed

    Calabrese, Ilaria; Cavallaro, Gennara; Scialabba, Cinzia; Licciardi, Mariano; Merli, Marcello; Sciascia, Luciana; Turco Liveri, Maria Liria

    2013-11-30

    The adsorption profiles of the antibiotic metronidazole (MNE) into the K10-montmorillonite (MMT-K10) clay and the subsequent release have been investigated as a function of pH and MNE/MMT-K10 ratio, in order to evaluate the potential of the MNE/MMT-K10 hybrids as controlled drug delivery system. The adsorption mechanism has been first elucidated by performing complementary equilibrium and kinetic studies and through the X-ray diffractometry (XRD) characterization of the obtained composite materials. The gathered results allowed us to propose a mechanism consisting of a multi-step pathway involving the neutral and the cationic form of the drug, which interact with different sites of the clay surfaces, i.e. the interlayer region and the faces of the lamella. In a second step the drug release kinetics has been studied under physiological pH mimicking conditions simulating the oral drug administration and delivery. For the sake of comparison the commercial formulation has also been employed for the release studies. The investigation of the release profiles and the comparison with the commercial formulation of the drug reveal that the new-tailor made formulation could be fruitful exploited for successfully prolonged the action of drug in the desired site. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young rats.

    PubMed

    Guillé, Beatriz E Perez; Alvarez, Fernando Villegas; Toledo López, Alejandra R; Bravo-Luna, Miguel A Jiménez; Soriano-Rosales, Rosa E; Lares-Asseff, Ismael; Arrellin, Gerardo; Guillé, Maria G Pérez

    2005-01-01

    Prophylactic and therapeutic management of portosystemic encephalopathies is based on protein restriction in the diet, and the use of lactulose and antibiotics such as metronidazole. These actions intend to reduce the main source of intestinal ammonia production and release into the systemic circulation. The aim of this study was to evaluate the medium-term effects of mesocaval shunt on the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis rats were divided into two groups. The first group was subjected to mesocaval shunt (MCS) and the other employed as a control. The following tests were carried out in both groups: metronidazole pharmacokinetics, determination of ALT, AST, albumin, urea and ammonium, liver weight and histomorphology. A loss in body and liver weight was registered in rats subjected to MCS. AST levels also increased compared to controls. Significant differences in almost all pharmacokinetic parameters were detected between MCS and control rats, especially in Kel, AUC and Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes without microstructural modification secondary to MCS were found. We suggest that individual drug-monitoring and pharmacokinetic analysis must be carried out in metronidazole medicated patients with modifications in portal circulation with or with out macro or micro liver structural alterations.

  16. Artifactual Depression of Serum Glutamic Oxaloacetic Transaminase by Metronidazole

    PubMed Central

    Rissing, J. Peter; Newman, Cheryl; Moore, William L.

    1978-01-01

    Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay. PMID:214030

  17. Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

    PubMed Central

    Mory, Francine; Carlier, Jean-Philippe; Alauzet, Corentine; Thouvenin, Maxime; Schuhmacher, Hélène; Lozniewski, Alain

    2005-01-01

    Metronidazole resistance among Prevotella spp. is rare. We report here the first case of bacteremia due to a high-level metronidazole-resistant Prevotella sp. responsible for treatment failure. PMID:16208024

  18. Plasma hydroxy-metronidazole/metronidazole ratio in hepatitis C virus-induced liver disease.

    PubMed

    Marchioretto, M A M; Ecclissato, C; da Silva, C M F; Cassiano, N M; Calafatti, S A; Mendonça, S; Ribeiro, M L; Bernasconi, G C R; Degger, M F; Piovesan, H; Pedrazzoli, J

    2005-03-01

    It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV) infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis), and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 +/- 0.0044 vs 0.0742 +/- 0.0232). Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 +/- 0.0032 vs 0.0438 +/- 0.0027 (moderate/severe chronic hepatitis) vs 0.0455 +/- 0.0026 (mild chronic hepatitis) and vs 0.0478 +/- 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals)). These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

  19. Putative metronidazole neurotoxicosis in a cat.

    PubMed

    Olson, E J; Morales, S C; McVey, A S; Hayden, D W

    2005-09-01

    A presumptive case of metronidazole toxicity in a 3.4-kg adult cat is described. The cat had been treated for suspected inflammatory bowel disease with an anti-inflammatory dose of prednisone and metronidazole (73.5-147 mg/kg PO q24h) for approximately 40 days prior to presentation. Clinical signs were primarily related to the central nervous system, including acute tetraparesis, unresponsiveness, tremors, and vocalization. The patient was euthanatized after 12 days of supportive care. Necropsy revealed no significant macroscopic lesions. Histologic evaluation revealed multifocal, fairly well-demarcated foci of necrosis in the brainstem, extending from the diencephalon to the medulla oblongata. To our knowledge, this is the first report to document histologic lesions associated with metronidazole administration in a cat.

  20. Formulation and evaluation of chitosan/polyethylene oxide nanofibers loaded with metronidazole for local infections.

    PubMed

    Zupančič, Špela; Potrč, Tanja; Baumgartner, Saša; Kocbek, Petra; Kristl, Julijana

    2016-12-01

    Nanofibers combined with an antimicrobial represent a powerful strategy for treatment of various infections. Local infections usually have a low fluid volume available for drug release, whereas pharmacopoeian dissolution tests include a much larger receptor volume. Therefore, the development of novel drug-release methods that more closely resemble the in-vivo conditions is necessary. We first developed novel biocompatible and biodegradable chitosan/polyethylene oxide nanofibers using environmentally friendly electrospinning of aqueous polymer solutions, with the inclusion of the antimicrobial metronidazole. Here, the focus is on the characterization of these nanofibers, which have high potential for bioadhesion and retention at the site of application. These can be used where prolonged retention of the delivery system at an infected target site is needed. Drug release was studied using three in-vitro methods: a dissolution apparatus (Apparatus 1 of the European Pharmacopoeia), vials, and a Franz diffusion cell. In contrast to other studies, here the Franz diffusion cell method was modified to introduce a small volume of medium with the nanofibers in the donor compartment, where the nanofibers swelled, eroded, and released the metronidazole, which then diffused into the receptor compartment. This set-up with nanofibers in a limited amount of medium released the drug more slowly compared to the other two in-vitro methods that included larger volumes of medium. These findings show that drug release from nanofibers strongly depends on the release method used. Therefore, in-vitro test methods should closely resemble the in-vivo conditions for more accurate prediction of drug release at a therapeutic site. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

    PubMed

    Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

    2016-10-01

    The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

  2. Mechanical and thermal studies of metronidazole crystals

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Jeyasudha, R.; Ramachandran, E.

    2013-10-01

    Single crystals of metronidazole have been synthesized natural evaporation method. The grown crystal has been confirmed using single crystal X-ray diffraction analysis. Mechanical behavior has been determined using Vickers hardness measurement. Work-hardening coefficient and Newtonian resistance pressure of the crystal have been estimated. Kinetic analysis of the thermogravimetric data has been carried out by using Coats-Redfern relation. Activation energy, frequency factor and order of reaction have been also calculated. The Arrhenius equation for metronidazole is k = 0.38 × 108 e-76.679/ RT mol-1 s-1. Thermodynamic parameters have been also determined.

  3. Nanostructured materials for ocular delivery: nanodesign for enhanced bioadhesion, transepithelial permeability and sustained delivery

    PubMed Central

    Kim, Jean; Schlesinger, Erica B; Desai, Tejal A

    2015-01-01

    Effective drug delivery to the eye is an ongoing challenge due to poor patient compliance coupled with numerous physiological barriers. Eye drops for the front of the eye and ocular injections for the back of the eye are the most prevalent delivery methods, both of which require relatively frequent administration and are burdensome to the patient. Novel drug delivery techniques stand to drastically improve safety, efficacy and patient compliance for ocular therapeutics. Remarkable advances in nanofabrication technologies make the application of nanostructured materials to ocular drug delivery possible. This article focuses on the use of nanostructured materials with nanoporosity or nanotopography for ocular delivery. Specifically, we discuss nanotopography for enhanced bioadhesion and permeation and nanoporous materials for controlled release drug delivery. As examples, application of polymeric nanostructures for greater transepithelial permeability, nanostructured microparticles for enhanced preocular retention time and nanoporous membranes for tuning drug release profile are covered. PMID:26652282

  4. Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment.

    PubMed

    da Silva, Marcio A C; Oliveira, Renata N; Mendonça, Roberta Helena; Lourenço, Talita G B; Colombo, Ana Paula V; Tanaka, Marcelo N; Tude, Elena M O; da Costa, Marysilvia F; Thiré, Rossana Mara S M

    2016-01-01

    Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3-hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3-hydroxybutyrate) membranes containing 0.5-2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick's law. Membranes were noncytotoxic. The amount of metronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the membranes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4. © 2015 Wiley Periodicals, Inc.

  5. [Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].

    PubMed

    Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C

    2009-12-01

    Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment.

  6. Development of Bioadhesive Transdermal Bupivacaine Gels for Enhanced Local Anesthetic Action

    PubMed Central

    Cho, Cheong-Weon; Kim, Deok-Bae; Shin, Sang-Chul

    2012-01-01

    Topical drug dosage forms such as ointments and creams can be easily removed through wetting, movement and contact. The new bioadhesive formulations with enhanced local anesthetic effects are needed for topical administration. The adhesive capacity of hydroxypropyl methylcellulose (HPMC) was determined by measuring the maximum detachment force and the adhesion work with an auto peeling tester. The release of drug from a HPMC gel was studied according to the drug concentration. Permeation study through the rat skin was performed at 37°C using phosphate buffer solution (pH = 7.4) as a receptor medium. To increase the skin permeation of bupivacaine from the HPMC gels, penetration enhancer such as the saturated and unsaturated fatty acids, the pyrrolidones, the propylene glycol derivatives, the glycerides, and the non-ionic surfactants were incorporated in the bupivacaine-HPMC gels. The local anesthetic effect of the formulated gel preparation was examined using a tail-flick analgesimeter. As the concentration of HPMC increased, the bioadhesive force and viscosity were increased. The rate of drug release was increased with increasing the drug concentration. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the most enhancing effects on drug permeation through the skin. In the rat tail flick test, the area under the efficacy curve of bupivacaine gel containing polyoxyethylene 2-oleyl ether and tetrahydrozoline showed a 2.36-fold increase in anesthetic activity compared to control gel without any additives. The bupivacaine gels containing both penetration enhancer and vasoconstrictor showed enhancement and prolonged efficacy compared to the control gel. To enhance the local anesthetic effects of bupivacaine, the transdermal bupivacaine gel formulation containing penetration enhancer and vasoconstrictor could be developed. PMID:24250466

  7. Metronidazole: newly recognized cause of autonomic neuropathy.

    PubMed

    Hobson-Webb, Lisa D; Roach, E Steve; Donofrio, Peter D

    2006-05-01

    Metronidazole is a commonly used antibiotic prescribed for the treatment of anaerobic and protozoal infections of the gastrointestinal and genitourinary tracts. It is associated with numerous neurologic complications, including peripheral neuropathy. Neuropathy is typically detected in patients on chronic therapy, although it has been documented in those taking large doses for acute infections. Numerous case reports have been published describing motor and sensory neuropathy, yet autonomic neuropathy has not been described with metronidazole use. A previously healthy 15-year-old girl presented with complaints of burning pain in her feet following a short course of metronidazole for vaginitis. She could obtain pain relief only by submerging her feet in ice water. Examination revealed cold and swollen lower extremities that became erythematous and very warm when removed from the ice water. Temperature perception was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were preserved. Nerve conduction studies demonstrated a peripheral neuropathy manifested by reduced sensory nerve and compound muscle action potentials. Reproducible sympathetic skin potential responses could not be obtained in the hand and foot, providing evidence of a concurrent autonomic neuropathy. A thorough evaluation revealed no other cause for her condition. Repeated nerve conduction studies and sympathetic skin potentials returned to normal over the course of 6 months, paralleling the patient's clinical improvement. Metronidazole is a potential cause of reversible autonomic neuropathy.

  8. Metronidazole-triazole conjugates: activity against Clostridium difficile and parasites.

    PubMed

    Jarrad, Angie M; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X; Kaeslin, Geraldine; Elliott, Alysha G; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A T; Cooper, Matthew A

    2015-08-28

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  9. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  10. Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends

    PubMed Central

    Siddam, Haritha; Kotla, Niranjan G.; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

    2016-01-01

    Introduction: Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Methods: Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. Results: The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. Conclusion: The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability. PMID:27051631

  11. Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends.

    PubMed

    Siddam, Haritha; Kotla, Niranjan G; Maddiboyina, Balaji; Singh, Sima; Sunnapu, Omprakash; Kumar, Anil; Sharma, Dinesh

    2016-01-01

    Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug. Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies. The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism. The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability.

  12. Nano-reservoir Bioadhesive Tablets Enhance Protein Drug Permeability Across the Small Intestine.

    PubMed

    Yin, Lifang; Wang, Yong; Wang, Cuifeng; Feng, Min

    2017-01-23

    Most therapeutic proteins are classified as class III drugs according to the Biopharmaceutical Classification System means that the low permeability across the intestinal epithelium is the rate-limited step for their oral absorption. Cationic chitosan nanoparticles have been found to open the tight junctions between epithelial cells. On the other hand, bioadhesive delivery devices could prolong the gastrointestinal residence time. In the present study, we developed a novel nano-reservoir bioadhesive tablets that combining the advantages of cationic nanoparticles and bioadhesive delivery devices anticipated achieving effective transport of sufficient protein drugs across the intestinal epithelium. The nano-reservoir in bioadhesive tablets was composed of chitosan nanoparticles (CS-NPs) loading a model protein drug bovine serum albumin (BSA). The formula of bioadhesive tablets was optimized by using rotatable central composite design and response surface methodology. The nano-reservoir, BSA-loaded CS-NPs, had an average particle diameter of 312.5 ± 12.89 nm and zeta-potential value of 26.76 ± 3.56 mV. Carboxymethyl chitosan added to the formula significantly ameliorated the tight junction damage of the Caco-2 cell monolayer induced by CS-NPs, meanwhile maintained the high transport efficiency of BSA. Permeability study exhibited that these nano-reservoir bioadhesive tablets combining the advantages of cationic nanoparticles and bioadhesive tablets significantly enhanced BSA transport through rabbit small intestine in comparison with either conventional bioadhesive tablets or CS-NPs. Therefore, these nano-reservoir bioadhesive tablets provided a great potential dosage form design for the oral delivery of protein drugs.

  13. Propionylcarnitine excretion is not affected by metronidazole administration to patients with disorders of propionate metabolism.

    PubMed

    Burns, S P; Iles, R A; Saudubray, J M; Chalmers, R A

    1996-01-01

    Propionylcarnitine (PC) excretion has been measured during a clinical trial of metronidazole therapy in two patients with propionic acidaemia and two patients with methylmalonic aciduria. All patients were in good metabolic control and were receiving L-carnitine. While total propionate excretion was reduced by up to 40% in all four patients during metronidazole therapy, the excretion of propionylcarnitine remained largely unchanged. PC comprised up to 80% of total propionate excretion in patients with propionic acidaemia. These results suggest an extra-hepatic source and/or differing compartmentation for PC formation from those for the production of other metabolites of propionyl-CoA.

  14. Cumulative irritation potential of metronidazole gel compared to azelaic acid gel after repeated applications to healthy skin.

    PubMed

    Ziel, Kristin; Yelverton, Christopher B; Balkrishnan, Rajesh; Feldman, Steven R

    2005-01-01

    Metronidazole 0.75% gel and azelaic acid 15% gel are commonly used to treat rosacea. Irritation is a common side effect. To assess the cumulative irritation potential of metronidazole 0.75% gel and azelaic acid 15% gel. Metronidazole 0.75% gel, azelaic acid 15% gel, and a white petrolatum negative control were applied under occlusive conditions to the upper back of a total of 33 healthy subjects. There were twelve 24-hour applications (4 times a week) and three 72-hour applications on weekends during a 3-week period. Skin reactions (erythema score +/- other local reaction) were assessed within 15 to 30 minutes of removal of the products. The mean cumulative irritancy index of metronidazole 0.75% gel was significantly lower than that of azelaic acid 15% gel and not significantly higher than the negative control product. There was increasing cumulative irritancy with azelaic acid; no cumulative irritancy was seen for either metronidazole or white petrolatum. Metronidazole 0.75% gel is less irritating in sustained use than azelaic acid 15% gel.

  15. Facile preparation of robust microcapsules by manipulating metal-coordination interaction between biomineral layer and bioadhesive layer.

    PubMed

    Zhang, Lei; Shi, Jiafu; Jiang, Zhongyi; Jiang, Yanjun; Meng, Ruijie; Zhu, Yuanyuan; Liang, Yanpeng; Zheng, Yang

    2011-02-01

    A novel approach combining biomimetic mineralization and bioadhesion is proposed to prepare robust and versatile organic-inorganic hybrid microcapsules. More specifically, these microcapsules are fabricated by sequential deposition of inorganic layer and organic layer on the surface of CaCO(3) microparticles, followed by the dissolution of CaCO(3) microparticles using EDTA. During the preparation process, protamine induces the hydrolysis and condensation of titania or silica precursor to form the inorganic layer or the biomineral layer. The organic layer or bioadhesive layer was formed through the rapid, spontaneous oxidative polymerization of dopamine into polydopamine (PDA) on the surface of the biomineral layer. There exist multiple interactions between the inorganic layer and the organic layer. Thus, the as-prepared organic-inorganic hybrid microcapsules acquire much higher mechanical stability and surface reactivity than pure titania or pure silica microcapsules. Furthermore, protamine/titania/polydopamine hybrid microcapsules display superior mechanical stability to protamine/silica/polydopamine hybrid microcapsules because of the formation of Ti(IV)-catechol coordination complex between the biomineral layer and the bioadhesive layer. As an example of application, three enzymes are respectively immobilized through physical encapsulation in the lumen, in situ entrapment within the wall and chemical attachment on the out surface of the hybrid microcapsules. The as-constructed multienzyme system displays higher catalytic activity and operational stability. Hopefully, the approach developed in this study will evolve as a generic platform for facile and controllable preparation of organic-inorganic hybrid materials with different compositions and shapes for a variety of applications in catalysis, sensor, drug/gene delivery.

  16. Preparation and evaluation of topical microemulsion system containing metronidazole for remission in rosacea.

    PubMed

    Tirnaksiz, Figen; Kayiş, Ayşegül; Çelebi, Nevin; Adişen, Esra; Erel, Arzu

    2012-01-01

    The aim of this study was to prepare a topical water-in-oil type microemulsion containing metronidazole and to compare its effectiveness with a commercial gel product in the treatment of rosacea. A pseudo-ternary phase diagram (K(m)=2:1) was constructed using lecithin/butanol/isopropyl myristate/water. The microemulsion was chosen from the microemulsion region in the phase diagram. The formulation was a water-in-oil type microemulsion (droplet size: 11.6 nm, viscosity: 457.3 mPa·s, conductivity: 1.5 µs/cm, turbidity: 6.89 NTU) and the addition of the metronidazole did not alter the properties of the system. The release experiment showed that the release rate of metronidazole from the commercial gel product was higher than that of the microemulsion. Stability experiments showed that the metronidazole microemulsion remained stable for at least 6 months; none of the characteristic properties of the microemulsion had changed, the system retained its clarity and there was no sign that crystallization of metronidazole has occurred. Microemulsion was compared to a gel product in a randomized, double-blind, baseline-controlled, split-face clinical trial for the treatment of patients. After the 6-week treatment period there was a statistically significant difference in reduction of the main symptoms of rosacea. Of the patients treated with the microemulsion, 17% experienced complete relief from inflammatory lesions, and 50% from erythema. The microemulsion resulted in complete relief in 38% of the patients with telangiectasia while the commercial product did not provide any relief of telangiectasia symptoms. In conclusion, the microemulsion containing metronidazole was found to be more effective in reducing the symptoms of rosacea compared to the commercial gel product.

  17. Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities.

    PubMed Central

    Müller, M; Gorrell, T E

    1983-01-01

    Three Trichomonas vaginalis isolates with low in vivo susceptibilities to metronidazole (95% curative dose, greater than 3 X 100 mg kg-1 in subcutaneous infections in mice) were compared with strain ATCC 30001 and with four isolates exhibiting high in vivo susceptibilities (95% curative dose, less than 3 X 15 mg kg-1). Activity of pyruvate:ferredoxin oxidoreductase, anaerobic fermentation, and anaerobic intracellular accumulation of [14C]metronidazole label showed no significant isolate-dependent differences which could be correlated with drug susceptibility. The results suggest that processes providing electrons for metronidazole activation are not defective in the resistant strains. Aerobiosis, known to inhibit the antimicrobial action of metronidazole, inhibited accumulation of label more strongly in resistant isolates than in susceptible ones. No differences were detected, however, between resistant and susceptible isolates in respiration, aerobic fermentation, and the specific activity of NADH and NADPH oxidases, the main terminal oxidases of T. vaginalis. These findings suggest that the production of electrons is not diminished under aerobic conditions. The inhibitory effect of aerobic conditions on metronidazole activation, possibly due to competition for the electrons, is markedly enhanced in the resistant isolates compared to the susceptible ones. The mechanism of this effect, however, remains unknown. PMID:6607028

  18. Preparation and evaluation of glyceryl monooleate-coated hollow-bioadhesive microspheres for gastroretentive drug delivery.

    PubMed

    Liu, Yuanfen; Zhang, Jianjun; Gao, Yuan; Zhu, Jiabi

    2011-07-15

    The purpose of this study was to produce hollow and bioadhesive microspheres to lengthen drug retention time in the stomach. In these microspheres, ethylcellulose was used as the matrix, Eudragit EPO was employed to modulate the release rate, and glyceryl monooleate (GMO) was the bioadhesive polymer in situ. The morphological characteristics of the microspheres were defined using scanning electron microscopy. The in vitro release test showed that the release rate of drug from the microspheres was pH-dependent, and was not influenced by the GMO coating film. The prepared microspheres demonstrated strong mucoadhesive properties with good buoyancy both in vitro and in vivo. Pharmacokinetic analysis indicated that the elimination half-life time of the hollow-bioadhesive microspheres was prolonged, and that the elimination rate was decreased. In conclusion, the hollow-bioadhesive synergic drug delivery system may be advantageous in the treatment of stomach diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Injectable Citrate-Based Mussel-Inspired Tissue Bioadhesives With High Wet Strength for Sutureless Wound Closure

    PubMed Central

    Mehdizadeh, M. Reza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian

    2012-01-01

    The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5–8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long × 0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. PMID:22902057

  20. Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure.

    PubMed

    Mehdizadeh, Mohammadreza; Weng, Hong; Gyawali, Dipendra; Tang, Liping; Yang, Jian

    2012-11-01

    The existing surgical adhesives are not ideal for wet tissue adhesion required in many surgeries such as those for internal organs. Developing surgical adhesives with strong wet tissue adhesion, controlled degradability and mechanical properties, and excellent biocompatibility has been a significant challenge. Herein, learning from nature, we report a one-step synthesis of a family of injectable citrate-based mussel-inspired bioadhesives (iCMBAs) for surgical use. Within the formulations investigated, iCMBAs showed 2.5-8.0 folds stronger wet tissue adhesion strength over the clinically used fibrin glue, demonstrated controlled degradability and tissue-like elastomeric mechanical properties, and exhibited excellent cyto/tissue-compatibility both in vitro and in vivo. iCMBAs were able to stop bleeding instantly and suturelessly, and close wounds (2 cm long×0.5 cm deep) created on the back of Sprague-Dawley rats, which is impossible when using existing gold standard, fibrin glue, due to its weak wet tissue adhesion strength. Equally important, the new bioadhesives facilitate wound healing, and are completely degraded and absorbed without eliciting significant inflammatory response. Our results support that iCMBA technology is highly translational and could have broad impact on surgeries where surgical tissue adhesives, sealants, and hemostatic agents are used. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Interaction of metronidazole with DNA repair mutants of Escherichia coli.

    PubMed Central

    Yeung, T C; Beaulieu, B B; McLafferty, M A; Goldman, P

    1984-01-01

    It has been proposed that one of metronidazole's partially reduced intermediates interacts either with DNA to exert a bactericidal effect or with water to form acetamide. To test this hypothesis we have examined the effect of metronidazole on several mutants of Escherichia coli that are defective in DNA repair. UV-susceptible RecA- and UvrB- point mutants have an increased susceptibility to metronidazole as manifested by both a decreased minimal inhibitory concentration and a greater bactericidal response to metronidazole in resting cultures. By these criteria, however, we find that UvrB- deletion mutants, which lack the ability to reduce nitrate and chlorate, are no more susceptible to metronidazole than is the wild type. We find, however, that these deletion mutants also lack the ability to reduce metronidazole and thus possibly to form its reactive species. When metronidazole's bactericidal effect is expressed in terms of the concurrent accumulation of acetamide derived from metronidazole, then all RecA- and UvrB- mutants are killed more efficiently than their wild types. The data are consistent, therefore, with metronidazole's lethal effect being mediated by a partially reduced intermediate on the metabolic pathway between metronidazole and acetamide. Defects in other aspects of the DNA repair system do not confer this increased susceptibility to the proposed intermediate. A Tag- mutant, for example, which is defective in 3-methyl-adenine-DNA glycosylase, does not have this increased susceptibility to the presumed precursor of acetamide. Thus, these results provide further support for the hypothesis that the bactericidal effect of metronidazole is mediated by a partially reduced intermediate in the metabolic conversion of metronidazole to acetamide and suggest that this intermediate interacts with DNA to produce a lesion similar to that caused by UV light. PMID:6367636

  2. Recent developments in the use of bioadhesive systems for delivery of drugs to the oral cavity.

    PubMed

    Smart, John D

    2004-01-01

    The delivery of therapeutic agents to, or via, the oral cavity is limited by the efficient removal mechanisms that exist in this area. Bioadhesive formulations have been developed to allow prolonged localized therapy and enhanced systemic delivery. The oral mucosa however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for "biopharmaceutical" products arising from the recent innovations in genomics and proteomics. Bioadhesive polymers are typically hydrophilic macromolecules containing numerous hydrogen-bonding groups. Second-generation bioadhesives include modified or new polymers that allow enhanced adhesion and/or drug delivery, along with site-specific ligands such as lectins. Over the last 20 years, a range of bioadhesive formulations have been developed for the oral cavity, but only comparatively few have found their way onto the market. This review will consider some recent developments in the use of bioadhesive buccal systems, notably the development of new polymers, advanced delivery systems, and the exploitation of the multifunctional properties of some bioadhesives.

  3. Open volume in bioadhesive detected by positron annihilation lifetime spectroscopy.

    PubMed

    Rätzke, Klaus; Wiegemann, Maja; Shaikh, Muhammad Qasim; Harms, Stephan; Adelung, Rainer; Egger, Werner; Sperr, Peter

    2010-07-01

    Barnacles attach to a wide variety of surfaces underwater and show substrate-specific adhesion mechanisms. Investigating and understanding these mechanisms is a key for developing new technical adhesives. We expected open volume (porosity) at the sub-nanometre scale to occur in barnacle adhesive. With positron annihilation lifetime spectroscopy (PALS) it is possible to detect porosity at the nanometre scale by determining the lifetime of positrons. This method has not been applied to bioadhesives so far. We showed that PALS is a suitable technique for the investigation of the barnacle base and its adhesive with respect to open volume. The results were interpreted using a standard model adapted from polymers. We thereby estimated pore sizes of 0.5 nm.

  4. Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer

    PubMed Central

    Diaz-Sanchez, Rosa-Maria; Pachón-Ibáñez, Jerónimo; Marín-Conde, Fátima; Rodríguez-Caballero, Ángela; Gutierrez-Perez, Jose-Luis

    2015-01-01

    Background To evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. Material and Methods In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. Results After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Conclusions Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn’t contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy. Key words: Chlorhexidine, mucositis, head and neck cancer. PMID:25662553

  5. Double-blind, randomized pilot study of bioadhesive chlorhexidine gel in the prevention and treatment of mucositis induced by chemoradiotherapy of head and neck cancer.

    PubMed

    Diaz-Sanchez, Rosa-Maria; Pachón-Ibáñez, Jerónimo; Marín-Conde, Fátima; Rodríguez-Caballero, Ángela; Gutierrez-Perez, Jose-Luis; Torres-Lagares, Daniel

    2015-05-01

    to evaluate, in an initial way, the effectiveness of bioadhesive chlorhexidine gel 0.2% versus placebo as a preventive and therapeutic intervention of oral mucositis induced by radiation therapy and chemotherapy in patients diagnosed with head and neck cancer treated with chemoradiotherapy. In this pilot study, 7 patients (range of age: 18- 65), having histological documented diagnosis of squamous carcinoma on the head and neck region in stage III and IV, and receiving combined radiation treatment and chemotherapy (cisplatin 100 mg/m2 IV on days 1, 22, and 43 of irradiation) were studied. Simultaneously, a topical application was performed with bioadhesive chlorhexidine gel 0.2% in the study group, and the placebo gel for the control group in 5 applications per day, from the time of initiation of cancer treatment to 2 weeks after completion of chemo-radiotherapy treatment (11 weeks of follow-up). The gradation of mucositis, pain, analgesic consumption, infectious complications, and treatment tolerance was measured. After 7 patients completed the protocol, any differences were observed between groups in an interval analysis. Mucositis, pain, and tolerance was similar in both groups. Our results must be interpreted with caution due to the reduced sample size, but the use of bioadhesive chlorhexidine gel 0.2% didn't contribute clinical improvement to the oral mucositis induced by radiation therapy and chemotherapy.

  6. Preparation and characterization of glycoprotein-resistant starch complex as a coating material for oral bioadhesive microparticles for colon-targeted polypeptide delivery.

    PubMed

    Situ, Wenbei; Li, Xiaoxi; Liu, Jia; Chen, Ling

    2015-04-29

    For effective oral delivery of polypeptide or protein and enhancement their oral bioavailability, a new resistant starch-glycoprotein complex bioadhesive carrier and an oral colon-targeted bioadhesive delivery microparticle system were developed. A glycoprotein, concanavalin A (Con A), was successfully conjugated to the molecules of resistant starch acetate (RSA), leading to the formation of resistant starch-glycoprotein complex. This Con A-conjugated RSA film as a coating material showed an excellent controlled-release property. In streptozotocin (STZ)-induced type II diabetic rats, the insulin-loaded microparticles coated with this Con A-conjugated RSA film exhibited good hypoglycemic response for keeping the plasma glucose level within the normal range for totally 44-52 h after oral administration with different insulin dosages. Oral glucose tolerance tests indicated that successive oral administration of these colon-targeted bioadhesive microparticles with insulin at a level of 50 IU/kg could achieve a hypoglycemic effect similar to that by injection of insulin at 35 IU/kg. Therefore, the potential of this new Con A-conjugated RSA film-coated microparticle system has been demonstrated to be capable of improving the oral bioavailability of bioactive proteins and peptides.

  7. 78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... Recommendations for Metronidazole Vaginal Gel; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Bioequivalence Recommendations for Metronidazole Vaginal Gel.'' The... abbreviated new drug applications (ANDAs) for metronidazole vaginal gel. DATES: Although you can comment on...

  8. Mussel-mimetic, bioadhesive polymers from plant-derived materials.

    PubMed

    Hiraishi, Noriko; Kaneko, Daisaku; Taira, Shu; Wang, Siqian; Otsuki, Masayuki; Tagami, Junji

    2015-02-01

    Mussel-mimetic, bioadhesive polymers are synthesized from plant-derived sources. The strong adhesive action is caused by interactions between the catechol groups at the end of the polymer terminal chains and the substrate surface. Here, we present a preliminary study of the adhesion properties and a discussion of the adhesion mechanism. Two bioadhesive polymers were synthesized from natural plant-derived monomers by the transesterification of: (a) caffeic acid (3,4-dihydroxycinnamic acid; DHCA) and p-coumaric acid (4-hydroxycinnamic acid; 4HCA) to produce poly(DHCA-co-4HCA); and (b) 4-dihydroxyhydrocinnamic acid (DHHCA) and 3-(3-hydroxyphenyl) propionic acid (3HPPA) to produce poly(DHHCA-co-3HPPA). Thermoplastic poly(DHCA-co-4HCA) or poly(DHHCA-co-3HPPA) was placed between glass, carbon, steel, or bovine dentin substrates, and a lap shear adhesion test was conducted to compare them using conventional cyanoacrylate glue and epoxy resin. The greatest adhesion for all tested substrates was exhibited by poly(DHHCA-co-3HPPA), followed by epoxy resin adhesive, poly(DHCA-co-4HCA), and cyanoacrylate adhesive. The adhesive strength of poly(DHHCA-co-3HPPA) was greater than 25.6 MPa for glass, 29.6 MPa for carbon, 15.7 MPa for steel, and 16.3 MPA for bovine dentin. The adhesion of poly(DHHCA-co-3HPPA) might be the strongest reported for a mussel-mimic adhesive system, and could be a feasible alternative to petroleum adhesives. © 2013 Wiley Publishing Asia Pty Ltd.

  9. Uptake of metronidazole in Artemia at different developmental life stages.

    PubMed

    Rodriguez, Loretta; Livengood, Elisa J; Miles, Richard D; Chapman, Frank A

    2011-06-01

    The purpose of this study was to examine the capacity of live brine shrimp Artemia spp. to accumulate metronidazole at different developmental life stages. Metronidazole is used in fish as an antiparasitic medication. An effective drug delivery method is to enrich the Artemia with metronidazole and offer them as live feed to the infected fish, usually ornamental species and other small fishes. Artemia cysts were hatched and then soaked in a metronidazole solution (0.05%) at instars 1-3 of larval development. Our findings indicated that Artemia were able to accumulate metronidazole at levels considered therapeutic to other animals and humans (25-100 mg/kg). However, the levels varied depending on the stage of larval development. Artemia accumulated the highest levels of metronidazole (137-143 mg/kg) when they started filter feeding (instar 2), whereas newly hatched Artemia (instar 1) contained the lowest level (85 mg/kg). Based on this study and a review of the literature, a new protocol recommended for enriching Artemia with metronidazole consists of soaking the Artemia in a 0.05% metronidazole solution for 3 h at room temperature. Because metronidazole is relatively insoluble in water, it must first be dissolved in warm water with continuous stirring.

  10. Bioadhesion to model thermally responsive surfaces

    NASA Astrophysics Data System (ADS)

    Andrzejewski, Brett Paul

    contrast possessed no adhesion to the pure component C11EG6OH SAM at both temperatures examined, 25 and 40°C. The protein adhesion data to the mixed SAM also supports the hypothesis that the mixed SAM displays a non-fouling molecular conformation at 25°C whereas it displays a dominantly fouling molecular conformation at 40°C. Advancing contact angles obtained through tensiometry were used to find the surface free energy of the mixed SAM before and after the thermal response using the van Oss-Good-Chaudhury method. The surface tension values obtained, 42 and 38 mN/m for 22 and 40°C, respectively, are not dissimilar enough with regard to error to make conclusions. In a similar manner, the surface free energy of another mixed SAM composed of alkyl and trimethylamine thiolates was also calculated. PNIPAAm brushes grown on a silicon substrate by atom-transfer radical polymerization (ATRP) were imaged by AFM and characterized by XPS. The height of the resulting brushes could be controlled from ˜5 to 55 nm by reaction time. A thermal response was observed for polymer brushes with a length greater than 20 nm. For polymer brush lengths greater than 20 nm, the static contact angle at 22°C was 35° and varied from 60 to 80° at 40°C. The thermal response was also observed using the captive bubble method. Force-distance curves of the PNIPAAm brushes were taken with an unmodified silicon nitride AFM cantilever at incremental temperature steps. At room temperature the force-distance data was fit to the Alexander-de Gennes model resulting in a hydrated polymer length of 235 nm. The Young's modulus was calculated using the Hertz model and changed from ˜80 MPa at 26°C to ˜350 MPa at 40°C. The solvent condition of the Alexander-de Gennes model was set to the case of good solvent and showed close match to the force-distance data at 26°C. The match was not as close when the solvent condition was set to theta solvent condition and compared to the force-distance data at 40

  11. Risk of Clostridium difficile infection in intensive care unit patients with sepsis exposed to metronidazole.

    PubMed

    Sabbah, Mohamad A; Schorr, Christa; Czosnowski, Quinn A; Hunter, Krystal; Torjman, Marc C; Fraimow, Henry S; Zanotti, Sergio; Tsigrelis, Constantine

    2015-04-01

    Antimicrobial agents used to treat Clostridium difficile infection (CDI), such as metronidazole and vancomycin, have been used during antibiotic treatment of other infections to try to prevent the development of CDI. We evaluated the hypothesis that intensive care unit (ICU) patients who receive metronidazole as part of an antibiotic treatment regimen for sepsis have a lower risk of subsequently developing CDI. This was a nested case-control study in a cohort of ICU patients who received antibiotic therapy for sepsis. A total of 10 012 patients aged ≥ 18 years were admitted to the Cooper University Hospital medical/surgical ICU from 1/1/2003 to 12/31/2008. After applying inclusion criteria including having received antibiotic therapy for sepsis and subsequently having developed CDI, 67 cases were identified. The cases were matched for age, gender, date of ICU admission, and hospital length of stay to 67 controls that also received antibiotic therapy for sepsis but did not subsequently develop CDI. In the multivariate analysis, there was no association between metronidazole exposure and the risk of CDI (odds ratio (OR) = 0.57; p = 0.23). The only significant associations on multivariate analysis were antifungal therapy (OR = 0.30; p = 0.02) and aminoglycoside and/or colistin therapy (OR = 0.17; p = 0.02). No association was found between metronidazole use and subsequent CDI in ICU patients who received antibiotic therapy for sepsis.

  12. Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation.

    PubMed

    Gómez-Arroyo, Sandra; Melchor-Castro, Sara; Villalobos-Pietrini, Rafael; Camargo, Estela Meléndez; Salgado-Zamora, Héctor; Campos Aldrete, Maria Elena

    2004-06-01

    Metronidazole (MTZ) and other nitroimidazole derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. However, the need for new derivatives with similar therapeutic activity but lower toxicity to human beings prevails. On this purpose, three metronidazole analogues were synthesized, namely: 1-(p-methylphenacyl)-2-methyl-4-nitro imidazole (CPMe), 1-(p-methoxyphenacyl)-2-methyl-4-nitroimidazole (CPMeO), and 1-(p-fluorphenacyl)-2-methyl-4-nitroimidazole (CPF), which at low concentrations (0.5-2 microg/ml) showed a higher activity against Entamoeba histolytica than MTZ (3-6 microg/ml). The aim of this work was to investigate the cytogenetic effect of the three MTZ analogues on human lymphocyte cultures with and without metabolic activation in vitro, using the sister chromatid exchange test (SCE), comparatively with MTZ. The effect of the compounds on the cell proliferation kinetics (CPK) measured by the replication index (RI) and the cytotoxic effect in the mitotic index (MI) was evaluated as well. The SCE frequencies with and without S9 metabolic activation in treated and control lymphocytes showed no significant statistical differences. However when metabolic activation was involved a significant increase in the amount of third division metaphases provoked the CPK increased significantly with all the tested compounds. The RI showed similar behaviour, except for compound CPF.

  13. The impact of AT1002 on the delivery of ritonavir in the presence of bioadhesive polymer, carrageenan.

    PubMed

    Song, Keon-Hyoung; Eddington, Natalie D

    2012-05-01

    New insights into the modification of the tight junctions theoretically offer the opportunity to regulate the diffusion barrier and then make it possible to investigate a permeation enhancer of low-bioavailability therapeutic agents. AT1002, a minimum biologically active fragment of zonula occludens toxin which reversibly opens intercellular tight junctions after binding to the Zonulin receptor, increased the transport of various molecular weight markers or low-bioavailability agents. The objective of this study was continuously to evaluate the permeation-enhancing ability of AT1002 in the presence of the bioadhesive agent, carrageenan after intranasal administration of the antiretroviral drug, ritonavir, and the permeation enhancement ratio compared with the previous results. The permeation-enhancing effect of AT1002 was significantly promoted by the bioadhesive agent, carrageenan. The administration of ritonavir with AT1002 and carrageenan resulted in a 2.55-fold increase in AUC(0-240min) and a 2.48-fold increase in C(max) compared with the control group. However, AT1002 in the absence of carrageenan did not produce a statistic enhancement in the absorption of ritonavir. Hence, AT1002 together with the addition of carrageenan may open a new approach of research in the tight junction modulated permeation enhancer, and allow the development of the mucosal drug delivery of therapeutic agents.

  14. Use of a chondroitin sulfate bioadhesive to enhance integration of bioglass particles for repairing critical-size bone defects.

