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Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD). Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release. Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved. Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area.

Objectives: The aim of our study was to assess the efficacy of intralesional metronidazole on Leishmania donovani cutaneous leishmaniasis (CL)., Material and Methods: A total of 188 patients with CL were randomly allocated to intralesional sodium stibogluconate (SSG) and intralesional metronidazole. Cure was assessed after 1-10 injections. Cure rates were assessed for statistical significance using chi-square test at p = .05 level (SLCTR/2014/028)., Results: When the treatment cutoff was taken at 100%, the rate of cure for SSG (n = 64, 65.6%) was higher than that of metronidazole (n = 45, 48.9%): statistically significant at p < .05 level (Yates corrected chi-square 5.37, df = 1, p < .5). When the treatment cutoff was taken at >80%, the rate of cure for SSG (n = 75, 77.1%) was also higher than that of metronidazole (n = 58, 63.0%): statistically significant at p < .05 level (Yates corrected chi-square 4.46, df = 1, p < .5). Since it is based on a smaller sample, we estimated the statistical power of the test at a cutoff of 100% [above 80%] results identified a risk ratio of 1.4 [1.3], and a statistical power based on normal approximation at 74.8% [70.0%], respectively., Conclusion: This study showed that intralesional SSG has the best response against CL, while intralesional metronidazole was an effective alternative treatment.

Objective: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases., Methods: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed., Results: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone., Conclusion: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.

Background: Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure., Methods: We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens., Results: Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%)., Conclusions: A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.

Background: Increasing resistance of Helicobacter pylori (H. pylori) to antibiotics calls for constant re-evaluation of multidrug regimens that have been used to eradicate the infection. The aim of this study was to evaluate the current antibiotic susceptibility of H. pylori in an Icelandic cohort., Methods: Patients referred for gastroscopy were recruited prospectively. Those found to have a positive rapid urease test were included in the study. Susceptibility testing was conducted by the Epsilometer test (E-test) method for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline. Results were obtained after three days of incubation in microaerophilic conditions at 37 °C, except for the metronidazole were the first 24 hours were anaerobic., Results: Of the 613 patients who underwent gastroscopy, 138 (23%) had a positive rapid urease test. H. pylori was successfully cultured from 105 (76%) of the urease test positive patients and the isolates were tested for antibiotic susceptibility. Five patients had prior H. pylori eradication. Antibiotic resistance for ampicillin, clarithromycin, levofloxacin, metronidazole and tetracycline was 0%, 9%, 4%, 1% and 0%, respectively. If those who had previously undergone eradication treatment were excluded, the resistance was 0%, 6%, 3%, 1% and 0%, respectively. Clarithromycin resistance was higher amongst women than men, 13% vs. 5%, however, not significantly. Clarithromycin resistance was 60% amongst those who had previously received eradication treatment compared to 6% of those who had not (p < .0001)., Conclusions: Clarithromycin resistance amongst the H. pylori isolates can be considered relatively low. Therefore, in the current cohort, standard triple-drug clarithromycin-containing regimen should remain the first-line treatment against H. pylori.

Background: This study investigated whether levofloxacin-containing concomitant therapy can effectively eradicate Helicobacter pylori infection in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 797 T2DM patients were screened for anti-H. pylori IgG antibodies, and the presence of H. pylori infection was confirmed by 13 C-urea breath test. We prospectively randomized 114 of these patients to receive either 10 d of levofloxacin-concomitant therapy (n = 55) or sequential therapy (n = 59). Antimicrobial resistance of H. pylori isolates collected from the patients with T2DM (n = 109) and dyspeptic controls without DM (n = 110) was determined using the E-test. This study was approved by our Institutional Review Board (A-BR-103-021)., Results: The H. pylori eradication rates with concomitant therapy were higher than sequential therapy in both intention-to-treat (96.4% versus 81.4%, p = 0.012) and per-protocol (100% versus 85.4%, p = 0.006) analysis. The adverse effects in both groups were similarly mild. In the patients who received sequential therapy, clarithromycin resistance was significantly associated with eradication failure (p = 0.02). There were no significant differences in the antibiotic-resistant rates to amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin between the patients with and without T2DM., Conclusions: Ten days of levofloxacin-containing concomitant therapy is an effective and well-tolerated treatment to eradicate H. pylori infection for T2DM patients. Key messages Ten days of levofloxacin-containing concomitant therapy is well tolerated and superior to clarithromycin-containing sequential therapy for first-line H. pylori eradication in patients with type 2 diabetes. Clarithromycin resistance to H. pylori is the main factor associated with eradication failure in clarithromycin-containing sequential therapy in diabetic patients.