    PubMed

    Yang, Shuqing; Guo, Qiongyu; Shores, Lucas S; Aly, Ahmed; Ramakrishnan, Meera; Kim, Ga Hye; Lu, Qiaozhi; Su, Lixin; Elisseeff, Jennifer H

    2015-01-01

    Replacement of autogenous or allograft bones by artificial graft materials represents a growing area of interest in current bone repair strategies. Bioactive ceramics in particulate form, such as Bioglass (BG) 45S5, stimulate bone mineralization comparable to autologous bone grafts, but have potential issues of particle migration and inflammation. The aim of this study was to employ a chondroitin sulfate- (CS-) based bioadhesive to improve integration of the bioglass (NovaBone Putty) to prevent particle migration and promote bone regeneration. This BG-CS composite can encapsulate bone marrow (BM) to form a mechanically stable construct, BG-CS-BM. Rheological characterization confirmed the formation of CS-BM hydrogel by reacting the CS-based bioadhesive with the BM. Compared to the bioglass, the BG-CS-BM composite demonstrated a superior capacity to maintain construct integrity under both aqueous and turbulent environments in vitro. After implantation for 4 weeks in a critical-size distal femoral bone defect in a rabbit model, there was significantly greater bone growth in BG-CS-BM as compared to bioglass-only and the empty control. Unlike BG-CS-BM, BG-CS recruited BM in situ from the bone defect. BG-CS demonstrated a similar effect in bone formation but at a comparatively slower rate than BG-CS-BM over 6-weeks' implantation.

  15. Effect of Plasma Pretreatments on the Bio-adhesive Functionalized by Biomimetic Catechol Groups to Human Dentin

    NASA Astrophysics Data System (ADS)

    Lee, Sangbae; Kim, Kwangmahn; Kim, Kyoungnam

    2012-10-01

    Plasma pretreatments have been introduced for modifying the surface chemistry of biomaterials. In an effort to improve the strength of the human dentin/bio-adhesive joint, oxygen plasma pretreatments to the bio-adhesive were investigated. Plasma treatments were carried out using custom-built and low pressure. Dentin were treated with plasma and used to prepare lap shear tests. Bio-adhesives were prepared synthesizing dopamine methacrylamide (DMA) monomer. DMA were copolymerized with 2-methoxyethylacrylate (MEA) by free radical polymerization. Proton nuclear magnetic resonance (^1H-NMR) and Gel permeation chromatography (GPC) analysis on samples of synthesized p(DMA-co-MEA) was performed to confirm that the resulting materials had the desired chemical structure. The effects of plasma pretreatments on surface chemistry were studied using Fourier transform infrared analysis (FTIR), and contact angle measurements. Oxygen plasma pretreatments enhanced adhesive strength by oxidizing of the catechol residue and creating a cross-linking as compared with control group. Furthermore plasma pretreatments lead to increase hydrophilicity of copolymers. Prospectively, the great potential of advanced technology in creation of the ``Plasma pretreatment to the DOPA adhesives'' would lead to the development of versatile method for coating to medial devices as well as dentin bonding.

  16. Cervicovaginal bacterial count and failure of metronidazole therapy for bacterial vaginosis.

    PubMed

    Luchiari, Heloise R; Ferreira, Carolina S T; Golim, Márjorie A; Silva, Márcia G; Marconi, Camila

    2016-03-01

    To evaluate whether total bacterial count in cervicovaginal fluid is associated with failure of metronidazole therapy for bacterial vaginosis. In a cross-sectional study, women attending a primary health center in Botucatu, São Paulo, Brazil, for routine cervical screening between September 2012 and October 2013 were enrolled. Women who tested positive for bacterial vaginosis (Nugent classification) were offered oral metronidazole. Women who completed metronidazole treatment and an equal number of control women with normal vaginal flora at initial screening were included in analyses of total bacterial count, assessed by flow cytometry of cervicovaginal fluid samples. Of 287 women who enrolled, 49 were excluded because they tested positive for trichomoniasis, chlamydial endocervicitis, gonorrhea, or candidiasis. Among the remaining 238, 85 (35.7%) had bacterial vaginosis. Among 36 women evaluated at follow-up, 23 (63.9%) had successfully restored lactobacilli-dominant flora, 12 (33.3%) had persistent bacterial vaginosis, and 1 (2.8%) had vaginal candidiasis (excluded from flow cytometry). Total bacterial count did not differ between 35 women with bacterial vaginosis and 35 with normal vaginal flora (P=0.62). Total bacterial count did not differ at enrollment between women who went on to have persistent bacterial vaginosis and those who had successful treatment (P=0.78). Failure of oral metronidazole therapy for bacterial vaginosis was not associated with total bacterial count in cervicovaginal fluid. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Comparison of local metronidazole and a local antiseptic in the treatment of bacterial vaginosis.

    PubMed

    Novakov Mikic, Aleksandra; Budakov, Dragan

    2010-07-01

    Bacterial vaginosis (BV) is characterized by a mixed flora of pathogenic anaerobic bacteria and associated with risks of pathologic conditions. In the present study, therapy with a local antiseptic spray (octenidine hydrochloride/phenoxyethanol, OHP) for 7 or 14 days is compared against the standard local therapy of BV (metronidazole) in a Serbian patient population. As much as 450 women were treated in groups with either 7 days metronidazole vaginal tablets, 7 days OHP, or 14 days OHP. Control smears were taken after each treatment period. In total, 63.2% of the women were without indications of BV after therapy (metronidazole: 61.0%, OHP 7 days: 57.6%, and OHP 14 days: 71.0%). Significantly fewer women were affected from infections after treatment with 14 days OHP compared to OHP for 7 days. Octenidine hydrochloride/phenoxyethanol spray was as effective as the standard therapy with metronidazole. Patients stated that OHP was more comfortable, easier to apply, and side effects were lesser.

  18. Efficacy of a new ketoconazole bioadhesive vaginal tablet on Candida albicans.

    PubMed

    Karasulu, H Yeşim; Hilmioğlu, Süleyha; Metin, Dilek Y; Güneri, Tamer

    2004-02-01

    To develop more effective treatment for vaginal candidasis, ketoconazole (KTZ) was formulated in bioadhesive tablet formulations that increase the time of contact of drug with the vaginal mucosa. The bioadhesive vaginal tablets delivery of KTZ was prepared by direct compression of sodium carboxymethyl cellulose or polyvinylpyrrolidone or hydroxypropylmethyl cellulose (HPMC-E(50)). Dissolution studies of bioadhesive tablets and commercial ovules were carried out with a new basket method (horizontal rotating basket). In vitro, a good sustained release action was obtained with bioadhesive tablets containing 1:1 and 1:2 drug/polymer ratio using HPMC-E(50). These bioadhesive tablets containing 400 mg of KTZ showed a zero-order drug release kinetic. KTZ solutions at increasing concentrations (0.16, 0.33, 0.5 and 0.66 mg/ml) were prepared for microbiological trials. These concentrations correspond to 25%, 50%, 75% and 100% of KTZ released from bioadhesive tablets, respectively. Yeast mixture was mixed with each concentration of KTZ at ratio of 1:10. One hundred microliters of this mixture was transferred in 900 microl liquid Sabouraud medium after a certain time interval for each concentration of KTZ and incubation at 37 degrees C for 24 h. Then this culture streaked onto Sabouraud-dextrose-agar plates, which were incubated at 37 degrees C for 48 h. The 0.16 and 0.33 mg/ml concentrations of KTZ showed fungistatic effect in 120 min. The 0.5 mg/ml concentration of KTZ was fungistatic in 90 and 120 min; and the 0.66 mg/ml concentration of the drug was fungistatic in 120 min as well as in 180 min. It was found that, in vitro antifungal activity of KTZ was dependent on its concentration and contact time with yeast cells. These results indicated that a new bioadhesive vaginal tablet formulations might be further developed for safe convenient and effective treatment of vaginal candidasis.

  19. Metronidazole-induced encephalopathy in a patient with Crohn's disease

    PubMed Central

    Kim, Jihye; Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kang, Jin Woo; Hwang, Seongjun; Ko, Sang-Bae; Im, Jong Pil; Kim, Joo Sung

    2017-01-01

    Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. PMID:28239323

  20. Preparation and Cyclodextrin Solubilization of the Antibacterial Agent Benzoyl Metronidazole

    PubMed Central

    Yang, Shuo

    2013-01-01

    A one-pot method for the preparation of benzoyl metronidazole was achieved by using N,N′-carbonyldiimidazole as a coupling reagent. Moreover, it was found that the byproduct imidazole as the catalyst promoted the reaction. In addition, the β-cyclodextrin solubilization of benzoyl metronidazole was investigated by phase-solubility method. The phase-solubility studies indicated that the solubility of benzoyl metronidazole (S = 0.1435 g/L) was substantially increased 9.7-fold (S′ = 1.3881 g/L) by formation of 1 : 1 benzoyl metronidazole/β-cyclodextrin complexes in water, and the association constant K a value was determined to be 251 (±23) dm3/mol. Therefore, β-cyclodextrin can work as a pharmaceutical solubilizer for benzoyl metronidazole and may improve its oral bioavailability. PMID:23970831

  1. [Reversible neurotoxicity secondary to metronidazole: report of one case].

    PubMed

    Retamal-Riquelme, Eva; Soto-San Martín, Hernán; Vallejos-Castro, José; Galdames-Poblete, Daniel

    2014-03-01

    Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

  2. Pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis.

    PubMed

    Wang, Xin; Nanovskaya, Tatiana N; Zhan, Ying; Abdel-Rahman, Susan M; Jasek, Marlo; Hankins, Gary D V; Ahmed, Mahmoud S

    2011-03-01

    The present study was undertaken to investigate the pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis. Twenty patients received metronidazole (Flagyl ®, Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning of day 4. Although absolute estimates of metronidazole total body exposure were highest in women during early term pregnancy, weight-corrected estimates of exposure maximum plasma drug concentration (C(max)) and the area under the plasma concentration-versus-time curve (AUC(0-12)), along with apparent oral clearance and distribution volume, were not significantly different between women at early, middle, and late stages of pregnancy and were in the range of reported values for nonpregnant patients receiving a similar dose. The pharmacokinetic profile of metronidazole did not change at the different time points assessed during pregnancy.

  3. Pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis

    PubMed Central

    Wang, Xin; Nanovskaya, Tatiana N.; Zhan, Ying; Abdel-Rahman, Susan M.; Jasek, Marlo; Hankins, Gary D.V.; Ahmed, Mahmoud S.

    2010-01-01

    Objective The present study was undertaken to investigate the pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis. Methods Twenty patients received metronidazole (Flagyl,® Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning of the day 4. Results Although absolute estimates of metronidazole total body exposure were highest in women during early term pregnancy, weight-corrected estimates of exposure maximum plasma drug concentration (Cmax, ) and the area under the plasma concentration-versus-time curve (AUC0-12), along with apparent oral clearance and distribution volume, were not significantly different between women at early, middle, and late stages of pregnancy and were in the range of reported values for nonpregnant patients receiving a similar dose. Conclusions The pharmacokinetic profile of metronidazole did not change at the different time points assessed during pregnancy. PMID:20608802

  4. Discriminative Dissolution Method for Benzoyl Metronidazole Oral Suspension.

    PubMed

    da Silva, Aline Santos; da Rosa Silva, Carlos Eduardo; Paula, Fávero Reisdorfer; da Silva, Fabiana Ernestina Barcellos

    2016-06-01

    A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.

  5. Comparative antimicrobial efficacy of Metapex, Metronidazole, BioPure MTAD, Aztreonam on Bacteroides fragilis and Propionibacterium acne

    PubMed Central

    Balakrishnan, Rajkumar; Dubey, Sandeep; Dhole, Tapan Kumar N; Boruah, Lalit C; Srivastava, Sanjeev

    2013-01-01

    Aim: The purpose of this study was to evaluate the comparative antibacterial efficacy of Biopure MTAD, Metapex, Metronidazole, and Aztreonam against two obligate anerobic bacteria. Materials and Methods: Antimicrobial efficacy of selected medicaments against two obligate anaerobic bacteria Bacteroides fragilis and Propionibacterium acnes was done by Agar disc-diffusion method. Pre-sterilized Whatman paper discs, 6 mm in diameter and soaked with the test solution, were prepared and placed onto the previously seeded agar Petri plates. Each plate was incubated in anaerobic jar for anerobic environment at 37°C for 48 hours. A zone of inhibition was recorded for each plate and the results were analysed statistically. Saline and ethanol used as control group in this study. Results: Biopure MTAD, Metapex and Metronidazole were effective against all the selected microorganisms. Aztreonam was effective against Bacteroides fragilis. Saline and ethanol used as control were ineffective. Conclusions: Metronidazole showed the superior antibacterial property amongst the tested medicaments. PMID:23956535

  6. Construction of microgels embedded robust ultrafiltration membranes for highly effective bioadhesion resistance.

    PubMed

    Xia, Yi; Cheng, Chong; Wang, Rui; He, Chao; Ma, Lang; Zhao, Changsheng

    2016-03-01

    Effective and robust anti-bioadhesion ultrafiltration membranes were fabricated in this paper via physically blending of anti-bioadhesion microgels. The microgels were synthesized by one-step cross-linking of antifouling segment, poly(ethylene glycol) methacrylate (PEGMA), and electrostatic repulsion segment, methylacrylic acid (MAA). Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) results indicated that large amounts of PEGMA and MAA polymers had been enriched on the membranes surface. Scanning electron microscope (SEM) indicated that the spherical PEGMA-MAA (PM) microgels might form interpenetrating structure with the membrane matrixes, and substantially increased the pore size of the membranes. Water contact angle (WCA), pore size distributions and ultrafiltration tests suggested that the hydrophilicity, porosity, water flux, and antifouling property for the modified membranes were significantly enhanced. More importantly, systematic anti-adhesion investigations of plasma proteins, platelets, bacteria and vein endothelial cells confirmed that the modified membranes owned strong resistance capability to the bioadhesion of various organisms. The results revealed that highly robust and effective anti-bioadhesion ultrafiltration membranes could be prepared via the proposed blending of PM microgels with membrane matrix, thus this approach should be potential in various biomedical or industrial filtration fields where anti-bioadhesion properties were highly demanded.

  7. The rigid curette technique for the application of fibrin bioadhesive during hip arthroscopy for articular cartilage lesions.

    PubMed

    Asopa, Vipin; Singh, Parminder J

    2014-04-01

    Encouraging midterm results have recently been reported for the arthroscopic treatment of delaminating articular cartilage lesions at the capsulolabral junction of the hip joint using fibrin bioadhesive. The needle used to introduce the bioadhesive is long, flexible, and often difficult to position. We describe a novel technique for introducing the needle that allows accurate placement behind the delaminated articular cartilage pocket during hip arthroscopy.

  8. Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%.

    PubMed

    Colón, Luz E; Johnson, Lori A; Gottschalk, Ronald W

    2007-04-01

    Topical therapy for rosacea aims to reduce inflammatory lesions and decrease erythema but can carry side effects such as stinging, pruritus, and burning. Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration-approved for the treatment of rosacea. The current study was conducted to assess the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study demonstrated a significantly greater poten tial for irritation from azelaic acid compared with metronidazole gel 0.75% (P < .0001), which had significantly greater potential for irritation compared with metronidazole gel 1% (P = .0054). Metronidazole gel 1% had a similar profile to white petrolatum.

  9. Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials.

    PubMed

    Tan, Hongying; Fu, Yunque; Yang, Chunlin; Ma, Jianting

    2017-06-01

    To evaluate the curative effect of metronidazole combined probiotics over metronidazole alone in the treatment of BV. We are searching randomized controlled trials on major online databases including PubMed, Science Direct, and Cochrane Database between 1990 and 2015. The primary outcome measure was the cure rate of BV. Cochran's Chi-square test (Q test) was used to test for heterogeneity among trials, and the I (2) index. We used mixed-effects modeling for parameters of the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs). Analysis suggests the cure rate of BV [RR = 1.12, 95% CI (0.94-1.32), p = 0.20], and the I (2) index was 83%. The value of I (2) index decreased to 16% after removing the study of Anukam et al., and Amsel 1.04 (95% CI 0.96-1.13) (p = 0.35), Nugent 1.02 (95% CI 0.94-1.11), short-term 1.01 (95% CI 0.93-1.10) (p = 0.79), long-term 1.06 (95% CI 0.98-1.14) (p = 0.13), Europe 1.06 (95% CI 0.95-1.19) (p = 0.32), Non-Europe 0.99 (95% CI 0.94-1.05) (p = 0.83). When the two same groups data were combined, respectively, the RRs for all studies were the same as 1.03 (95% CI 0.96-1.09) (p = 0.42) showing that there is not statistically significant in relevant stratums. The result has showed an overall little significance for the efficacy of metronidazole combined probiotics over metronidazole alone for the treatment of BV. We need more further studies to provide enough evidence to confirm the benefits of probiotics in the treatment of BV.

  10. Formulation and evaluation of anise-based bioadhesive vaginal gels.

    PubMed

    Gafiţanu, Carmen A; Filip, Daniela; Cernătescu, Corina; Ibănescu, Constanţa; Danu, Maricel; Pâslaru, Elena; Rusu, Daniela; Tuchiluş, Cristina G; Macocinschi, Doina

    2016-10-01

    Various formulations of anise-based bioadhesive gels are prepared. Freeze-drying method was successfully employed and superporous scaffolds were obtained. The resulting porous microarchitectures are strongly influenced by the composition of hydrogel formulations and temperature of freezing. Anise-based hydrogels frozen in liquid nitrogen and lyophilized generate regular assembly of polyhedral pores. For Carbopol 934-based hydrogels it was determined G'>G'' for whole tested strain amplitude range indicating solid-like behaviour due to their dense network and entanglement and interaction through hydrogen bonds and van-der Waals forces. For sodium alginate-based hydrogels it was determined G''>G' for whole tested strain amplitude range accompanied by the extended linear viscoelastic region indicating liquid-like behaviour due to the formation of a stable "pseudo-gel" structure. Biocompatibility features of tested hydrogels were evaluated by contact angle measurements and determination of surface tension parameters. It was found that all anise-based hydrogel formulations manifest modest activity against S. aureus and S. lutea and no activity against tested Gram negative bacteria. Carbopol 934-based hydrogels containing anise exhibit antifungal activity against C. albicans, C. glabrata and C. Parapsilosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Bioadhesive film for dermal and transdermal drug delivery.

    PubMed

    Padula, Cristina; Nicoli, Sara; Aversa, Vincenzo; Colombo, Paolo; Falson, Françoise; Pirot, Fabrice; Santi, Patrizia

    2007-01-01

    This paper describes an innovative transdermal drug delivery system, a monolaminated bioadhesive film in which the usual constituents of transdermal patches (backing, drug and adhesive) have been condensed in one single layer, denominated Patch-non-Patch. The main characteristics of the film is that it is not self-adhesive in the dry state but becomes adhesive only when applied on wet skin. This characteristic is due to the presence of a small amount of adhesive, unable to make the system self-adhesive, but capable of restoring the adhesiveness in contact with a small amount of water. From the results obtained to date, it appears that the technology Patch-non-Patch has the potentiality to be successfully applied to the pharmaceutical and cosmetic market. On the skin the film is flexible, invisible and adapts to all skin irregularities. The system has been shown to be highly efficient, releasing a high percentage of the active included in most cases. Additionally, the inclusion of other excipients can modulate drug delivery, thus improving the versatility of the product. Finally, the second generation Patch-non-Patch, made occlusive on the skin surface, can further broaden the potential application.

  12. Bioadhesion in ascidians: a developmental and functional genomics perspective

    PubMed Central

    Pennati, Roberta; Rothbächer, Ute

    2015-01-01

    The development of bioadhesives inspired from marine animals is a promising approach to generate new tissue-compatible medical components. A number of marine species, through their adhesive properties, also represent significant foulers that become increasingly problematic to aquaculture, shipping or local biodiversity. In order to develop more sophisticated man-made glues and/or efficient fouling resistant surfaces, it is important to understand the mechanical, structural and molecular properties of adhesive organs in selected species. Ascidians are marine invertebrates with larvae that opportunistically attach to almost any type of submerged surface to undergo metamorphosis into permanently sessile adults. Not only do they represent a globally important fouling organism, but they are becoming increasingly popular as model organisms for developmental biology. The latter is due to their phylogenetic position as the sister group to the vertebrates and their cellular and molecular accessibility for experimentation. In this paper, we review the mechanisms of larval adhesion in ascidians and draw conclusions from comparative analyses of selected species. We further discuss how knowledge from a developmental and functional genomics point of view can advance our understanding of cellular and molecular signatures and their hierarchical usage in animal adhesive organs. PMID:25657840

  13. Transparent and durable superhydrophobic coatings for anti-bioadhesion.

    PubMed

    Zhao, Xia; Yu, Bo; Zhang, Junping

    2017-09-01

    Although thousands of superhydrophobic coatings have been reported, transparent ones with high durability are rare. Here, transparent and durable superhydrophobic coatings were prepared by using multiwalled carbon nanotubes (MWCNTs) as the templates. The superhydrophobic coatings were prepared by spray-coating the homogeneous suspension of polysiloxane-modified MWCNTs (MWCNTs@POS) in toluene onto glass slides, calcination in air at 500°C to form the silica nanotubes (SNTs), and then chemical vapor deposition of polydimethylsiloxane at 200°C onto the surface of the SNTs coatings. The MWCNTs@POS suspension was prepared by hydrolytic condensation of hexadecyltrimethoxysilane and tetraethoxysilane on the surface of MWCNTs. The coatings showed excellent superhydrophobicity (water contact angle=166.6°, sliding angle=1°) and high transparency (83.1% at 600nm). In addition, the transparent superhydrophobic coatings featured high mechanical, chemical and thermal durability. The coatings retained the excellent superhydrophobicity after intensive water jetting at 100kPa for 60min, immersion in various corrosive liquids for 24h, or kept at 390°C for 1h. Moreover, the transparent and durable superhydrophobic coatings exhibited very good anti-bioadhesive properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules.

    PubMed

    Yamada, Yuji; Schneider, Joel P

    2016-08-08

    Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOX-PDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (∼10 kPa) and adherent (adhesive stress ∼ 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death.

  15. Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces.

    PubMed

    Huang, Y; Leobandung, W; Foss, A; Peppas, N A

    2000-03-01

    Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug in the body fluids, and allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels have been used extensively as mucoadhesive systems. They are well suited for bioadhesion due to their flexibility and nonabrasive characteristics in the partially swollen state, which reduce damage-causing attrition to the tissues in contact. Crosslinked polymeric devices may be rendered adhesive to the mucosa. For example, adhesive capabilities of these hydrogels can be improved by tethering of long flexible chains to their surfaces. Tethering of long poly(ethylene glycol) (PEG) chains on poly(acrylic acid) hydrogels and their copolymers can be achieved by grafting reactions, or by copolymerization in the presence of several PEG-containing acrylates. The ensuing hydrogels exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure. Experimental results indicate that the chain interpenetration is a strong function of the PEG molecular weight, the polymer swelling ratio and the mucosa composition.

  16. Fast-drying multi-laminate bioadhesive films for transdermal and topical drug delivery.

    PubMed

    Donnelly, Ryan F; McCarron, Paul A; Morrow, Desmond I J; Woolfson, A David

    2013-11-01

    No bioadhesive patch-based system is currently marketed. This is despite an extensive number of literature reports on such systems detailing their advantages over conventional pressure sensitive adhesive-based patches in wet environments and describing successful delivery of a diverse array of drug substances. This lack of proprietary bioadhesive patches is largely due to the fact that such systems are exclusively water-based, meaning drying is difficult. In this paper we describe, for the first time, a novel multiple lamination method for production of bioadhesive patches. In contrast to patches produced using a conventional casting approach, which took 48 hours to dry, bioadhesive films prepared using the novel multiple lamination method were dried in 15 min and were folded into formed patches in a further 10 min. Patches prepared by both methods had comparable physicochemical properties. The multiple lamination method allowed supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices. However, drug release studies were unable to show an advantage for supersaturation with this particular drug, due to its water high solubility. The multiple lamination method allowed greater than 90% of incorporated nicotine to remain within formed patches, in contrast to the 48% achieved for patches prepared using a conventional casting approach. The procedure described here could readily be adapted for automation by industry. Due to the reduced time, energy and ensuing finance now required, this could lead to bioadhesive patch-based drug delivery systems becoming commercially viable. This would, in turn, mean that pathological conditions occurring in wet or moist areas of the body could now be routinely treated by prolonged site-specific drug delivery, as mediated by a commercially produced bioadhesive patch.

  17. A rare adverse effect of metronidazole: nervous system symptoms.

    PubMed

    Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

    2013-06-01

    Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

  18. Bioinspired bioadhesive polymers: dopa-modified poly(acrylic acid) derivatives.

    PubMed

    Laulicht, Bryan; Mancini, Alexis; Geman, Nathanael; Cho, Daniel; Estrellas, Kenneth; Furtado, Stacia; Hopson, Russell; Tripathi, Anubhav; Mathiowitz, Edith

    2012-11-01

    The one-step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa-grafted hydrophobic backbone polymers exhibit as much as 2.5 × the fracture strength and 2.8 × the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Risk of Clostridium difficile infection in hospitalized patients receiving metronidazole for a non-C difficile infection.

    PubMed

    Rodriguez, Sandra; Hernandez, Marlow B; Tarchini, Giorgio; Zaleski, Megan; Vatanchi, Marjon; Cardona, Lyssette; Castro-Pavia, Fernando; Schneider, Alison

    2014-11-01

    Antibiotics often are given to prevent infections but also constitute a risk factor for Clostridium difficile infection (CDI). Metronidazole is an effective treatment for CDI. We investigated whether prophylactic administration of metronidazole to patients before they receive other antibiotics reduces the risk of CDI. We performed a retrospective cohort analysis of data collected from 12,026 high-risk patients admitted to Cleveland Clinic Foundation Hospitals from 2008 through 2012. High-risk patients were defined as age 55 or older who received a broad-spectrum antibiotic (piperacillin-tazobactam or ciprofloxacin) and a gastric acid suppressant (a proton pump inhibitor or a histamine-2 receptor blocker) during their hospitalization. Development of CDI was compared between patients who received metronidazole for non-CDI indications before broad-spectrum antibiotics (n = 811) and those who did not (n = 11,215). Logistic regression was used to control for patient demographics and comorbidities. The rate of CDI was 1.4% (n = 11) among the patients who received metronidazole for non-CDI indications and 6.5% (n = 728) among those who did not. This was observed to be an 80% reduction in CDI among patients who received metronidazole (odds ratio, 0.21; 95% confidence interval, 0.11-0.38; P < .001), adjusted for age, sex, and comorbidities. Based on a retrospective analysis, metronidazole might be used to prevent CDI in certain high-risk patients. Prospective controlled trials are necessary before making further recommendations. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Significant Reduction of Brain Cysts Caused by Toxoplasma gondii after Treatment with Spiramycin Coadministered with Metronidazole in a Mouse Model of Chronic Toxoplasmosis

    PubMed Central

    Chew, Wai Kit; Ambu, Stephen; Mak, Joon Wah

    2012-01-01

    Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC0–∞) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC0–∞ values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical

  1. Significant reduction of brain cysts caused by Toxoplasma gondii after treatment with spiramycin coadministered with metronidazole in a mouse model of chronic toxoplasmosis.

    PubMed

    Chew, Wai Kit; Segarra, Ignacio; Ambu, Stephen; Mak, Joon Wah

    2012-04-01

    Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC(0-∞)) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC(0-∞) values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical

  2. DNA breakage due to metronidazole treatment.

    PubMed

    Menéndez, D; Rojas, E; Herrera, L A; López, M C; Sordo, M; Elizondo, G; Ostrosky-Wegman, P

    2001-07-01

    The mutagenicity of metronidazole [1-(hidroxyethyl)-2-methyl-5-nitroimidazole] (MTZ) has been shown in different prokaryotic systems. However, data on human cells are still contradictory. In this study DNA damage was determined by the single cell gel electrophoresis (SCGE) assay, in lymphocytes from 10 healthy subjects treated with therapeutic doses of this drug. Samples were obtained before treatment, as well as 1 and 15 days after ending treatment. Results showed a significant increase of DNA strand breaks 1 day after ending treatment, although, an inverse correlation between the amount of DNA damage and plasma concentrations of MTZ was obtained. Thus, the observed damage may be induced by some MTZ metabolite rather than by the parent drug. Interestingly, the amount of DNA damage returned to basal levels 15 days after ending treatment, except in two individuals. This persistent damage should be further investigated.

  3. Vulvoperineal Crohn's disease responsive to metronidazole*

    PubMed Central

    Rosmaninho, Aristóteles; Sanches, Madalena; Salgado, Marta; Alves, Rosário; Selores, Manuela

    2013-01-01

    Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of the cases, the cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. We describe the case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement, that was successfully managed with metronidazole. PMID:24346884

  4. [In vitro anti-Trichomonas vaginalis effects of a mixture of dihydroartemisinin and metronidazole].

    PubMed

    Tang, Zi-Hao; Liu, Ke-Yue; Mei, Jun; Gao, Xing-Zheng

    2010-12-30

    To observe the effect of a mixture of dihydroartemisinin and metronidazole on ultrastructure of Trichomonas vaginalis trophozoites in vitro for exploring trichomonacidal mechanism of the drug mixture. The trophozoites were cultivated with liver extract solution medium that contained 2.5 x 10(6) parasites/ml. There were dihydroartemisinin 0.5 mg/ml and metronidazole 0.002 mg/ml in the experimental tubes of the drug mixture group. Groups of control (without drug), dihydroartemisinin (1 mg/ml) and metronidazole (5 mg/ml) were established and performed in the same experimental conditions. The parasites were observed by scanning and transmission electron microscopes after having treated with the drugs at 37 degrees for 3.5-5 h. Under scanning electron microscope, the cell membrane of T. vaginalis treated only with dihydroartemisinin for 35 h was damaged, part of pellicle peeled off. Although the surface of the trophozoites treated only with metronidazole for 5 h showed many small bubbles and hollows, the cell membrane looked integral. However, surface of the parasite exposed to the drug mixture for 3.5-4.2 h showed deep folds and cracks, the cell membrane was damaged and even peeled off. When the cell ruptured, the nucleus, axostyle, pelta and hydrogenosomes were exposed, and the cytoplasm spilled out. Transmission electron microscopy showed that the membrane system of the trophozoites treated only with dihydroartemisinin for 3.5 h was damaged considerably. The cytoplasm of damaged parasite spilled out. The cytoplasm of the parasite treated only with metronidazole for 3.5-5 h was damaged seriously. Vacuoles and crevices were visible in the cytoplasm. The cell membrane and the content of the parasites treated with the drug mixture for 3.5-4.5 h were damaged seriously. There were some vacuoles and crevices, dilated endoplasmic reticulum, injured and deformed hydrogenosomes in the cytoplasm. The cell organelles mostly disappeared. Crevices also existed in the nucleus. The

  5. Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole.

    PubMed

    Hawkins, Isobel; Carne, Christopher; Sonnex, Christopher; Carmichael, Andrew

    2015-08-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy. © The Author(s) 2014.

  6. Metronidazole Toxicity in Cockayne Syndrome: A Case Series.

    PubMed

    Wilson, Brian T; Strong, Andrew; O'Kelly, Sean; Munkley, Jennifer; Stark, Zornitza

    2015-09-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by small stature, intellectual disability, and accelerated pathologic aging. Through the Cockayne Syndrome Natural History Study, we have identified 8 cases of acute hepatic failure after metronidazole administration (8% of our cohort), 3 of which were fatal. The interval between initial administration and death was 6 to 11 days. Two of these patients also experienced acute neurologic deficit. Both hepatotoxicity and acute neurologic deficit have been reported previously as extremely rare adverse events after metronidazole administration. However, we have not identified any patients with CS who have received metronidazole without serious adverse effects. We recommend that a diagnosis of CS be considered an absolute contraindication to the use of metronidazole.

  7. Tinidazole versus Metronidazole for the Treatment of Bacterial Vaginosis

    PubMed Central

    SCHWEBKE, Jane R.; DESMOND, Renee A.

    2010-01-01

    Objective To compare the efficacy of two different doses of tinidazole with metronidazole for treatment of bacterial vaginosis and compare side effects of the drugs. Study design Women were randomized to metronidazole 500 mg BID, tinidazole 500 mg BID, or tinidazole 1 gm BID all for 7 days. Follow-up visits were conducted at day 14 and day 28. Results 593 women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at one month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have BV at follow-up. There were no significant differences in adverse events across treatment arms. Conclusions There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens studied. In addition, there were no important differences in the side effect profiles of metronidazole and tinidazole. PMID:21167471

  8. Preparation and evaluation of gastroretentive floating pellets of metronidazole using Na-alginate and hydroxyl propyl methyl cellulose polymers.

    PubMed

    Biswas, S K; Paul, S; Chowdhury, A; Das, J

    2012-03-15

    Gastroretentive floating pellets of metronidazole were formulated to prolong the gastric residence time in order to obtain controlled release characteristics of the drug. Nine formulations of metronidazole floating pellets such as AX, BX, CX, AY, BY, CY, AZ, BZ and CZ were prepared by extrusion method using different quantities of hydroxyl propyl methyl cellulose (HPMC) polymers such as methocel K4M premium and methocel K100LV premium in the ratio of 2:1, 1:2 and 1.5:1.5 while the amount of Na-alginate used in the formulations was 3.50, 5.25 and 7.0 g, respectively. The in vitro dissolution studies were carried out in 900 mL of phosphate buffer (pH 1.2) at 37 +/- 0.5 degrees C and 50 rpm for 6 h using USP XXIV paddle method and the content of drug release was done by UV spectrophotometer at 277 nm. It was found that the percent release of metronidazole from different formulations was different with passing of time. The drug release profile of the formulation (AX) having Na-alginate 3.50 g methocel K4M premium and methocel K100LV premium in the ratio of 2:1 showed best fit to Higuchi release kinetics with R2 value of 0.994. Finally, it might be concluded that the polymers had significant effect on drug release kinetics of metronidazole from floating pellets. The selection and use of suitable polymers in appropriate ratio might be very important in designing floating pellets and using the capabilities of these polymers, suitable floating pellets of metronidazole with desirable release rate could be formulated. Thus, in vivo research studies by the future researchers will confirm the appropriateness of these formulated metronidazole floating pellets.

  9. Entamoeba histolytica and Trichomonas vaginalis: trophozoite growth inhibition by metronidazole electro-transferred water.

    PubMed

    Heredia-Rojas, J Antonio; Torres-Flores, Antonio Cayetano; Rodríguez-De la Fuente, Abraham O; Mata-Cárdenas, Benito David; Rodríguez-Flores, Laura E; Barrón-González, María Porfiria; Torres-Pantoja, Antonio Cayetano; Alcocer-González, Juan M

    2011-01-01

    The influence of low-frequency electromagnetic (LF-EM) waves on microorganisms has been a subject of experimental investigations for more than two decades and the results are promising. In parallel, an interesting procedure known as biophysical-information-therapy or bioresonance therapy (BRT) which in principle is based on LF-EM stimulation, has emerged. BRT was discovered in the late 1980's but it is still poorly studied. This paper demonstrates that by transferring metronidazole information to water samples by an electronic amplifier (BRT device), the growth of axenically cultured trophozoites of Entamoeba histolytica and Trichomonasvaginalis is significantly inhibited, compared with those cultures treated with non and sham electro-transferred water samples. A positive control of metronidazole, a well-known cytotoxic drug against parasites, was used as a reference. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Indirect electroreduction as pretreatment to enhance biodegradability of metronidazole.

    PubMed

    Saidi, I; Soutrel, I; Floner, D; Fourcade, F; Bellakhal, N; Amrane, A; Geneste, F

    2014-08-15

    The removal of metronidazole, a biorecalcitrant antibiotic, by coupling an electrochemical reduction with a biological treatment was examined. Electroreduction was performed in a home-made flow cell at -1.2V/SCE on graphite felt. After only one pass through the cell, analysis of the electrolyzed solution showed a total degradation of metronidazole. The biodegradability estimated from the BOD5/COD ratio increased from 0.07 to 0.2, namely below the value usually considered as the limit of biodegradability (0.4). In order to improve these results, indirect electrolysis of metronidazole was performed with a titanium complex known to reduce selectively nitro compounds into amine. The catalytic activity of the titanium complex towards electroreduction of metronidazole was shown by cyclic voltammetry analyses. Indirect electrolysis led to an improvement of the biodegradability from 0.07 to 0.42. To confirm the interest of indirect electroreduction to improve the electrochemical pretreatment, biological treatment was then carried out on activated sludge after direct and indirect electrolyses; different parameters were followed during the culture such as pH, TOC and metronidazole concentration. Both electrochemical processes led to a more efficient biodegradation of metronidazole compared with the single biological treatment, leading to an overall mineralization yield for the coupling process of 85%. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Subjective adverse reactions to metronidazole in patients with amebiasis.

    PubMed

    Ohnishi, Kenji; Sakamoto, Naoya; Kobayashi, Ken-Ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi; Ajisawa, Atsushi; Yamauchi, Yuko; Takeshita, Nozomi; Yamamoto, Yasuyuki; Tsunoda, Takafumi; Yoshimura, Yukihiro; Tachikawa, Natsuo; Uehira, Tomoko

    2014-10-01

    Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Metronidazole activation and isolation of Clostridium acetobutylicum electron transport genes.

    PubMed Central

    Santangelo, J D; Jones, D T; Woods, D R

    1991-01-01

    An Escherichia coli F19 recA, nitrate reductase-deficient mutant was constructed by transposon mutagenesis and shown to be resistant to metronidazole. This mutant was a most suitable host for the isolation of Clostridium acetobutylicum genes on recombinant plasmids, which activated metronidazole and rendered the E. coli F19 strain sensitive to metronidazole. Twenty-five E. coli F19 clones containing different recombinant plasmids were isolated and classified into five groups on the basis of their sensitivity to metronidazole. The clones were tested for nitrate reductase, pyruvate-ferredoxin oxidoreductase, and hydrogenase activities. DNA hybridization and restriction endonuclease mapping revealed that four of the C. acetobutylicum insert DNA fragments on recombinant plasmids were linked in an 11.1-kb chromosomal fragment. DNA sequencing and amino acid homology studies indicated that this DNA fragment contained a flavodoxin gene which encoded a protein of 160 amino acids that activated metronidazole and made the E. coli F19 mutant very sensitive to metronidazole. The flavodoxin and hydrogenase genes which are involved in electron transfer systems were linked on the 11.1-kb DNA fragment from C. acetobutylicum. Images PMID:1991710

  13. Absence of Strand Breaks in Deoxyribonucleic Acid Treated with Metronidazole

    PubMed Central

    LaRusso, Nicholas F.; Tomasz, Maria; Kaplan, David; Müller, Miklós

    1978-01-01

    The deoxyribonucleic acid (DNA)-degrading potential of metronidazole was evaluated in vitro by three techniques: determination of melting curve, measurement of viscosity, and centrifugation in neutral or alkaline sucrose gradients. Studies were performed on calf thymus DNA and on 3H-labeled or unlabeled pneumococcal and T7 phage DNA after treatment with metronidazole alone or metronidazole reduced by sodium dithionite in the presence of DNA. This latter process is known to elicit covalent binding of metronidazole to DNA. Reduced or unreduced metronidazole had no effect on the melting properties, viscosity, or sedimentation velocity of the nucleic acids studied. Sodium dithionite alone, however, caused a 25% decrease in the intrinsic viscosity of pneumococcal DNA, and decreased the sedimentation velocity of pneumococcal and T7 phage DNA in both neutral and alkaline sucrose gradients. These data suggest that degradation of DNA is not important in the interaction of metronidazole with nucleic acids, an interaction assumed relevant to the cytotoxic, radiosensitizing, and mutagenic activities of this compound. PMID:626487

  14. Piroxicam bioadhesive ocular inserts: physicochemical characterization and evaluation in prostaglandin-induced inflammation.

    PubMed

    Gilhotra, Ritu Mehra; Gilhotra, Neeraj; Mishra, D N

    2009-12-01

    An attempt has been made in the present research to formulate piroxicam into bioadhesive ocular inserts with an objective to sustain drug release, reduce frequency of dosing, and enhance ocular bioavailability of piroxicam. Drug matrices were prepared using film forming polymer, PVP and bioadhesive polymers, HPMC, CMC, and carbopol. Ocular inserts were prepared by film casting method and prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, ex vivo bioadhesion, and in vitro drug release. The optimized formulation was tested and compared with eye drops of piroxicam for ocular anti-inflammatory activity in rabbits against PGE(2)-induced inflammation. The physicochemical, bioadhesive, and swelling properties of films were found to vary significantly depending on the type of the polymers and their combination. The above properties were found to be optimum for all films; however, formulation containing carbopol 0.5% and HPMC 1% was found to be the best film as it shows good adhesion, acceptable pH, and gives a reasonable drug release (99% at 12 hr). Kinetic studies indicated both diffusion and swelling as mechanism of drug release from this matrix. Further in vivo studies with this formulation indicated a significant inhibition of PGE(2)-induced lid closure and PMN migration as compared to eye drops formulation. Formulation was found promising, as it sustained the drug release and enhanced the ocular bioavailability of piroxicam as compared to piroxicam eye drops.

  15. Potentials of Chitosan-Based Delivery Systems in Wound Therapy: Bioadhesion Study

    PubMed Central

    Hurler, Julia; Škalko-Basnet, Nataša

    2012-01-01

    Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force. PMID:24956514

  16. A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis

    PubMed Central

    Solaymani-Mohammadi, Shahram; Genkinger, Jeanine M.; Loffredo, Christopher A.; Singer, Steven M.

    2010-01-01

    Background Metronidazole is the most commonly used drug for the treatment of giardiasis in humans. In spite of its therapeutic efficacy for giardiasis, low patient compliance, especially in children, side effects, and the emergence of metronidazole-resistant strains may restrict its use. Albendazole has been used to treat Giardia duodenalis infections in recent years. However, efficacy studies in vivo and in vitro have produced diverse results as to its effectiveness. A moderately benign side effect profile, combined with established efficacy against many helminths, renders it promising for treatment of giardiasis in humans. Methodology and Principal Findings We performed a search in the PubMed, Scopus, EMBASE, the ISI Web of Science, LILIACS, and Cochrane Controlled Trials Register for trials published before February 2010 as well as in references of relevant research and review articles. Eight randomized clinical trials (including 900 patients) comparing the effectiveness of albendazole with that of metronidazole were included in meta-analysis. After extracting and validating the data, the pooled risk ratio (RR) was calculated using an inverse-variance random-effects model. Albendazole was found to be equally as effective as metronidazole in the treatment of giardiasis in humans (RR 0.97; 95% CI, 0.93, 1.01). In addition, safety analysis suggested that patients treated with albendazole had a lower risk of adverse effects compared with those who received metronidazole (RR 0.36; 95% CI, 0.10, 1.34), but limitations of the sample size precluded a definite conclusion. Conclusions/Significance The effectiveness of albendazole, when given as a single dose of 400 mg/day for 5 days, was comparable to that of metronidazole. Patients treated with albendazole tended to have fewer side effects compared with those who took metronidazole. Given the safety, effectiveness, and low costs of albendazole, this drug could be potentially used as an alternative and/or a replacement

  17. The restoration of the vaginal microbiota after treatment for bacterial vaginosis with metronidazole or probiotics.

    PubMed

    Ling, Zongxin; Liu, Xia; Chen, Weiguang; Luo, Yueqiu; Yuan, Li; Xia, Yaxian; Nelson, Karen E; Huang, Shaolei; Zhang, Shaoen; Wang, Yuezhu; Yuan, Jieli; Li, Lanjuan; Xiang, Charlie

    2013-04-01

    Whether or not treatment with antibiotics or probiotics for bacterial vaginosis (BV) is associated with a change in the diversity of vaginal microbiota in women was investigated. One hundred fifteen women, consisting of 30 healthy subjects, 30 BV-positive control subjects, 30 subjects with BV treated with a 7-day metronidazole regimen, and 25 subjects with BV treated with a 10-day probiotics regimen, were analyzed to determine the efficacy and disparity of diversity and richness of vaginal microbiota using 454 pyrosequencing. Follow-up visits at days 5 and 30 showed a greater BV cure rate in the probiotics-treated subjects (88.0 and 96 %, respectively) compared to the metronidazole-treated subjects (83.3 and 70 %, respectively [p = 0.625 at day 5 and p = 0.013 at day 30]). Treatment with metronidazole reduced the taxa diversity and eradicated most of the BV-associated phylotypes, while probiotics only suppressed the overgrowth and re-established vaginal homeostasis gradually and steadily. Despite significant interindividual variation, the microbiota of the actively treated groups or participants constituted a unique profile. Along with the decrease in pathogenic bacteria, such as Gardnerella, Atopobium, Prevotella, Megasphaera, Coriobacteriaceae, Lachnospiraceae, Mycoplasma, and Sneathia, a Lactobacillus-dominated vaginal microbiota was recovered. Acting as vaginal sentinels and biomarkers, the relative abundance of Lactobacillus and pathogenic bacteria determined the consistency of the BV clinical and microbiologic cure rates, as well as recurrent BV. Both 7-day intravaginal metronidazole and 10-day intravaginal probiotics have good efficacy against BV, while probiotics maintained normal vaginal microbiota longer due to effective and steady vaginal microbiota restoration, which provide new insights into BV treatment.

  18. The treatment of Gardnerella vaginalis vaginosis: a randomized comparison of pivampicillin with metronidazole.

    PubMed

    Csángó, P A; Jagars, G; Tommelstad, T

    1985-01-01

    The efficacy of pivampicillin and metronidazole were compared in the treatment of Gardnerella vaginalis associated bacterial vaginosis. In a multicenter trial 86 women were given pivampicillin (P) 700 mg twice daily for 6 days and 86 women received metronidazole (M) 400 mg three times daily for 7 days. At control, 2 weeks from the start of treatment, patients in group P showed the best clinical results, 77.9% in group P vs. 64.0% in group M (p = 0.066). P showed a higher clinical efficacy than M, both in women using intra-uterine device and in patients using other forms of contraception. Negative post-treatment cultures were seen in 43% of women in group P and 64% in group M (p less than 0.002). Bacteriological cure was unrelated to disappearance of discharge, odour and itching, although it correlated significantly with a negative amine test (p less than 0.00005). Pivampicillin in the dosages used in the present investigation is a useful alternative to metronidazole therapy.

  19. Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy.

    PubMed

    Mitchell, Caroline; Balkus, Jennifer; Agnew, Kathy; Lawler, Richard; Hitti, Jane

    2009-11-01

    Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment. This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1beta, -6, -8 (IL-1beta, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test). Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1beta dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013). Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli.

  20. Preparation and evaluation of bioadhesive dibucaine gels for enhanced local anesthetic action.

    PubMed

    Kang, Chung; Shin, Sang-Chul

    2010-08-01

    In relieving local pains, dibucaine, one of ester type local anesthetics, has been used. In case of their application such as ointments and creams, it is difficult to expect their effects for a required period of time, because they are easily removed by wetting, movement and contacting. To develop suitable bioadhesive gels, the bioadhesive force of hydroxypropyl cellulose (HPC) was tested using auto-peeling tester. The effect of drug concentration on drug release was studied from the prepared 2% HPC-HF gels using synthetic cellulose membrane at 37 +/- 0.5 degrees C. We investigated the enhancing effects on drug permeation into skins, using some kind of enhancers such as the glycols, the non-ionic surfactants, the fatty acids, and the propylene glycol derivatives. Anesthetic effects of dibucaine gels containing polyoxyethylene 2-oleyl ether were measured by tail flick analgesic meter. The bioadhesive force of various types of HPC such as GF, MF, and HF, was 0.0131, 0.0501, and 0.1346 N, at 2% HPC concentration, respectively. The HPC-HF gels showed the highest bioadhesive force. As the concentration of HPC-HF increased, the drug release increased. As the temperature increased, the drug release increased. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects. According to the rat tail flick test, 1% drug gels containing polyoxyethylene 2-oleyl ether showed the prolonged local anesthetic effects. In conclusion, the dibucaine gel containing penetration enhancer and vasoconstrictor showing enhanced local anesthetic action could be developed by using the bioadhesive polymer, HPC.

  1. Metronidazole loaded pectin microspheres for colon targeting.

    PubMed

    Vaidya, Ankur; Jain, Aviral; Khare, Piush; Agrawal, Ram K; Jain, Sanjay K

    2009-11-01

    A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  2. Metronidazole decreases viability of DLD-1 colorectal cancer cell line.

    PubMed

    Sadowska, Anna; Krętowski, Rafał; Szynaka, Beata; Cechowska-Pasko, Marzanna; Car, Halina

    2013-10-01

    The aim of our study was to evaluate the impact of metronidazole (MTZ) on DLD-1 colorectal cancer cell (CRC) line. Toxicity of MTZ was determined by MTT test. Cells were incubated with MTZ used in different concentrations for 24, 48, and 72 hours. The effect of MTZ on DNA synthesis was measured as [3H]-thymidine incorporation. The morphological changes in human DLD-1 cell line were defined by transmission electron microscope OPTON 900. The influence of MTZ on the apoptosis of DLD-1 cell lines was detected by flow cytometry and fluorescence microscopy, while cell concentration, volume, and diameter were displayed by Scepter Cell Counter from Millipore. Our results show that cell viability was diminished in all experimental groups in comparison with the control, and the differences were statistically significant. We did not find any significant differences in [3H]-thymidine incorporation in all experimental groups and times of observation. Cytofluorimetric assays demonstrated a statistically significant increase of apoptotic rate in MTZ concentrations 10 and 50 μg/mL after 24 hours; 0.1, 10, 50, and 250 μg/mL after 48 hours; and in all concentrations after 72 hours compared with control groups. In the ultrastructural studies, necrotic or apoptotic cells were occasionally seen. In conclusion, MTZ affects human CRC cell line viability. The reduction of cell viability was consistent with the apoptotic test.

  3. Bioinspired polyethylene terephthalate nanocone arrays with underwater superoleophobicity and anti-bioadhesion properties

    NASA Astrophysics Data System (ADS)

    Liu, Wendong; Liu, Xueyao; Fangteng, Jiaozi; Wang, Shuli; Fang, Liping; Shen, Huaizhong; Xiang, Siyuan; Sun, Hongchen; Yang, Bai

    2014-10-01

    This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the functionalized nanocone arrays can be transformed from the superoleophobic state with OCA about 151° to the oleophilic state with OCA about 25° reversibly. Due to the high-throughput, parallel fabrication and cost-efficiency of this method, it will be favourable for researchers to introduce oleophobic properties to various substrate and device surfaces. Due to the superoleophobicity and simple functionalizing properties, the PET nanocone arrays are very promising surfaces for anti-adhesion, self-cleaning and have potential applications in material, medical, and biological fields.This paper presents a facile method to fabricate bioinspired polyethylene terephthalate (PET) nanocone arrays via colloidal lithography. The aspect ratio (AR) of the nanocones can be finely modulated ranging from 1 to 6 by regulating the etching time. The samples with the AR value of 6 can present underwater superoleophobicity with the underwater oil contact angle (OCA) of 171.8°. The as-prepared PET nanocone arrays perform anti-bioadhesion behavior, which inhibits the formation of the actin cytoskeleton when it used as the substrate for cell culture. Moreover, the oil wettability is temperature controlled after modifying the PET nanocone arrays with PNIPAAm film, and the oil wettability of the

  4. Metronidazole-induced encephalopathy: not always a reversible situation.

    PubMed

    Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

    2015-06-01

    Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.

  5. Busulfan and metronidazole: an often forgotten but significant drug interaction.

    PubMed

    Gulbis, Alison M; Culotta, Kirk S; Jones, Roy B; Andersson, Borje S

    2011-07-01

    To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM). A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.5 mg/kg was administered. On the day of the first busulfan therapeutic dose, TDM was performed and the clearance of busulfan was significantly decreased by 46%. After 2 doses of busulfan therapy, the course area under the curve was exceeded, requiring discontinuation of busulfan. Metronidazole is not known to affect glutathione or the glutathione S-transferase A1 (GSTA1) enzyme system or cytochrome P450 (CYP) 3A4. Busulfan is a bifunctional alkylating agent widely used in pretransplant conditioning regimens in patients undergoing stem cell transplantation for hematologic malignancies. Busulfan metabolism is best described by hepatic conjugation to glutathione by GSTA1, although some CYP-dependent pathways have been described. Currently there is 1 publication describing the drug interaction between oral busulfan and oral metronidazole, in which concomitant use of metronidazole resulted in higher busulfan trough concentrations and higher risk of veno-occlusive disease. Our case represents a possible drug interaction based on the Horn Drug Interaction Probability Scale. Though the mechanistic basis for this interaction is unknown, the risks and benefits of using metronidazole during and in close proximity to busulfan should be carefully considered and therapeutic alternatives to metronidazole should be used when appropriate.

  6. Metronidazole-induced central nervous system toxicity: a systematic review.

    PubMed

    Kuriyama, Akira; Jackson, Jeffrey L; Doi, Asako; Kamiya, Toru

    2011-01-01

    To assess patient and medication factors that contribute to metronidazole toxicity. We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies. Case reports or case series reporting metronidazole-induced central nervous toxicity. Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings. Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients' ages averaged 53.3 years (range, 12-87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49-0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities. Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.

  7. Effect of post-induction nutrient feeding strategies on the production of bioadhesive protein in Escherichia coli.

    PubMed

    Wong, H H; Kim, Y C; Lee, S Y; Chang, H N

    1998-11-05

    The effect of post-induction nutrient feeding strategies on the production of bioadhesive protein using an IPTG inducible expression system in Escherichia coli was investigated. Cells were cultured in an exponential fed-batch mode to the OD600 of ca. 100 (48 gDCW/L) prior to induction. Six different post-induction nutrient feeding strategies (pH-stat, exponential, constant and linear change in feeding rate with three different slopes) were then applied, and bioadhesive protein production was examined. It was found that post-induction cell growth was independent of nutrient feeding rate. However, bioadhesive protein production was significantly affected by post-induction feeding strategies. Linearly changing post-induction feeding rate with a suitable slope allowed production of bioadhesive protein up to 5.3 g/L, which was higher than that obtained by the other post-induction feeding strategies. Copyright 1998 John Wiley & Sons, Inc.

  8. Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis

    PubMed Central

    Kong, Eric F.; Tsui, Christina; Boyce, Heather; Ibrahim, Ahmed; Hoag, Stephen W.; Karlsson, Amy J.; Meiller, Timothy F.

    2015-01-01

    Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV+ individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent. PMID:26596951

  9. Synthesis and evaluation of sulfate conjugated metronidazole as a colon-specific prodrug of metronidazole.

    PubMed

    Kim, Hyunjeong; Lee, Yonghyun; Yoo, Hansun; Kim, Jihye; Kong, Hyesik; Yoon, Jeong-Hyun; Jung, Yunjin; Kim, Young Mi

    2012-04-01

    For an effort to improve therapeutic property of metronidazole (MTZ) which is a drug of choice for protozoal infections such as luminal amoebiasis, sulfate conjugated metronidazole (MTZS) was prepared and evaluated as a colon-specific prodrug of MTZ. The apparent partition coefficient of MTZ was greatly reduced by the sulfate conjugation. While (bio)chemically stable in the contents of the upper intestine, MTZS was rapidly cleaved to liberate MTZ on incubation with the cecal contents of rats. MTZ liberated from MTZS metabolized quickly at least partly by a microbial nitroreductase, suggesting the relevance of the metabolism to bioactivation of MTZ for antimicrobial action. Consistent with the hypothesis, MTZS elicited antibacterial activity in the cecal contents, which was as potent as free MTZ. The systemic absorption of MTZS was very low after oral administration of MTZS. In parallel with this, whereas MTZ disappeared mostly during the transit of the proximal small intestine, a substantial amount of MTZS remained in the small intestine, moving down to the large intestine where it metabolized rapidly. In addition to the efficient colonic delivery of MTZS, MTZS markedly reduced the systemic absorption of MTZ. Taken together, MTZS may be a potential colon-specific prodrug of MTZ which possesses improved therapeutic and toxicological properties.

  10. Comparison of cefixime and amoxicillin plus metronidazole in the treatment of chronic periodontitis.

    PubMed

    Dukić, Smiljka; Matijević, Stevo; Daković, Dragana; Cutović, Tatjana

    2016-06-01

    Despite significant advances in current medicine and improvement of overall health education, chronic periodontitis is still a widespread disease. Losing teeth is the most serious complication of this particular illness. The aim of this study was to examine patients with chronic periodontitis in order to evaluate the efficacy of non-surgical therapy and combination of amoxicillin and metronidazole compared with cefixime, which has not been so far used for the treatment of this disease. Adult patients with chronic periodontitis (n = 90) underwent non-surgical periodontal treatment (zero-day) and then randomly divided into three groups. The group I served as a control, the group II was additionally treated with the combination of amoxicillin and metronidazole (for 7 days), while the group III was treated with cefixime (also for 7 days). To assess the condition of periodontium before and seven days after the therapy, four clinical parameters were used: gingival index (GI), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL). On the day 7 after the beginning of the therapy, we found that all the three groups of patients had statistically significant clinical improvement of three parameters: GI, BOP and PD, but not of the CAL. However, the improvement of PD was only statistically, but not clinically significant. The improvement in the control group of patients on the day 7 was 19% in BOP and 28% in GI; this improvement was statistically highly significant after the addition of amoxicillin plus metronodazole (71% in BOP and 77% in GI) or cefixime (62% in BOP and 82% in GI). Compared to the combination of amoxicillin and metronidazole, cefixim was statistically significantly more effective for GI (p < 0.05), while for the other three clinical parameters their effects were equal. The conjunction of amoxicillin plus metronidazole or cefixime to the causal treatment of patients with chronic periodontitis led to statistically significant

  11. One year results of a randomized controlled clinical study evaluating the effects of non-surgical periodontal therapy of chronic periodontitis in conjunction with three or seven days systemic administration of amoxicillin/metronidazole

    PubMed Central

    Cosgarea, Raluca; Heumann, Christian; Juncar, Raluca; Tristiu, Roxana; Lascu, Liana; Salvi, Giovanni E.; Arweiler, Nicole B.; Sculean, Anton

    2017-01-01

    Background To evaluate the clinical outcomes 12 months after systemic administration of amoxicillin (AMX) and metronidazole (MET) adjunctive to subgingival debridement (SD) in patients with severe chronic periodontitis (sChP). Material and methods 102 patients with sChP were treated randomly as follows: SD within 2 consecutive days and placebo for 7 days (group A), SD+AMX+MET (both 500mg x3 times daily TID) for 3 days (group B), SD+AMX+MET (both 500mg x 3 TID) for 7 days (group C). At baseline, at 3-, 6-, and 12-months post-treatment probing pocket depth (PD), clinical attachment level (CAL), furcation involvement, bleeding on probing (BOP), full-mouth plaque score (FMPS) were determined. The reduction in the number of sites with PD≥6mm was defined as main outcome variable. Results 75 patients completed the study. At 12 months, all three treatment groups showed statistically significant improvements (p<0.001) of mean PD, CAL, BOP and number of sites with PD≥6mm compared to baseline. Mean residual PD were statistically significantly lower and CAL gain statistically significantly greater in the two antibiotic groups as compared to placebo. While PD reductions (p = 0.012) and CAL gain (p = 0.017) were statistically significantly higher in group C compared to group A, only the 3-day AB group showed statistically significantly fewer sites with PD≥6mm at 12 m (p = 0.003). The reduction in the number of sites with PD≥6 mm (primary outcome) showed no statistical significant differences between the 3 treatment groups. However, in both antibiotic groups significantly more patients compared to the placebo group reached a low risk for disease progression at 12 months (≤4 sites with PD≥5mm). Conclusion At 12 months, both adjunctive antibiotic protocols resulted in statistically significantly greater clinical improvements compared to placebo. PMID:28662049

  12. The Rigid Curette Technique for the Application of Fibrin Bioadhesive During Hip Arthroscopy for Articular Cartilage Lesions

    PubMed Central

    Asopa, Vipin; Singh, Parminder J.

    2014-01-01

    Encouraging midterm results have recently been reported for the arthroscopic treatment of delaminating articular cartilage lesions at the capsulolabral junction of the hip joint using fibrin bioadhesive. The needle used to introduce the bioadhesive is long, flexible, and often difficult to position. We describe a novel technique for introducing the needle that allows accurate placement behind the delaminated articular cartilage pocket during hip arthroscopy. PMID:24904770

  13. Effects of metronidazole and its metabolites on histamine immunosuppression activity.

    PubMed

    Elizondo, G; Ostrosky-Wegman, P

    1996-01-01

    We have previously reported that metronidazole treatment increases human lymphocyte proliferation showing individual differences. This drug and its metabolites are imidazole compounds like histamine and cimetidine. The first is an endogenous amine that inhibits T-helper lymphocyte proliferation, and the second is a histamine antagonist. We presently report the in vitro effects of histamine, cimetidine, imidazole, metronidazole and its two principal metabolites (the acetic acid and hydroxy forms), on the mitogenic response to phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes. Histamine decreased lymphocyte proliferation while (in order of potency) cimetidine, the hydroxy metabolite of metronidazole, imidazole and metronidazole, increased the mitogenic response to PHA in a dose-response fashion. The acetic acid metabolite lacked immunomodulatory effects. Competitive studies showed that cimetidine, metronidazole, and the hydroxy metabolite blocked the inhibitory effect of histamine on lymphocyte proliferation in a dose-related manner. This blockage was non-competitive, suggesting that the target of the imidazole compounds was not the active site of the H2 receptor.

  14. Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis.

    PubMed

    Schuyler, Jessica A; Mordechai, Eli; Adelson, Martin E; Sobel, Jack D; Gygax, Scott E; Hilbert, David W

    2016-01-01

    Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G. vaginalis has a population structure that consists of 4 clades: clades 1 and 3 are associated with BV, whereas clades 2 and 4 are not. To determine if metronidazole susceptibility is associated with population structure, we analyzed 87 clinical isolates and found that metronidazole resistance (MIC ≥32 μg/mL) was highly associated with clade (P<0.0001), as 14/14 clade 3 isolates (100%) and 22/22 clade 4 isolates (100%) exhibited resistance, compared to only 16/37 clade 1 isolates (35%) and 1/14 clade 2 isolates (7.1%). The identification of intrinsically metronidazole-resistant G. vaginalis clades will facilitate future studies on the relationship between metronidazole resistance and BV treatment failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Prevalence of metronidazole-resistant Helicobacter pylori in dyspeptic patients.

    PubMed

    Xia, H X; Daw, M A; Beattie, S; Keane, C T; O'Morain, C A

    1993-03-01

    Susceptibility to metronidazole of 213 clinical strains of H. pylori from dyspeptic patients was determined by a plate dilution method. Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189). The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p < 0.001). The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%). There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%). These data indicated that metronidazole resistance in H. pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation. Therefore, testing of susceptibility of H. pylori to metronidazole is important. A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform.

  16. A meta-analysis of metronidazole and vancomycin for the treatment of Clostridium difficile infection, stratified by disease severity.

    PubMed

    Di, Xiuzhen; Bai, Nan; Zhang, Xin; Liu, Bin; Ni, Wentao; Wang, Jin; Wang, Kai; Liang, Beibei; Liu, Youning; Wang, Rui

    2015-01-01

    The aim of this meta-analysis was to compare the efficacy of metronidazole and vancomycin for the treatment of Clostridium difficile infection, especially to investigate which agent was superior for treating either mild or severe C. difficile infection. A meta-analysis of randomized controlled trials and cohort studies identified in Pubmed, Embase, and the Cochrane Library was conducted. Four randomized controlled trials and two cohort studies involving 1218 patients were included in this meta-analysis. Metronidazole was inferior to vancomycin for treating C. difficile infection in terms of both initial clinical cure rates (risk ratio, RR=0.91, 95% confidence interval, CI=0.84-0.98, p=0.02) and sustained cure rates (RR=0.88, 95% CI=0.82-0.96, p=0.003). For mild C. difficile infection, the efficacy of metronidazole and vancomycin resulted in similar clinical cure rates (RR=0.94, 95% CI=0.84-1.04, p=0.21) and sustained cure rates (RR=0.93, 95% CI=0.83-1.05, p=0.26). For severe C. difficile infection the efficacy of vancomycin was superior to metronidazole in terms of clinical cure rates (RR=0.81, 95% CI=0.69-0.95, p=0.009), whereas sustained cure rates were similar (RR=0.86, 95% CI=0.72-1.02, p=0.08). Regarding microbiological cure metronidazole therapy was as effective as vancomycin therapy (RR=0.88, 95% CI=0.64-1.21, p=0.43). Recurrence rates with metronidazole and vancomycin for both mild C. difficile infection (RR=0.95, 95% CI=0.56-1.60, p=0.85) and severe C. difficile infection (RR=1.27, 95% CI=0.85-1.91, p=0.25) were not different. Likewise, no difference in all-cause mortality was found as well (RR=0.87, 95% CI=0.56-1.35, p=0.53). In conclusion, vancomycin provides improved initial clinical and sustained cure rates in patients with C. difficile infection compared with metronidazole, especially in patients with severe C. difficile infection. In view of these data, vancomycin may be considered first line therapy for severe C. difficile infection. Copyright

  17. [Metronidazole-resistant trichomoniasis and successful therapy following high dosage].

    PubMed

    Weihe, J; Metelmann, C; Borner, K; Meingassner, J; Orfanos, C E

    1988-04-01

    A patient is reported who suffered for several months from a Trichomonas vaginalis infection that was resistant to the usual low-dose treatment with 5-nitro-imidazole derivatives. Following various ineffective therapeutic trials, the agent was isolated in order to determine its sensitivity to 5-nitro-imidazole. The resistance of the isolate to metronidazole was confirmed in vitro and in an animal experiment; the patient was therefore treated with high daily doses of metronidazole, 3 x 750 mg orally as well as 2 x 100 mg topically for 14 days. Substitution therapy with zinc was administered in order to normalize the patient's relatively low zinc serum levels. These measures finally led to a clinical cure and elimination of the pathogenic agent. This is the first confirmed case of a metronidazole-resistant Trichomonas vaginalis infection reported in the Federal Republic of Germany.

  18. Metronidazole-Induced Bullous Pemphigoid: A Case Report

    PubMed Central

    Moitra, Saibal; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-01-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  19. The influence of stabilizer and bioadhesive polymer on the permeation-enhancing effect of AT1002 in the nasal delivery of a paracellular marker.

    PubMed

    Song, Keon-Hyoung; Eddington, Natalie D

    2012-02-01

    Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential. Thus, this paper focused on the susceptibility of AT1002 for identifying additives to minimize the instability of AT1002, and the permeation-enhancing effect of AT1002 when co-administered with a bioadhesive polymer. The stability study showed that AT1002 were unstable in neutral to basic pH conditions and with increasing incubation time, and 5% dextrose and the 1% mixture of amino acids (arginine, cysteine, glycine) significantly minimized the instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the intranasal study of a paracellular marker, the administration of mannitol with AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17-fold increases in C(max) and AUC(0-360min) in the presence of carrageenan over the control. Thus, the addition of carrageenan as a bioadhesive polymer and dextrose as a stabilizer together with AT1002 may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents.

  20. Failure of thiabendazole and metronidazole in the treatment and suppression of guinea worm disease.

    PubMed

    Belcher, D W; Wunapa, F K; Ward, W B

    1975-05-01

    Guinea worm disease is endemic in West Africa. In 1973 a field drug trial was conducted to compare effectiveness, cost, and side-effects of thiabendazole and metronidazole in treating active guinea worm disease and preventing latent worms from emerging. A mass chemotherapy campaign was planned to follow the drug trial. Only 15.5% of the treated patients expelled the worm completely, and in 28.4% of the cases worms continued to appear. Both drugs were equally unsatisfactory in their anti-helminthic effect. Consequently, our efforts to control guinea worm have shifted from chemotherapy to chemical control of cyclops and improvement of rural water supplies.

  1. [Mycoplasma hominis symbiosis and Trichomonas vaginalis metronidazole resistance].

    PubMed

    Wang, Pin-Jia; Xie, Cheng-Bin

    2012-06-30

    To investigate the relation of Mycoplasma hominis symbiosis and the resistance of Trichomonas vaginalis to metronidazole. From November 2010 to July 2011, 160 isolates of T. vaginalis were collected from the genital tract secretion of gynecological out-patients at the Sichuan Provincial Hospital for Women and Children. The minimum lethal concentration (MLC) to metronidazole of these isolates was determined by an in vitro sensitivity assay with different concentration gradients of metronidazole (from 1 to 1 024 microg/ml), and M. hominis DNA in T. vaginalis was detected by polymerase chain reaction (PCR) technique with specific 16S rRNA primers. After clearance of M. hominis from the parasites by 32 microg/ml doxycycline, MLC was determined and compared with that before clearance. MLC of metronidazole in T. vaginalis ranged from 1 to 256 microg/ml, with 61.3% isolates (98/160) ranging from 1 to 8 microg/ml, 26.3% isolates (42/160) ranging from 16 to 32 microg/ml, and 12.5% isolates (20/160) ranging from 64 to 256 microg/ml. 61 isolates were PCR positive for M. hominis DNA in the 160 isolates of T. vaginalis. The M. hominis DNA positive rate was significantly higher in the T. vaginalis isolates with higher MLC than those isolates with lower MLC (P<0.01). However, when M. hominis was cleared by doxycycline from 8 isolates among the 61 ones, no change was observed in sensitivity of the isolates to metronidazole. M. hominis symbiosis might be associated with the metronidazole-resistance of T. vaginalis. However, it needs direct evidence.

  2. Metronidazole hydrazone conjugates: Design, synthesis, antiamoebic and molecular docking studies.

    PubMed

    Ansari, Mohammad Fawad; Siddiqui, Shadab Miyan; Agarwal, Subhash M; Vikramdeo, Kunwar Somesh; Mondal, Neelima; Azam, Amir

    2015-09-01

    Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Structuring of composite hydrogel bioadhesives and its effect on properties and bonding mechanism.

    PubMed

    Pinkas, Oded; Goder, Daniella; Noyvirt, Roni; Peleg, Sivan; Kahlon, Maayan; Zilberman, Meital

    2017-03-15

    Bioadhesives are polymeric hydrogels that can adhere to a tissue after crosslinking and are an essential element in nearly all surgeries worldwide. Several bioadhesives are commercially available. However, none of them are ideal. The main limitation of current tissue adhesives is the tradeoff between biocompatibility and mechanical strength, especially in wet hemorrhagic environments. Our novel bioadhesives are based on the natural polymers gelatin (coldwater fish) and alginate, crosslinked by carbodiimide (EDC). Two types of hemostatic agents with a layered silicate structure, montmorillonite (MMT) and kaolin, were loaded in order to improve the sealing ability in a hemorrhagic environment. The effect of the adhesive's components on its mechanical strength was studied by three different methods - burst strength, lap shear and compression. The viscosity, gelation time and structural features of the adhesive were also studied. A qualitative model that describes the effect of the bioadhesive's parameters on the cohesive and adhesive strength was developed. A formulation based on 400mg/mL gelatin, 10mg/mL alginate and 20mg/mL EDC was found as optimal, enabling a burst strength of 387mmHg. Incorporation of kaolin increased the burst strength by 25% due to microcomposite structuring, whereas MMT increased the burst strength by 50% although loaded in a smaller concentration, due to nano-structuring effects. This research clearly shows that the incorporation of kaolin and MMT in gelatin-alginate surgical sealants is a very promising novel approach for improving the bonding strength and physical properties of surgical sealants for use in hemorrhagic environments.

  4. Physical-mechanical, moisture absorption and bioadhesive properties of hydroxypropylcellulose hot-melt extruded films.

    PubMed

    Repka, M A; McGinity, J W

    2000-07-01

    The objective of this study was to investigate the moisture absorption, physical-mechanical and bioadhesive properties of hot-melt extruded hydroxypropylcellulose (HPC) films containing polymer additives. These additives included polyethylene glycol (PEG) 5%, polycarbophil 5%, carbomer 5%, Eudragit E-100 5%, and sodium starch glycolate (SSG) 5%. Relative humidity (RH) and temperature parameters of the films studied included 25 degree C at 0, 50, 80 and 100% RH, and 40 degrees C at 0 and 100% RH, stored for 2 weeks. Tensile strength and percent elongation were determined on an Instron according to the ASTM standards. The bioadhesive properties of the HPC/PEG 3350 5% film and the polycarbophil 5% containing films, with and without PEG, were investigated in vivo on the human epidermis. Although all films studied exhibited an increase in percent water content as the percent RH increased, the SSG containing film exhibited an almost three-fold increase in percent water content compared to that of the HPC/PEG film. The temperature storage condition of 40 degrees C/100% RH (versus 25 degrees C/100% RH) increased the percent water content of the SSG containing film. Percent elongation was highest for films containing polycarbophil 5% (without PEG). In addition, the HPC film containing polycarbophil 5% exhibited a greater force of adhesion and elongation at adhesive failure in vivo, and a lower modulus of adhesion when compared to the HPC/PEG film. A novel approach to determine bioadhesion of films to the human epidermis is presented.

  5. Formulation of Topical Bioadhesive Gel of Aceclofenac Using 3-Level Factorial Design

    PubMed Central

    Singh, Sanjay; Parhi, Rabinarayan; Garg, Anuj

    2011-01-01

    The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations. PMID:24250375

  6. Tensile bond strength of a polymeric intra-buccal bioadhesive: the mucin role.

    PubMed

    Pedrazzi, V; Lara, E H; Dal Ciampo, J O; Panzeri, H

    2001-01-01

    The intra-bucal polymeric bioadhesive systems that can stay adhered to the oral soft tissues for drug programmed release, with the preventive and/or therapeutic purpose have been employed for large clinical situations. A system based on hydroxypropyl methyl cellulose/Carbopol 934TM/magnesium stearate (HPMC/Cp/StMg), was developed with the sodium fluoride as an active principle. This kind of system was evaluated according to its resistance to the removal by means of physical test of tensile strength. Swine buccal mucosa extracted immediately after animals' sacrifice was employed as a substrate for the physical trials to obtain 16 test bodies. Artificial saliva with or without mucin was used to involve the substrate/bioadhesive system sets during the trials. Artificial salivas viscosity were determined by means of Brookfield viscometer, and they showed 10.0 cP artificial saliva with mucin, and 7.5 cP artificial saliva without mucin. The tensile strength assays showed the following averages: 12.89 Pa for the group "artificial saliva with mucin", and 12.35 Pa for the group "without mucin". Statistical analysis showed no significant difference between the assays for both artificial salivas, and we can conclude that the variable mucin did not interfere with the bioadhesion process for the polymeric devices.

  7. Temperature Stability and Bioadhesive Properties of Δ9-Tetrahydrocannabinol Incorporated Hydroxypropylcellulose Polymer Matrix Systems

    PubMed Central

    Repka, Michael A.; Munjal, Manish; ElSohly, Mahmoud A.; Ross, Samir A.

    2010-01-01

    The purpose of this study was to determine and compare the bioadhesive profiles of hydroxypropylcellulose (HPC) polymer matrices as a function of Δ9-tetrahydrocannabinol (THC) content. In addition, the effect of processing temperature on the stability of THC and its extent of degradation to cannabinol (CBN) was investigated. A hot-melt cast molding method was used to prepare HPC polymer matrix systems incorporated with THC at 0, 4, 8, and 16 percent. Bioadhesive measurements including peak adhesive force, area under the curve, and elongation at adhesive failure were recorded utilizing the TA.XT2i Texture Analyzer™. Data obtained from these tests at various contact time intervals suggested that the incorporation of THC led to an increase in the bioadhesive strength of the HPC polymer matrices. To determine the stability of THC and the resulting CBN content in the matrices, three different processing temperatures were utilized (120, 160, and 200°C). Post-production High Performance Liquid Chromotography (HPLC) analysis revealed that the processed systems contained at least 94% of THC and the relative percent formation of CBN was 0.5% at 120°C and 0.4% at 160°C compared to 1.6% at 200°C. These findings indicate that the cannabinoid may be a plausible candidate for incorporation into systems utilizing hot-melt extrusion techniques for the development of an effective mucoadhesive transmucosal matrix system for delivery of THC. PMID:16455601

  8. Peptide derived from Pvfp-1 as bioadhesive on bio-inert surface.

    PubMed

    Jiang, Zhen; Yu, Yabiao; Du, Lina; Ding, Xiyu; Xu, Hui; Sun, Yanan; Zhang, Qiqing

    2012-02-01

    Surface property is one important characteristic of materials, especially for ones that are bio-inert but designed for bio-medical application. In this study, we designed a series of peptides and compared their capacities as bioadhesive to improve the surface bioactivity of bio-inert material. The peptides were designed according to the sequence of Perna viridis foot protein 1 (Pvfp-1), one of the Mfp-1s (mussel foot protein 1) which play key roles in wet adhesion of mussel byssus. And the Teflon (PTFE) was chosen as a model of bio-inert material. With adsorption, adhesion and coating analysis, it was found that peptide C2 (M) (derived from the non-repeating region of Pvfp-1, contains modified DOPA) has superior coating and adhesion abilities especially on the bio-inert surface of PTFE. After coating with peptide C2 (M), the cell adhesion and spreading of osteoblast MC3T3-E1 cells on PTFE were significantly improved compared with those on non-coated surface, and the peptide-coating did not show any cell toxicity. Therefore, peptide C2 (M) is effective for improving the bioactivity of bio-inert PTFE, and could be potentially used as a bioadhesive on other bio-inert materials for biomedical application. Moreover, this study also provided new insights in designing other peptide-based bioadhesive materials.

  9. Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins.

    PubMed

    Li, Ying; Zhang, Yun; Zhu, Chun-Yan

    2017-02-01

    The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  10. Poly(acrylic acid-co-methyl methacrylate)/metronidazole systems: synthesis and complexation.

    PubMed

    Bialik-Wąs, Katarzyna; Pielichowski, Krzysztof

    2013-01-01

    We report on preparation of poly(acrylic acid-co-methyl methacrylate) (PAM) micro- and nanoparticles and, in the subsequent stage, complexation reaction with the active substance - metronidazole (MET). The drug release behavior of MET - loaded PAM micro- and nanoparticles was evaluated in water and phosphate buffered saline (PBS, 0.9% NaCl) at 37ºC. It has been found that introduction of MET into PAM micro- and nanoparticles enabled gradual and controlled release of the active substance. Structural analysis using FT-IR (ATR) and (1)H NMR, as well as surface morphology assessment by SEM, were performed.

  11. Investigation of Metronidazole Use during Pregnancy and Adverse Birth Outcomes

    PubMed Central

    Koss, Catherine A.; Baras, Dana C.; Lane, Sandra D.; Aubry, Richard; Marcus, Michele; Markowitz, Lauri E.

    2012-01-01

    To assess whether treatment with metronidazole during pregnancy is associated with preterm birth, low birth weight, or major congenital anomalies, we conducted chart reviews and an analysis of electronic data from a cohort of women delivering at an urban New York State hospital. Of 2,829 singleton/mother pairs, 922 (32.6%) mothers were treated with metronidazole for clinical indications, 348 (12.3%) during the first trimester of pregnancy and 553 (19.5%) in the second or third trimester. There were 333 (11.8%) preterm births, 262 (9.3%) infants of low birth weight, and 52 infants (1.8%) with congenital anomalies. In multivariable analysis, no association was found between metronidazole treatment and preterm birth (odds ratio [OR], 1.02 [95% confidence interval [CI], 0.80 to 1.32]), low birth weight (OR, 1.05 [95% CI, 0.77 to 1.43]), or treatment in the first trimester and congenital anomalies (OR, 0.86 [0.30 to 2.45]). We found no association between metronidazole treatment during the first or later trimesters of pregnancy and preterm birth, low birth weight, or congenital anomalies. PMID:22751543

  12. Sudden death due to metronidazole/ethanol interaction.

    PubMed

    Cina, S J; Russell, R A; Conradi, S E

    1996-12-01

    Metronidazole (Flagyl), a commonly prescribed antimicrobial agent, can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol. This drug/chemical interaction results in accumulation of acetaldehyde in the blood. Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic; no lethal serum acetaldehyde level has been established. Sudden death has been reported in patients taking disulfiram while using ethanol; no fatalities have been reported due to ethanol/ metronidazole interactions. Described is a case of a 31-year-old woman who died moments after an assault by a male companion, during which he inflicted minor physical trauma to her upper arm. Toxicologic analysis yielded elevated concentrations of serum ethanol (162 mg/d), acetaldehyde (4.6 mg/d), and metronidazole (0.42 mg/L). The cause of death was reported to be cardiac dysrhythmia due to acetaldehyde toxicity due to an ethanol/ metronidazole interaction. Autonomic stress associated with the assault is likely to have contributed to this woman's death. The mechanism of death is examined.

  13. Metronidazole in the treatment of non-specific vaginitis (NSV).

    PubMed Central

    Jerve, F; Berdal, T B; Bohman, P; Smith, C C; Evjen, O K; Gjønnaess, H; Gaasemyr, M; Hausken, L; Hesla, K; Hoftvedt, E

    1984-01-01

    In a large multicentre study of 429 patients with the usual signs and symptoms of non-specific vaginitis (NSV), we studied the effect of different doses of metronidazole. The patients were divided into five treatment groups as follows: group A was given 400 mg metronidazole three times daily for seven days, group B 2000 mg as a single dose, group C 2000 mg on days 1 and 2, group D 2000 mg on days 1 and 3, and group E was given 1200 mg metronidazole once daily for five days. At follow up examination four weeks from the start of treatment, patients in groups D and E showed the best clinical results with cure rates of 94.0% and 93.6% respectively. In addition the rate of reisolation of Gardnerella vaginalis was lowest in group D. We therefore recommend metronidazole 2000 mg on days 1 and 3 as routine treatment for non-specific or vaginitis associated with gardnerella. PMID:6375804

  14. [Metronidazole effect on active oxygen production by human blood neutrophils].

    PubMed

    Shchepetkin, I A

    1997-01-01

    The in vitro effect of metronidazole on production of active oxygen by neutrophila and in the enzymatic system of glucose-glucose oxidase-peroxidase was studied by luminol-dependent chemiluminescence. An increase in the spontaneous and zymozan-stimulated chemiluminescence and a decrease in the phorbolmyristate acetate (PMA)-stimulated chemiluminescence after 2-hour preincubation of the neutrophils with 8.5 mM of metronidazole were observed. In concentrations of 0.9 to 8.7 mM metronidazole (without washing) dose-dependently lowered the neutrophil chemiluminescence in response to the effect of PMA and ionophore A23187 and to a lesser degree to that of zymozan. In doses of 20 to 100 mM the drug had an insignificant effect on production of active oxygen by the neutrophils in response to the cell stimulation by PMA, ionophore A23187 and zymozan. The data are in conformity with the scavenger effect of metronidazole on active oxygen radicals generating in the cell-free enzymatic system both in the presence and in the absence of superoxide dismutase.

  15. A Redox Basis for Metronidazole Resistance in Helicobacter pylori▿

    PubMed Central

    Kaakoush, N. O.; Asencio, C.; Mégraud, F.; Mendz, G. L.