Nitroimidazoles are not authorised for the treatment of honey bees in the European Union. However, they can be found in honey largely because they are illegally used in apiculture for the treatment of Nosema. The aim of the study was to examine the possible transfer of nitroimidazoles (metronidazole, ronidazole, dimetridazole and ipronidazole) from contaminated beeswax to honey. The wax foundations fortified with a mixture of four nitroimidazoles at three concentration levels (1000, 10,000 and 100,000 μg kg - 1 ) were placed in beehives to let the honeybees (Apis mellifera L.) draw out the contaminated wax foundations to honeycombs. At 1 month from the start, the frames filled with capped honey were removed from the hives for a first sampling of honey. Next, the honeycombs were further incubated for 5 months in the laboratory at 35°C and sampled monthly. In the sampled honey, the concentrations of nitroimidazoles and their main metabolites (hydroxymetronidazole, 2-hydroxymethyl-1-methyl-5-nitroimidazole, hydroxyipronidazole) were determined by LC-MS/MS and compared with those determined in the nitroimidazole-containing wax foundations. Each of the tested nitroimidazoles could migrate from beeswax to honey kept in the contaminated combs at each tested concentration level. Higher maximum concentrations of residues in honey sampled from contaminated combs at 1000, 10,000 and 100,000 μg kg - 1 were observed for metronidazole (28.9, 368.5 and 2589.4 μg kg - 1 respectively) and ronidazole (27.4, 232.9 and 2351.2 μg kg - 1 respectively), while lower maximum concentrations were measured for dimetridazole (0.98, 8.4 and 67.7 μg kg - 1 ) and ipronidazole (0.9, 7.9 and 35.7 μg kg - 1 respectively). When we took into account that a frame completely filled with honey on both sides of the comb contained 110 g of beeswax and 2488 g of honey, and that this ratio was constant, then maximum amounts of initial metronidazole, ronidazole, dimetridazole and ipronidazole that migrated from contaminated wax foundations to honey could be calculated: 65-89%, 55-63%, 1.7-2.7% and 1.4-2.3%, respectively.

Objectives: To determine whether a new antibiotic regimen could reduce the frequency of intra-amniotic inflammation/infection in patients with preterm PROM., Study Design: This retrospective cohort study was conducted to evaluate the effect of antibiotics on the frequency of intra-amniotic inflammation/infection based on the results of follow-up transabdominal amniocenteses from 89 patients diagnosed with preterm PROM who underwent serial amniocenteses. From 1993-2003, ampicillin and/or cephalosporins or a combination was used ("regimen 1"). A new regimen (ceftriaxone, clarithromycin and metronidazole) was used from 2003-2012 ("regimen 2"). Amniotic fluid was cultured and matrix metalloproteinase-8 (MMP-8) concentrations were measured., Results: (1) The rates of intra-amniotic inflammation and intra-amniotic inflammation/infection in patients who received regimen 2 decreased during treatment from 68.8% to 52.1% and from 75% to 54.2%, respectively. In contrast, in patients who received regimen 1, the frequency of intra-amniotic inflammation and infection/inflammation increased during treatment (31.7% to 55% and 34.1% to 58.5%, respectively); and (2) intra-amniotic inflammation/infection was eradicated in 33.3% of patients who received regimen 2, but in none who received regimen 1., Conclusion: The administration of ceftriaxone, clarithromycin and metronidazole was associated with a more successful eradication of intra-amniotic inflammation/infection and prevented secondary intra-amniotic inflammation/infection more frequently than an antibiotic regimen which included ampicillin and/or cephalosporins in patients with preterm PROM.