    2009-01-01

    Metronidazole resistance in Helicobacter pylori has been attributed to mutations in rdxA or frxA. Insufficient data correlating RdxA and/or FrxA with the resistant phenotype, and the emergence of resistant strains with no mutations in either rdxA or frxA, indicated that the molecular basis of H. pylori resistance to metronidazole required further characterization. The rdxA and frxA genes of four matched pairs of metronidazole-susceptible and -resistant strains were sequenced. The resistant strains had mutations in either rdxA, frxA, neither gene, or both genes. The reduction rates of five substrates suggested that metabolic differences between susceptible and resistant strains cannot be explained only by mutations in rdxA and/or frxA. A more global approach to understanding the resistance phenotype was taken by employing two-dimensional gel electrophoresis combined with tandem mass spectrometry analyses to identify proteins differentially expressed by the matched pair of strains with no mutations in rdxA or frxA. Proteins involved in the oxireduction of ferredoxin were downregulated in the resistant strain. Other redox enzymes, such as thioredoxin reductase, alkyl hydroperoxide reductase, and superoxide dismutase, showed a pI change in the resistant strain. The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance. PMID:19223619

  16. Tinidazole vs metronidazole for the treatment of bacterial vaginosis.

    PubMed

    Schwebke, Jane R; Desmond, Renee A

    2011-03-01

    The purpose of this study was to compare the efficacy of 2 different doses of tinidazole with metronidazole for the treatment of bacterial vaginosis and to compare the side effects of the drugs. Women were assigned randomly to receive metronidazole 500 mg twice daily, tinidazole 500 mg twice daily, or tinidazole 1 g twice, all for 7 days. Follow-up visits were conducted at days 14 and 28. Five hundred ninety-three women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at 1 month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have bacterial vaginosis at the follow-up visit. There were no significant differences in adverse events across treatment arms. There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens that were studied. In addition, there were no important differences in the side-effect profiles of metronidazole and tinidazole. Copyright © 2011 Mosby, Inc. All rights reserved.

  17. Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant Giardia, Trichomonas, and Entamoeba spp.

    PubMed Central

    Upcroft, Jacqueline A.; Campbell, Raymond W.; Benakli, Kamel; Upcroft, Peter; Vanelle, Patrice

    1999-01-01

    The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via SRN1 and subsequent reactions, were assayed against the protozoan parasites Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica. Two metronidazole-sensitive lines and two metronidazole-resistant lines of Giardia and one line each of metronidazole-sensitive and -resistant Trichomonas were tested. All except one of the compounds were as effective or more effective than metronidazole against Giardia and Trichomonas, but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against Entamoeba. Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas. However, some drugs were lethal to metronidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole. PMID:9869568

  18. Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

    PubMed

    Powers, Anna; Loesch, Erin B; Weiland, Anthony; Fioravanti, Nicole; Lucius, David

    2017-07-01

    To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard

  19. Depletion of metronidazole in brook trout (Salvelinus fontinalis).

    PubMed

    Watson, Lynn; MacNeil, James D; Potter, Ross; Hellou, Jocelyne

    2015-01-01

    Metronidazole (MNZ), which is effective in the treatment of intestinal infections in fish, is also a suspected carcinogen and has been banned in numerous jurisdictions for use in any food-producing animal, including fish. Few reports have been published on the depletion of MNZ in fish. A depletion study was therefore undertaken using MNZ in feed provided to trout under controlled conditions. The water was maintained at 17.5 ± 0.9°C throughout the medication and depletion periods in the study. Following a 20-day acclimatisation period in the holding tanks, the trout (approximately 150-200 g bodyweight at the start of the study) were subjected to two separate medication and withdrawal periods: (A) 5 day medication/5 day withdrawal and (B) 5 day medication/16 day withdrawal. This simulated a potential multiple dosing in an aquaculture setting. In both medication periods, the trout were dosed with medicated feed containing 3 g MNZ kg(-1) fish. Fish were sacrificed in accordance with accepted animal care protocols and tissue samples were analysed by UPLC-MS/MS. Analyte concentrations in trout muscle ranged from a high of 27,000 ± 10,000 ng g(-1) for MNZ and 830 ± 570 ng g(-1) for MNZ-OH on day 1 of withdrawal period A to a low of 1.8 ± 2.3 ng g(-1) for MNZ and < 0.4 ng g(-1) for MNZ-OH on day 16 of withdrawal period B. The results demonstrate that when using the UPLC-MS/MS method, residues of MNZ may be detected in fish treated with MNZ after 16 days of withdrawal.

  20. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives

    PubMed Central

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-01-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID:26874283

  1. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives.

    PubMed

    Guo, Jinshan; Wang, Wei; Hu, Jianqing; Xie, Denghui; Gerhard, Ethan; Nisic, Merisa; Shan, Dingying; Qian, Guoying; Zheng, Siyang; Yang, Jian

    2016-04-01

    Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long-term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti-bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Comparative evaluation of locally delivered minocycline and metronidazole in the treatment of periodontitis

    PubMed Central

    Pandit, Nymphea; Dahiya, Ritu; Gupta, Rajan; Bali, Deepika; Kathuria, Abhinav

    2013-01-01

    Objective: The aim of this study was to evaluate and compare the efficacy of subgingivally delivered Minocycline microspheres and 25% Metronidazole gel when used as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. Materials and Methods: A randomized, controlled, single center study was conducted involving 60 sites in 20 patients suffering from moderate to advanced chronic periodontitis. Each patient contributed three sites which were randomized to three treatment groups: SRP + insertion of Minocycline microspheres at day 1 (Group A), SRP + insertion of Metronidazole gel at day 1 and at day 7 (Group B), and SRP alone (Group C). Gingival index (GI), plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded at day 1, 1 month, and 3 months post therapy. Results: All treatments showed significant reductions in PPD and CAL at 1 and 3 months when compared to baseline values (P < 0.001). At 3 months, sites treated with minocycline showed an additional reduction in PPD of 0.85 ± 0.03 mm, significantly greater than SRP alone. Differences in mean PPD reduction between Group B and Group C and between Group A and Group B were not significant. At 3 months, difference in CAL gain between Group A and C was 0.50 ± 0.45, which was statistically significant and between Group B and C was 0.35 ± 0.11, which was not found to be statistically significant (P = 0.20). Differences in relative CAL between Group A and Group B were also not found to be statistically significant (P = 0.53). Conclusion: The results concluded that treatment with Minocycline microspheres and Metronidazole gel improve PPD and CAL in patients with periodontitis compared to SRP alone. PMID:23853452

  3. Comparative evaluation of locally delivered minocycline and metronidazole in the treatment of periodontitis.

    PubMed

    Pandit, Nymphea; Dahiya, Ritu; Gupta, Rajan; Bali, Deepika; Kathuria, Abhinav

    2013-01-01

    The aim of this study was to evaluate and compare the efficacy of subgingivally delivered Minocycline microspheres and 25% Metronidazole gel when used as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. A randomized, controlled, single center study was conducted involving 60 sites in 20 patients suffering from moderate to advanced chronic periodontitis. Each patient contributed three sites which were randomized to three treatment groups: SRP + insertion of Minocycline microspheres at day 1 (Group A), SRP + insertion of Metronidazole gel at day 1 and at day 7 (Group B), and SRP alone (Group C). Gingival index (GI), plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded at day 1, 1 month, and 3 months post therapy. All treatments showed significant reductions in PPD and CAL at 1 and 3 months when compared to baseline values (P < 0.001). At 3 months, sites treated with minocycline showed an additional reduction in PPD of 0.85 ± 0.03 mm, significantly greater than SRP alone. Differences in mean PPD reduction between Group B and Group C and between Group A and Group B were not significant. At 3 months, difference in CAL gain between Group A and C was 0.50 ± 0.45, which was statistically significant and between Group B and C was 0.35 ± 0.11, which was not found to be statistically significant (P = 0.20). Differences in relative CAL between Group A and Group B were also not found to be statistically significant (P = 0.53). The results concluded that treatment with Minocycline microspheres and Metronidazole gel improve PPD and CAL in patients with periodontitis compared to SRP alone.

  4. Changes in the Vaginal Microenvironment with Metronidazole Treatment for Bacterial Vaginosis in Early Pregnancy

    PubMed Central

    Balkus, Jennifer; Agnew, Kathy; Lawler, Richard; Hitti, Jane

    2009-01-01

    Abstract Objective Bacterial vaginosis (BV) is associated with preterm delivery, but there is little evidence that treatment improves pregnancy outcomes. We examined whether oral or vaginal metronidazole treatment for BV in early pregnancy was more effective in restoring the normal vaginal environment. Methods This was a randomized controlled trial comparing oral and intravaginal metronidazole for treatment of BV in early pregnancy (<20 weeks). Vaginal samples collected at baseline and 4 weeks after treatment were evaluated using gram stain, culture, colorimetric detection of sialidase, and immunoassay for measurement of proinflammatory cytokines interleukins-1β, -6, -8 (IL-1β, IL-6, IL-8) and secretory leukocyte protease inhibitor (SLPI). We compared the effect of treatment between groups (using chi-square and t test) and within individuals (McNemar's test). Results Of 126 subjects, 108 (86%) completed follow-up (55 oral, 53 intravaginal). Of the study population, 34% achieved therapeutic cure, and this was not different between treatment groups. BV-associated bacteria were significantly reduced in both groups, but few subjects regained colonization with protective lactobacilli. Among women who achieved therapeutic cure, the level of IL-1β dropped significantly (p < 0.001) and SLPI increased (p = 0.003). More women in the vaginal treatment group had undetectable sialidase after treatment (p = 0.013). Conclusions Treatment with oral or intravaginal metronidazole in early pregnancy reduced colonization with BV-associated bacteria but was not effective in achieving therapeutic cure or in restoring healthy vaginal lactobacilli. PMID:19951217

  5. Appearance of a metronidazole-resistant Helicobacter pylori strain in an infected-ICR-mouse model and difference in eradication of metronidazole-resistant and -sensitive strains.

    PubMed Central

    Matsumoto, S; Washizuka, Y; Matsumoto, Y; Tawara, S; Ikeda, F; Yokota, Y; Karita, M

    1997-01-01

    We tested whether antibiotic-resistant strains appeared in vivo after the failure of treatment using the Helicobacter pylori-infected euthymic mouse model. The numbers of colonies isolated from 56 ICR mice 2 weeks after 4 days of treatment with metronidazole (3.2, 10, or 32 mg/kg of body weight) or amoxicillin (1, 3.2 or 10 mg/kg), with treatment started 4 days after H. pylori CPY2052 inoculation, were counted, and the isolated strains were tested for their sensitivities to two antibiotics to rule out the presence of antibiotic-resistant strains. One metronidazole-resistant strain was detected in a mouse treated with 10 mg of metronidazole per kg, and the MIC of metronidazole for this strain was 25 microg/ml, compared to a MIC of 1.56 microg/ml for the original strain. However, no resistant strain was detected in the amoxicillin treatment group. After the examination described above, mice challenged with a metronidazole-resistant or -sensitive strain isolated from the stomach of a mouse were treated with metronidazole or amoxicillin. The metronidazole-resistant strain was more difficult to eradicate in vivo than the sensitive strain after treatment with metronidazole but not after treatment with amoxicillin. Thus, a metronidazole-resistant H. pylori strain was selected by insufficient treatment, but no resistant strain was selected with amoxicillin. Eradication of a metronidazole-resistant H. pylori strain in vivo required a higher dosage than eradication of a metronidazole-sensitive H. pylori strain. These results may explain one of the reasons for H. pylori treatment failure. PMID:9420026

  6. Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an In Vitro Polymicrobial Subgingival Biofilm Model

    PubMed Central

    Teles, Flavia; Starr, Jacqueline R.; Feres, Magda; Patel, Michele; Martin, Lynn

    2015-01-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs. PMID:25733510

  7. Effects of azithromycin, metronidazole, amoxicillin, and metronidazole plus amoxicillin on an in vitro polymicrobial subgingival biofilm model.

    PubMed

    Soares, Geisla M S; Teles, Flavia; Starr, Jacqueline R; Feres, Magda; Patel, Michele; Martin, Lynn; Teles, Ricardo

    2015-05-01

    Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy. In vitro biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an in vitro multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting in vitro biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (q = 0.0207) but 54% more than AMX (q = 0.0031), 72% more than MTZ (q = 0.0031), and 67% more than AZM (q = 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these in vitro multispecies biofilms than expected on the basis of the independent effects of the drugs.

  8. The effect of systemic metronidazole after non-surgical treatment in moderate and advanced periodontitis in young adults.

    PubMed

    Söder, P O; Frithiof, L; Wikner, S; Wouters, F; Engström, P E; Rubin, B; Nedlich, U; Söder, B

    1990-05-01

    The effect of adjunctive systemic metronidazole was studied in patients with moderate and advanced periodontitis recalcitrant to comprehensive non-surgical treatment. The material originated from a randomly selected part of the population aged 31 to 40 years. After non-surgical treatment of 149 patients, 98 with persisting pathological pockets greater than or equal to 5 mm (52 men and 46 women) became the subjects for the study. Clinical parameters were registered and pocket contents subjected to laboratory analysis. The subjects were randomized into two groups according to a code list known only by the manufacturer and the statistician. The test group took three 400 mg metronidazole tablets daily for 1 week and the control group took placebo tablets. Reassessment 6 months later showed statistically significant clinical improvement, with a reduction in the number of sites greater than or equal to 5 mm in both test and control groups. Complete healing, with no pockets greater than or equal to 5 mm, was noted in 30% of the test group and 9% of the control group. The difference is statistically significant and shows the supplementary effect of adjunctive metronidazole in non-surgical treatment of moderate and advanced periodontitis.

  9. Study of the Influence of Formulation Variables in Bioadhesive Emulgels Using Response Surface Methodology.

    PubMed

    Ochoa-Andrade, Ana; Parente, M Emma; Jimenez-Kairuz, Álvaro; Boinbaser, Lucía; Torregrosa, Annibal

    2017-08-01

    The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels. The effects of concentration of carbomer interpolymer type A (Polym1), xanthan gum (Polym2) and mineral oil (Oil) on detachment force (Fdetch), spreadability (Spread), and phase separation by mechanical stress (PhSep) were investigated. RSM and desirability functions were applied for data analysis. Emulgels were further characterized by viscosity and extrudability measurements. Polym1 showed a positive effect on Fdetch, while the increase in concentrations of Polym2 and Oil decreased this property. Polym1 and Polym2 favored emulgel PhSep. However, their interaction effect decreased it. The combination of 0.4-0.6% of carbomer and 0.2-0.3% of gum was able to produce easy-to-spread bioadhesive emulgels with mineral oil as discontinuous phase in the presence of a low surfactant concentration. Based on the DoE results, value ranges for the variables, which could achieve for the experimental domain to get the critical quality attributes of emulgels jointly within the specification limits, were able to be identified using RSM supported by desirability functions.

  10. A case of metronidazole-resistant Trichomonas vaginalis in pregnancy.

    PubMed

    Forbes, Georgina L; Drayton, Rachel; Forbes, Gavin D

    2016-09-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in vulvo-vaginitis and altered vaginal discharge in symptomatic women. Trichomoniasis has been implicated in causing adverse pregnancy outcomes such as low birth weight and pre-term labour. Metronidazole is the recommended first-line treatment for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or re-infection, although metronidazole resistance has previously been documented. Antimicrobial susceptibility testing for T. vaginalis is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. We present the case of a patient with presumed resistant infection during pregnancy, and the additional treatment issues that this presented. © The Author(s) 2015.

  11. Crystal growth by solvent evaporation and characterization of metronidazole

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Ramachandran, E.

    2012-07-01

    Single crystals of metronidazole were crystallized by the slow solvent evaporation method and used as seeds to grow bulk crystals of size 8.0×6.5×2.0 mm3 using top-seeded submerged solution growth. The crystals were characterized using single crystal X-ray diffraction. Fourier transform infrared spectral analysis was made for the absorption bands of various functional groups present in the crystal. UV-vis absorption spectrum was used to identify the presence of nitroimidazole in metronidazole. Morphology study revealed that the growth is prominent along the c-axis and the prominent face is {010}. Thermal stability and thermal decomposition were analyzed using thermo calorimetry.

  12. Possible pharmacokinetic interaction with quinidine: ciprofloxacin or metronidazole?

    PubMed

    Cooke, C E; Sklar, G E; Nappi, J M

    1996-04-01

    To discuss a potential pharmacokinetic interaction between quinidine, ciprofloxacin, and metronidazole. A 51-year-old black woman was admitted for shortness of breath, abdominal pain, and atrial fibrillation. Procainamide and diltiazem were begun for the atrial fibrillation and ciprofloxacin and metronidazole for suspected diverticulitis. The therapy was switched to quinidine on day 5 because of adverse events associated with procainamide. A trough serum quinidine concentration (SQC) on day 7 was 6.3 micrograms/mL (normal 2-5) with normal QT and QTc intervals. On day 8, the patient was discharged in normal sinus rhythm. She took her last doses of antibiotics on day 15 and a follow-up SQC on day 18 was 2.3 micrograms/mL. The possible explanations for the changes in SQCs include: (1) laboratory error, (2) compliance with medication regimen, and (3) altered hepatic metabolism. The first two are not likely in this case. The laboratory verified the elevated SQC and the patient had her prescriptions refilled within appropriate time limits. The third explanation seems more plausible. Quinidine is metabolized by the hepatic mixed-function oxidase system, specifically cytochrome P450 (CYP) 3A4. We found that metronidazole has been shown to inhibit CYP3A activity and ciprofloxacin has been shown to inhibit certain isozymes in the cytochrome P450 system as well. When metronidazole and ciprofloxacin are administered concomitantly with quinidine, clinicians should be aware of this potential interaction. Quinidine concentrations should be monitored and patients should be assessed for signs and symptoms of quinidine toxicity.

  13. Efficacy of the treatment of dogs with leishmaniosis with a combination of metronidazole and spiramycin.

    PubMed

    Pennisi, M G; De Majo, M; Masucci, M; Britti, D; Vitale, F; Del Maso, R

    2005-03-12

    Twenty-seven dogs infected naturally with Leishmania infantum were used in a randomised controlled trial to compare the clinical and parasitological efficacy of an oral treatment with a combination of metronidazole and spiramycin (13 dogs) with the efficacy of conventional treatment with meglumine antimonate and allopurinol (14 dogs) as controls. In the test group one dog had to be withdrawn from the treatment because it developed pemphigus foliaceus; 10 of the dogs were clinically responsive but none was cured parasitologically. In the control group four dogs were withdrawn from the treatment because of side effects; eight of the dogs were clinically responsive but none was cured parasitologically. The control group showed signs of improvement after an average of 30 days, whereas the test group did not show signs of improvement until after an average of 45 days.

  14. Biowaiver monographs for immediate release solid oral dosage forms: metronidazole.

    PubMed

    Rediguieri, Camila F; Porta, Valentina; G Nunes, Diana S; Nunes, Taina M; Junginger, Hans E; Kopp, Sabine; Midha, Kamal K; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2011-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing metronidazole are reviewed. Metronidazole can be assigned to Biopharmaceutics Classification System Class I. Most BE studies that were identified reported the investigated formulations to be bioequivalent, indicating the risk of bioinequivalence to be low. Formulations showing differences in bioavailability showed dissimilarities in in vitro dissolution profiles. Furthermore, metronidazole has a wide therapeutic index. It is concluded that a biowaiver for solid IR formulations is justified, provided: (a) the test product and its comparator are both rapidly dissolving; (b) meet similarity of the dissolution profiles at pH 1.2, 4.5, and 6.8; (c) the test product contains only excipients present in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form; and (d) if the test product contains sorbitol, sodium laurilsulfate, or propylene glycol, the test product needs to be qualitatively and quantitatively identical to its comparator with respect to these excipients [corrected]..

  15. Effects of metronidazole on hepatic CYP3A4 activity.

    PubMed

    Haas, C E; Kaufman, D C; DiCenzo, R C

    2001-10-01

    To evaluate the effect of a short course of oral metronidazole, commonly used for bowel-preparation regimens, on hepatic cytochrome P450 (CYP) 3A4 activity, as measured by the [14C N-methyl]-erythromycin breath test (ERMBT) in healthy volunteers. Prospective, nonrandomized, interventional study University-affiliated, community, teaching hospital. Five healthy male volunteers. Subjects underwent a baseline ERMBT in the morning before receiving three oral doses of metronidazole 500 mg administered at 3 P.M., 7 P.M., and 11 P.M. Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. Changes in ERMBT values were compared with baseline results using Freidman's repeated-measures analysis of variance on ranks. The ERMBT values did not change significantly compared with baseline (p=0.82). Median (range) ERMBT values expressed as a percentage of baseline at 24, 72, and 96 hours were 110.3 (96.2-136.9), 101.3 (99.3-115.0), and 101.8 (95.5-116.3), respectively A short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity as measured by the ERMBT.

  16. Effect of metronidazole supplemented with hydroquinone on the adhesion of Lactobacillus acidophilus in ovine vaginal cells.

    PubMed

    Coletti Zabala, Tamara L; Zerbatto, María E; Perotti, Elda B R; Smacchia, Ana M; Ombrella, Adriana; Pidello, Alejandro R

    This work demonstrates that the addition of metronidazole together with a ubiquitous quinone compound reduces adherence of Lactobacillus acidophilus to ovine vaginal cells. Spectrophotometric and voltammetric studies have shown that neoformed compounds were observed in these systems; there were also changes in their electroactive composition, and the oxidant status had a significantly higher value compared to the control (p<0.05). Based on reduction potential (E; mV), the distribution of electroactive compound concentrations suggests that the compounds with low reduction potential induce this behavior, which would indicate that the addition of metronidazole with a ubiquitous quinone compound to the vaginal system might increase the reductive capacity of these systems. This work shows that the study of behavior and fluctuations of the redox compounds that compose the vaginal environment, in terms of concentration and species of redox molecules, must be hierarchized in order to better understand the early stages of colonization by microorganisms. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile.

    PubMed

    Prabhakaran, Molamma P; Zamani, Maedeh; Felice, Betiana; Ramakrishna, Seeram

    2015-11-01

    Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. 'Electrospraying' was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946±407nm and 1774±167nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug-polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

    PubMed

    Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

    2011-08-01

    In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

  19. Draft Genome Sequence of a Metronidazole-Resistant Gardnerella vaginalis Isolate

    PubMed Central

    Schuyler, Jessica A.; Chadwick, Sean G.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a Gardnerella vaginalis strain (3549624) isolated from a vaginal specimen. G. vaginalis is associated with bacterial vaginosis, the most common cause of vaginal discharge, which is often treated with metronidazole. This isolate is highly resistant to metronidazole (MIC, 500 µg/ml) and may be useful for comparative genomic studies to determine the molecular basis of metronidazole resistance in this species. PMID:26337887

  20. Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

    PubMed

    Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

    2012-01-01

    This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

  1. Ethnicity association of Helicobacter pylori virulence genotype and metronidazole susceptibility

    PubMed Central

    Alfizah, Hanafiah; Rukman, Awang Hamat; Norazah, Ahmad; Hamizah, Razlan; Ramelah, Mohamed

    2013-01-01

    AIM: To characterise the cag pathogenicity island in Helicobacter pylori (H. pylori) isolates by analysing the strains’ vacA alleles and metronidazole susceptibilities in light of patient ethnicity and clinical outcome. METHODS: Ninety-five H. pylori clinical isolates obtained from patients with dyspepsia living in Malaysia were analysed in this study. Six genes in the cagPAI region (cagE, cagM, cagT, cag13, cag10 and cag67) and vacA alleles of the H. pylori isolates were identified by polymerase chain reaction. The isolates’ metronidazole susceptibility was also determined using the E-test method, and the resistant gene was characterised by sequencing. RESULTS: More than 90% of the tested isolates had at least one gene in the cagPAI region, and cag67 was predominantly detected in the strains isolated from the Chinese patients, compared with the Malay and Indian patients (P < 0.0001). The majority of the isolates (88%) exhibited partial deletion (rearrangement) in the cagPAI region, with nineteen different patterns observed. Strains with intact or deleted cagPAI regions were detected in 3.2% and 8.4% of isolates, respectively. The prevalence of vacA s1m1 was significantly higher in the Malay and Indian isolates, whereas the isolates from the Chinese patients were predominantly genotyped as vacA s1m2 (P = 0.018). Additionally, the isolates from the Chinese patients were more sensitive to metronidazole than the isolates from the Malay and Indian patients (P = 0.047). Although we attempted to relate the cagPAI genotypes, vacA alleles and metronidazole susceptibilities to disease outcome, no association was observed. The vacA alleles were distributed evenly among the strains with intact, partially deleted or deleted cagPAI regions. Interestingly, the strains exhibiting an intact cagPAI region were sensitive to metronidazole, whereas the strains with a deleted cagPAI were more resistant. CONCLUSION: Successful colonisation by different H. pylori genotypes is

  2. Cloning of Bacteroides fragilis plasmid genes affecting metronidazole resistance and ultraviolet survival in Escherichia coli

    SciTech Connect

    Wehnert, G.U.; Abratt, V.R.; Goodman, H.J.; Woods, D.R. )

    1990-03-01

    Since reduced metronidazole causes DNA damage, resistance to metronidazole was used as a selection method for the cloning of Bacteroides fragilis genes affecting DNA repair mechanisms in Escherichia coli. Genes from B. fragilis Bf-2 were cloned on a recombinant plasmid pMT100 which made E. coli AB1157 and uvrA, B, and C mutant strains more resistant to metronidazole, but more sensitive to far uv irradiation under aerobic conditions. The loci affecting metronidazole resistance and uv sensitivity were linked and located on a 5-kb DNA fragment which originated from the small 6-kb cryptic plasmid pBFC1 present in B. fragilis Bf-2 cells.

  3. Differential Expression and Immunolocalization of Antioxidant Enzymes in Entamoeba histolytica Isolates during Metronidazole Stress

    PubMed Central

    Iyer, Lakshmi Rani; Singh, Nishant; Verma, Anil Kumar; Paul, Jaishree

    2014-01-01

    Entamoeba histolytica infections are endemic in the Indian subcontinent. Five to eight percent of urban population residing under poor sanitary conditions suffers from Entamoeba infections. Metronidazole is the most widely prescribed drug used for amoebiasis. In order to understand the impact of metronidazole stress on the parasite, we evaluated the expression of two antioxidant enzymes, peroxiredoxin and FeSOD, in Entamoeba histolytica isolates during metronidazole stress. The results reveal that, under metronidazole stress, the mRNA expression levels of these enzymes did not undergo any significant change. Interestingly, immunolocalization studies with antibodies targeting peroxiredoxin indicate differential localization of the protein in the cell during metronidazole stress. In normal conditions, all the Entamoeba isolates exhibit presence of peroxiredoxin in the nucleus as well as in the membrane; however with metronidazole stress the protein localized mostly to the membrane. The change in the localization pattern was more pronounced when the cells were subjected to short term metronidazole stress compared to cells adapted to metronidazole. The protein localization to the cell membrane could be the stress response mechanism in these isolates. Colocalization pattern of peroxiredoxin with CaBp1, a cytosolic protein, revealed that the membrane and nuclear localization was specific to peroxiredoxin during metronidazole stress. PMID:25013795

  4. Differential expression and immunolocalization of antioxidant enzymes in Entamoeba histolytica isolates during metronidazole stress.

    PubMed

    Iyer, Lakshmi Rani; Singh, Nishant; Verma, Anil Kumar; Paul, Jaishree

    2014-01-01

    Entamoeba histolytica infections are endemic in the Indian subcontinent. Five to eight percent of urban population residing under poor sanitary conditions suffers from Entamoeba infections. Metronidazole is the most widely prescribed drug used for amoebiasis. In order to understand the impact of metronidazole stress on the parasite, we evaluated the expression of two antioxidant enzymes, peroxiredoxin and FeSOD, in Entamoeba histolytica isolates during metronidazole stress. The results reveal that, under metronidazole stress, the mRNA expression levels of these enzymes did not undergo any significant change. Interestingly, immunolocalization studies with antibodies targeting peroxiredoxin indicate differential localization of the protein in the cell during metronidazole stress. In normal conditions, all the Entamoeba isolates exhibit presence of peroxiredoxin in the nucleus as well as in the membrane; however with metronidazole stress the protein localized mostly to the membrane. The change in the localization pattern was more pronounced when the cells were subjected to short term metronidazole stress compared to cells adapted to metronidazole. The protein localization to the cell membrane could be the stress response mechanism in these isolates. Colocalization pattern of peroxiredoxin with CaBp1, a cytosolic protein, revealed that the membrane and nuclear localization was specific to peroxiredoxin during metronidazole stress.

  5. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

    PubMed

    Aguin, Tina; Akins, Robert A; Sobel, Jack D

    2014-05-01

    The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

  6. Outcome of metronidazole therapy for Clostridium difficile disease and correlation with a scoring system.

    PubMed

    Belmares, Jaime; Gerding, Dale N; Parada, Jorge P; Miskevics, Scott; Weaver, Frances; Johnson, Stuart

    2007-12-01

    To determine the response rate of Clostridium difficile disease (CDD) to treatment with metronidazole and assess a scoring system to predict response to treatment with metronidazole when applied at the time of CDD diagnosis. Retrospective review of patients with CDD who received primary treatment with metronidazole. We defined success as diarrhea resolution within 6 days of therapy. A CDD score was defined prospectively using variables suggested to correlate with disease severity. Among 102 evaluable patients, 72 had a successful response (70.6%). Twenty-one of the remaining 30 patients eventually responded to metronidazole, but required longer treatment, leaving 9 'true failures'. The mean CDD score was higher among true failures (2.89+/-1.4) than among all metronidazole responders (0.77+/-1.0) (p<.0001). The score was greater than 2 in 67% of true failures and 2 or less in 94% of metronidazole responders. Leukocytosis and abnormal CT scan findings were individual factors associated with a higher risk of metronidazole failure. Only 71% of CDD patients responded to metronidazole within 6 days, but the overall response rate was 91%. A CDD score greater than 2 was associated with metronidazole failure in 6 of 9 true failures. The CDD score will require prospective validation.

  7. Furazolidone- and Nitrofurantoin-Resistant Helicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

    PubMed Central

    Kwon, Dong H.; Lee, Miae; Kim, J. J.; Kim, J. G.; El-Zaatari, F. A. K.; Osato, M. S.; Graham, D. Y.

    2001-01-01

    The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant. rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection. PMID:11120984

  8. New transdermal bioadhesive film containing oxybutynin: In vitro permeation across rabbit ear skin.

    PubMed

    Nicoli, S; Penna, E; Padula, C; Colombo, P; Santi, P

    2006-11-15

    Oxybutynin is used extensively in the treatment of patients with overactive bladder. The aim of this work was to realize and test in vitro a new transdermal bioadhesive film containing oxybutynin. Transdermal films were prepared by dissolving in water an adhesive (Plastoid), a film-forming polymer (polyvinyl alcohol), a plasticizer (sorbitol) and the drug. The mixture was then spread on siliconized paper and oven-dried. Permeation experiments were conducted in Franz-type diffusion cells using rabbit ear skin as barrier. The donor compartment contained a water solution, the prepared film (with or without backing) or the commercial patch (Oxytrol). The experiments were performed for 24h. Oxybutynin showed good permeation characteristics across the skin. When the film was applied in occlusive conditions the release profiles were much higher than in non-occlusive conditions, reaching 50% of drug permeated after 24h. Compared to the commercial patch Oxytrol, the film was more efficient suggesting that a smaller area or a lower drug loading could be employed. The results obtained show that the bioadhesive film can be a promising and innovative therapeutic system for the transdermal administration of oxybutynin.

  9. Effect of a hydrophobic phospholipid lining of the gastric mucosa in bioadhesion.

    PubMed

    Park, Jae Han; Robinson, Joseph R

    2008-01-01

    The role of a model hydrophobic phospholipid simulating lining of the gastric mucosa, as to adhesion of polymers with different surface functional groups and surface hydrophobicities, was evaluated using an in vitro gastric mucus model. Front-faced fluorescence measurement was used to determine adhesion of fluorescent polystyrene microspheres with different surface functional groups. Contact angle measurements and sticking bubble technique were used to measure relative surface hydrophobicity of the polymers. Adhesion of fluorescent polystyrene microspheres using front-faced fluorescence measurement revealed the hydrophobic phospholipid lining of the in vitro gastric mucus model did not allow adhesion of microspheres with -COOH and -NH(2) functional groups, whereas it did allow adhesion of microspheres with hydrophobic attributes. In addition, in vitro adhesive force studies using diblock copolymers of polystyrene and polyacrylate showed that the in vitro adhesive force between the hydrophobic phospholipid lining of the in vitro gastric mucus model and the polymer increased when the surface hydrophobicity of the polymer increased. The hydrophobic phospholipid acts as an adhesion barrier to hydrophilic bioadhesive polymers and polymers with surface functional groups of carboxylic acid and amine. The hydrophobic phospholipid lining of the gastric mucosa should be taken into considerations for screening and designing of a new gastric bioadhesive polymer.

  10. Evaluation of a water-soluble bioadhesive patch for photodynamic therapy of vulval lesions.

    PubMed

    McCarron, Paul A; Donnelly, Ryan F; Zawislak, Agnieszka; Woolfson, A David; Price, John H; McClelland, Raymond

    2005-04-11

    An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 Ncm(-2). Patient evaluation demonstrated comfort and firm attachment for up to 4h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

  11. Bioadhesive lipid compositions: self-assembly structures, functionality, and medical applications.

    PubMed

    Barauskas, Justas; Christerson, Lars; Wadsäter, Maria; Lindström, Fredrick; Lindqvist, Anna-Karin; Tiberg, Fredrik

    2014-03-03

    Lipid-based liquid crystalline compositions of phospholipids and diglycerides have unique bioadhesive properties with several medical applications, as exemplified by a lipid-based medical device indicated for management and relief of intraoral pain. The present paper describes the relation between self-assembly properties of phosphatidyl choline (PC) and glycerol dioleate (GDO) mixtures in the presence of aqueous fluids and functional attributes of the system, including: film formation and bioadhesion, intraoral coverage, acceptance by patients, and potential as a drug delivery system. The phase behavior of PC/GDO was characterized using synchrotron small-angle X-ray scattering. Functional properties, including the presence of study formulations at intraoral surfaces, ease of attachment, taste, and degree of and intraoral pain, were assessed in a crossover clinical pilot study in head and neck cancer patients. An optimum in functional properties was indicated for formulations with a PC/GDO weight ratio of about 35/65, where the lipids form a reversed cubic liquid crystalline micellar phase structure (Fd3m space group) over the relevant temperature range (25-40 °C).

  12. Bioadhesive film formed from a novel organic-inorganic hybrid gel for transdermal drug delivery system.

    PubMed

    Guo, Ruiwei; Du, Xiaoyan; Zhang, Rui; Deng, Liandong; Dong, Anjie; Zhang, Jianhua

    2011-11-01

    A novel organic-inorganic hybrid film-forming agent for TDDS was developed by a modified poly(vinyl alcohol) (PVA) gel using γ-(glycidyloxypropyl)trimethoxysilane (GPTMS) as an inorganic-modifying agent, poly(N-vinyl pyrrolidone) (PVP) as a tackifier and glycerol (GLY) as a plasticizer. The prepared gels can be applied to the skin by a coating method and in situ form very thin and transparent films with good performance, comfortable feel and cosmetic attractiveness. The key properties of the bioadhesive films produced from the hybrid gels were investigated and the results showed that the incorporation of appropriate GPTMS (GPTMS/(PVA+GPTMS) in the range of 20-30%) into the PVA matrix not only can significantly enhance mechanical strength and skin adhesion properties of the resultant film, but also can decrease the crystalline regions of PVA and hence facilitate the diffusion of water vapor and drug. Furthermore, the investigations into in vivo skin irritation suggested the films caused non-irritation to skin after topical application for 120 h. In conclusion, the bioadhesive films formed from organic-inorganic hybrid gels possessed very good qualities for application on the skin and may provide a promising formulation for TDDS, especially when the patient acceptability from an aesthetic perspective of the dosage form is a prime consideration. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Evaluation of a mucoadhesive buccal patch for delivery of peptides: in vitro screening of bioadhesion.

    PubMed

    Li, C; Bhatt, P P; Johnston, T P

    1998-10-01

    We have assessed the bioadhesive properties of several different mucoadhesive buccal patches. The patches consisted of custom coformulations of silicone polymers and Carbopol 974P. The contact angle of water was measured for each of the test formulations, using an ophthalmic shadow scope. The corresponding work of adhesion between the water and the patches (W1), and between the patches and freshly-excised rabbit buccal mucosa (W2) was then calculated, using a modification of Dupre's equation. The bioadhesive strength between the patches and excised rabbit buccal mucosa was also assessed. The results of the contact-angle measurements indicated that the contact angle decreased with an increase in the amount of Carbopol in the formulation. Additionally, the calculated values of both W1 and W2 increased with an increase in the amount of Carbopol in the buccal-patch formulations. A correlation (r not equal to 0.9808) was found between the measured contact angle and the calculated values for W2. The direct measurement of the force required to separate a buccal patch from excised rabbit buccal mucosa with the INSTRON demonstrated that the adhesive strength increased with an increase in the amount of Carbopol. This preliminary study has shown that the measurement of contact angles alone may provide a useful technique for estimating the work of adhesion, and may serve as a convenient and rapid screening procedure to identify potential mucoadhesive buccal-patch formulations.

  14. Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis

    PubMed Central

    Hani, Umme; Shivakumar, H.G.; Osmani, Riyaz Ali M.; Srivastava, Atul; Kumar Varma, Naga Sravan

    2016-01-01

    The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment. PMID:27610145

  15. Bioadhesive micelles of d-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery.

    PubMed

    Agrawal, Poornima; Sonali; Singh, Rahul Pratap; Sharma, Gunjan; Mehata, Abhishesh K; Singh, Sanjay; Rajesh, Chellapa V; Pandey, Bajarangprasad L; Koch, Biplob; Muthu, Madaswamy S

    2017-04-01

    The aim of this work was to prepare targeted bioadhesive d-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50 values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48h of treatments, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Design and evaluation of an innovative floating and bioadhesive multiparticulate drug delivery system based on hollow structure.

    PubMed

    Zhang, Chungang; Tang, Jingya; Liu, Dechun; Li, Xuetao; Cheng, Lan; Tang, Xing

    2016-04-30

    In this study a gastric-retentive delivery system was prepared by a novel method which is reported here for the first time. An innovative floating and bioadhesive drug delivery system with a hollow structure was designed and prepared. The floating and bioadhesive drug delivery system was composed of a hollow spherical shell, a waterproof layer (Stearic acid), a drug layer (Ofloxacin), a release retarding film (the novel blended coating materials) and a bioadhesive layer (Carbomer 934P) prepared by using a liquid multi-layering process. A novel blended coating material was designed and investigated to solve the problem of the initial burst release of the formulation and the release mechanism of the novel material was analyzed in this study. The optimized formulation provided the sustained release characteristic and was able to float for 24h. The SEM cross-section images showed that the particulates were hollow with a spherical shell. X-ray images and pharmacokinetic studies (Frel = 124.1 ± 28.9%) in vivo showed that the gastric-retentive delivery system can be retained in the stomach for more than 6h. The floating and bioadhesive particulate drug delivery system based on a hollow structure with a dual function presented here is a viable alternative to other for gastroretentive drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Synthesis and characterization of injectable bioadhesive hydrogels for nucleus pulposus replacement and repair of the damaged intervertebral disc.

    PubMed

    Vernengo, J; Fussell, G W; Smith, N G; Lowman, A M

    2010-05-01

    Bioadhesive polymers are natural or synthetic materials that can be used for soft tissue repair. The aim of this investigation was to develop an injectable, bioadhesive hydrogel with the potential to serve as a synthetic replacement for the nucleus pulposus of the intervertebral disc or as an annulus closure material. Branched copolymers of poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (PEG) were blended with poly(ethylene imine) (PEI). This three component injectable system can form a precipitated gel at physiological temperature due to the phase transition of PNIPAAm. The injection of glutaraldehyde into the gel core will adhere the implant to the surrounding tissues. (1)H NMR results indicated the successful physical incorporation of PEI into the PNIPAAm-PEG network by blending. In addition, the covalent crosslinking between the amine functionalities on the PEI and the aldehyde functionalities on the glutaraldehyde was verified using FTIR difference spectroscopy. Mechanical characterization of these blends showed a significant increase (p < 0.05) in compressive modulus following glutaraldehyde injection. The in vitro bioadhesive force studies with porcine skin showed a significant increase (p < 0.05) in the mean maximum force of detachment for PNIPAAm-PEG/PEI gels when glutaraldehyde was injected into the gel core. The results of this study indicate that the reactivity between amines and aldehyde functionalities can be exploited to impart bioadhesive properties to PNIPAAm-PEG/PEI copolymers.

  18. THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

    PubMed

    Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

    2016-04-01

    Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

  19. Effect of different sterilisation methods on the properties of bioadhesive powders and ocular minitablets, and clinical evaluation.

    PubMed

    Weyenberg, W; Vermeire, A; D'Haese, E; Vanhaelewyn, G; Kestelyn, P; Callens, F; Nelis, H J; Remon, J P; Ludwig, A

    2004-09-01

    The purpose of this study was to evaluate the influence of gamma-irradiation and dry heat sterilisation on the properties of a bioadhesive powder mixture containing ciprofloxacin and its corresponding ocular minitablets. The molecular weight characteristics of drum dried waxy maize starch (DDWM), employed as major component of the bioadhesive formulation, the decay kinetics of radicals, the rheological properties of the bioadhesive polymers and the microbial activity of ciprofloxacin were studied. The influence of the different sterilisation methods on the characteristics of the ocular minitablets was investigated by measuring the crushing strength, the friability, and the in vitro release of ciprofloxacin from the minitablets. Finally, the clinical value of the selected sterilised minitablets was evaluated in seven healthy volunteers. Both sterilisation methods similarly affected the properties of the bioadhesive formulation by inducing stable radicals and decreasing the molecular weight of DDWM, although no changes in the microbiological activity of ciprofloxacin were measured. An obvious influence of both sterilisation methods was observed in the in vitro release study. The crushing strength and friability of the minitablets were not significantly influenced by gamma-irradiation. Based on these data, gamma-irradiation was more adequate as sterilisation method for the bioadhesive ocular minitablets than dry heat sterilisation, because it affected the least the physical properties of the minitablets. Therefore, the gamma-sterilised minitablets were selected for an in vivo evaluation in seven volunteers. The concentration of ciprofloxacin in the tear film remained above its MIC value for the most common ocular pathogens for at least 8 h. Consequently, the gamma-irradiated minitablets containing ciprofloxacin can be considered as a promising formulation to treat bacterial keratitis and conjunctivitis.

  20. Planar bioadhesive microdevices: a new technology for oral drug delivery

    PubMed Central

    Fox, Cade B.; Chirra, Hariharasudhan D.; Desai, Tejal A.

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. PMID:25219863

  1. Planar bioadhesive microdevices: a new technology for oral drug delivery.

    PubMed

    Fox, Cade B; Chirra, Hariharasudhan D; Desai, Tejal A

    2014-01-01

    The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery.

  2. [Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

    PubMed

    Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

    2015-10-01

    Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

  3. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

    PubMed

    Graves, Tracey D; Condon, Marie; Loucaidou, Marina; Perry, Richard J

    2009-10-15

    Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

  4. Universal high-level primary metronidazole resistance in Helicobacter pylori isolated from children in Egypt.

    PubMed

    Sherif, May; Mohran, Zaynab; Fathy, Hanan; Rockabrand, David M; Rozmajzl, Patrick J; Frenck, Robert W

    2004-10-01

    Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter pylori recovered from Egyptian children undergoing routine endoscopies. The isolates were universally highly resistant to metronidazole, but resistance to other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin, and azithromycin resistance versus 2% for ciprofloxacin and ampicillin resistance). Use of metronidazole for the treatment of H. pylori in Egypt should be avoided.

  5. Interaction of calcium sulfate with xanthan gum: effect on in vitro bioadhesion and drug release behavior from xanthan gum based buccal discs of buspirone.

    PubMed

    Jaipal, A; Pandey, M M; Abhishek, A; Vinay, S; Charde, S Y

    2013-11-01

    Bioadhesive polymers in buccal drug delivery systems play an important role in delivery of therapeutic drug molecules for local and systemic action. Xanthan gum, a GRAS listed natural polymer was used to design buccal discs of buspirone hydrochloride by direct compression method. Effect of calcium sulfate on bioadhesive and drug release behavior of xanthan gum buccal discs was studied. Varying amount of calcium sulfate (0%, 5%, 10%, 20%, 30%, 40% and 50%, w/w) in combination with xanthan gum was used to prepare buccal bioadhesive discs. Increase in calcium sulfate concentration resulted in faster drug release and decreased the bioadhesive strength of the designed discs. Further, in rheological evaluation it was observed that viscosity of xanthan gum gel reduces with increasing concentration of calcium sulfate. Compatibility of drug with various excipients was assessed using DSC and FTIR techniques.

  6. Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection

    PubMed Central

    Shankar, Gita N.; Alt, Carsten

    2014-01-01

    Objectives Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. Methods We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic® F-127) and polycarbophil USP (Noveon® AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. Results Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. Conclusions We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection. PMID:25139839

  7. Intravaginally applied metronidazole is as effective as orally applied in the treatment of bacterial vaginosis, but exhibits significantly less side effects.

    PubMed

    Brandt, M; Abels, C; May, T; Lohmann, K; Schmidts-Winkler, I; Hoyme, U B

    2008-12-01

    Metronidazole is the drug of choice for the treatment of bacterial vaginosis (BV). However, so far the oral administration has not been clinically compared to the intravaginal application regarding efficacy, side effects and patient satisfaction in a scientific sound fashion. Therefore, this randomized, double-blind, placebo-controlled clinical trial was designed to demonstrate non-inferiority of short-term intravaginal (i.vag.) application of metronidazole (2x 1000 mg pessaries 24h apart) vs. a single oral dose (p.o.) of metronidazole (1 x 2000 mg tablets) in 263 patients with BV (double-dummy design). The follow-up period was 12 weeks. In addition, the number and the type of adverse events induced by the two regimens were compared, assuming better tolerability of the intravaginal application. Following the diagnosis of BV a total of 129 women (mean age 36.2 years) was orally treated with a single dose of 2g metronidazole whereas a total of 134 patients (mean age 35.5 years) was treated intravaginally with 1g metronidazole each day on two consecutive days and included in the per-protocol analysis. Non-inferiority of i.vag. application compared to p.o. administration was statistically significant regarding efficacy: Following intravaginal application the cure rate, assessed on day 8 after starting of the treatment, was 92.5% as compared to 89.9% after oral administration. Nausea was the most common adverse event reported in 10.2% i.vag. vs. 30.4% p.o. of all cases (p<0.001), abdominal pain in 16.8% i.vag. vs. 31.9% p.o. (p<0.01), a "metallic taste" in 8.8% i.vag. vs. 17.9% p.o. (p<0.05). Women treated i.vag. were highly satisfied with the treatment and more content as compared to the women treated p.o. with metronidazole (p<0.05, intent-to-treat analysis). In this clinical trial the intravaginal application was as effective as the oral administration of metronidazole in treating BV. However, significantly less adverse events were reported after short

  8. Comparison between the efficacy of metronidazole vaginal gel and Berberis vulgaris (Berberis vulgaris) combined with metronidazole gel alone in the treatment of bacterial vaginosis

    PubMed Central

    Masoudi, Mansoure; Kopaei, Mahmoud Rafieian; Miraj, Sepideh

    2016-01-01

    Background Bacterial vaginosis is one of the most prevalent complications among reproductive-aged women. Antibacterial and antifungal effects of Berberis vulgaris have been demonstrated in vitro and in vivo. Objectives This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) with metronidazole vaginal gel 0.75% on bacterial vaginosis on 80 patients referred to the Hajar Hospital from January 2012 to April 2013. Methods This study was a randomized clinical trial research on 80 women affected by bacterial vaginosis, who were randomly divided into two groups of 40 participants. Diagnostic criteria were Amsel’s criteria and Gram stain. Berberis vulgaris 5% (in metronidazole gel base) or metronidazole vaginal gel for five-night usage was prescribed to each group, and after two to seven days therapeutic effects and Amsel criteria were assessed. Data analysis was performed by SPSS 16 using Student t-test, chi-square, and ANOVA tests. Results Findings of the study showed a statistically significant difference with regard to treatment response between the study groups (p<0.001), and the Berberis vulgaris group had a better response than the metronidazole gel group. The patients in groups of Berberis vulgaris in a metronidazole gel base did not experience any relapse, but, in the metronidazole group, 30% of patients experienced relapse during three weeks’ follow-up. Conclusions Findings of the study showed that adding Berberis vulgaris fruit extract on metronidazole improve the efficacy of bacterial vaginosis therapy. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT201411102085N13. Funding Shahrekord University of Medical Sciences supported this research. PMID:27757195

  9. Comparison between the efficacy of metronidazole vaginal gel and Berberis vulgaris (Berberis vulgaris) combined with metronidazole gel alone in the treatment of bacterial vaginosis.

    PubMed

    Masoudi, Mansoure; Kopaei, Mahmoud Rafieian; Miraj, Sepideh

    2016-08-01

    Bacterial vaginosis is one of the most prevalent complications among reproductive-aged women. Antibacterial and antifungal effects of Berberis vulgaris have been demonstrated in vitro and in vivo. This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) with metronidazole vaginal gel 0.75% on bacterial vaginosis on 80 patients referred to the Hajar Hospital from January 2012 to April 2013. This study was a randomized clinical trial research on 80 women affected by bacterial vaginosis, who were randomly divided into two groups of 40 participants. Diagnostic criteria were Amsel's criteria and Gram stain. Berberis vulgaris 5% (in metronidazole gel base) or metronidazole vaginal gel for five-night usage was prescribed to each group, and after two to seven days therapeutic effects and Amsel criteria were assessed. Data analysis was performed by SPSS 16 using Student t-test, chi-square, and ANOVA tests. Findings of the study showed a statistically significant difference with regard to treatment response between the study groups (p<0.001), and the Berberis vulgaris group had a better response than the metronidazole gel group. The patients in groups of Berberis vulgaris in a metronidazole gel base did not experience any relapse, but, in the metronidazole group, 30% of patients experienced relapse during three weeks' follow-up. Findings of the study showed that adding Berberis vulgaris fruit extract on metronidazole improve the efficacy of bacterial vaginosis therapy. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT201411102085N13. Shahrekord University of Medical Sciences supported this research.

  10. A novel metronidazole fluorescent nanosensor based on graphene quantum dots embedded silica molecularly imprinted polymer.

    PubMed

    Mehrzad-Samarin, Mina; Faridbod, Farnoush; Dezfuli, Amin Shiralizadeh; Ganjali, Mohammad Reza

    2017-06-15

    A novel optical nanosensor for detection of Metronidazole in biological samples was reported. Graphene quantum dots embedded silica molecular imprinted polymer (GQDs-embedded SMIP) was synthesized and used as a selective fluorescent probe for Metronidazole detection. The new synthesized GQDs-embedded SMIP showed strong fluorescent emission at 450nm excited at 365nm which quenched in presence of Metronidazole as a template molecule.. The quenching was proportional to the concentration of Metronidazole in a linear range of at least 0.2μM to 15μM. The limit of detection for metronidazole determination was obtained 0.15μM. The nanosensor successfully worked in plasma matrixes. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. D-allose and D-psicose reinforce the action of metronidazole on trichomonad.

    PubMed

    Harada, Masakazu; Kondo, Emi; Hayashi, Hiromi; Suezawa, Chigusa; Suguri, Setsuo; Arai, Meiji

    2012-04-01

    The effects of D-allose and D-psicose on Tritrichomonas foetus were examined. They were cultured in F-bouillon medium including glucose, but had never increased when glucose was substituted to those sugars. When cultured in a medium including a dose of ED(50) metronidazole and those sugars, trichomonad density was significantly less than that in a medium with metronidazole only. D-Allose remarkably reinforced the action of metronidazole. This means there are some interactions between metronidazole and those sugars. Although the mechanism is not clear, by using those sugars for treatment with metronidazole, the drug dosage could be lowered and the development of drug resistance of trichomonad parasites might be prevented.

  12. [Helicobacter pylori resistance against metronidazole in Switzerland: implications for eradication therapy?].

    PubMed

    Sieber, C C; Frei, R; Beglinger, C; Mossi, S; Binek, J; Schaufelberger, H; Fried, R; Stalder, G A

    1994-08-09

    Gastroduodenal ulcers are strongly associated with Helicobacter pylori (HP) infection. Successful eradication drastically diminishes ulcer recurrence. Most of the eradication schemes include metronidazole (Flagyl). The present study was designed to establish the metronidazole resistance rate in Switzerland. Antral biopsies were taken in 153 patients with suspected ulcers (115 men, 38 women, mean age 46 +/- 16 [SD] years) during upper endoscopy for bacteriological testing. Metronidazole resistance (> 8 micrograms/ml) was found in 47/153 (31%) of the isolates. Resistance was found in no case to amoxicillin (Clamoxyl) (0/104 = 0%) and only in 3% (2/66) to clarithromycin (Klazid). Metronidazole resistance of HP in a third of the isolates studied is comparable to numbers found in other European countries. These findings raise the question whether eradication schemes including metronidazole without prior sensitivity testing are justified. Amoxicillin and clarithromycin appear to be valid alternatives.

  13. A Rapid and Validated RP-HPLC Method for the Simultaneous Quantification of Benzoic Acid, Metronidazole and Miconazole Nitrate in Vaginal Formulations.

    PubMed

    Sahoo, Dibya Ranjan; Jain, Sourabh

    2016-07-03

    A rapid, specific, precise and accurate reversed-phase high-performance liquid chromatography method has been developed and validated for the determination of benzoic acid, metronidazole and miconazole nitrate in vaginal formulations of cream and tablet (excluding benzoic acid). The validation was carried out with reference to ICH guidelines. The chromatography was carried out on a Zorbax SB-CN column (250 × 4.6 mm, 5 µm) linear gradient elution with mixture of solvent A (phosphate buffer) and solvent B (acetonitrile) as a mobile phase at the flow rate of 1.0 mL/min and dual mode of detection that is 233 nm for benzoic acid and miconazole nitrate and 319 nm for metronidazole. The limit of detection and limit of quantification are 1.07, 0.79 and 0.62 μg/mL and 3.23, 2.40 and 1.88 μg/mL for benzoic acid, metronidazole and miconazole nitrate, respectively. The linearity of benzoic acid, metronidazole and miconazole nitrate showed a correlation coefficient of 0.9997, 0.9995 and 0.9993, respectively. The good results were achieved with respect to repeatability of relative standard deviation ≤2% and recovery within 98.0-102.0%. The selected column in this study performed well. The method is simple, accurate and precise, and may be recommended for routine quality control test for any dosage forms containing benzoic acid, metronidazole and miconazole nitrate. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System.

    PubMed

    Kumar, Manoj; Awasthi, Rajendra

    2015-01-01

    Crohn’s disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn’s disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR). The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ・} 1.51–81.02 ・} 2.14%)and cumulative drug release (64.14 ・} 0.83–79.69 ・} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free-flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi’s model. The release mechanism of

  15. A prospective study of risk factors and historical trends in metronidazole failure for Clostridium difficile infection

    PubMed Central

    Hu, Mary Y.; Maroo, Seema; Kyne, Lorraine; Cloud, Jeffrey; Tummala, Sanjeev; Katchar, Kianoosh; Dreisbach, Valley; Noddin, Laura; Kelly, Ciarán P.

    2009-01-01

    Background & Aims Recent studies of C. difficile infection (CDI) indicate a dramatic increase in metronidazole failure. The aims of this study were to compare current and historical rates of metronidazole failure and identify risk factors for metronidazole failure. Methods 89 patients with CDI in 2004–2006 were followed for 60 days. Data were compared to a historical cohort of 63 CDI patients studied prospectively in 1998. Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin. Stool samples were analyzed for the presence of NAP-1 strain. Results Metronidazole failure rates were 35% in both the 1998 and 2004–2006 cohorts. There was no difference in the median time to resolution of diarrhea (8 vs. 5 days, p = 0.52) or the proportion with more than 10 days of diarrhea (35% vs. 29%, p = 0.51). Risk factors for metronidazole failure included recent cephalosporin use (OR 32, 95% CI 5–219), CDI on admission (OR 23, 95% CI 3–156), and transfer from another hospital (OR 11, 95% CI 2–72). The frequency of NAP-1 infection in patients with and without metronidazole failure was similar (26% vs. 21%, p = 0.67). Conclusions We found no difference in metronidazole failure rates in 1998 and 2004–2006. Patients with recent cephalosporin use, CDI on admission, and transfer from another hospital were more likely to fail metronidazole and may benefit from early aggressive therapy. Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI. PMID:19081526

  16. Tribulus terrestris ameliorates metronidazole-induced spermatogenic inhibition and testicular oxidative stress in the laboratory mouse

    PubMed Central

    Kumari, Mrinalini; Singh, Poonam

    2015-01-01

    Objective: The present study was undertaken to evaluate the protective effects of the fruit extract of Tribulus terrestris (TT) on the metronidazole (MTZ)-induced alterations in spermatogenesis, sperm count, testicular functions, and oxidative stress. Materials and Methods: Thirty adult Swiss strain mice were divided into six groups. Animals of Groups I and II served as untreated and vehicle-treated controls, while that of Groups III and IV were administered with MTZ (500 mg/kg BW/day) and TT (200 mg/kg BW/day) alone for 28 days, respectively. Low (100 mg/kg BW/day) and high (200 mg/kg BW/day) doses of TT along with MTZ (500 mg/kg BW/day) were administered for 28 days in the mice of Groups V and VI, respectively. Twenty four hours after the last treatment, all the animals were euthanized to study the histological changes in the testis and sperm count in the epididymis. Testicular functional markers, lipid peroxidation (LPO) and the activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were also assessed in the mice of all the groups. Results: Metronidazole caused marked alterations in the testicular weight, spermatogenesis, activities of antioxidant enzymes, lactate dehydrogenase, alkaline phosphatase, and the level of LPO. The epididymal sperm count also declined significantly in MTZ-treated group. These changes were partially restored following co-administration of 500 mg/kg BW/day of MTZ and 100 mg/kg BW/day of TT. However, in the mice co-administered with 500 mg/kg BW/day of MTZ and 200 mg/kg BW/day of TT, the changes reverted back completely, similar to that of the controls. Conclusion: The fruit extract of TT ameliorates the MTZ-induced alterations in the testis. PMID:26069369

  17. Mussel adhesion-employed water-immiscible fluid bioadhesive for urinary fistula sealing.

    PubMed

    Kim, Hyo Jeong; Hwang, Byeong Hee; Lim, Seonghye; Choi, Bong-Hyuk; Kang, Seok Ho; Cha, Hyung Joon

    2015-12-01

    Urinary fistulas, abnormal openings of a urinary tract organ, are serious complications and conventional management strategies are not satisfactory. For more effective and non-invasive fistula repair, fluid tissue adhesives or sealants have been suggested. However, conventional products do not provide a suitable solution due to safety problems and poor underwater adhesion under physiological conditions. Herein, we proposed a unique water-immiscible mussel protein-based bioadhesive (WIMBA) exhibiting strong underwater adhesion which was employed by two adhesion strategies of marine organisms; 3,4-dihydroxy-l-phenylalanine (DOPA)-mediated strong adhesion and water-immiscible coacervation. The developed biocompatible WIMBA successfully sealed ex vivo urinary fistulas and provided good durability and high compliance. Thus, WIMBA could be used as a promising sealant for urinary fistula management with further expansion to diverse internal body applications.

  18. Factors affecting the bioadhesive property of tablets consisting of hydroxypropyl cellulose and carboxyvinyl polymer.

    PubMed

    Satoh, K; Takayama, K; Machida, Y; Suzuki, Y; Nakagaki, M; Nagai, T

    1989-05-01

    The bioadhesive property of tablets consisting of hydroxypropyl cellulose (HPC) and carboxyvinyl polymer (CP) was investigated using the mouse peritoneal membrane. The adhesion force was significantly affected by the mixing ratio of HPC and CP in the tablet, and the weakest adhesion force was observed at the ratio of 3:2 (HPC:CP). Interpolymer complex formation was confirmed between HPC and CP in the acidic medium by turbidity and viscosity measurements. The interaction between CP carboxyl groups and HPC molecules was considered to be a possible mechanism for this complex formation on the basis of a Fourier-transform infrared spectroscopy. These observations suggested that the adhesion force of the HPC--CP tablet to the mucous membrane was significantly affected by the interpolymer complex formation between HPC and CP.

  19. A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization.

    PubMed

    Dobaria, Nitin B; Badhan, A C; Mashru, R C

    2009-01-01

    The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. Itraconazole was formulated in bioadhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. In addition, percentage drug retained on vaginal mucosa was evaluated using a simulated dynamic vaginal system as function of time. A polymeric film containing 100 mg itraconazole per unit (2.5 cm x 2.5 cm) have been developed using generally regarded as safe listed excipients. The pH of vaginal film was found to be slightly acidic (4.90 +/- 0.04) in simulated vaginal fluid and alkaline (7.04 +/- 0.07) in water. The little moisture content (7.66 +/- 0.51% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break (9.64 N/mm(2) and 67.56% for ITRF(65)) reveal that the formulations were found to be soft and tough. The films (ITRF(65)) contained solid dispersion of itraconazole (2.5)/hydroxypropyl cellulose (1)/polyethylene glycol 400 (0.5), which was found to be the optimal composition for a novel bioadhesive vaginal formulation, as they showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. Also, the film did not markedly affect normal vaginal flora (lactobacillus) and was noncytotoxic as indicated by the negligible decrease in cell viability.

  20. Bioadhesive chitosan-coated cyclodextrin-based superamolecular nanomicelles to enhance the oral bioavailability of doxorubicin

    NASA Astrophysics Data System (ADS)

    Liu, Yuhai; Zhai, Yinglei; Han, Xiaopeng; Liu, Xiaohong; Liu, Wanjun; Wu, Chunnuan; Li, Lin; Du, Yuqian; Lian, He; Wang, Yongjun; He, Zhonggui; Sun, Jin

    2014-10-01

    In order to improve the oral bioavailability of doxorubicin (Dox), a novel bioadhesive nanomicelle based on host-guest interaction was developed in this study. Hyaluronic acid-linked β-cyclodextrin (HA-CD) was synthesized. The primary nanomicelles were formed through the self-assemble of HA-CD and retinoic acid (RA) which was included as the hydrophobic core to anchor CD cavity by host-guest interaction. Chitosan (CS) was then coated on the surface of primary nanomicelles by ionic interaction with the negatively charged HA. The critical micellar concentration of HA-CD-RA was as low as 22.5 μg/mL. Dox was successfully encapsulated into the hydrophobic core of CS-coated HA-CD-RA nanomicelles (CS/HA-CD-RA-Dox), with encapsulation efficiency as high as 89.2 %. The CS/HA-CD-RA-Dox particle size was 234 nm and was stable over 30 days. In vitro Dox release showed that CS/HA-CD-RA nanomicelles were more sustained than HA-CD-RA nanomicelles, and Dox encapsulated into CS-coated nanomicelles was stable at low pH. The in situ single pass intestinal perfusion revealed that encapsulation of Dox into CS/HA-CD-RA nanomicelles could significantly improve the intestinal permeability of Dox. The mucoadhesion results indicated that the retention percentage of CS/HA-CD-RA nanomicelles was significantly higher than that of HA-CD-RA nanomicelles in gastrointestinal tract. In vivo pharmacokinetic study revealed that AUC(0-∞) of CS/HA-CD-RA nanomicelles was about fourfold higher than that of Dox solution. The present study suggested that CS/HA-CD-RA nanomicelles as biodegradable, biocompatible, and bioadhesive nanostructure can be a promising nanocarrier in improving the bioavailability of anticancer drugs to facilitate the oral chemotherapy.

  1. Quality analysis of salmon calcitonin in a polymeric bioadhesive pharmaceutical formulation: sample preparation optimization by DOE.

    PubMed

    D'Hondt, Matthias; Van Dorpe, Sylvia; Mehuys, Els; Deforce, Dieter; DeSpiegeleer, Bart

    2010-12-01

    A sensitive and selective HPLC method for the assay and degradation of salmon calcitonin, a 32-amino acid peptide drug, formulated at low concentrations (400 ppm m/m) in a bioadhesive nasal powder containing polymers, was developed and validated. The sample preparation step was optimized using Plackett-Burman and Onion experimental designs. The response functions evaluated were calcitonin recovery and analytical stability. The best results were obtained by treating the sample with 0.45% (v/v) trifluoroacetic acid at 60 degrees C for 40 min. These extraction conditions did not yield any observable degradation, while a maximum recovery for salmon calcitonin of 99.6% was obtained. The HPLC-UV/MS methods used a reversed-phase C(18) Vydac Everest column, with a gradient system based on aqueous acid and acetonitrile. UV detection, using trifluoroacetic acid in the mobile phase, was used for the assay of calcitonin and related degradants. Electrospray ionization (ESI) ion trap mass spectrometry, using formic acid in the mobile phase, was implemented for the confirmatory identification of degradation products. Validation results showed that the methodology was fit for the intended use, with accuracy of 97.4+/-4.3% for the assay and detection limits for degradants ranging between 0.5 and 2.4%. Pilot stability tests of the bioadhesive powder under different storage conditions showed a temperature-dependent decrease in salmon calcitonin assay value, with no equivalent increase in degradation products, explained by the chemical interaction between salmon calcitonin and the carbomer polymer.

  2. Discriminatory bio-adhesion over nano-patterned polymer brushes

    NASA Astrophysics Data System (ADS)

    Gon, Saugata

    Surfaces functionalized with bio-molecular targeting agents are conventionally used for highly-specific protein and cell adhesion. This thesis explores an alternative approach: Small non-biological adhesive elements are placed on a surface randomly, with the rest of the surface rendered repulsive towards biomolecules and cells. While the adhesive elements themselves, for instance in solution, typically exhibit no selectivity for various compounds within an analyte suspension, selective adhesion of targeted objects or molecules results from their placement on the repulsive surface. The mechanism of selectivity relies on recognition of length scales of the surface distribution of adhesive elements relative to species in the analyte solution, along with the competition between attractions and repulsions between various species in the suspension and different parts of the collecting surface. The resulting binding selectivity can be exquisitely sharp; however, complex mixtures generally require the use of multiple surfaces to isolate the various species: Different components will be adhered, sharply, with changes in collector composition. The key feature of these surface designs is their lack of reliance on biomolecular fragments for specificity, focusing entirely on physicochemical principles at the lengthscales from 1 - 100 nm. This, along with a lack of formal patterning, provides the advantages of simplicity and cost effectiveness. This PhD thesis demonstrates these principles using a system in which cationic poly-L-lysine (PLL) patches (10 nm) are deposited randomly on a silica substrate and the remaining surface is passivated with a bio-compatible PEG brush. TIRF microscopy revealed that the patches were randomly arranged, not clustered. By precisely controlling the number of patches per unit area, the interfaces provide sharp selectivity for adhesion of proteins and bacterial cells. For instance, it was found that a critical density of patches (on the order of

  3. Amoxicillin and metronidazole as an adjunct to full-mouth scaling and root planing of chronic periodontitis.

    PubMed

    Cionca, Norbert; Giannopoulou, Catherine; Ugolotti, Giovanni; Mombelli, Andrea

    2009-03-01

    It has been suggested that scaling and root planing of all pockets within a few hours and chlorhexidine treatments (full-mouth disinfection) may reduce the need for supplementary therapies. The aim of this study was to evaluate the clinical benefit of amoxicillin and metronidazole administered immediately after completion of full-mouth periodontal debridement in patients with chronic periodontitis. This was a single-center, double-masked, placebo-controlled, randomized longitudinal study of 6 months' duration. Fifty-one patients received full-mouth periodontal debridement, performed within 48 hours. Twenty-five subjects received metronidazole, 500 mg, and amoxicillin, 375 mg, three times a day for 7 days; 26 subjects received a placebo. Forty-seven patients could be followed up to month 6. No differences in clinical parameters were noted before treatment. The overall mean probing depth decreased from 4.3 +/- 0.4 mm to 3.0 +/- 0.2 mm in the test group and from 4.4 +/- 0.4 mm to 3.1 +/- 0.3 mm in the control group (P = 0.05, difference between groups). More importantly, test subjects had a significantly lower mean number of persisting pockets >4 mm and bleeding on probing that required further treatment (P = 0.005): 6 months after full-mouth debridement plus antibiotics, only 0.4 +/- 0.8 persisting pockets were still present, whereas 3.0 +/- 4.3 persisting pockets were still present in the control group. The protective risk of the antibiotics for having more than one pocket deeper than 4 mm and bleeding on probing per subject after 6 months was 8.85. Systemic metronidazole and amoxicillin significantly improved the 6-month clinical outcomes of full-mouth non-surgical periodontal debridement, thus significantly reducing the need for additional therapy.

  4. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants: A Propensity Score-matched Cohort Study.

    PubMed

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-10-01

    Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants.A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases.A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171-11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365-27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors for stage II NEC progressing to

  5. Zero order and signal processing spectrophotometric techniques applied for resolving interference of metronidazole with ciprofloxacin in their pharmaceutical dosage form

    NASA Astrophysics Data System (ADS)

    Attia, Khalid A. M.; Nassar, Mohammed W. I.; El-Zeiny, Mohamed B.; Serag, Ahmed

    2016-02-01

    Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of metronidazole as interference. The methods under study are area under the curve, simultaneous equation in addition to smart signal processing techniques of manipulating ratio spectra namely Savitsky-Golay filters and continuous wavelet transform. All the methods were validated according to the ICH guidelines where accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can therefore be used for the routine analysis of ciprofloxacin in quality-control laboratories.

  6. Formulation and evaluation of different floating tablets containing metronidazole to target stomach.

    PubMed

    Loh, Zhiao C; Elkordy, Amal A

    2015-01-01

    The purpose of this study is to formulate and develop tablets dosage form containing Metronidazole which has swelling and floating properties as a gastroretentive controlled-release drug delivery system to improve drug bioavailability. Fifteen different formulations of effervescence-forming floating systems were designed using HPMC K15M, xanthan gum, co-povidone, Eudragit® RL PO, pluronic® F-127 and/or polypropylene foam powder as swelling agents and sodium bicarbonate with/ without citric acid as gas-forming agents at different compositions. Six out of these 15 formulations which have satisfactory tablet floating behaviour were further studied with the incorporation of Metronidazole. The tablets were evaluated based on tablet physicochemical properties, floating behaviour, swelling ability and drug dissolution studies which were carried out using 0.1M HCl at 37°C for 8 hours. Furthermore, evaluation of the powder mixtures using Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and scanning electron microscope (SEM) were investigated. Most of the tablets show good physicochemical properties except for F11 which contains pluronic® F-127 as its release-retarding matrix-forming polymer. Other formulations show high swelling capacity, ability to float for at least 8 hours in vitro and have sustained drug release characteristics. Data obtained indicated that F3 which contains HPMC (12.5%w/w), xanthan gum (25%w/w), co-povidone (12.5%w/w) and sodium bicarbonate (31.7%w/w) is a suitable formulation with short floating lag time, good floating behaviour and sustained drug release for at least 8 hours in vitro with a zero order kinetic. Combinations of HPMC K15M and xanthan gum as swelling agents show synergistic effect in retarding drug release and are suitable in providing the most sustained drug release system.

  7. Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains.

    PubMed

    Vuotto, Claudia; Moura, Ines; Barbanti, Fabrizio; Donelli, Gianfranco; Spigaglia, Patrizia

    2016-03-01

    Resistance mechanism to metronidazole is still poorly understood, even if the number of reports on Clostridium difficile strains with reduced susceptibility to this antibiotic is increasing. In this study, we investigated the ability of the C. difficile strains 7032994, 7032985 and 7032989, showing different susceptibility profiles to metronidazole but all belonging to the PCR ribotype 010, to form biofilm in vitro in presence and absence of subinhibitory concentrations of metronidazole. The quantitative biofilm production assay performed in presence of metronidazole revealed a significant increase in biofilm formation in both the susceptible strain 7032994 and the strain 7032985 exhibiting a reduced susceptibility to this antibiotic, while antibiotic pressure did not affect the biofilm-forming ability of the stable-resistant strain 7032989. Moreover, confocal microscopy analysis showed an abundant biofilm matrix production by the strains 7032994 and 7032885, when grown in presence of metronidazole, but not in the stable-resistant one. These results seem to demonstrate that subinhibitory concentrations of metronidazole are able to enhance the in vitro biofilm production of the above-mentioned PCR ribotype 010 C. difficile strains, susceptible or with reduced susceptibility to this antibiotic, suggesting a possible role of biofilm formation in the multifactorial mechanism of metronidazole resistance developed by C. difficile. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

    PubMed

    Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

    2016-10-01

    Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Characterization of a Stable, Metronidazole-Resistant Clostridium difficile Clinical Isolate

    PubMed Central

    Lynch, Tarah; Chong, Patrick; Zhang, Jason; Hizon, Romeo; Du, Tim; Graham, Morag R.; Beniac, Daniel R.; Booth, Timothy F.; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Mulvey, Michael R.

    2013-01-01

    Background Clostridium difficile are Gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15–35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. Methodology/Principal Findings Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. Conclusions/Significance This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described. PMID:23349739

  10. Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate.

    PubMed

    Lynch, Tarah; Chong, Patrick; Zhang, Jason; Hizon, Romeo; Du, Tim; Graham, Morag R; Beniac, Daniel R; Booth, Timothy F; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Mulvey, Michael R

    2013-01-01

    Clostridium difficile are gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15-35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.

  11. Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination.

    PubMed

    Weil, J; Bell, G D; Powell, K; Morden, A; Harrison, G; Gant, P W; Jones, P H; Trowell, J E

    1990-12-01

    Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.

  12. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis.

    PubMed

    Sobel, Jack D; Ferris, Daron; Schwebke, Jane; Nyirjesy, Paul; Wiesenfeld, Harold C; Peipert, Jeffrey; Soper, David; Ohmit, Suzanne E; Hillier, Sharon L

    2006-05-01

    Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis. Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

  13. Proteomic Analysis of a NAP1 Clostridium difficile Clinical Isolate Resistant to Metronidazole

    PubMed Central

    Chong, Patrick M.; Lynch, Tarah; McCorrister, Stuart; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Westmacott, Garrett R.; Mulvey, Michael R.

    2014-01-01

    Background Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. Methodology/Principal Findings NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. Conclusions/Significance This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair. PMID:24400070

  14. Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing.

    PubMed

    Binh, Tran Thanh; Suzuki, Rumiko; Trang, Tran Thi Huyen; Kwon, Dong Hyeon; Yamaoka, Yoshio

    2015-04-01

    Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

    PubMed

    Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

    2016-10-01

    Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Search for Novel Candidate Mutations for Metronidazole Resistance in Helicobacter pylori Using Next-Generation Sequencing

    PubMed Central

    Binh, Tran Thanh; Suzuki, Rumiko; Trang, Tran Thi Huyen; Kwon, Dong Hyeon

    2015-01-01

    Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance. PMID:25645832

  17. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  18. Proteomic analysis of a NAP1 Clostridium difficile clinical isolate resistant to metronidazole.

    PubMed

    Chong, Patrick M; Lynch, Tarah; McCorrister, Stuart; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Westmacott, Garrett R; Mulvey, Michael R

    2014-01-01

    Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair.

  19. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    PubMed Central

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  20. A quantity survey of intravenous administration of metronidazole in its different forms in a tertiary teaching hospital.

    PubMed

    Lee, L L; Rowland, J; Ling, C H Y; Fiakos, E

    2010-08-01

    The aim of this paper is to examine the prescribing patterns and cost of various formulations of metronidazole in a hospital setting over a 3-month period. Oral metronidazole has high bioavailability (98.9%) with peak plasma concentrations averaged at 2.3 h after dosing. Despite the high bioavailability of oral metronidazole, many patients continue to receive metronidazole intravenously when they are suitable for oral preparation. An audit of 120 consecutive patients prescribed metronidazole was conducted at the Liverpool Hospital, NSW, from March to July 2005. There were 65 men and 55 women (age 18-93). Of the 120 patients, 16 were on oral, 1 on rectal and 103 were on intravenous metronidazole. Treatment was initiated based on clinical diagnoses. Potential pathogens were subsequently identified on only 21 occasions. The use of metronidazole as an oral preparation was contraindicated in 27 patients (22.5%) who were nil-by-mouth. Of these, rectally administered metronidazole was contraindicated in only eight patients. The average course of intravenous metronidazole was 8.0 +/- 9.7 days (mean +/- SD). The total number of intravenous metronidazole treatment days was 824. Oral metronidazole would have been possible in 618 out of the 824 days. The estimated cost to administer each dose of oral, suppository and intravenous forms of metronidazole is $A0.11, $A1.34 and $A6.09 respectively. Thus, substantial savings could be achieved if oral metronidazole were to be administered whenever possible. The early use of oral or rectal metronidazole should be encouraged when there are no clinical contraindications.

  1. [Investigation of in vitro metronidazole resistance in the clinical isolates of Trichomonas vaginalis].

    PubMed

    Ertabaklar, Hatice; Yaman Karadam, Senem; Malatyalı, Erdoğan; Ertuğ, Sema

    2016-10-01

    Trichomonas vaginalis, a flagellated, urogenital anaerobic protozoon is reported as an important cause of vaginitis with a global distribution. Although metronidazole is the primary choice of drug for the treatment of trichomoniasis, the presence of resistant isolates from many different countries highlights the need of novel drugs for the treatment. Many studies from Turkey mostly dealing with the in vitro effects of compounds and natural products against T.vaginalis have been reported, however, only one study has been encountered searching the metronidazole resistance in a single T.vaginalis isolate. The aim of this study was to determine the in vitro metronidazole resistance and minimum lethal concentrations (MLCs) of the isolates from symptomatic cases. T.vaginalis strains isolated from vaginal discharge samples of symptomatic women that were sent to Adnan Menderes University Faculty of Medicine, Research and Training Hospital Parasitology Laboratory, between 2009-2014 period, were included in the study. The strains were isolated by the inoculation of samples into trypticase-yeast-maltose medium supplemented with 10% fetal calf serum. A total of 40 T.vaginalis isolates stored by cryopreservation were revived before the experiments. T.vaginalis trophozoites were incubated with different concentrations of metronidazole (200, 100, 50, 25, 12.5, 6.25, 3.12, 1.56 μg/ml) and the viability of cells were examined in both aerobic and anaerobic conditions under phase contrast microscope. Additionally, non-motile isolates were further inoculated into fresh media and viability was checked. The wells containing motile trophozoites after 48 hours of incubation with 15 µg/ml and/or higher metronidazole concentration in anaerobic condition and 75 µg/ml and/or higher metronidazole concentration in aerobic conditions were determined as resistant isolates. Of the 40 T.vaginalis isolates three (7.5%) were resistant to metronidazole. MLC mean values of metronidazole

  2. The role of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea.

    PubMed

    Tart, Serina B

    2013-10-01

    For the treatment of Clostridium difficile-associated diarrhea (CDAD), metronidazole and vancomycin remain the most commonly used agents. The major advantage of metronidazole is its low cost, while the advantage of oral vancomycin is a more favorable pharmacokinetic profile. The epidemiology and clinical severity of CDAD have changed due to the emergence of a hypervirulent strain (BI/NAP1/027). In 2010, the Infectious Diseases Society of America/Society for Health Care Epidemiology of America expert panel defined severe CDAD and recommended oral vancomycin to treat these patients. Metronidazole remains the preferred agent for treatment of mild to moderate CDAD.

  3. Draft Genome Sequence of a Metronidazole-Susceptible Atopobium vaginae Isolate

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a vaginal isolate of Atopobium vaginae vaginae (strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species. PMID:26337886

  4. Regional Differences in Metronidazole Resistance and Increasing Clarithromycin Resistance among Helicobacter pylori Isolates from Japan

    PubMed Central

    Kato, Mototsugu; Yamaoka, Yoshio; Kim, Jae J.; Reddy, Rita; Asaka, Masahiro; Kashima, Kei; Osato, Michael S.; El-Zaatari, Fouad A. K.; Graham, David Y.; Kwon, Dong H.

    2000-01-01

    The patterns of antibiotic resistance in Helicobacter pylori were assessed in two different regions in Japan. Overall, prevalences of resistance to metronidazole and clarithromycin were 12.4 and 12.9%, respectively. While there was no difference in clarithromycin resistance, the prevalence of metronidazole resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From 1996 to 1999, the prevalence of metronidazole resistance did not change but the prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%). PMID:10898707

  5. Improvement of an encapsulation process for the preparation of pro- and prebiotics-loaded bioadhesive microparticles by using experimental design.

    PubMed

    Pliszczak, D; Bourgeois, S; Bordes, C; Valour, J P; Mazoyer, M A; Orecchioni, A M; Nakache, E; Lantéri, P

    2011-09-18

    The purpose of this study was to design a new vaginal bioadhesive delivery system based on pectinate-hyaluronic acid microparticles for probiotics and prebiotics encapsulation. Probiotic strains and prebiotic were selected for their abilities to restore vaginal ecosystem. Microparticles were produced by emulsification/gelation method using calcium as cross-linking agent. In the first step, preliminary experiments were conducted to study the influence of the main formulation and process parameters on the size distribution of unloaded microparticles. Rheological measurements were also performed to investigate the bioadhesive properties of the gels used to obtain the final microparticles. Afterwards an experimental design was performed to determine the operating conditions suitable to obtain bioadhesive microparticles containing probiotics and prebiotics. Experimental design allowed us to define two important parameters during the microencapsulation process: the stirring rate during the emulsification step and the pectin concentration. The final microparticles had a mean diameter of 137μm and allowed a complete release of probiotic strains after 16h in a simulated vaginal fluid at +37°C.

  6. Bioadhesive and biocompatible films as wound dressing materials based on a novel dendronized chitosan loaded with ciprofloxacin.

    PubMed

    García, Mónica C; Aldana, Ana A; Tártara, Luis I; Alovero, Fabiana; Strumia, Miriam C; Manzo, Rubén H; Martinelli, Marisa; Jimenez-Kairuz, Alvaro F

    2017-11-01

    The bioadhesive polymeric films as topical drug delivery systems are interesting alternatives to improve the pharmacotherapy and patient compliances. New derivate biomaterials based on weisocyanate- dendronized PVP- crosslinked chitosan and loaded with ciprofloxacin (CIP), as model drug, were used to prepare bioadhesive films. Relevant in vitro/in vivo attributes to define main physicochemical and biopharmaceutical characteristics for topical wound-healing applications were evaluated. A high proportion of CIP, uniformly dispersed along throughout the film, was loaded. An extended release of CIP and different behaviors of release profiles, depending on the presence of dendron, were observed. The films loaded with CIP were effective in inhibiting the growth of both Gram positive and Gram negative bacteria. In addition, biocompatibility and bioadhesion into conjuntival-sacs of the rabbits suggests that these films have good properties to be applied over skin wounds for topical applications, allowing a reduction of the frequency of administration and improving the residence time of the films. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Novel aryl carbamate derivatives of metronidazole as potential antiamoebic agents.