Objective: Antibiotic administration is a standard practice in preterm premature rupture of membranes (PROM). Specific anti-microbial agents often include ampicillin and/or erythromycin. Anaerobes and genital mycoplasmas are frequently involved in preterm PROM, but are not adequately covered by antibiotics routinely used in clinical practice. Our objective was to compare outcomes of PROM treated with standard antibiotic administration versus a new combination more effective against these bacteria., Study Design: A retrospective study compared perinatal outcomes in 314 patients with PROM <34 weeks receiving anti-microbial regimen 1 (ampicillin and/or cephalosporins; n = 195, 1993-2003) versus regimen 2 (ceftriaxone, clarithromycin and metronidazole; n = 119, 2003-2012). Intra-amniotic infection/inflammation was assessed by positive amniotic fluid culture and/or an elevated amniotic fluid MMP-8 concentration (>23 ng/mL)., Results: (1) Patients treated with regimen 2 had a longer median antibiotic-to-delivery interval than those with regimen 1 [median (interquartile range) 23 d (10-51 d) versus 12 d (5-52 d), p < 0.01]; (2) patients who received regimen 2 had lower rates of acute histologic chorioamnionitis (50.5% versus 66.7%, p < 0.05) and funisitis (13.9% versus 42.9%, p < 0.001) than those who had received regimen 1; (3) the rates of intra-ventricular hemorrhage (IVH) and cerebral palsy (CP) were significantly lower in patients allocated to regimen 2 than regimen 1 (IVH: 2.1% versus 19.0%, p < 0.001 and CP: 0% versus 5.7%, p < 0.05); and (4) subgroup analysis showed that regimen 2 improved perinatal outcomes in pregnancies with intra-amniotic infection/inflammation, but not in those without intra-amniotic infection/inflammation (after adjusting for gestational age and antenatal corticosteroid administration)., Conclusion: A new antibiotic combination consisting of ceftriaxone, clarithromycin, and metronidazole prolonged the latency period, reduced acute histologic chorioamnionitis/funisitis, and improved neonatal outcomes in patients with preterm PROM. These findings suggest that the combination of anti-microbial agents (ceftriaxone, clarithromycin, and metronidazole) may improve perinatal outcome in preterm PROM.

Objective: The objective of this study is to compare, in Greece, a region with >20% local resistance to clarithromycin, the efficacy rates of the concomitant versus the sequential H. pylori eradication therapy., Materials and Methods: Our prospective randomized study included 364 patients with newly diagnosed H. pylori infection, randomized to receive a 10-day concomitant or 10-day sequential therapy. Treatment outcome was assessed by C(13)-urea breath test at least 4 weeks after therapy. Intention to treat (ITT) and per protocol (PP) analysis of the eradication rates were performed. Secondary end points included patient compliance and safety., Results: The concomitant therapy group achieved statistically significant higher eradication rates when compared with the sequential treatment group, both in the ITT and in the PP analysis (84.6% versus 70.9%, p = 0.002, and 90.6% versus 78.1%, p = 0.001, respectively), after adjusting for age, gender, smoking status, and the presence or not of ulcer and/or non-ulcer dyspepsia. Both groups displayed excellent compliance rates (99.5% for the concomitant therapy group and 96.2% for the sequential therapy group, p = 0.067). Regarding treatment safety, major adverse events that led to the discontinuation of both regimens were few, with no statistical difference between the two groups (7.0% for the concomitant therapy group and 2.9% for the sequential therapy group)., Conclusions: Concomitant therapy led to statistically significant higher eradication rates over sequential therapy. Both therapies showed excellent compliance and an acceptable safety profile. The 10-day quadruple concomitant scheme should be the adopted for first-line H. pylori eradication in Greece.

Context: Bioadhesiviness of polyacrylic acid polymers make them promising hydrogels to design topical drug delivery systems, allowing a close contact with biological substrate as well as an enhanced local concentration gradient, both factors that may improve the biological performance of the drugs., Aim: Texture and bioadhesive properties of hydrogels were assessed by using texture analyzer and they were correlated with their rheological behavior and performance as drug delivery systems., Methods: Aqueous dispersions of both polymers were prepared at 0.5%, 1.0% and 1.5% w/v. Hardness, compressibility, adhesiveness, cohesiveness, bioadhesion, continuous flow, oscillatory dynamic test and in vitro drug release were evaluated., Results: Rheological and texture parameters were dependent on polymer concentration and C974P polymer built the strongest structures. Both 1.5% hydrogels presented high bioadhesion values. About 50% of the metronidazole (MTZ) was sustained released from hydrogels within 2 h with an initial burst release at early stage. After, the release rates were decreased and 10% of the MTZ was released in the next 10 h. The drug release process was driven by Fickian diffusion and complex mechanism for PP and C974P hydrogels, respectively., Conclusion: The set of results demonstrated that these hydrogels are promising to be used as topical controlled drug delivery system.