    PubMed

    Hayat, Faisal; Wahedi, Hussain Mustatab; Park, Seonghyeok; Tariq, Saba; Azam, Amir; Shin, Dongyun

    2016-01-01

    A series of novel aryl carbamate derivatives of metronidazole (MNZ) were designed, synthesized, and screened for antiamoebic activity. As compared to MNZ, most of the derivatives exhibited moderate to excellent activity against the HM1:IMSS strain of Entamoeba histolytica. Compounds 7, 14, 16, 19, and 21 exhibited the most promising antiamoebic activity with IC50 values of 0.24, 0.08, 0.26, 0.26, and 0.15 μM, respectively, compared to that of MNZ (1.78 μM). Moreover, from the toxicological studies of these compounds on human melanocytes, the melan-a cell line revealed that the potent compounds are nontoxic at concentrations ranging from 2.5 to 50 μM.

  8. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

    PubMed

    Hussein, Rola; El-Halabi, Mustapha; Ghaith, Ola; Jurdi, Nawaf; Azar, Cecilio; Mansour, Nabil; Sharara, Ala I

    2011-03-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

  9. Broad-spectrum Antibiotic Plus Metronidazole May Not Prevent the Deterioration of Necrotizing Enterocolitis From Stage II to III in Full-term and Near-term Infants

    PubMed Central

    Luo, Li-Juan; Li, Xin; Yang, Kai-Di; Lu, Jiang-Yi; Li, Lu-Quan

    2015-01-01

    Abstract Necrotizing enterocolitis (NEC) is the most common and frequently dangerous neonatal gastrointestinal disease. Studies have shown broad-spectrum antibiotics plus anaerobic antimicrobial therapy did not prevent the deterioration of NEC among very low birth preterm infants. However, few studies about this therapy which focused on full-term and near-term infant with NEC has been reported. The aim of this study was to evaluate the effect of broad-spectrum antibiotic plus metronidazole in preventing the deterioration of NEC from stage II to III in full-term and near-term infants. A retrospective cohort study based on the propensity score (PS) 1:1 matching was performed among the full-term and near-term infants with NEC (Bell stage ≥II). All infants who received broad-spectrum antibiotics were divided into 2 groups: group with metronidazole treatment (metronidazole was used ≥4 days continuously, 15 mg/kg/day) and group without metronidazole treatment. The depraved rates of stage II NEC between the 2 groups were compared. Meanwhile, the risk factors associated with the deterioration of stage II NEC were analyzed by case-control study in the PS-matched cases. A total of 229 infants met the inclusion criteria. Before PS-matching, we found the deterioration of NEC rate in the group with metronidazole treatment was higher than that in the group without metronidazole treatment (18.1% [28/155] vs 8.1% [6/74]; P = 0.048). After PS-matching, 73 pairs were matched, and the depraved rate of NEC in the group with metronidazole treatment was not lower than that in the group without metronidazole treatment (15.1% vs 8.2%; P = 0.2). Binary logistic regression analysis showed that sepsis after NEC (odds ratio [OR] 3.748, 95% confidence interval [CI] 1.171–11.998, P = 0.03), the need to use transfusion of blood products after diagnosis of NEC (OR 8.003, 95% CI 2.365–27.087, P = 0.00), and the need of longer time for nasogastric suction were risk factors

  10. EVALUATION OF ALGINATE MICROSPHERES WITH METRONIDAZOLE OBTAINED BY THE SPRAY DRYING TECHNIQUE.

    PubMed

    Szekalska, Marta; Winnicka, Katarzyna; Czajkowska-Kośnik, Anna; Sosnowska, Katarzyna; Amelian, Aleksandra

    2015-01-01

    In the present study, nine formulations (F1-F9) of alginate microspheres with metronidazole were prepared by the spray drying technique with using different drug:polymer ratio (1:2, 1:1, 2:1) and different sodium alginate concentration (1, 2, 3%). The obtained microspheres were characterized for size, morphology, drug loading, (potential and swelling degree. Mucoadhesive properties were examined using texture analyzer and three different models of adhesive layers--gelatin discs, mucin gel and porcine vaginal mucosa. In vitro drug release, mathematical release profile and physical state of microspheres were also evaluated. The obtained results indicate that sodium alginate is a suitable polymer for developing mucoadhesive dosage forms of metronidazole. The optimal formulation F3 (drug:polymer ratio 1:2 and 1% alginate solution) was characterized by the highest metronidazole loading and sustained drug release. The results of this study indicate promising potential of ALG microspheres as alternative dosage forms for metronidazole delivery.

  11. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    ERIC Educational Resources Information Center

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  12. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    ERIC Educational Resources Information Center

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  13. Metronidazole-resistant clinical isolates of Trichomonas vaginalis have lowered oxygen affinities.

    PubMed

    Yarlett, N; Yarlett, N C; Lloyd, D

    1986-05-01

    Oxygen affinities of metronidazole susceptible and resistant isolates of the parasitic flagellate protozoon Trichomonas vaginalis were determined by mass spectrometric methods. Apparent O2Km values for the respiration of non-proliferating cell suspensions were about 10-fold higher for metronidazole resistant strains than for the susceptible strains C1-NIH or NYH-286. Simultaneous monitoring of hydrogen evolution in the presence of increasing O2 tensions enabled apparent Ki values for H2 to be determined; and this function was independent of metronidazole susceptibility. Apparent O2 affinities of the hydrogenosomal and non-sedimentable fractions were determined for the strains CDC 85 (metronidazole resistant) and C1-NIH, which showed the deficiency in the O2 scavenging capacity by the resistant strain to be associated with the hydrogenosome-containing fraction.

  14. Down-regulation of flavin reductase and alcohol dehydrogenase-1 (ADH1) in metronidazole-resistant isolates of Trichomonas vaginalis

    PubMed Central

    Leitsch, David; Drinić, Mirjana; Kolarich, Daniel; Duchêne, Michael

    2012-01-01

    The microaerophilic parasite Trichomonas vaginalis is a causative agent of painful vaginitis or urethritis, termed trichomoniasis, and can also cause preterm delivery or stillbirth. Treatment of trichomoniasis is almost exclusively based on the nitroimidazole drugs metronidazole and tinidazole. Metronidazole resistance in T. vaginalis does occur and is often associated with treatment failure. In most cases, metronidazole-resistant isolates remain susceptible to tinidazole, but cross resistance between the two closely related drugs can be a problem. In this study we measured activities of thioredoxin reductase and flavin reductase in four metronidazole-susceptible and five metronidazole-resistant isolates. These enzyme activities had been previously found to be downregulated in T. vaginalis with high-level metronidazole resistance induced in the laboratory. Further, we aimed at identifying factors causing metronidazole resistance and compared the protein expression profiles of all nine isolates by application of two-dimensional gel electrophoresis (2DE). Thioredoxin reductase activity was nearly equal in all strains assayed but flavin reductase activity was clearly down-regulated, or even absent, in metronidazole-resistant strains. Since flavin reductase has been shown to reduce oxygen to hydrogen peroxide, its down-regulation could significantly contribute to the impairment of oxygen scavenging as reported by others for metronidazole-resistant strains. Analysis by 2DE revealed down-regulation of alcohol dehydrogenase 1 (ADH1) in strains with reduced sensitivity to metronidazole, an enzyme that could be involved in detoxification of intracellular acetaldehyde. PMID:22449940

  15. Enhanced amperometric detection of metronidazole in drug formulations and urine samples based on chitosan protected tetrasulfonated copper phthalocyanine thin-film modified glassy carbon electrode.

    PubMed

    Meenakshi, S; Pandian, K; Jayakumari, L S; Inbasekaran, S

    2016-02-01

    An enhanced electrocatalytic reduction of metronidazole antibiotic drug molecule using chitosan protected tetrasulfonated copper phthalocyanine (Chit/CuTsPc) thin-film modified glassy carbon electrode (GCE) has been developed. An irreversible reduction occurs at -0.47V (vs. Ag/AgCl) using Chit/CuTsPc modified GCE. A maximum peak current value is obtained at pH1 and the electrochemical reduction reaction is a diffusion controlled one. The detection limit is found to be 0.41nM from differential pulse voltammetry (DPV) method. This present investigation method is adopted for electrochemical detection of metronidazole in drug formulation and urine samples by using DPV method.

  16. High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study.

    PubMed

    Aguin, Tina J; Akins, Robert A; Sobel, Jack D

    2014-04-01

    The purpose of this study was to evaluate high-dose intravaginal metronidazole, with or without miconazole, in enhancing cure rates in women with recurrent BV. A total of 43 women with symptomatic recurrent BV were enrolled in a 4-arm study comparing 500 mg versus 750 mg of metronidazole, with or without miconazole, intravaginally for 7 days. Test of cure by saline wet mount and 10% potassium chloride microscopy, pH, Gram stain for Nugent score, and yeast culture were performed 3 times after treatment: 3 to 7 days, 30 to 35 days, and 60 to 70 days. Overall cure rate for the entire group was 92.6% at visit 2, 62.1% at visit 3, and 51.4% at visit 4. At visit 2, there was no difference in cure rates among patients who received metronidazole 750 mg ± miconazole daily (90.5%) compared with metronidazole 500 mg ± miconazole daily (85%). At visit 3, there was a significant improvement in cure rates among patients who received metronidazole 750 mg ± miconazole daily (78.9%) compared with metronidazole 500 mg ± miconazole daily (44.4%) (p < .05). At visit 4, a significant difference in clinical cure rates persisted among patients who received metronidazole 750 mg ± miconazole daily (68.4%) compared with of metronidazole 500 mg ± miconazole daily (33.3%; p < .05). Poor responses (Nugent score > 4 or pH > 4.4) at the first visit alter treatment-predicted recurrence. The addition of miconazole did not enhance BV response rates. Cure rates for BV were high in this refractory cohort and seemed dose dependent.

  17. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    PubMed

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  18. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    PubMed

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2017-09-05

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.

  19. Anti-anaerobic activity of levofloxacin alone and combined with clindamycin and metronidazole.

    PubMed

    Credito, K L; Jacobs, M R; Appelbaum, P C

    2000-11-01

    Microdilution MICs of levofloxacin against twelve anaerobes ranged between 0.5-8.0 microg/ml and those of clindamycin and metronidazole between 0.008-2.0 and 0.25->16.0 microg/ml, respectively. Combination of levofloxacin with clindamycin and/or metronidazole in time-kill tests led to synergy at levofloxacin concentrations at or below the MIC in 7/12 strains.

  20. Pharmacokinetics of metronidazole, tetracycline and bismuth in healthy volunteers after oral administration of compound tablets containing a combination of metronidazole, tetracycline hydrochloride and bismuth oxide.

    PubMed

    Wu, Y; Ding, L; Huang, N-Y; Wen, A-D; Liu, B; Li, W-B

    2015-02-01

    To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125 mg, tetracycline hydrochloride 125 mg and bismuth oxide 40 mg has been developed. To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation. A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48 h in every period. After single high dose administration under fed condition, the C max of metronidazole, tetracycline and bismuth were 6.833 ± 0.742 μg/mL, 0.8513 ± 0.1253 μg/mL and 3.32 ± 1.89 ng/mL, respectively. The C max and AUC 0-48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C av of metronidazole, tetracycline and bismuth were 20.75 ± 3.52 μg/mL, 1.900 ± 0.243 μg/mL and 5.61 ± 1.34 ng/mL, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Evaluation of metronidazole nanofibers in patients with chronic periodontitis: A clinical study

    PubMed Central

    Chaturvedi, Thakur Prasad; Srivastava, Ruchi; Srivastava, Anand Kumar; Gupta, Varun; Verma, Pushpendra Kumar

    2012-01-01

    Aim: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found to be inadequate in achieving periodontal health in chronic periodontitis, local antimicrobial agents are used as an adjunct to scaling and root planing (SRP), which produces encouraging results. In the present study, an attempt was made to develop a low-dose controlled-release delivery system for the treatment of periodontal infections. A new sustained release drug system of poly e-caprolactone (PCL) nanofibers containing metronidazole (MET) was successfully electrospun and evaluated clinically for periodontal diseases. The retentive nanofibres were shown to provide a controlled delivery of the drugs. Materials and Methods: Nanofibers were prepared with MET in PCL by electrospinning technique. The drug-coated nanofibers provided sustained effect up to a period of 11 days (264 h) and followed first-order release. Forty sites in seven patients (four females and three males) with chronic periodontitis (5–8 mm probing depth) were allocated in two experimental treatment groups: Group A treated with SRP + MET nanofibers and Group B treated with SRP alone (control group). All these patients were evaluated clinically for probing depth (PD), plaque index (PI), and gingival index (GI). Results: Both the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD, PI, and GI. Conclusion: Combination of SRP + MET nanofibers (Group A) resulted in added benefits, compared to the control group. PMID:23580938

  2. Challenges in oral administration of metronidazole dissolved in drinking water to rhesus monkeys (Macaca mulatta).

    PubMed

    Labberton, Linda; Bakker, Jaco; Klomp, Rianne; Langermans, Jan A M; van Geijlswijk, Ingeborg M

    2013-06-01

    Intestinal pathogens such as Entamoeba spp. and Giardia spp. protozoans are not uncommon among rhesus macaques (Macaca mulatta) in research facilities. These infections affect the health of the macaques, potentially causing severe diarrhea, and also pose a risk of zoonotic transmission to human caretakers. Infections must therefore be treated, but no standard treatment for intestinal protozoans in macaques has been developed. Metronidazole is commonly used to treat infections with Giardia spp. and Entamoeba spp. in veterinary medicine, but evidence-based information on effectiveness and dosages for nonhuman primates is lacking, and administration of drugs to nonhuman primates is challenging. The authors designed a study to determine whether oral administration of metronidazole dissolved in drinking water would be successful in rhesus macaques. They monitored daily fluid intake of macaques given water with or without metronidazole and with or without flavored syrup. Metronidazole addition, with or without flavored syrup, resulted in a decrease in fluid intake. Although it was possible to administer metronidazole in drinking water to some macaques, the authors conclude that this strategy is not a practical clinical method because of variation in the amount of water and metronidazole ingested by the macaques.

  3. Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants

    PubMed Central

    Sampson, Mario R.; Bloom, Barry T.; Arrieta, Antonio; Capparelli, Edmund; Benjamin, Daniel K.; Smith, P. Brian; Kearns, Gregory L.; van den Anker, John; Cohen-Wolkowiez, Michael

    2014-01-01

    Objectives In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. Study design We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. Results Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p=0.006). Conclusion While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants. PMID:25318626

  4. Effect of temperature on the metronidazole BSA interaction: Multi-spectroscopic method

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Jiang, Xin Yu; Chen, Xiao Qing; Chen, Yue

    2008-03-01

    The interaction between metronidazole and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy (FS) and resonance light scattering spectroscopy (RLS). The apparent binding constants ( Ka) between metronidazole and BSA were 3.42 × 10 4 (20 °C), 5.78 × 10 4 (30 °C) and 8.23 × 10 4 L mol -1 (40 °C), and the binding sites values ( n) were 1.48 ± 0.03. The experimental results showed that the metronidazole could be inserted into the BSA, quenching the inner fluorescence by forming the metronidazole-BSA complex. The addition of increasing metronidazole to BSA solution leads to the gradual enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The entropy change and enthalpy change were positive, which indicated that the interaction of metronidazole and BSA was driven mainly by hydrophobic forces. The process of binding was a spontaneous process in which Gibbs free energy change was negative.

  5. Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

    PubMed

    Korosh, Travis; Bujans, Emmanuel; Morada, Mary; Karaalioglu, Canan; Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L; Yarlett, Nigel

    2017-10-01

    A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10 H20 ) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2'-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure-activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads. © 2017 John Wiley & Sons A/S.

  6. Trichomonas vaginalis Flavin Reductase 1 and its Role in Metronidazole Resistance

    PubMed Central

    Leitsch, David; Janssen, Brian D.; Kolarich, Daniel; Johnson, Patricia J.; Duchêne, Michael

    2015-01-01

    Summary The enzyme flavin reductase 1 (FR1) from Trichomonas vaginalis, formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defense in T. vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole-resistant T. vaginalis, resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis genome. However, out of these, only FR1 has an affinity for flavins, i.e. FMN, FAD, and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis. PMID:24256032

  7. ASSOCIATION OF CALCIUM HYDROXIDE AND METRONIDAZOLE IN THE TREATMENT OF DOG'S TEETH WITH CHRONIC PERIAPICAL LESION

    PubMed Central

    Panzarini, Sônia Regina; Souza, Valdir; Holland, Roberto; Dezan, Eloi

    2006-01-01

    One of the primary objectives of endodontic treatment of teeth with pulp necrosis is the elimination of microorganisms from the root canal system, as effectively as possible, especially in cases with chronic periapical lesions. AIM: The purpose of this study was to analyze the response of the periapical tissue of dogs' teeth with chronic periapical lesions to endodontic treatment performed with utilization of metronidazole, calcium hydroxide, and an association of both as root canal dressings. METHODOLOGY: Forty root canals were submitted to pulpectomy and the root canals were kept exposed to the oral environment for 6 months. Then, they were submitted to biomechanical preparation and divided into 4 study groups with 10 specimens: group I – no root canal dressing; group II – calcium hydroxide; group III – metronidazole; group IV – calcium hydroxide associated to metronidazole. After 15 days, the root canals were filled with Fill Canal sealer. After 90 days, the animals were killed and the especimens processed for histological analysis. RESULTS: Calcium hydroxide dressing provided a significantly better outcome compared to other experimental groups (α = 0.01). Also, the results of the association of metronidazole and calcium hydroxide were similar to those observed for the metronidazole group. The worst results were obtained by the no root canal dressing group. CONCLUSION: The use of metronidazole alone or associated with Calcium hydroxide, did not improve periapical healing when compared to Calcium hydroxide dressing. PMID:19089054

  8. The mutation of the rdxA gene in metronidazole-resistant Helicobacter pylori clinical isolates.

    PubMed

    Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian

    2014-01-01

    Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance.

  9. The mutation of the rdxA gene in metronidazole-resistant Helicobacter pylori clinical isolates

    PubMed Central

    Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian

    2014-01-01

    Backgrounds: Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. Objective: This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. Materials and Methods: MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. Results: The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. Conclusion: An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance. PMID:24761398

  10. Metronidazole prodrugs: synthesis, physicochemical properties, stability, and ex vivo release studies.

    PubMed

    Mura, Carla; Valenti, Donatella; Floris, Costantino; Sanna, Roberta; De Luca, Maria Antonietta; Fadda, Anna Maria; Loy, Giuseppe

    2011-09-01

    The aim of the present study was to develop a colon targeted delivery system for metronidazole using polymeric prodrug formulation. Two chitosan amide conjugates of metronidazole were prepared by using two different spacers to covalently link the drug to the amino group of the chitosan glucosamine units. Glutaric and succinic hemiesters of metronidazole were thus prepared and then coupled to chitosan to obtain metronidazole-glutaryl- and metronidazole-succinyl-chitosan conjugates. Polymeric prodrugs were characterized by solid state NMR method, namely carbon 13 cross polarization magic angle spinning ((13)C NMR CPMAS). Prodrug stability study was carried out in acid (pH = 1.2) and in alkaline (pH = 7.4) buffers in a thermostatic bath at 37 °C. Drug release from the two prodrugs was studied by incubating each of them with 10% w/v cecal and colonic content of rats. Obtained results showed that both prodrugs were adequately stable in acid environment, while the succinyl conjugate was more stable than the glutaryl one in alkaline buffer. Both the prodrugs released the drug in cecal and colonic content, showing that the two systems could serve as colon specific delivery systems of metronidazole. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  11. High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents.

    PubMed

    Ogata, Silvio K; Godoy, Anita P Ortiz; da Silva Patricio, Francy R; Kawakami, Elisabete

    2013-06-01

    The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.

  12. Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

    PubMed

    Peretz, Avi; Paritsky, Maya; Nasser, Omar; Brodsky, Diana; Glyatman, Tatyana; Segal, Sofia; On, Avi

    2014-08-01

    The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19-79 years) and 76 from children (7-17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

  13. Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance.

    PubMed

    Leitsch, David; Janssen, Brian D; Kolarich, Daniel; Johnson, Patricia J; Duchêne, Michael

    2014-01-01

    The enzyme flavin reductase 1 (FR1) from Trichomonas vaginalis, formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defence in T. vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole-resistant T. vaginalis, resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis genome. However, out of these, only FR1 has an affinity for flavins, i.e. FMN, FAD and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis.

  14. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy.

    PubMed

    Hanson, J M; McGregor, J A; Hillier, S L; Eschenbach, D A; Kreutner, A K; Galask, R P; Martens, M

    2000-11-01

    To compare the efficacy and safety of 0.75% metronidazole vaginal gel with oral metronidazole for the treatment of bacterial vaginosis (BV). Nonpregnant women with BV were enrolled in a multicenter, randomized, investigator-blind treatment trial. Patients were randomly assigned to either 0.75% metronidazole vaginal gel (5 g twice daily for five days) or oral metronidazole (500 mg twice daily for seven days). Follow-up visits occurred approximately two and five weeks after initiation of therapy. BV was clinically eliminated at the first follow-up visit in 83.7% (36/43, 95% CI 72.3-95.1%) of the intravaginal group and 85.1% (40/47, 95% CI 74.6-95.6%) of the oral group. At the final visit, BV was eliminated in 70.7% (29/41, 95% CI 56.3-85.1%) of the intravaginal group and 71.1% (32/45, 95% CI 57.4-84.8%) of the oral group. Significantly more patients in the oral treatment group (51.8%) reported gastrointestinal complaints as compared to the intravaginal treatment group (32.7%, P = .04). The efficacy of 0.75% metronidazole vaginal gel twice daily for five days in treating BV was similar to that of standard oral metronidazole treatment and was associated with fewer gastrointestinal complaints.

  15. A novel vaginal drug delivery system: anti-HIV bioadhesive film containing abacavir.

    PubMed

    Ghosal, Kajal; Ranjan, Alok; Bhowmik, Benoy Brata

    2014-07-01

    Women are very much susceptible for acquired immunodeficiency syndrome (AIDS) and other sexually transmitted diseases (STDs), mainly due to unprotected heterosexual vaginal intercourse and for some other social and economical disadvantages. Our aim was to formulate and optimize vaginal film of abacavir, a potent nucleoside reverse transcriptase inhibitor, for the treatment of AIDS and HIV. Abacavir films were prepared by solvent evaporation method using sodium alginate (Na-alginate) as the main polymer, Hydroxypropyl Methylcellulose E 15 (HPMC E 15) as the copolymer and glycerol as a humectant. Abacavir sulphate (ABC) was used here as a drug. Films were optimized for various physicochemical parameters such as tensile strength, % elongation at break, swelling capacity, drug content (mg/cm(2)), thickness, folding endurance, bioadhesion, pH, moisture content and SEM. Drug polymer interaction was studied by FTIR Spectra. The drug release study was accomplished in dissolution apparatus. In vivo study was also carried out. This newly formed film was one kind of sustain release type and can be considered as a novel drug carrier system for the treatment of AIDS and other STDs. It was suitable for local as well as systemic effect. The films showed good physicochemical property with good aesthetic appeal.

  16. Monitoring the Long-Term Degradation Behavior of Biomimetic Bioadhesive using Wireless Magnetoelastic Sensor

    PubMed Central

    Lin, Meng-Hsien; Anderson, Jonathan; Pinnaratip, Rattapol; Meng, Hao; Konst, Shari; DeRouin, Andrew J.; Rajachar, Rupak

    2015-01-01

    The degradation behavior of a tissue adhesive is critical to its ability to repair a wound while minimizing prolonged inflammatory response. Traditional degradation tests can be expensive to perform, as they require large numbers of samples. The potential for using magnetoelastic resonant sensors to track bioadhesive degradation behavior was investigated. Specifically, biomimetic poly(ethylene glycol)- (PEG-) based adhesive was coated onto magnetoelastic (ME) sensor strips. Adhesive-coated samples were submerged in solutions buffered at multiple pH levels (5.7, 7.4 and 10.0) at body temperature (37°C) and the degradation behavior of the adhesive was tracked wirelessly by monitoring the changes in the resonant amplitude of the sensors for over 80 days. Adhesive incubated at pH 7.4 degraded over 75 days, which matched previously published data for bulk degradation behavior of the adhesive while utilizing significantly less material (~103 times lower). Adhesive incubated at pH 10.0 degraded within 25 days while samples incubated at pH 5.7 did not completely degrade even after 80 days of incubation. As expected, the rate of degradation increased with increasing pH as the rate of ester bond hydrolysis is higher under basic conditions. As a result of requiring a significantly lower amount of samples compared to traditional methods, the ME sensing technology is highly attractive for fully characterizing the degradation behavior of tissue adhesives in a wide range of physiological conditions. PMID:26087077

  17. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

    PubMed Central

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

  18. In vitro and In vivo Studies on a Novel Bioadhesive Colloidal System: Cationic Liposomes of Ibuprofen.

    PubMed

    Gai, Xiumei; Cheng, Lizhen; Li, Ting; Liu, Dandan; Wang, Yanyan; Wang, Tuanjie; Pan, Weisan; Yang, Xinggang

    2017-10-02

    The objective of this study was to develop an ocular drug delivery system built on the cationic liposomes, a novel bioadhesive colloidal system, which could enhance the precorneal residence time, ocular permeation, and bioavailability of ibuprofen. The optimal formulation of cationic liposomes prepared by ethanol injection method was ultimately confirmed by an orthogonal L9 (3(3)) test design. In addition, γ-scintigraphic technology and the microdialysis technique were utilized in the assessment of in vivo precorneal retention capability and ocular bioavailability individually. In the end, we acquired the optimal formulation of ibuprofen cationic liposomes (Ibu-CL) by orthogonal test design, and the particle size and entrapment efficiency (EE%) were 121.0 ± 3.5 nm and 72.9 ± 3.4%, respectively. In comparison to ibuprofen eye drops (Ibu-ED), Ibu-CL could significantly prolong the T max to 100 min and the AUC to 1.53-folds, which indicated that the Ibu-CL could improve the precorneal retention time and bioavailability of ibuprofen. Consequently, these outcomes designated that the ibuprofen cationic liposomes we researched probably are a promising application in ocular drug delivery system.

  19. Development of hydrocolloid Bi-layer dressing with bio-adhesive and non-adhesive properties.

    PubMed

    Khan, M Iqbal H; Islam, Jahid M M; Kabir, Wasifa; Rahman, Ataur; Mizan, Maria; Rahman, M Fizur; Amin, Jakia; Khan, Mubarak A

    2016-12-01

    Bio-active bi-layer thin film having both bio-adhesive and non-adhesive end composed of polyvinyl alcohol (PVA) and gelatin/chitosan/polyethylene glycol (PEG) blend was developed for biomedical applications especially as an alternative of advanced tissue scaffold. The developed composite film was subjected to mechanical, thermal and physico-chemical characterization such as tensile strength (TS) and elongation at break (Eb), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), fluid drainage capacity and biocompatibility. Suitable packaging was also selected and stability study and aging test of the composite film were performed after packing. The incorporation of chitosan and PEG into gelatin showed improved mechanical properties of both TS and Eb, which suggested the occurrence of interaction among gelatin, chitosan and PEG molecules in the composite film. The presence of crosslinking as an interaction of above three polymers was also confirmed by FTIR study. Results from the DSC study suggested increased thermal stability after crosslinking. On the other hand, water uptake studies suggested excellent fluid drainage capability and hydro-stability of the composite film. The proposed dressing also showed excellent biocompatibility. Based on the studies related to the performance with confirmed identity, we concluded that our developed bi-layer film is very potential as an ideal wound dressing material. Copyright © 2016. Published by Elsevier B.V.

  20. Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 2. Cerebrospinal Fluid Concentration Measurements in Patients with External Ventricular Drain

    PubMed Central

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

    2014-01-01

    This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0–τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0–τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF. PMID:24277050

  1. Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

  2. The synergy between natural polyphenol-inspired catechol moieties and plant protein-derived bio-adhesive enhances the wet bonding strength.

    PubMed

    Wang, Zhong; Zhao, Shujun; Song, Ruyuan; Zhang, Wei; Zhang, Shifeng; Li, Jianzhang

    2017-08-29

    Novel soybean meal-based biomimetic (STP) adhesives were fabricated via soybean meal (SM) and enhanced by tannic acid (TA) and polyetheylenimine (PEI) (TAPI) co-crosslinking network based on natural polyphenol-inspired chemistry. The multiple physico-chemical interactions (including intermolecular H-bonding and covalent bonding) between the TAPI co-crosslinking system and SM matrices were examined by the Fourier transform infrared spectroscopy, solid-state (13)C nuclear magnetic resonance, X-ray diffraction, thermogravimetric analysis, and scanning electron microscopy. The results showed that a dense, robust, and water-resistant adhesive layer was constructed between network-bound catechol moieties in the TAPI and SM system, endowing the STP adhesive with high wet bonding strength for plywood. As expected, TAPI-modified SM adhesives showed a 156.1% increase in wet bonding strength compared to the control SM adhesive. The adhesion meets standard requirements for interior-use plywood. Both the solid content and residual mass analysis also confirmed that the enhancement in the STP adhesive was attributable to the network crosslinking density and stiffness after integrating the TAPI system. Moreover, the thermal stability of the resultant STP adhesive exhibited a significant improvement. The proposed STP adhesive may be a promising cost-effective and wet-resistant bio-adhesive for the application in the wood composites industry.

  3. Effect of MMX® mesalamine coadministration on the pharmacokinetics of amoxicillin, ciprofloxacin XR, metronidazole, and sulfamethoxazole: results from four randomized clinical trials

    PubMed Central

    Pierce, David; Corcoran, Mary; Martin, Patrick; Barrett, Karen; Inglis, Susi; Preston, Peter; Thompson, Thomas N; Willsie, Sandra K

    2014-01-01

    Background MMX® mesalamine is a once daily oral 5-aminosalicylic acid formulation, effective in induction and maintenance of ulcerative colitis remission. Patients on long-term mesalamine maintenance may occasionally require concomitant antibiotic treatment for unrelated infections. Aim To evaluate the potential for pharmacokinetic interactions between MMX mesalamine and amoxicillin, ciprofloxacin extended release (XR), metronidazole, or sulfamethoxazole in four open-label, randomized, placebo-controlled, two-period crossover studies. Methods In all four studies, healthy adults received placebo once daily or MMX mesalamine 4.8 g once daily on days 1–4 in one of two treatment sequences. In studies 1 and 2, subjects also received a single dose of amoxicillin 500 mg (N=62) or ciprofloxacin XR 500 mg (N=30) on day 4. In studies 3 and 4, subjects received metronidazole 750 mg twice daily on days 1–3 and once on day 4 (N=30); or sulfamethoxazole 800 mg/trimethoprim 160 mg twice daily on days 1–3 and once on day 4 (N=44). Results MMX mesalamine had no significant effects on systemic exposure to amoxicillin, ciprofloxacin, or metronidazole; the 90% confidence intervals (CIs) around the geometric mean ratios (antibiotic + MMX mesalamine: antibiotic + placebo) for maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) fell within the predefined equivalence range (0.80–1.25). Sulfamethoxazole exposure increased by a statistically significant amount when coadministered with MMX mesalamine; however, increased exposure (by 12% in Cmax at steady state; by 15% in AUC at steady state) was not considered clinically significant, as the 90% CIs for each point estimate fell entirely within the predefined equivalence range. Adverse events in all studies were generally mild. Conclusion MMX mesalamine may be coadministered with amoxicillin, ciprofloxacin, metronidazole, or sulfamethoxazole, without affecting pharmacokinetics or safety of

  4. Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system.

    PubMed

    Narayanan, Sabrina; Hünerbein, Andreas; Getie, Melkamu; Jäckel, Andreas; Neubert, Reinhard H H

    2007-08-01

    Reactive oxygen species (ROS) play a vital role in the pathophysiology of the skin disease rosacea, a chronic, genetically-determined and UV-triggered disease, leading to facial redness and blemishes and exhibiting a deep impact on a patient's self-esteem and quality of life. ROS can cause oxidative damage to nucleic acids, sugars, proteins and lipids, thereby contributing to adverse effects on the skin. Metronidazole has been the first-line topical agent therapy for many years; nevertheless the mechanism of action is still not well understood. The therapeutic efficacy of metronidazole has been attributed to its antioxidant effects, which can involve two pathways: decreased generation of ROS within tissues or scavenging and inactivation of existing ROS. Previous investigations have shown that metronidazole reduces ROS by decreasing ROS production in cellular in-vitro systems. The aim of the following study was to demonstrate that metronidazole additionally exhibits antioxidative properties in a cell-free system, by acting as an antioxidant scavenger. A simple skin lipid model (oxidative) system and a complex skin adapted lipid system in conjunction with thiobarbituric acid (TBA) test, a quantitative assay for the detection of malondialdehyde (MDA) and therefore lipid peroxidation, were used to determine the antioxidative properties of metronidazole after UV irradiation. Results clearly show that metronidazole has antioxidative properties in a cell-free environment, acting as a free radical scavenger. Simple skin lipid model: in the presence of 10, 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 25, 36 and 49%, respectively. Complex skin lipid system: in the presence of 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 19 and 34%, respectively. The results obtained in this study and from previous publications strongly suggest that metronidazole exhibits antioxidative effects via two mechanisms: decrease in ROS

  5. Chemical stability and bioadhesive properties of an ester prodrug of Delta 9-tetrahydrocannabinol in poly(ethylene oxide) matrices: effect of formulation additives.

    PubMed

    Thumma, Sridhar; Majumdar, Soumyajit; ElSohly, Mahmoud A; Gul, Waseem; Repka, Michael A

    2008-10-01

    The objective of the present research was to stabilize a novel hemiglutarate ester prodrug of Delta(9)-tetrahydrocannabinol (THC), in polyethylene oxide (PEO) polymeric matrices produced by hot-melt fabrication, for systemic delivery of THC through the oral transmucosal route. For this purpose, the influence of pH modifiers and antioxidants employed as stabilizing agents in these matrices was investigated. Based on the stability studies, two final formulations were made, and the stability of the active was assessed in these systems. In addition, the bioadhesive properties of PEO matrices were studied as a function of bioadhesive polymer type and concentration, contact time, drug loading and wetting time. Of all of the polymers investigated, bioadhesion was highest with Carbopol 971p. Bioadhesion increased with bioadhesive polymer concentration and wetting time to a certain level beyond which there was no further contribution. Both the contact time and drug loading influenced the bioadhesion. Severe degradation of the prodrug was observed during storage, even at room temperature (75% at the end of 3 months). Incorporation of the stabilizing agents in the PEO matrices reduced the degradation of the prodrug considerably. Citric acid was the most effective of all of the pH modifiers studied. Among the various antioxidants utilized, degradation was observed least in presence of BHT and ascorbic acid. Only 7.6% and 8.2% of prodrug degraded in these matrices, respectively, as compared to the PEO-only matrices (59.4%) at the end of 3 months at 25 degrees C/60% RH. The prodrug was very stable in both of the final formulations at the end of the 3 months at 40 degrees C/75% RH.

  6. Chemical Stability and Bioadhesive Properties of an Ester Prodrug of Δ9-Tetrahydrocannabinol in Poly (Ethylene Oxide) Matrices: Effect of Formulation Additives

    PubMed Central

    Thumma, Sridhar; Majumdar, Soumyajit; ElSohly, Mahmoud A.; Gul, Waseem; Repka, Michael A.

    2008-01-01

    The objective of the present research was to stabilize a novel hemiglutarate ester prodrug of Δ9-tetrahydrocannabinol (THC), in polyethylene oxide (PEO) polymeric matrices produced by hot-melt fabrication, for systemic delivery of THC through the oral transmucosal route. For this purpose, the influence of pH modifiers and antioxidants employed as stabilizing agents in these matrices was investigated. Based on the stability studies, two final formulations were made, and the stability of the active was assessed in these systems. In addition, the bioadhesive properties of PEO matrices were studied as a function of bioadhesive polymer type and concentration, contact time, drug loading and wetting time. Of all of the polymers investigated, bioadhesion was highest with Carbopol® 971p. Bioadhesion increased with bioadhesive polymer concentration and wetting time to a certain level beyond which there was no further contribution. Both the contact time and drug loading influenced the bioadhesion. Severe degradation of the prodrug was observed during storage, even at room temperature (75% at the end of 3 months). Incorporation of the stabilizing agents in the PEO matrices reduced the degradation of the prodrug considerably. Citric acid was the most effective of all of the pH modifiers studied. Among the various antioxidants utilized, degradation was observed least in presence of BHT and ascorbic acid. Only 7.6% and 8.2% of prodrug degraded in these matrices, respectively, as compared to the PEO only matrices (59.4%) at the end of 3 months at 25 °C/60% RH. The prodrug was very stable in both of the final formulations at the end of the 3 months at 40 °C/75% RH. PMID:18652884

  7. Effects of metronidazole (Flagyl) on the determination of serum ASAT on the SMA 12/60 Auto Analyser.

    PubMed

    Karlsen, R L; Kristiansen, G; Solberg, J H

    1983-04-01

    Therapeutic serum concentrations of metronidazole will lead to under-estimation of ASAT activity when a SMA 12/60 Auto Analyser is used. This interference is due to metronidazole entering the colorimeter through the dialyser membrane in the SMA 12/60 Auto Analyser. This drug is one of the few with a relatively high therapeutic serum concentration, absorbing light in the 340 nm range. Metronidazole will similarily affect other 340 nm methods (LDH, ALAT) available on the SMA 12/60. This interference with metronidazole on the SMA 12/60 can easily be solved by the introduction of a separate serum blank channel for the 340 nm methods.

  8. Implications of metronidazole pharmacodynamics for therapy of trichomoniasis.

    PubMed

    Larsen, B; Wilson, A H; Glover, D D; Charles, D

    1986-01-01

    A liquid chromatographic technique for the detection of metronidazole (MDZ) and its major metabolites, combined with a vaginal sampling technique employing extraction of drug from vaginal swabs, was used to evaluate the concentration of MDZ in the vaginal fluid during therapy. Wide variation in the absolute concentration of unchanged drug was noted, although the average vaginal levels were about half the serum concentration 2 h after treatment had been initiated and comparable to the serum levels 6 and 24 h after treatment. Oral administration of MDZ invariably resulted in the presence of the drug in the serum and urine but the drug was not always detected in the vaginal secretions. The presence of the relatively inactive acetyl metabolite in the vaginal fluid of patients who failed to respond to therapy for trichomoniasis suggested the possible role of drug modification as a contributing factor in the lack of therapeutic success. The presence of MDZ in women in whom the cervix had previously been surgically removed attests to the transport or transudation of the drug across the vaginal epithelium without involvement of the secretory activity of the cervix.

  9. Lon protease affects the RdxA nitroreductase activity and metronidazole susceptibility in Helicobacter pylori.

    PubMed

    Tu, I-Fan; Liao, Jiahn-Haur; Yang, Feng-Ling; Lin, Nien-Tsung; Chan, Hong-Lin; Wu, Shih-Hsiung

    2014-10-01

    The lon gene of Helicobacter pylori strains is constitutively expressed during growth. However, virtually nothing is understood concerning the role of Lon in H. pylori. This study examined the function and physiological role of Lon in H. pylori (HpLon) using a trapping approach to identify putative Lon binding partners in the bacterium. Protease-deficient Lon was expressed and served as the bait in trapping approach to capture the interacting partners in H. pylori. The antibiotic susceptibility of wild-type and lon derivative mutants was determined by the E test trips and the disc diffusion assay. The effect of HpLon on RdxA activity was detected the change in NADPH oxidation and metronidazole reduction by spectrophotometer. Lon in Helicobacter pylori (HpLon) interacting partners are mostly associated with metronidazole activation. lon mutant presents more susceptible to metronidazole than that of the wild type, and this phenotype is recovered by complementation of the wild-type Lon. We found that the ATPases associated with a variety of cellular activities (AAA(+) ) module of HpLon causes a decrease in both NADPH oxidase and Mtz reductase activity in RdxA, a major Mtz-activating enzyme in H. pylori. Metronidazole resistance of H. pylori causes the serious medical problem worldwide. In this study, HpLon is involved in metronidazole susceptibility among H. pylori strains. We provide the evidence that HpLon alters RdxA activity in vitro. The decrease in metronidazole activation caused by HpLon is possibly prior to accumulate mutation in rdxA gene before the metronidazole-resistant strains to be occurred. © 2014 John Wiley & Sons Ltd.

  10. An in vitro metronidazole susceptibility test for trichomoniasis using the InPouch TV test.

    PubMed

    Borchardt, K A; Li, Z; Zhang, M Z; Shing, H

    1996-04-01

    An efficient anaerobic culture system, the InPouch TV test, was used to determine the susceptibility of Trichomonas vaginalis to metronidazole. Glacial acetic acid was employed as a solvent for metronidazole. T vaginalis isolates were cultured from 16 symptomatic female patients. The 11 who responded to oral metronidazole, 250 mg tid for 7 days, were considered as having sensitive trichomonads; the 5 who remained infected after treatment were considered to have resistant organisms. All isolates were cultured for minimum lethal concentrations (MLC). Metronidazole was added to a series of pouches; two-fold dilution of the most concentrated was 50 micrograms/ml and the least was 0.4 micrograms/ml. The inoculum of viable trichomonads was 1 x 105/ml in each pouch. Pouches were incubated at 37 degrees C for 48 h, examined microscopically for motile trichomonads, and then 0.5 ml was subcultured to drug free pouches. After 5 days incubation at 37 degrees C, each subculture and culture were examined microscopically for viable trichomonads. Eleven isolates of T vaginalis from patients responding to metronidazole treatment had MLC between 0.4 to 3.1 micrograms/ml. The MLC from the 5 treatment failure patients were between 12.5 to 50 micrograms/ml. For the 16 patients in this study, the MLC values determined with the InPouch TV test differentiated between infection caused by metronidazole sensitive and resistant trichomonads. The mean MLC of clinically resistant isolates was approximately eleven fold higher than the mean MLC of clinically sensitive isolates (15 micrograms/ml vs 1.32 micrograms/ml). There was a significant difference between clinically resistant and sensitive isolates (t = 5.47, p < 0.0005). This study suggests that the InPouch TV test could be used for distinguishing between metronidazole resistant and sensitive isolates.

  11. Effect of calcium phosphate-based fillers on the structure and bonding strength of novel gelatin-alginate bioadhesives.

    PubMed

    Cohen, Benny; Panker, Maoz; Zuckerman, Eyal; Foox, Maytal; Zilberman, Meital

    2014-05-01

    Interest in soft and hard tissue adhesives as alternatives for conventional wound closing and bone fixation applications has increased in recent decades as a result of numerous possible advantages such as better comfort and lower cost. A novel bioadhesive based on the natural polymers GA has recently been developed and studied in our laboratory. Hydroxyapatite and tricalcium phosphate are two bioactive ceramics known for their ability to enhance bone regeneration. In the current study, these two bioactive fillers were incorporated into the bioadhesive at concentrations of 0.125, 0.25 and 0.5% w/v, and their effects on the resulting adherence properties to soft and hard tissues were studied. Porcine skin and cortical portions of bovine femurs were used as soft and hard tissue specimens, respectively. The bonding strength was evaluated using an Instron universal testing machine in tensile mode, and the microstructure analysis was based on environmental scanning electron microscope observations. Both bioactive fillers were found to have a reinforcing effect on the adhesives, significantly improving their adhesion to soft tissues in certain concentrations. The best bonding strength results were obtained for 0.25% hydroxyapatite and 0.5% w/v tricalcium phosphate-18.1 ± 4.0 and 15.2 ± 2.6 kPa, respectively, compared with 8.4 ± 2.3 kPa for adhesive with no fillers. The improved adherence is probably related to the stiffness of the insoluble hydroxyapatite and tricalcium phosphate particles which reinforce the adhesive. These particles can clearly be observed in the environmental scanning electron microscope analysis. The potential of these fillers to increase the bonding strength of the adhesive to hard tissues was also demonstrated. Hydroxyapatite and tricalcium phosphate thus improve our new gelatin-alginate bioadhesives, which can be used for both soft and hard tissue adhesive applications.

  12. Injectable dopamine-modified poly(α,β-aspartic acid) nanocomposite hydrogel as bioadhesive drug delivery system.

    PubMed

    Gong, Chu; Lu, Caicai; Li, Bingqiang; Shan, Meng; Wu, Guolin

    2017-04-01

    Hydrogel systems based on cross-linked polymeric materials with adhesive properties in wet environments have been considered as promising candidates for tissue adhesives. The 3,4-dihydroxyphenylalanine (DOPA) is believed to be responsible for the water-resistant adhesive characteristics of mussel adhesive proteins. Under the inspiration of DOPA containing adhesive proteins, a dopamine-modified poly(α,β-aspartic acid) derivative (PDAEA) was successfully synthesized by successive ring-opening reactions of polysuccinimide (PSI) with dopamine and ethanolamine, and an injectable bioadhesive hydrogel was prepared via simply mixing PDAEA and FeCl3 solutions. The formation mechanism of the hydrogel was investigated by ultraviolet-visible (UV-vis) spectroscopic, Fourier transformation infrared (FT-IR) spectroscopic, visual colorimetric measurements and EDTA immersion methods. The study demonstrated that the PDAEA-Fe(3+) hydrogel is a dual cross-linking system composed of covalent and coordination crosslinks. The PDAEA-Fe(3+) hydrogel is suitable to serve as a bioadhesive agent according to the rheological behaviors and the observed significant shear adhesive strength. The slow and sustained release of the model drug curcumin from the hydrogel in vitro demonstrated the hydrogel could also be potentially used for drug delivery. Moreover, the cytotoxicity tests in vitro suggested the prepared polymer and hydrogel possessed excellent cytocompatibility. All the results indicated that the dopamine modified poly(α,β-aspartic acid) derivative based hydrogel was a promising candidate for bioadhesive drug delivery system. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1000-1008, 2017.

  13. Ex vivo mucoadhesion and in vivo bioavailability assessment and correlation of ketoprofen tablet dosage forms containing bioadhesives.

    PubMed

    Zaghloul, A; Taha, E; Afouna, M; Khattab, I; Nazzal, S

    2007-05-01

    The purposes of this study were to assess the mucoadhesion and bioavailability and their correlation for ketoprofen tablet dosage forms (F1-F6) containing polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives, Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non compressible vehicles such as lactose and starch. For mucoadhesion assessment, we used sheep gastric mucosa and for bioavailability we used six human volunteers in an open randomized seven-way crossover study. Young's modulus (YM) and relative bioavailability (RB) parameters were used for evaluation of mucoadhesion and bioavailability, respectively. The results indicated that F2 containing Na CMC (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2% for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/- 2.46 in F6, respectively. The highest RB (152.3 +/- 2.56) was observed in F5 containing starch and Avicel pH 101. This formulation showed 6 +/- 0.87 for YM. F4 containing PC (10%) showed 5.1 +/- 0.43 and 74.15 +/- 1.98 for YM and RB respectively. The lowest value of YM was observed in F1 containing Avicel pH 101 (0.27 +/- 0.01) which also showed low RB (93.3 +/- 2.3). In conclusion, formulations containing bioadhesives and/or starch in high concentration showed high values of YM and RB which indicate good correlation between mucoadhesion and bioavailability. Bioadhesives may show a high potential to improve bioavailability and therapeutic efficacy of ketoprofen in tablet dosage forms.

  14. Preparation and characterization of a photocrosslinkable bioadhesive inspired by marine mussel.

    PubMed

    Xue, Jie; Wang, Tao; Nie, Jun; Yang, Dongzhi

    2013-02-05

    Synthetic adhesives inspired by marine mussel have attracted great attention due to its excellent water-resistance and good biocompatibility. In this study, a photocrosslinkable bioadhesive containing 3,4-Dihydroxy-l-phenylalanine (DOPA) functional group, which is central to curing mussel adhesive proteins, was prepared by ultraviolet (UV) irradiation of a new photocurable monomer ethylene glycol acrylate methacrylate-dopamine (EGAMA-DOPA) and a UV photocrosslinkable crosslinking agent poly(vinyl alcohol) (UV-PVA) derivative. The chemical structures of EGAMA-DOPA and UV-PVA were confirmed by Fourier Transform Infrared Reflection (FTIR) and (1)H NMR spectroscopy, respectively. The effects of UV light intensity, content of photoinitiator, EGAMA-DOPA and UV-PVA on the photopolymerization kinetics were studied, and the effects of the content of UV-PVA and temperature on the adhesive strength were also investigated. It was found that the higher UV light intensity, the faster polymerization rate and the higher final conversion that was the same as the trend of photoinitiator, EGAMA-DOPA and UV-PVA. And the adhesion strength measurement showed that, for gels with 30wt.% EGAMA-DOPA, the adhesion strength was obviously improved by about 150% with 3.0wt.% UV-PVA instead of pure PVA, and for gels containing 40wt.% EGAMA-DOPA, the adhesion strength sharply enhanced by 123% with increasing the content of UV-PVA from 1.0wt.% to 3.0wt.%. Cell attachment results showed good cell viability of L929 cell on the EGAMA-DOPA/UV-PVA adhesive gels. Thanks to its strong adhesion strength and good biocompatibility, such photocrosslinkable gels could be applied to the areas of biomedical field. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Overall adsorption rate of metronidazole, dimetridazole and diatrizoate on activated carbons prepared from coffee residues and almond shells.

    PubMed

    Flores-Cano, J V; Sánchez-Polo, M; Messoud, J; Velo-Gala, I; Ocampo-Pérez, R; Rivera-Utrilla, J

    2016-03-15

    This study analyzed the overall adsorption rate of metronidazole, dimetridazole, and diatrizoate on activated carbons prepared from coffee residues and almond shells. It was also elucidated whether the overall adsorption rate was controlled by reaction on the adsorbent surface or by intraparticle diffusion. Experimental data of the pollutant concentration decay curves as a function of contact time were interpreted by kinetics (first- and second-order) and diffusion models, considering external mass transfer, surface and/or pore volume diffusion, and adsorption on an active site. The experimental data were better interpreted by a first-order than second-order kinetic model, and the first-order adsorption rate constant varied linearly with respect to the surface area and total pore volume of the adsorbents. According to the diffusion model, the overall adsorption rate is governed by intraparticle diffusion, and surface diffusion is the main mechanism controlling the intraparticle diffusion, representing >90% of total intraparticle diffusion.

  16. Exposure to Metronidazole In Vivo Readily Induces Resistance in Helicobacter pylori and Reduces the Efficacy of Eradication Therapy in Mice

    PubMed Central

    Jenks, Peter J.; Labigne, Agnes; Ferrero, Richard L.

    1999-01-01

    The Helicobacter pylori SS1 mouse model was used to characterize the development of resistance in H. pylori after treatment with metronidazole monotherapy and to examine the effect of prior exposure to metronidazole on the efficacy of a metronidazole-containing eradication regimen. Mice colonized with the metronidazole-sensitive H. pylori SS1 strain were treated for 7 days with either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole once a day or three times per day (TID). In a separate experiment, H. pylori-infected mice were administered either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole TID for 7 days, followed 1 month later by either peptone trypsin broth or the mouse equivalent of 20 mg of omeprazole, 250 mg of clarithromycin, and 400 mg of metronidazole twice a day for 7 days. At least 1 month after the completion of treatment, the mice were sacrificed and their stomachs were cultured for H. pylori. The susceptibilities of isolates to metronidazole were assessed by agar dilution determination of the MICs. Mixed populations of metronidazole-resistant and -sensitive strains were isolated from 70% of mice treated with 400 mg of metronidazole TID. The ratio of resistant to sensitive strains was 1:100, and the MICs for the resistant strains varied from 8 to 64 μg/ml. In the second experiment, H. pylori was eradicated from 70% of mice treated with eradication therapy alone, compared to 25% of mice pretreated with metronidazole (P < 0.01). Mice still infected after treatment with metronidazole and eradication therapy contained mixed populations of metronidazole-resistant and -sensitive isolates in a ratio of 1:25. These results demonstrate that H. pylori readily acquires resistance to metronidazole in vivo and that prior exposure of the organism to metronidazole is associated with failure of eradication therapy. H. pylori-infected mice provide a suitable model for the study of resistance mechanisms in H. pylori

  17. Comparison of the Effect of Vaginal Zataria multiflora Cream and Oral Metronidazole Pill on Results of Treatments for Vaginal Infections including Trichomoniasis and Bacterial Vaginosis in Women of Reproductive Age.

    PubMed

    Abdali, Khadijeh; Jahed, Leila; Amooee, Sedigheh; Zarshenas, Mahnaz; Tabatabaee, Hamidreza; Bekhradi, Reza

    2015-01-01

    Effect of Zataria multiflora on bacterial vaginosis and Trichomonas vaginalis is shown in vivo and in vitro. We compare the effectiveness of Zataria multiflora cream and oral metronidazole pill on results of treatment for vaginal infections including Trichomonas and bacterial vaginosis; these infections occur simultaneously. The study included 420 women with bacterial vaginosis, Trichomonas vaginalis, or both infections together, who were randomly divided into six groups. Criteria for diagnosis were wet smear and Gram stain. Vaginal Zataria multiflora cream and placebo pill were administered to the experiment groups; the control group received oral metronidazole pill and vaginal placebo cream. Comparison of the clinical symptoms showed no significant difference in all three vaginitis groups receiving metronidazole pill and vaginal Zataria multiflora cream. However, comparison of the wet smear test results was significant in patients with trichomoniasis and bacterial vaginosis associated with trichomoniasis in the two treatment groups (p = 0.001 and p = 0.01). Vaginal Zataria multiflora cream had the same effect of oral metronidazole tablets in improving clinical symptoms of all three vaginitis groups, as well as the treatment for bacterial vaginosis. It can be used as a drug for treatment of bacterial vaginosis and elimination of clinical symptoms of Trichomonas vaginitis.

  18. Comparison of the Effect of Vaginal Zataria multiflora Cream and Oral Metronidazole Pill on Results of Treatments for Vaginal Infections including Trichomoniasis and Bacterial Vaginosis in Women of Reproductive Age

    PubMed Central

    Abdali, Khadijeh; Jahed, Leila; Amooee, Sedigheh; Zarshenas, Mahnaz; Tabatabaee, Hamidreza; Bekhradi, Reza

    2015-01-01

    Effect of Zataria multiflora on bacterial vaginosis and Trichomonas vaginalis is shown in vivo and in vitro. We compare the effectiveness of Zataria multiflora cream and oral metronidazole pill on results of treatment for vaginal infections including Trichomonas and bacterial vaginosis; these infections occur simultaneously. The study included 420 women with bacterial vaginosis, Trichomonas vaginalis, or both infections together, who were randomly divided into six groups. Criteria for diagnosis were wet smear and Gram stain. Vaginal Zataria multiflora cream and placebo pill were administered to the experiment groups; the control group received oral metronidazole pill and vaginal placebo cream. Comparison of the clinical symptoms showed no significant difference in all three vaginitis groups receiving metronidazole pill and vaginal Zataria multiflora cream. However, comparison of the wet smear test results was significant in patients with trichomoniasis and bacterial vaginosis associated with trichomoniasis in the two treatment groups (p = 0.001 and p = 0.01). Vaginal Zataria multiflora cream had the same effect of oral metronidazole tablets in improving clinical symptoms of all three vaginitis groups, as well as the treatment for bacterial vaginosis. It can be used as a drug for treatment of bacterial vaginosis and elimination of clinical symptoms of Trichomonas vaginitis. PMID:26266260

  19. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis.

    PubMed

    Raja, Indu M; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1(st) week and 4(th) week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4(th) week (P = 0.0013), but not at 1(st) week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile.

  20. Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples.

    PubMed

    Kulik Kunz, Eva M; Lenkeit, Krystyna; Waltimo, Tuomas; Weiger, Roland; Walter, Clemens

    2014-06-01

    The aim of the present study was to analyze in vitro the combinatorial effects of the antibiotic combination of amoxicillin plus metronidazole on subgingival bacterial isolates. Aggregatibacter (Actinobacillus) actinomycetemcomitans, Prevotella intermedia/nigrescens, Fusobacterium nucleatum and Eikenella corrodens from our strain collection and subgingival bacteria isolated from patients with periodontitis were tested for their susceptibility to amoxicillin and metronidazole using the Etest. The fractional inhibitory concentration index (FICI), which is commonly used to describe drug interactions, was calculated. Synergy, i.e. FICI values ≤ 0.5, between amoxicillin and metronidazole was shown for two A. actinomycetemcomitans (FICI: 0.3), two F. nucleatum (FICI: 0.3 and 0.5, respectively) and one E. corrodens (FICI: 0.4) isolates. Indifference, i.e. FIC indices of >0.5 but ≤4, occurred for other isolates and the 14 P. intermedia/nigrescens strains tested. Microorganisms resistant to either amoxicillin or metronidazole were detected in all samples by Etest. Combinatorial effects occur between amoxicillin and metronidazole on some strains of A. actinomycetemcomitans, F. nucleatum and E. corrodens. Synergy was shown for a few strains only. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis

    PubMed Central

    Raja, Indu M.; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    Objective: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. Patients and Methods: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. Results: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Conclusion: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile. PMID:28066102

  2. [MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia].

    PubMed

    Takase, Kei-ichiro; Santa, Yo; Ohta, Sumio; Yoshimura, Takeo

    2005-05-01

    A 69-year-old man was referred to our department because of acute onset nausea, vomiting, dysphagia, dysarthria and gait disturbance. He had a 50-day-history of amebic dysentery and had been treated with 1,500 mg metronidazole per day. Neurological examination revealed dysphagia, ataxic speech, ataxia of the left extremities and the trunk, and hyperactive deep tendon reflexes in all extremities. Sensory impairment of all modalities was apparent in a glove and stocking pattern, with mild paresthesia. Brain MRI showed T2 high signal lesions in the bilateral cerebellar dentate nuclei, more markedly on the left. On brain SPECT, obvious low blood perfusion was observed in the left cerebellar hemisphere. These findings well explained the ataxia of the left limbs. One month after discontinuing metronidazole, the cerebellar ataxia, dysphagia and MRI abnormalities completely cleared. Therefore, central nervous system damage induced by metronidazole is considered reversible. In spite of the presence of the MRI lesion in the right dentate nucleus, the patient had no ataxia of the right extremities and there was no hypoperfusion in the right cerebellar hemisphere. Thus, metronidazole does not appear to have a direct neurotoxic effect on the central nervous system. On the other hand, nerve conduction studies showed axonal polyneuropathy, which was not improved one month after cessation of the drug; thus metronidazole seems to exert more damage on peripheral nerves.

  3. Pyruvate Decarboxylase, the Target for Omeprazole in Metronidazole-Resistant and Iron-Restricted Tritrichomonas foetus

    PubMed Central

    Sutak, Róbert; Tachezy, Jan; Kulda, Jaroslav; Hrdý, Ivan

    2004-01-01

    The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 μg/ml [63 μM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 μg/ml). Metronidazole-susceptible T. foetus, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells, T. foetus cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation. PMID:15155220

  4. Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.

    PubMed Central

    Nilsson-Ehle, I; Ursing, B; Nilsson-Ehle, P

    1981-01-01

    We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected. PMID:7294765

  5. Metronidazole and spiramycin therapy of mixed Bacteroides spp. and Neisseria gonorrhoeae infection in mice.

    PubMed

    Brook, I

    1989-01-01

    The in vitro and in vivo activity of metronidazole and spiramycin, used singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. and Neisseria gonorrhoeae alone or in combination. The in vitro tests consisted of determinations of the minimal inhibitory concentrations (MIC), carried out with or without the addition of a constant amount of the other antimicrobials. The MIC of both Bacteroides bivius and Bacteroides fragilis for metronidazole were significantly reduced by the addition of spiramycin (from 0.5 to 0.125 micrograms/ml). The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the bacterial contents of abscesses induced by subcutaneous injection of bacterial suspension. Synergism between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused by either Bacteroides spp. alone, or in combination with N. gonorrhoeae. Furthermore, an additional reduction in the number of N gonorrhoeae was noted in mixed infection with Bacteroides that was treated with metronidazole alone. This study demonstrates the in vitro and in vivo efficacy of the combination of metronidazole and spiramycin in the treatment of infections caused by either Bacteroides spp. alone or in combination with N. gonorrhoeae.

  6. Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole

    SciTech Connect

    Johansen, L.V.; Overgaard, J.; Elbrond, O.

    1988-02-15

    The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split-course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty-four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose-response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split-course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High-dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days.

  7. A new-generation 5-nitroimidazole can induce highly metronidazole-resistant Giardia lamblia in vitro

    PubMed Central

    Dunn, Linda A.; Burgess, Anita G.; Krauer, Kenia G.; Eckmann, Lars; Vanelle, Patrice; Crozet, Maxime D.; Gillin, Frances D.; Upcroft, Peter; Upcroft, Jacqueline A.

    2010-01-01

    The 5-nitroimidazole (NI) compound C17, with a side chain carrying a remote phenyl group in the 2-position of the imidazole ring, is at least 14-fold more active against the gut protozoan parasite Giardia lamblia than the 5-NI drug metronidazole (MTR), with a side chain in the 1-position of the imidazole ring, which is the primary drug for the treatment of giardiasis. Over 10 months, lines resistant to C17 were induced in vitro and were at least 12-fold more resistant to C17 than the parent strains. However, these lines had ID90 values (concentration of drug at which 10% of control parasite ATP levels are detected) for MTR of >200 μM, whilst lines induced to be highly resistant to MTR in vitro have maximum ID90 values around 100 μM (MTR-susceptible isolates typically have an ID90 of 5–12.8 μM). The mechanism of MTR activation in Giardia apparently involves reduction to toxic radicals by the activity of pyruvate:ferredoxin oxidoreductase (PFOR) and the electron acceptor ferredoxin. MTR-resistant Giardia have decreased PFOR activity, which is consistent with decreased activation of MTR in these lines, but C17-resistant lines have normal levels of PFOR. Therefore, an alternative mechanism of resistance in Giardia must account for these super-MTR-resistant cells. PMID:20456926

  8. PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration

    PubMed Central

    Ho, Ming-Hua; Chang, Hao-Chieh; Chang, Yu-Chia; Claudia, Jeiannete; Lin, Tzu-Chiao; Chang, Po-Chun

    2017-01-01

    This study aimed to develop a functionally graded membrane (FGM) to prevent infection and promote tissue regeneration. Poly(l-lactide-co-d,l-lactide) encapsulating platelet-derived growth factor (PDLLA-PDGF) or metronidazole (PDLLA-MTZ) was electrospun to form a nanofibrous layer on the inner or outer surface of a clinically available collagen membrane, respectively. The membrane was characterized for the morphology, molecule release profile, in vitro and in vivo biocompatibility, and preclinical efficiency for alveolar ridge regeneration. The PDLLA-MTZ and PDLLA-PDGF nanofibers were 800–900 nm in diameter, and the thicknesses of the functional layers were 20–30 μm, with sustained molecule release over 28 days. All of the membranes tested were compatible with cell survival in vitro and showed good tissue integration with minimal fibrous capsule formation or inflammation. Cell proliferation was especially prominent on the PDLLA-PDGF layer in vivo. On the alveolar ridge, all FGMs reduced wound dehiscence compared with the control collagen membrane, and the FGM with PDLLA-PDGF promoted osteogenesis significantly. In conclusion, the FGMs with PDLLA-PDGF and PDLLA-MTZ showed high biocompatibility and facilitated wound healing compared with conventional membrane, and the FGM with PDLLA-PDGF enhanced alveolar ridge regeneration in vivo. The design represents a beneficial modification, which may be easily adapted for future clinical use. PMID:28831251

  9. PDGF-metronidazole-encapsulated nanofibrous functional layers on collagen membrane promote alveolar ridge regeneration.

    PubMed

    Ho, Ming-Hua; Chang, Hao-Chieh; Chang, Yu-Chia; Claudia, Jeiannete; Lin, Tzu-Chiao; Chang, Po-Chun

    2017-01-01

    This study aimed to develop a functionally graded membrane (FGM) to prevent infection and promote tissue regeneration. Poly(l-lactide-co-d,l-lactide) encapsulating platelet-derived growth factor (PDLLA-PDGF) or metronidazole (PDLLA-MTZ) was electrospun to form a nanofibrous layer on the inner or outer surface of a clinically available collagen membrane, respectively. The membrane was characterized for the morphology, molecule release profile, in vitro and in vivo biocompatibility, and preclinical efficiency for alveolar ridge regeneration. The PDLLA-MTZ and PDLLA-PDGF nanofibers were 800-900 nm in diameter, and the thicknesses of the functional layers were 20-30 μm, with sustained molecule release over 28 days. All of the membranes tested were compatible with cell survival in vitro and showed good tissue integration with minimal fibrous capsule formation or inflammation. Cell proliferation was especially prominent on the PDLLA-PDGF layer in vivo. On the alveolar ridge, all FGMs reduced wound dehiscence compared with the control collagen membrane, and the FGM with PDLLA-PDGF promoted osteogenesis significantly. In conclusion, the FGMs with PDLLA-PDGF and PDLLA-MTZ showed high biocompatibility and facilitated wound healing compared with conventional membrane, and the FGM with PDLLA-PDGF enhanced alveolar ridge regeneration in vivo. The design represents a beneficial modification, which may be easily adapted for future clinical use.

  10. Properties of bioadhesive ketoprofen liquid suppositories: preparation, determination of gelation temperature, viscosity studies and evaluation of mechanical properties using texture analyzer by 4 × 4 factorial design.

    PubMed

    Ozgüney, Işık; Kardhiqi, Anita

    2014-12-01

    Development and evaluation of thermosensitive and bioadhesive liquid suppositories containing ketoprofen (KP). This study was conducted to develope thermosensitive and bioadhesive liquid suppositories containing KP using poloxamer and different bioadhesive polymers and to investigate their gelation temperature, viscosity and mechanical properties. Bioadhesive liquid suppositories were prepared by the cold method using poloxamer 407 (P 407), Poloxamer 188 (P 188) and various amounts of different bioadhesive polymers. Their gelation temperatures, viscosity values and mechanical properties were determined using texture analyzer by 4 × 4 factorial design. It was seen that in presence of KP, gelation temperature of formulation P 407/P 188 (4/20%) significantly decreased from 64 to 37.1 °C. It is to be noted that addition of increasing concentrations of bioadhesive polymers lowered gelation temperature and its decrease was highest with addition of Carbopol 934 P (C). Results of texture profile analysis (TPA) showed that formulations containing C have significantly higher hardness and adhesiveness values than other bioadhesive formulations. According to TPA, gel structure of liquid suppository formulation F5, containing P 407/P 188/KP/C (4/20/2.5/0.8%), exhibited the greatest hardness, compressibilty, adhesiveness and besides greatest viscosity. According to mechanical properties and viscosity values, it was concluded that F5 could be a promising formulation.

  11. Prevalence of Helicobacter pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands.

    PubMed

    Debets-Ossenkopp, Y J; Herscheid, A J; Pot, R G; Kuipers, E J; Kusters, J G; Vandenbroucke-Grauls, C M

    1999-04-01

    Successful treatment of Helicobacter pylori infection is becoming compromised by emerging resistance. We report the prevalence rates of H. pylori resistance to metronidazole, clarithromycin, amoxycillin, tetracycline and trovafloxacin in The Netherlands. A total of 231 H. pylori clinical isolates were collected throughout the country over a period of 6 months during 1997-1998. The MICs of the above-mentioned antibiotics were determined in a single laboratory. The overall percentage of resistance for clarithromycin and metronidazole was 1.7% and 21.2%, respectively. None of the strains was resistant to amoxycillin or tetracycline. The primary resistance rate of trovafloxacin was as high as 4.7%. Since trovafloxacin has not yet been introduced on to the Dutch market, the resistance is probably induced by the use of other quinolones. Our data indicate that treatment outcome would benefit from susceptibility testing before starting therapy, especially when prescribing metronidazole.

  12. Lymphocyte proliferation kinetics and sister-chromatid exchanges in individuals treated with metronidazole.

    PubMed

    Elizondo, G; Montero, R; Herrera, J E; Hong, E; Ostrosky-Wegman, P

    1994-03-01

    Metronidazole, an effective agent for the treatment of protozoan infections, is frequently used in developing countries. However, the employment of this drug has been questioned in view of its mutagenicity in bacteria and carcinogenicity in mice. A genotoxic study was carried out in which cellular proliferation kinetics and the frequency of sister-chromatid exchanges were determined in human peripheral blood lymphocytes from 12 individuals treated with therapeutic doses of metronidazole. No effect was observed on mitotic index with the treatment, although a significant increase was found in three individuals after treatment. No increase of sister-chromatid exchanges was detected. The rate of lymphocyte proliferation kinetics showed an increase after the metronidazole treatment in all patients, indicating a possible immunostimulatory action.

  13. Coordination of metronidazole to Cu(II): Structural characterization of a mononuclear square-planar compound

    NASA Astrophysics Data System (ADS)

    Palmer, Joshua H.; Wu, Ja-Shin; Upmacis, Rita K.

    2015-07-01

    The reaction between metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, MET] and CuCl2ṡ2H2O in methanol solution has allowed isolation of blue crystals of composition Cu(MET)2Cl2ṡMeOH. These crystals have been shown by X-ray diffraction to consist of mononuclear square-planar trans-Cu(MET)2Cl2 molecules in which the metronidazole ligands are trans to each other, as are the Cl ligands. The structure of this compound is very different from other compounds that have been obtained from the reaction between CuCl2ṡ2H2O and metronidazole, namely [Cu(MET)2(μ-Cl)Cl]2 and [Cu(MET)2(μ-Cl)(OH2)]2[Cl]2, which are dimers featuring bridging chloride ligands.

  14. The use of metronidazole, tinidazole and dimetridazole in eliminating trichomonads from laboratory mice.

    PubMed

    Roach, P D; Wallis, P M; Olson, M E

    1988-10-01

    Metronidazole, tinidazole and dimetridazole were administered in the drinking water for 5 days to mice experimentally infected with Tritrichomonas muris and Tetratrichomonas microta. Mice were successfully infected with T. muris and T. microta recovered from infected gerbils. The trichomonas infection was successfully eliminated in mice given a 1% sucrose solution containing 2.5 mg/ml metronidazole or tinidazole. Mice receiving 1.0 mg/ml metronidazole, 1.0 mg/ml tinidazole and 1.2, 5.0 and 10.0 mg/ml dimetridazole failed to eliminate the trichomonas organism. A reduction in water intake was only noted with mice receiving 10 mg/ml dimetridazole. In mice receiving only 1% sucrose the infection was not eliminated.

  15. A simple reagent-free spectrophotometric assay for monitoring metronidazole therapy in aquarium water.

    PubMed

    Webb, D Harry; Marrero, Cynthia; Ellis, Helen; Merriwether, Lea; Dove, Alistair D M

    2013-09-01

    A reagent-free spectrophotometric assay was developed to measure the concentration of metronidazole (a 5-nitroimidazole) in both freshwater and seawater matrices. This assay is simple, repeatable, sensitive, and precise and is ideal for use when a rapid, selective test to determine metronidazole concentration in aqueous matrices is necessary. The assay was practically tested on a South American fishes display during treatment with metronidazole for an outbreak of the flagellated parasite Spironucleus in a mixed cichlid (family Cichlidae) and tetra (family Characidae) community. The assay clearly illustrated the course of treatment for the system during a real clinical application. The assay is not without limitations, as interferences can occur from other drugs in the matrix with similar absorbance spectra. Nonetheless, this type of assay illustrates the potential for use of native absorbance assays in aqueous matrices for this and other therapeutic compounds.

  16. Effects of metronidazole, ipronidazole, and dibromochloropropane on rabbit and human sperm motility and fertility.

    PubMed

    Foote, Robert H

    2002-01-01

    Treatment of protozoal pathogens in the reproductive system with chemical agents exposes flagellated sperm cells to potential toxicants. A widely used antiprotozoal agent is metronidazole. Its effect on rabbit and human sperm was compared with a more soluble 5-nitroazole compound, ipronidazole, and with a systemic environmental toxicant, dibromochloropropane (DBCP). The percentages of motile rabbit and human sperm incubated with the compounds, the velocity of sperm, migration of sperm in polyacrylamide gel, young born in rabbits, and penetration of hamster oocytes by treated human sperm were measured in seven experiments. Up to 10mg/ml metronidazole and 1mg/ml DBCP had little effect on most sperm characteristics. However, 10mg/ml metronidazole and 5mg/ml of ipronidazole increased attachment of human sperm to hamster oocytes, but oocyte penetration was unaffected. Rabbit sperm exposed to 5mg/ml ipronidazole were infertile. No oocytes were penetrated by DBCP-treated human sperm.

  17. Metronidazole Appears Not to Be a Human Teratogen: Review of Literature

    PubMed Central

    Struthers, Barbara J.

    1997-01-01

    Metronidazole is used to treat trichomoniasis, bacterial vaginosis, and other diseases. As is the case with many drugs, physicians often hesitate to use it during pregnancy, particularly in the first trimester. A review of the nearly four decades' worth of published literature on metronidazole use in pregnant women indicates that it is not teratogenic, regardless of the trimester in which it is used. On the other hand, a number of published studies indicate that bacterial vaginosis and trichomoniasis are associated with preterm birth and low birth weight. Treatment of these conditions with metronidazole during pregnancy may decrease the incidence of preterm birth and low birth weight, thus potentially decreasing the complications that can result from prematurity. PMID:18476180

  18. Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole.

    PubMed

    de Freitas, Michele C R; Resende, Juliana A; Ferreira-Machado, Alessandra B; Saji, Guadalupe D R Q; de Vasconcelos, Ana T R; da Silva, Vânia L; Nicolás, Marisa F; Diniz, Cláudio G

    2016-01-01

    Bacteroides fragilis, member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their

  19. Low antibiotic resistance among anaerobic Gram-negative bacteria in periodontitis 5 years following metronidazole therapy.

    PubMed

    Dahlen, G; Preus, H R

    2017-02-01

    The objective of this study was to assess antibiotic susceptibility among predominant Gram-negative anaerobic bacteria isolated from periodontitis patients who 5 years prior had been subject to mechanical therapy with or without adjunctive metronidazole. One pooled sample was taken from the 5 deepest sites of each of 161 patients that completed the 5 year follow-up after therapy. The samples were analyzed by culture. A total number of 85 anaerobic strains were isolated from the predominant subgingival flora of 65/161 patient samples, identified, and tested for antibiotic susceptibility by MIC determination. E-tests against metronidazole, penicillin, amoxicillin, amoxicillin + clavulanic acid and clindamycin were employed. The 73/85 strains were Gram-negative rods (21 Porphyromonas spp., 22 Prevotella/Bacteroides spp., 23 Fusobacterium/Filifactor spp., 3 Campylobacter spp. and 4 Tannerella forsythia). These were all isolated from the treated patients irrespective of therapy procedures (+/-metronidazole) 5 years prior. Three strains (Bifidobacterium spp., Propionibacterium propionicum, Parvimonas micra) showed MIC values for metronidazole over the European Committee on Antimicrobial Susceptibility Testing break point of >4 μg/mL. All Porphyromonas and Tannerella strains were highly susceptible. Metronidazole resistant Gram-negative strains were not found, while a few showed resistance against beta-lactam antibiotics. In this population of 161 patients who had been subject to mechanical periodontal therapy with or without adjunct metronidazole 5 years prior, no cultivable antibiotic resistant anaerobes were found in the predominant subgingival microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Optimization of metronidazole sustained-release films using D-optimal design.

    PubMed

    Peerapattana, Jomjai; Ngamsupsiri, Teeraphat; Cheucharoenvasuchai, Nopadol; Saikaew, Charnnarong

    2015-04-30

    The aim of this study was to develop sustained-release metronidazole films for periodontal pockets using a computer-aided statistical approach. The studied independent variables were the amount of polycaprolactone, metronidazole, hydroxypropylmethyl cellulose and glyceryl monostearate. The response of interest was the cumulative percentage release of metronidazole at 1, 2, 3, 4 and 5 days. The films were prepared using a melt method. The physicochemical properties and release profiles of the films were investigated. Model validation was also performed. The produced films were thin white sheets with a smooth and glossy surface. Each sheet had an average weight of 9.31 ± 0.10mg. The metronidazole was uniformly dispersed in the film, and the percentage of drug loading was 100.12 ± 4.38%. The thickness of the film was 325 ± 5.27 μm. The puncture strength, % elongation and Young's modulus were 11.58 ± 0.51 N/mm(2), 33.51 ± 3.61%, and 0.347 ± 0.02 1N/mm(2), respectively. The actual drug release profiles of the optimal formulation films were close to the predicted responses. Metronidazole was slowly released from the matrices over a period of at least 5 days. The release mechanism of the films followed Fickian diffusion. This study demonstrates that appropriate D-optimal design and optimization techniques can be successfully used in the development of metronidazole sustained-release films. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Exploratory Investigation of Bacteroides fragilis Transcriptional Response during In vitro Exposure to Subinhibitory Concentration of Metronidazole

    PubMed Central

    de Freitas, Michele C. R.; Resende, Juliana A.; Ferreira-Machado, Alessandra B.; Saji, Guadalupe D. R. Q.; de Vasconcelos, Ana T. R.; da Silva, Vânia L.; Nicolás, Marisa F.; Diniz, Cláudio G.

    2016-01-01

    Bacteroides fragilis, member from commensal gut microbiota, is an important pathogen associated to endogenous infections and metronidazole remains a valuable antibiotic for the treatment of these infections, although bacterial resistance is widely reported. Considering the need of a better understanding on the global mechanisms by which B. fragilis survive upon metronidazole exposure, we performed a RNA-seq transcriptomic approach with validation of gene expression results by qPCR. Bacteria strains were selected after in vitro subcultures with subinhibitory concentration (SIC) of the drug. From a wild type B. fragilis ATCC 43859 four derivative strains were selected: first and fourth subcultures under metronidazole exposure and first and fourth subcultures after drug removal. According to global gene expression analysis, 2,146 protein coding genes were identified, of which a total of 1,618 (77%) were assigned to a Gene Ontology term (GO), indicating that most known cellular functions were taken. Among these 2,146 protein coding genes, 377 were shared among all strains, suggesting that they are critical for B. fragilis survival. In order to identify distinct expression patterns, we also performed a K-means clustering analysis set to 15 groups. This analysis allowed us to detect the major activated or repressed genes encoding for enzymes which act in several metabolic pathways involved in metronidazole response such as drug activation, defense mechanisms against superoxide ions, high expression level of multidrug efflux pumps, and DNA repair. The strains collected after metronidazole removal were functionally more similar to those cultured under drug pressure, reinforcing that drug-exposure lead to drastic persistent changes in the B. fragilis gene expression patterns. These results may help to elucidate B. fragilis response during metronidazole exposure, mainly at SIC, contributing with information about bacterial survival strategies under stress conditions in their

  2. Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases.

    PubMed

    Evans, Jason; Levesque, Donald; Knowles, Kim; Longshore, Randy; Plummer, Scott

    2003-01-01

    The currently recommended treatment for metronidazole toxicosis is drug discontinuation and supportive therapy. Reported recovery times are 1-2 weeks. The records of 21 dogs with metronidazole toxicosis were retrospectively analyzed to determine whether diazepam improved recovery. The dosage and duration of metronidazole therapy and the response and recovery times of 13 dogs treated with diazepam were compared to those of 8 dogs receiving only supportive care. Response time was defined as the time to resolution of the debilitating clinical signs. Recovery time was the time to resolution of all residual clinical signs. The average dosage and duration of metronidazole administration for the diazepam-treated and untreated groups were 60.3 mg/kg/d for 44.9 days and 65.1 mg/kg/d for 37.25 days. The protocol for diazepam administration consisted of an initial i.v. bolus and then diazepam PO q8h for 3 days. The average dosage of both the i.v. and PO diazepam was 0.43 mg/kg. The average response time for the diazepam-treated dogs was 13.4 hours compared to 4.25 days for the untreated group. Recovery time also was markedly shorter for the diazepam-treated dogs (38.8 hours) compared to the untreated group (11 days). Results of this study showed that dogs with metronidazole toxicosis recover faster when treated with diazepam. Although the mechanism of metronidazole toxicosis or how diazepam exerts its favorable effect is not known, it is likely related to modulation of the gamma-aminobutyric acid (GABA) receptor within the cerebellar and vestibular systems.

  3. Safe and effective deodorization of malodorous fungating tumors using topical metronidazole 0.75 % gel (GK567): a multicenter, open-label, phase III study (RDT.07.SRE.27013).

    PubMed

    Watanabe, Kazuhiro; Shimo, Arata; Tsugawa, Kouichiro; Tokuda, Yutaka; Yamauchi, Hideko; Miyai, Eriko; Takemura, Kimitoshi; Ikoma, Akihiko; Nakamura, Seigo

    2016-06-01

    Malignant fungating tumors are neoplastic tumors associated with skin ulcers, which are susceptible to microbial colonization. Bacterial infection and proliferation may lead to malodor causing distress to patients. Metronidazole-an effective agent against anaerobes-may contribute to deodorization and improvement in quality of life (QOL). This study investigated the efficacy and safety of topical metronidazole 0.75 % gel for alleviation of malodor in anaerobically infected fungating neoplastic tumors. This was a multicenter, open-label, non-controlled, phase III study including subjects aged 20 years or older with cutaneous fungating tumors releasing malodor (minimum score of 2 (mildly offensive smell) on a scale from 0 (no smell) to 4 (extremely offensive smell) based on investigator's assessment). Subjects applied metronidazole 0.75 % gel once or twice daily at the investigator's discretion for 14 days. Success was defined as an odor score of 0 or 1 at day 14, as assessed by the investigator. Patient satisfaction was assessed using a satisfaction questionnaire. Adverse events (AEs) that occurred after application of metronidazole 0.75 % gel were also reported. A total of 21 subjects at a median age of 65.0 years were enrolled. The success rate of deodorization at day 14 was 95.2 % (20/21 subjects). The patient satisfaction assessment showed that 71.4 % (15/21) of subjects were markedly or moderately improved. The treatment was well tolerated with only two AE cases of skin neoplasm bleeding (one mild and one moderate). Metronidazole 0.75 % gel is an effective and safe treatment for deodorization of malodorous fungating tumors.