Thirty-seven adult Caucasian patients (9 males and 28 females), with erythemato-telangiectatic rosacea accompanied by stinging and burning sensation, were treated with a cream containing 5% potassium azeloyl diglycinate and 1% hydroxypropyl chitosan. All patients were previously treated at other centers with topical azelaic acid and/or metronidazole. The cream was applied twice daily for 12 weeks. The objective of the study was the evaluation of the soothing effect of the cream: stinging and burning sensation were measured by means of a 4-point scale (0 = absent, 1 = mild, 2 = moderate, and 3 = severe). All patients were clinically evaluated every 4 weeks. Of 37 patients (81.1%), 30 were considered evaluable. Before the beginning of the study, the total score of stinging and burning sensation was 66 (mean: 2.2 points/patient); at the end of the study, it was 37 points (-29) (mean: 1.2 points/patient), with a reduction of 56.1%. No side effects were reported or observed. This study shows that the fixed combination potassium azeloyl diglycinate - hydroxypropyl chitosan is effective in reducing stinging and burning sensation in patients with erythemato-telangiectatic rosacea.

Controlled-release metronidazole, mucoadhesive gel proposed as a drug-delivery system for periodontal application was developed and characterized. The system was based on a mixture of glycerylmonooleate (GMO) and ethylcellulose (EC). The mechanism of release depends: firstly, on the ability of GMO to form a viscous liquid crystalline mesophases and secondly on the solubilized EC to form a hydrophobic network when the mixture comes into contact with water resulting in sustaining the release of the drug. Ethylcellulose dissolved in GMO had a profound influence on the rate of drug release, reduced the initial drug release and prolonged the sustained release of metronidazole. Propylene glycol (PG) was added to increase the solubility of the drug and water was added with PG to control the viscosity. A controlled release formulation containing w/w, 20% metronidazole, 10% PG, 5% water and 65% GMO that contains 7% EC was found to be mucoadhesive, easily injectable at room temperature, and to follow Fickian diffusion release mechanism. When the drug loading was increased the drug release was accelerated, and the mechanism followed anomalous controlled-release mechanism. Stability studies indicated that the formulation should be stored at 4 °C in a dark place.

Unlabelled: The management of Clostridium difficile infection (CDI) has become very daunting over the past decade because of increased incidence and severity both in hospital and the community. Guidelines recommend metronidazole, vancomycin, or fidaxomicin, depending on clinical presentation., Objective: Our objective was to describe CDI management and assess empirical CDI therapy complying with practice guidelines., Methods: We performed a 2-year prospective cohort study in a university teaching hospital in Lyon, France. Criteria assessing the conformity of CDI patient management were: time elapsed between testing and start of treatment specific to CDI, antibiotics to fight CDI and treatment duration according to infection severity, concomitant therapy, and use of antidiarrheal drugs., Results: Among 118 patients with confirmed CDI, 98 (83%) were specifically treated for CDI. Severe CDI was observed in 63 patients (53.9%). Treatment included metronidazole alone in 72 patients (73.5%), vancomycin alone in 1 patient (1%), and both in 25 patients (25.5%). The percentage of CDI treatment compliance with published guidelines in our hospital at the study period varied between 22% and 93%. A total of 16 patients (13.6%) died within 30 days after diagnosis. Death was related to CDI in nine patients (56.3% of deceased cases)., Conclusion: This study identified significant gaps in our knowledge of CDI treatment. Increasing disease severity highlights the need to investigate antibiotic treatment in severely ill CDI patients, as data on this group are currently lacking.

Objective: To test the efficacy of lansoprazole, bismuth, levofloxacin, and amoxicillin therapy compared to bismuth metronidazole tetracycline (BMT) quadruple therapy for second-line treatment of Helicobacter pylori infection., Methods: A total of 284 patients who failed prior H. pylori eradication were randomized to receive 14-day regimens containing lansoprazole 30 mg twice a day (b.i.d.), bismuth subcitrate 240 mg b.i.d., and either amoxcillin, 1 g b.i.d. and levofloxacin 500 mg once daily (qd) (levofloxacin/bismuth therapy) or metronidazole 400 mg four times daily (q.i.d.) and tetracycline, 500 mg q.i.d. (BMT quadruple therapy