  4. Bismuth, lansoprazole, amoxicillin and metronidazole or clarithromycin as first-line Helicobacter pylori therapy.

    PubMed

    Zhang, Wei; Chen, Qi; Liang, Xiao; Liu, Wenzhong; Xiao, Shudong; Graham, David Y; Lu, Hong

    2015-11-01

    To evaluate the efficacy and tolerability of replacing tetracycline with amoxicillin in bismuth quadruple therapy. Subjects who were infected with Helicobacter pylori and naïve to treatment were randomly (1:1) assigned to receive a 14-day modified bismuth quadruple therapy: lansoprazole 30 mg, amoxicillin 1 g, bismuth potassium citrate 220 mg (elemental bismuth), twice a day with metronidazole 400 mg four times a day (metronidazole group) or clarithromycin 500 mg twice a day (clarithromycin group). Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. This was a non-inferiority trial. Two hundred and fifteen subjects were randomised. Metronidazole and clarithromycin containing regimens achieved high cure rates: 94 of 97 (96.9%, 95% CI 93.5% to 100%) and 93 of 98 (94.9%, 95% CI 90.5% to 99.3%) by per-protocol and 88.9% (95% CI 83.0% to 94.8%) and 88.8% (95% CI 82.8% to 94.8%) by intention-to-treat, respectively. Amoxicillin, metronidazole and clarithromycin resistance rates were 1.5%, 45.5% and 26.5%, respectively. Only clarithromycin resistance reduced treatment success (e.g., susceptible 98.6%, resistant 76.9%, p=0.001). Adverse events were more common in the metronidazole group. These results suggest that amoxicillin can substitute for tetracycline in modified 14 day bismuth quadruple therapy as first-line treatment and still overcome metronidazole resistance in areas with high prevalence of metronidazole and clarithromycin resistance. Using clarithromycin instead of metronidazole was only effective in the presence of susceptible strains. NCT02175901. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) induced by oral metronidazole.

    PubMed

    Şikar Aktürk, Aysun; Bayramgürler, Dilek; Salman, Selma; Yıldız, Kürşat Demir; Odyakmaz Demirsoy, Evren

    2014-12-01

    Baboon syndrome is a special form of systemic contact dermatitis to systemic or local administration of contact allergens. Baboon syndrome without known previous cutaneous sensitisation was also described as drug-related baboon syndrome or symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). The major drugs causing SDRIFE was beta-lactam antibiotic such as amoxicillin and ampicillin. We report a case of 16-year-old woman who developed pruritic eruptions after oral metronidazole treatment for diarrhea. She was diagnosed SDRIFE according to her clinical and histopathological findings. To our knowledge, our patient is the first case who developed SDRIFE due to metronidazole in the literature.

  6. Development of serratiopeptidase and metronidazole based alginate microspheres for wound healing.

    PubMed

    Rath, G; Johal, E S; Goyal, Amit K

    2011-02-01

    The objective of this study was to establish an effective therapy system for wound management. The present work describes preparation of metronidazole/serratiopeptidase loaded alginate microspheres by emulsification method. In vitro characterizations like particle size analysis, % yield, % encapsulation, and in vitro release were carried out. Wound healing assessment was determined by physical, histological, and biochemical methods. Wound healing performance of experimental formulations was compared with marketed product in rabbits. Result obtained for alginate microspheres showed good loading efficiency with spherical in shape. Experimentation suggests wound healing is improved by using serratiopeptidase and metronidazole in full thickness wounds in rabbits.

  7. Susceptibility of bacterial vaginosis (BV)-associated bacteria to secnidazole compared to metronidazole, tinidazole and clindamycin.

    PubMed

    Petrina, Melinda A B; Cosentino, Lisa A; Rabe, Lorna K; Hillier, Sharon L

    2017-05-15

    Secnidazole, a 5-nitroimidazole with a longer half-life, is structurally related to metronidazole and tinidazole. For treatment of bacterial vaginosis (BV), secnidazole is a suitable single-dose oral drug having a longer serum half-life than metronidazole. The objective of this study was to evaluate the antimicrobial susceptibility of vaginal isolates of facultative and anaerobic bacteria to secnidazole, metronidazole, tinidazole and clindamycin. A total of 605 unique BV-related bacteria and 108 isolates of lactobacilli recovered from the human vagina of US women during the years 2009-2015 were tested for antimicrobial susceptibility by the agar dilution CLSI reference method to determine the minimal inhibitory concentration (MIC). The MIC90 (μg/mL) for secnidazole was similar to metronidazole and tinidazole for Anaerococcus tetradius (secnidazole: MIC90 2; metronidazole: MIC90 2; tinidazole: MIC90 4), Atopobium vaginae (32; >128; 128), Bacteroides species (2; 2; 2), Finegoldia magna (2; 2; 4), Gardnerella vaginalis (128; 64; 32), Mageeibacillus indolicus (2; 2; 2), Megasphaera-like bacteria (0.5; 0.25; 0.5), Mobiluncus curtisii (128; >128; >128) and Mobiluncus mulieris (>128; >128; >128), Peptoniphilus lacrimalis (4; 4; 4) and Peptoniphilus harei (2; 2; 4), Porphyromonas species (0.25; 0.5; 0.25), Prevotella bivia (8; 8; 8), Prevotella amnii (2; 1; 2) and Prevotella timonensis (2; 2; 2). In this evaluation, 14 (40%) of 35 P. bivia, 5 (14%) of 35 P. amnii and 21 (58%) of 36 P. timonensis isolates were resistant to clindamycin with MIC values of >128 μg/mL. Secnidazole, like metronidazole, was superior to clindamycin for Prevotella spp., Bacteroides spp., Peptoniphilus spp., Anaerococcus tetradius and Finegoldia magna. Clindamycin had greater activity against Atopobium vaginae, Gardnerella vaginalis and Mobiluncus spp. compared to the nitroimidazoles. All 27 Lactobacillus crispatus, 26 (96%) of 27 L. jensenii, 5 (19%) of 27 L. gasseri and 18 (67%) of 27 L

  8. Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis.

    PubMed

    Veeranagouda, Yaligara; Husain, Fasahath; Boente, Renata; Moore, Jane; Smith, C Jeffrey; Rocha, Edson R; Patrick, Sheila; Wexler, Hannah M

    2014-10-01

    Metronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear. A transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole. Thirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo. Selection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2014. This work is written by US Government employees and is in the public domain in the US.

  9. Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis

    PubMed Central

    Veeranagouda, Yaligara; Husain, Fasahath; Boente, Renata; Moore, Jane; Smith, C. Jeffrey; Rocha, Edson R.; Patrick, Sheila; Wexler, Hannah M.

    2014-01-01

    Background Metronidazole is the most commonly used antimicrobial for Bacteroides fragilis infections and is recommended for prophylaxis of colorectal surgery. Metronidazole resistance is increasing and the mechanisms of resistance are not clear. Methods A transposon mutant library was generated in B. fragilis 638R (BF638R) to identify the genetic loci associated with resistance to metronidazole. Results Thirty-two independently isolated metronidazole-resistant mutants had a transposon insertion in BF638R_1421 that encodes the ferrous transport fusion protein (feoAB). Deletion of feoAB resulted in a 10-fold increased MIC of metronidazole for the strain. The metronidazole MIC for the feoAB mutant was similar to that for the parent strain when grown on media supplemented with excess iron, suggesting that the increase seen in the MIC of metronidazole was due to reduced cellular iron transport in the feoAB mutant. The furA gene repressed feoAB transcription in an iron-dependent manner and disruption of furA resulted in constitutive transcription of feoAB, regardless of whether or not iron was present. However, disruption of feoAB also diminished the capacity of BF638R to grow in a mouse intraperitoneal abscess model, suggesting that inorganic ferrous iron assimilation is essential for B. fragilis survival in vivo. Conclusions Selection for feoAB mutations as a result of metronidazole treatment will disable the pathogenic potential of B. fragilis and could contribute to the clinical efficacy of metronidazole. While mutations in feoAB are probably not a direct cause of clinical resistance, this study provides a key insight into intracellular metronidazole activity and the link with intracellular iron homeostasis. PMID:25028451

  10. Synergistic effects of fenbendazole and metronidazole against Giardia muris in Swiss mice naturally infected.

    PubMed

    Bezagio, Renata Coltro; Colli, Cristiane Maria; Romera, Liara Izabela Lopes; Ferreira, Érika Cristina; Falavigna-Guilherme, Ana Lúcia; Gomes, Mônica Lúcia

    2017-03-01

    In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.

  11. Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma

    PubMed Central

    Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M.

    2015-01-01

    Purpose: We prepared and characterized topical ophthalmic formulations containing brimonidine-loaded bioadhesive cationic chitosan or anionic alginate nanoparticles (NPs) for sustained release of brimonidine as once daily regimen for management of glaucoma. Methods: Nanoparticles were prepared using a spontaneous emulsification solvent diffusion method. Different concentrations of polymers, emulsifiers, and NPs stabilizers were used for formulation optimization. Nanoparticles were characterized regarding particle size, zeta potential, morphology, and drug content. Brimonidine-loaded NPs were incorporated into eye drops, a temperature-triggered in situ gelling system, and a preformed gel. They then were characterized regarding their pH, viscosity, uniformity of drug content, in vitro release characteristics, in vitro cytotoxicity, and in vivo intraocular pressure (IOP) lowering effects. Results: Characteristics of optimized brimonidine-loaded chitosan and alginate NPs, respectively, are: particle size, 115.67 ± 3.58 and 157.67 ± 5.53 nm; zeta potential, +35.27 ± 3.39 and −37.8 ± 3.77 mV; encapsulation efficiency, 74.34% ± 2.05% and 70.40% ± 2.77%; drug loading, 11.81% ± 0.67% and 13.14% ± 0.90%; and yield, 87.91% ± 5.92% and 76.53% ± 3.32%. Transmission electron microscope (TEM) analyses revealed that NPs have spherical shapes with a dense core and distinct coat. Formulations possessed uniform drug content. Furthermore, pH and viscosity were compatible with the eye. Formulations showed a sustained release without any burst effect with a Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are biocompatible. Importantly, all formulations possessed a sustained IOP lowering effect compared to the marketed brimonidine tartrate eye drops. Conclusions: These formulations provide a great improvement in topical ocular brimonidine delivery. The application of a single drop is sufficient to provide extended IOP reduction

  12. Design of novel bioadhesive materials based on mussel-derived glues

    NASA Astrophysics Data System (ADS)

    Lee, Bruce Po-Shu

    2005-11-01

    mechanical tests of DOPA-modified gels submerged in an aqueous medium demonstrated strong adhesive interaction to TiO 2, and it was confirmed that the reduced form of DOPA was responsible for the adhesion. This thesis work addressed several needs in the development of novel bioadhesive materials with improved properties in an effort to bring them closer for clinical applications.

  13. Population pharmacokinetic modeling and Monte Carlo simulation of varying doses of intravenous metronidazole.

    PubMed

    Sprandel, Kelly A; Drusano, George L; Hecht, David W; Rotschafer, John C; Danziger, Larry H; Rodvold, Keith A

    2006-08-01

    Population pharmacokinetic modeling and Monte Carlo simulation (MCS) are approaches used to determine probability of target attainment (PTA) of antimicrobial therapy. The objectives of this study were 1) to determine a population pharmacokinetic model (PPM) using metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients, and 2) to determine the probability of attaining the pharmacodynamic target area under the plasma concentration (AUC)/MIC ratio >or=70 against 218 clinical isolates of Bacteroides fragilis using MCS. Eighteen healthy subjects were randomized to 3 dosages of intravenous metronidazole (500 mg every 8 h, 1000 mg day(-1), 1500 mg day(-1)) in an open-label 3-way crossover fashion. Serial blood samples were collected over 25.5 h on the 3rd day of each study period. An additional of 8 critically ill patients received intravenous metronidazole 500 mg every 8 h. Serial blood samples were collected over 8 h after the 2nd day of dosing. Plasma metronidazole and hydroxy-metronidazole concentrations were analyzed using a high-performance liquid chromatographic assay. The 834 plasma concentrations from 62 data sets were simultaneously modeled with Non-Parametric Adaptive Grid population modeling program. A 4-compartment model with a metabolite and zero-order infusion into the central compartment was used. The mean parameter vector and covariance matrix from PPM were inserted into the simulation module of ADAPT II. A 10,000-subject MCS was performed to determine the probability of PTA for a total drug AUC to MIC ratio >or=70 against 218 isolates of B. fragilis (MIC range, 0.125-2.0 mg L(-1)). Mean parameter values were CL(non-OH), 3.08 L h(-1); Vc, 35.4 L; K(OH), 0.04 h(-1); CL(OH), 2.78 L h(-1); and V(OH), 9.66 L. The regression values of the observed versus predicted concentrations (r2) of metronidazole and hydroxy-metronidazole were 0.972 and 0.980, respectively. The PTA for metronidazole 1500 mg day(-1) or 500 mg

  14. Impact of metronidazole and amoxicillin combination on matrix metalloproteinases-1 and tissue inhibitors of matrix metalloproteinases balance in generalized aggressive periodontitis

    PubMed Central

    Cifcibasi, Emine; Kantarci, Alpdogan; Badur, Selim; Issever, Halim; Cintan, Serdar

    2015-01-01

    Objective: Generalized aggressive periodontitis (GAgP) is a complex periodontal disease affecting the entire dentition with a rapid destruction of the periodontium and resulting in loss of teeth. We hypothesized that better clinical healing of adjunctive use of amoxicillin plus metronidazole combination may be related to the effect of this combination therapy to restore imbalance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) which is associated with connective tissue and alveolar bone destruction in patients with GAgP. Materials and Methods: Twenty-eight subjects diagnosed with GAgP were recruited. Patients were randomly assigned to test or control groups. MMP-1/TIMP-1 ratio was compared between groups receiving scaling and root planning (SRP) alone (control) or in combination with amoxicillin plus metronidazole (test). Clinical periodontal variables were measured. Gingival crevicular fluid samples were obtained and analyzed for MMP-1 and TIMP-1. Measurements were taken at baseline and repeated at 3 and 6 months after therapy. Results: Total MMP-1 levels were significantly decreased in both groups (P < 0.05) at 3 and 6 months. MMP-1 concentration levels showed a similar pattern to MMP-1 total levels decreasing significantly at 3 months (P < 0.05). TIMP-1 concentration levels increased in the test group throughout the study period, while the difference did not reach statistical significance (P > 0.05). TIMP-1/MMP-1 balance was restored in test group at 6 months significantly better than the control group (P < 0.05). Conclusion: The results of this study suggest that metronidazole and amoxicillin combination as an adjunct to SRP results in better clinical healing through restoring TIMP-1/MMP-1 balance. PMID:25713485

  15. Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis: A Dose-Ranging Study

    PubMed Central

    Chavoustie, Steven E.; Jacobs, Mark; Reisman, Howard A.; Waldbaum, Arthur S.; Levy, Sharon F.; Hillier, Sharon L.; Nyirjesy, Paul

    2015-01-01

    Objective Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration–approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. Materials and Methods This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. Results In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Conclusions Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days. PMID:24983350

  16. Metronidazole vaginal gel 1.3% in the treatment of bacterial vaginosis: a dose-ranging study.

    PubMed

    Chavoustie, Steven E; Jacobs, Mark; Reisman, Howard A; Waldbaum, Arthur S; Levy, Sharon F; Hillier, Sharon L; Nyirjesy, Paul

    2015-04-01

    Metronidazole vaginal gel (MVG) 0.75% is a US Food and Drug Administration-approved, 5-day treatment for bacterial vaginosis (BV). This study tested the hypothesis that a shorter treatment course at a higher dose (MVG 1.3%) would yield similar efficacy to 5 days of MVG 0.75%. This phase 2, multicenter, randomized, controlled, investigator-blinded, dose-ranging study enrolled women with a clinical diagnosis of BV. Patients were assigned to MVG 1.3% once daily for 1, 3, or 5 days or MVG 0.75% once daily for 5 days. The therapeutic cure rate, requiring clinical and bacteriological cure, at the end-of-study visit was determined for the per-protocol population. A Kaplan-Meier analysis was used to estimate median time-to-symptom resolution. In total, 255 women (mean age = 35 y) were enrolled. The per-protocol population included 189 patients. The therapeutic cure rate was higher in the 1-day (13/43, 30.2%), 3-day (12/48, 25.0%), and 5-day (16/49, 32.7%) MVG 1.3% groups versus the MVG 0.75% group (10/49, 20.4%). Median time-to-resolution of fishy odor was shorter in the 3 MVG 1.3% groups versus the MVG 0.75% group. The 5-day MVG 1.3% group had the lowest rate of symptom return. No clinically important differences were observed in adverse events across treatment groups; most events were mild or moderate in intensity and considered unrelated to treatment. Similar results were found in the modified intent-to-treat population. Metronidazole vaginal gel 1.3% applied once daily for 1, 3, or 5 days showed similar efficacy, safety, and tolerability as MVG 0.75% once daily for 5 days.

  17. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs.

    PubMed

    Jenkins, Eileen K; Lee-Fowler, Tekla M; Angle, T Craig; Behrend, Ellen N; Moore, George E

    2016-08-01

    OBJECTIVE To determine effects of oral administration of metronidazole or doxycycline on olfactory function in explosives detection (ED) dogs. ANIMALS 18 ED dogs. PROCEDURES Metronidazole was administered (25 mg/kg, PO, q 12 h for 10 days); the day prior to drug administration was designated day 0. Odor detection threshold was measured with a standard scent wheel and 3 explosives (ammonium nitrate, trinitrotoluene, and smokeless powder; weight, 1 to 500 mg) on days 0, 5, and 10. Lowest repeatable weight detected was recorded as the detection threshold. There was a 10-day washout period, and doxycycline was administered (5 mg/kg, PO, q 12 h for 10 days) and the testing protocol repeated. Degradation changes in the detection threshold for dogs were assessed. RESULTS Metronidazole administration resulted in degradation of the detection threshold for 2 of 3 explosives (ammonium nitrate and trinitrotoluene). Nine of 18 dogs had a degradation of performance in response to 1 or more explosives (5 dogs had degradation on day 5 or 10 and 4 dogs had degradation on both days 5 and 10). There was no significant degradation during doxycycline administration. CONCLUSIONS AND CLINICAL RELEVANCE Degradation in the ability to detect odors of explosives during metronidazole administration at 25 mg/kg, PO, every 12 hours, indicated a potential risk for use of this drug in ED dogs. Additional studies will be needed to determine whether lower doses would have the same effect. Doxycycline administered at the tested dose appeared to be safe for use in ED dogs.

  18. Biomimetic sensor based on molecularly imprinted polymer with nitroreductase-like activity for metronidazole detection.

    PubMed

    Gu, Yue; Yan, Xiaoyi; Li, Cong; Zheng, Bo; Li, Yaru; Liu, Weilu; Zhang, Zhiquan; Yang, Ming

    2016-03-15

    The utility of molecularly imprinted polymer (MIP) as electrochemical sensor often suffers from its limited catalytic efficiency. Here, we proposed an alternative approach by combining the concept of MIP with the use of mimetic enzyme. A metronidazole imprinted polymer with nitroreductase-like activity was successfully achieved via an electrochemical method, where melamine served two purposes: functional monomer of MIP and component of mimetic enzyme. During the imprinting process, the redox-active center, which is responsible for catalysis, was introduced into the imprinted cavities. Accordingly, the imprinted polymer, having both catalysis centers and recognition sites, exhibited enhanced electrocatalytic activity and selectivity. The sensing performances of this metronidazole imprinted biomimetic sensor were evaluated in detail. Results revealed that the response to metronidazole was linear in the concentration range of 0.5-1000 μM, and the detection limit was 0.12 μM (S/N=3). In addition, we applied the proposed sensor to detect metronidazole in an injection solution and the results implied its feasibility for practical application. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori

    PubMed Central

    Hanafi, Aimi; Lee, Woon Ching; Loke, Mun Fai; Teh, Xinsheng; Shaari, Ain; Dinarvand, Mojdeh; Lehours, Philippe; Mégraud, Francis; Leow, Alex Hwong Ruey; Vadivelu, Jamuna; Goh, Khean Lee

    2016-01-01

    Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains. PMID:28018334

  20. Molecular and Proteomic Analysis of Levofloxacin and Metronidazole Resistant Helicobacter pylori.

    PubMed

    Hanafi, Aimi; Lee, Woon Ching; Loke, Mun Fai; Teh, Xinsheng; Shaari, Ain; Dinarvand, Mojdeh; Lehours, Philippe; Mégraud, Francis; Leow, Alex Hwong Ruey; Vadivelu, Jamuna; Goh, Khean Lee

    2016-01-01

    Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori. Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA. This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains.

  1. Resistance pattern of Helicobacter pylori strains to clarithromycin, metronidazole, and amoxicillin in Isfahan, Iran.

    PubMed

    Khademi, Farzad; Faghri, Jamshid; Poursina, Farkhondeh; Esfahani, Bahram Nasr; Moghim, Sharareh; Fazeli, Hossein; Adibi, Peyman; Mirzaei, Nasrin; Akbari, Mojtaba; Safaei, Hajieh Ghasemian

    2013-12-01

    Helicobacter pylori (H. pylori) resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients. In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM) were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin. H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this study, we had one multidrug resistance (MDR) isolates from patient with gastritis and peptic ulcer disease. Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy.

  2. Resistance pattern of Helicobacter pylori strains to clarithromycin, metronidazole, and amoxicillin in Isfahan, Iran

    PubMed Central

    Khademi, Farzad; Faghri, Jamshid; Poursina, Farkhondeh; Esfahani, Bahram Nasr; Moghim, Sharareh; Fazeli, Hossein; Adibi, Peyman; Mirzaei, Nasrin; Akbari, Mojtaba; Safaei, Hajieh Ghasemian

    2013-01-01

    Background: Helicobacter pylori (H. pylori) resistance to antibiotics has become a global problem and is an important factor in determining the outcome of treatment of infected patients. The purpose of this study was to determine the H. pylori resistance to clarithromycin, metronidazole, and amoxicillin in gastrointestinal disorders patients. Materials and Methods: In this study, a total of 260 gastric antrum biopsy specimens were collected from patients with gastrointestinal disorders who referred to Endoscopy Section of the Isfahan Hospitals. The E-test and Modified Disk Diffusion Method (MDDM) were used to verify the prevalence of antibiotic resistance in 78 H. pylori isolates to the clarithromycin, metronidazole, and amoxicillin. Results: H. pylori resistance to clarithromycin, metronidazole, and amoxicillin were 15.3, 55.1, and 6.4%, respectively. In this study, we had one multidrug resistance (MDR) isolates from patient with gastritis and peptic ulcer disease. Conclusion: Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. According to the results obtained in this study, H. pylori resistance to clarithromycin and metronidazole was relatively high. MDR strains are emerging and will have an effect on the combination therapy. PMID:24523796

  3. The effect of methylcellulose on metronidazole release from polyacrylic acid hydrogels.

    PubMed

    Musial, Witold

    2007-08-01

    Topical treatment of acne rosacea, a chronic condition characterized by recurrent course for many years, is primarily based on metronidazole preparations. The aim of this study was to evaluate the effect of various acrylic acid polymers, in composition with methylcellulose on metronidazole release rate from hydrogels proposed for the treatment of acne rosacea. Viscosity and release studies using "Paddle over Disk" system with semipermeable membrane of MWCO 3500 were performed. Compositions of Carbopol 971P and methylcellulose revealed an increase in viscosity with increasing concentration of methylcellulose in the range of 17200-26166 mPa.s. In all the examined formulations, the release process was characterized by a two-stage course. Among bipolymeric formulations, the highest first-stage release rate of 9.18 x 10(-3) min(-1) was determined for the gel consisting of 2.00% Carbopol 980NF with 1.00% methylcellulose. The second-stage release rates ranged between 2.88 x 10(-3) and 8.00 x 10(-3) min(-1). Two-stage release course can thus be attributed to metronidazole distribution into two compartments of hydrogel matrix. Proposed gels, with similar rheological properties, may be used for ex vivo and in vivo studies to obtain a suitable drug activity of metronidazole in the treatment of acne rosacea.

  4. A Reprofiled Drug, Auranofin, Is Effective against Metronidazole-Resistant Giardia lamblia

    PubMed Central

    Tejman-Yarden, Noa; Miyamoto, Yukiko; Leitsch, David; Santini, Jennifer; Debnath, Anjan; Gut, Jiri; McKerrow, James H.; Reed, Sharon L.

    2013-01-01

    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains. PMID:23403423

  5. Stability of metronidazole, tetracycline HCl and famotidine alone and in combination.

    PubMed

    Wu, Yunqi; Fassihi, Reza

    2005-02-16

    Metronidazole, tetracycline HCl and famotidine are commonly used for the treatment of Helicobacter pylori-associated peptic ulcer. In this paper, stabilities of these drugs and their combinations in solid and liquid states were studied as part of preformulation in the development of a combination drug delivery system. Solubility studies of metronidazole and tetracycline HCl were investigated, which indicated that both metronidazole and tetracycline HCl have high solubilities at and around pH 2.0. Metronidazole is relatively stable with little degradation in liquid phase. Tetracycline HCl in the dry state is stable when stored at room temperature regardless of exposure to light or humidity in the range of 20-65%. Enhanced temperature associated humidity effect was responsible for the instabilities of tetracycline HCl and famotidine to different extents. Elevated temperature accelerated the degradation of all the drugs in liquid phase but light exposure was not a factor for the degradation. The degradation processes of tetracycline HCl and famotidine were highly dependent on the pH of the solution, and relatively stable profiles were achieved at pH 4.0. No potential incompatibility between the drugs under storage conditions was observed in the development of a new multi-drug delivery tablet.

  6. A reprofiled drug, auranofin, is effective against metronidazole-resistant Giardia lamblia.

    PubMed

    Tejman-Yarden, Noa; Miyamoto, Yukiko; Leitsch, David; Santini, Jennifer; Debnath, Anjan; Gut, Jiri; McKerrow, James H; Reed, Sharon L; Eckmann, Lars

    2013-05-01

    Giardiasis is one of the most common causes of diarrheal disease worldwide. Treatment is primarily with 5-nitro antimicrobials, particularly metronidazole. Resistance to metronidazole has been described, and treatment failures can occur in up to 20% of cases, making development of alternative antigiardials an important goal. To this end, we have screened a chemical library of 746 approved human drugs and 164 additional bioactive compounds for activity against Giardia lamblia. We identified 56 compounds that caused significant inhibition of G. lamblia growth and attachment. Of these, 15 were previously reported to have antigiardial activity, 20 were bioactive but not approved for human use, and 21 were drugs approved for human use for other indications. One notable compound of the last group was the antirheumatic drug auranofin. Further testing revealed that auranofin was active in the low (4 to 6)-micromolar range against a range of divergent G. lamblia isolates representing both human-pathogenic assemblages A and B. Most importantly, auranofin was active against multiple metronidazole-resistant strains. Mechanistically, auranofin blocked the activity of giardial thioredoxin oxidoreductase, a critical enzyme involved in maintaining normal protein function and combating oxidative damage, suggesting that this inhibition contributes to the antigiardial activity. Furthermore, auranofin was efficacious in vivo, as it eradicated infection with different G. lamblia isolates in different rodent models. These results indicate that the approved human drug auranofin could be developed as a novel agent in the armamentarium of antigiardial drugs, particularly against metronidazole-resistant strains.

  7. Chromosome studies of bone marrow cells from metronidazole-treated patients.

    PubMed

    Salamanca-Gomez, F; Castaneda, G; Farfan, J; Del C Santillan, M; Munoz, O; Armendares, S

    1980-01-01

    Chromosome studies were performed in bone-marrow cells from thirty nine patients with hepatic or intestinal amibiasis, and/or giardiasis, who had been treated with metronidazole during ten days. There was no significant difference in chromosome aberration frequency between the samples before and after treatment.

  8. A comparative study of oral single dose of metronidazole, tinidazole, secnidazole and ornidazole in bacterial vaginosis.

    PubMed

    Thulkar, Jyoti; Kriplani, Alka; Agarwal, Nutan

    2012-03-01

    To compare the cure rates of oral single dose of metronidazole (2 g), tinidazole (2 g), secnidazole (2 g), and ornidazole (1.5 g) in cases of bacterial vaginosis. This was a prospective, comparative, randomized clinical trial on 344 Indian women (86 women in each group) who attended a gynecology outpatient department with complaint of abnormal vaginal discharge or who had abnormal vaginal discharge on Gynecological examination but they did not complaint of it. For diagnosis and cure rate of bacterial vaginosis, Amsel's criteria were used. Statistical analysis was done by Chi-square test of proportions. The cure rate was compared considering metronidazole cure rate as gold standard. At 1 week, the cure rate of tinidazole and ornidazole was 100% and at 4 weeks, it was 97.7% for both drugs (P<0.001). Secnidazole had cure rate of 80.2% at 4 weeks (P=NS). Metronidazole showed a cure rate of 77.9% at 4 weeks, which is the lowest of all four drugs. Tinidazole and ornidazole have better cure rate as compared to metronidazole in cases of bacterial vaginosis.

  9. Cultivation-independent analysis of changes in bacterial vaginosis flora following metronidazole treatment.

    PubMed

    Ferris, Michael J; Norori, Johana; Zozaya-Hinchliffe, Marcela; Martin, David H

    2007-03-01

    PCR was used to survey bacterial vaginosis flora before and after metronidazole treatment. The species composition for pretreatment patients was variable. Lactobacillus iners was prominent in all patients posttreatment. Atopobium vaginae concentrations were highest for patients who failed or responded incompletely to treatment and lowest for patients who were cured.

  10. Draft Genome Sequence of a Metronidazole-Resistant Derivative of Gardnerella vaginalis Strain ATCC 14019

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the genome sequence of a metronidazole-resistant derivative of Gardnerella vaginalis ATCC 14019. This strain was obtained after serial selection to increase the MIC from 4 to ≥500 µg/ml. Two coding changes, in genes encoding a response regulator and an NAD+ synthetase, arose during selection. PMID:26564054

  11. Gram stain as a relapse predictor of bacterial vaginosis after metronidazole treatment.

    PubMed

    Huang, Mei; Wang, Jen Hsien

    2005-04-01

    Bacterial vaginosis is the most prevalent disease of the female genital tract. In spite of various effective antibiotics in the treatment of bacterial vaginosis, its high relapse rate is a common problem. Bacterial species causing bacterial vaginosis are generally unable to be cultured by conventional methods. It is impractical and inadequate to use culture methods to guide initial treatment. Gram stain of vaginal secretion is a practical tool to establish the diagnosis of bacterial vaginosis. We enrolled 78 cases of Gram stain-proven bacterial vaginosis and tried to use Gram stain as a predictor of relapse after 1 week of treatment with metronidazole. Possible predictive factors for relapse in Gram stain were analyzed, including absence of large Gram-positive rods, presence of small Gram-negative rods, small Gram-variable rods, curved Gram-variable rods, or Gram-positive cocci. Gram stain was repeated immediately after treatment, and at 1 month and 3 months after treatment. All cases showed beneficial clinical effect after metronidazole treatment. Eighteen cases (23.1%) relapsed during the follow-up period. All 16 cases with significant Gram-positive cocci in pretreatment smears relapsed after metronidazole treatment. Presence of small Gram-negative rods, small Gram-variable rods, and curved Gram-variable rods, or absence of large Gram-positive rods did not predict relapse. Gram-positive cocci in pretreatment smear was a good predictor of relapse after metronidazole treatment.

  12. Metronidazole-induced encephalopathy in a uremic patient: a case report.

    PubMed

    Arik, N; Cengiz, N; Bilge, A

    2001-09-01

    A variety of neurologic disorders may develop in patients with chronic renal failure. Drug toxicity must be thought of in the differential diagnosis of these disorders. We report a case with renal failure developing serious neurotoxicity after metronidazole use. Copyright 2001 S. Karger AG, Basel

  13. Systemic moxifloxacin vs amoxicillin/metronidazole adjunct to non-surgical treatment in generalized aggressive periodontitis

    PubMed Central

    Gurgan, Cem-Abdulkadir

    2015-01-01

    Background The objective of this randomized clinical study was to evaluate the effect of systemic administration of moxifloxacin compared to amoxicillin and metronidazole, combined with non-surgical treatment in patients with generalized aggressive periodontitis (GAgP) in a 6-month follow-up. Material and Methods A total of 39 systemically healthy patients with GAgP were evaluated in this randomized clinical trial. Periodontal parameters were recorded at the baseline during the 1st, 3rd and 6th month. Patients received either 400 mg of moxifloxacin per os once daily or 500 mg of metronidazole and 500 mg amoxicillin per os three times daily for 7 days consecutively. Results No significant differences between groups were found in any parameters at the baseline. Both groups led to a statistically significant decrease in all clinical periodontal parameters compared to the baseline (PI, p<0.001 and GI, PD, BOP, CAL, p<0.01). There were no differences between the 1st and 3rd months or the 3rd and 6th months for clinical parameters in the groups. Also, no intergroup difference was observed in any parameters at any time, except the gingival index at 6th months. Conclusions Systemic administration of moxifloxacin as an adjunct to non-surgical treatment significantly improves clinical outcomes and provides comparable clinical improvement with less adverse events to that of combination of amoxicillin and metronidazole in the treatment of GAgP. Key words: Aggressive periodontitis, amoxicillin, metronidazole, moxifloxacin, nonsurgical periodontal debridement. PMID:26034931

  14. Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

  15. Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

    PubMed Central

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

    2014-01-01

    The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0–τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml−1. This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution. PMID:24277041

  16. Comparative Evaluation of Propolis, Metronidazole with Chlorhexidine, Calcium Hydroxide and Curcuma Longa Extract as Intracanal Medicament Against E.faecalis– An Invitro Study

    PubMed Central

    Nair, Rashmi; Asrani, Hemant

    2015-01-01

    Introduction The increase of potential side effects and safety concerns of conventional medicaments have led to the recent popularity of herbal alternative medications. The herbal products are known for its high antimicrobial activity, biocompatibility, anti-inflammatory and antioxidant properties. Aim The purpose of this study was to investigate and compare the effectiveness of Propolis, Metronidazole with Chlorhexidine gel, Curcuma Longa and Calcium Hydroxide for elimination of E.faecalis bacteria in extracted teeth samples. Materials and Methods Ninety extracted single rooted intact teeth were taken for the study. Decoronation, removal of apices and chemomechanical preparation was done for all samples. These sterilized samples were then contaminated with pure culture of E.faecalis under laminar flow. The samples were incubated for a period of 21 days. The infected samples were assigned to 5 groups: Group I- Propolis; Group II- Metronidazole with Chlorhexidine gel; Group III- Calcium hydroxide; Group IV- Curcuma Longa; and control group- Saline. Efficacy of newer intracanal medicaments against E.faecalis were carried out in the samples at the end of 1, 2 & 5 days for each group with the help of colorimeter. Student paired t-test, ANOVA and multiple tukey test were used for statistical analysis. Results The value of optical density was statistically significant in all groups when compared to that of control group. Group I (Propolis) produced better antimicrobial efficacy followed by Chlorhexidine Metronidazole combination, Curcuma Longa and Calcium hydroxide. Conclusion Within the limitations of this study, it can be concluded that Propolis showed better antimicrobial properties against E.faecalis than other medicaments. PMID:26673857

  17. Reducing surgical site infections after hysterectomy: metronidazole plus cefazolin compared with cephalosporin alone.

    PubMed

    Till, Sara R; Morgan, Daniel M; Bazzi, Ali A; Pearlman, Mark D; Abdelsattar, Zaid; Campbell, Darrell A; Uppal, Shitanshu

    2017-08-01

    Organisms that are isolated from vaginal cuff infections and pelvic abscesses after hysterectomy frequently include anaerobic vaginal flora. Metronidazole has outstanding coverage against nearly all anaerobic species, which is superior to both cefazolin and second-generation cephalosporins. Cefazolin plus metronidazole has been demonstrated to reduce infectious morbidity compared with either cefazolin or second-generation cephalosporins in other clean-contaminated procedures, which include both as colorectal surgery and cesarean delivery. The purpose of this study was to evaluate whether the combination of cefazolin plus metronidazole before hysterectomy was more effective in the prevention of surgical site infection than existing recommendations of cefazolin or second-generation cephalosporin. This was a retrospective cohort study of patients in the Michigan Surgical Quality Collaborative from July 2012 through February 2015. The primary outcome was surgical site infection. Patients who were >18 years old and who underwent abdominal, vaginal, laparoscopic, or robotic hysterectomy for benign or malignant indications were included if they received 1 of the following prophylactic antibiotic regimens: cefazolin, second-generation cephalosporin, or cefazolin plus metronidazole. Multivariate logistic regression modeling was performed to evaluate the independent effect of an antibiotic regimen, and propensity score matching was used to validate the findings. The study included 18,255 hysterectomies. The overall rate of surgical site infection was 1.8% (n=329). The unadjusted rate of surgical site infection was 1.8% (n=267) for cefazolin, 2.1% (n=49) for second-generation cephalosporin, and 1.4% (n=13) for cefazolin plus metronidazole. After adjustment for differences in patient and operative factors among the antibiotic cohorts, compared with cefazolin plus metronidazole, we found the risk of surgical site infection was significantly higher for patients who received

  18. Waste Material of Propolis as a Film Forming Agent Intended to Modify the Metronidazole Release: Preparation and Characterization.

    PubMed

    de Toledo, Lucas de Alcântara Sica; Rosseto, Hélen Cássia; Ravani, Laura; Cortesi, Rita; Bruschi, Marcos Luciano

    2016-01-01

    Metronidazole is an antimicrobial agent utilized for the treatment of protozoa and anaerobic bacteria infections. Many times, it is necessary to modify the metronidazole release, and the development of modified release systems may be suggested. In this study, we are able to investigate the use of the residue normally thrown out from the preparation of propolis extracts (BP) as strategy to modify the metronidazole release. We prepared films containing polymeric adjuvant (gelatin or ethylcellulose) and metronidazole, by solvent casting method. Density, mechanical properties, water vapor permeability (WVP), moisture uptake capacity (MUC), thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy (FT-IR), and in vitro metronidazole release were investigated. Thickness and density of the preparations indicated that the compounds were homogeneously dispersed throughout. Mechanical properties were influenced by film composition. Films containing gelatin showed higher resistance to stress while those containing ethylcellulose presented greater flexibility. The greater the adjuvant concentrations lower the resistance to rupture and the elasticity, but higher MUC and WVP of formulations. FT-IR tests suggested interactions between BP and the adjuvants. Films were capable to protect the metronidazole and changed its release profile. BP films are of great practical importance constituting a novel strategy to modify the metronidazole release.

  19. Stability of cefazolin sodium and metronidazole at 8 degrees C for use as an i.v. admixture.

    PubMed

    Rivers, T E; McBride, H A; Trang, J M

    1993-01-01

    The stability of cefazolin 1 g in metronidazole 500 mg/100 mL at 8 degrees C was studied for use as an IV admixture. The commercially available injection of cefazolin sodium 1 g vial was diluted to 5 mL with 0.9% sodium chloride injection and added to metronidazole 500 mg/100 mL. Following dilution of 2 mL to 100 mL with water, 1-mL aliquots were transferred to glass vials, refrigerated at 8 degrees, and assayed for cefazolin and metronidazole concentration at 0, 1, 2, 4, 8, 12, 24, 36, 48, and 72 hours after preparation. The concentration of cefazolin and metronidazole was determined by a stability-indicating high-performance liquid chromatographic method. The range of concentration was determined to be within 5% of the 0-hour mean concentration. Over the 72-hour period, the mean concentration of cefazolin at all assay times was within 98.4 to 101.0% of the initial concentration. The mean concentration of metronidazole at each assay time was 96.9 to 104.9% of the initial concentration. Cefazolin sodium 10 mg/mL and metronidazole 5 mg/mL, prepared by adding reconstituted cefazolin to a glass bottle of metronidazole ready-to-use solution, were stable for 72 hours when stored at 8 degrees C.

  20. Metronidazole susceptibility testing for Helicobacter pylori: comparison of disk, broth, and agar dilution methods and their clinical relevance.

    PubMed Central

    DeCross, A J; Marshall, B J; McCallum, R W; Hoffman, S R; Barrett, L J; Guerrant, R L

    1993-01-01

    Since the methods for metronidazole susceptibility testing of Helicobacter pylori have not been standardized or validated, we compared three methods that are used to test the metronidazole susceptibilities of 25 isolates of H. pylori. Specifically, we examined the methods of Steer's replicator agar dilution, tube broth microdilution, and modified Kirby-Bauer disk diffusion. The metronidazole disk zone sizes obtained by the disk diffusion method correlated well (r = 0.74) with the MICs obtained by the agar dilution method. Afterward, the disk diffusion method was used to characterize the metronidazole susceptibilities of 44 isolates of H. pylori. Dual therapy (bismuth and metronidazole) proved to be highly effective against metronidazole-susceptible strains (81.6% eradication rate) but fared poorly against resistant strains (16.7% eradication rate; P < 0.01). Using agar dilution testing, we validated the modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of H. pylori and conclude that it is practical, accurate, and clinically applicable. PMID:8370723

  1. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result.

    PubMed

    Ursing, B; Alm, T; Bárány, F; Bergelin, I; Ganrot-Norlin, K; Hoevels, J; Huitfeldt, B; Järnerot, G; Krause, U; Krook, A; Lindström, B; Nordle, O; Rosén, A

    1982-09-01

    Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded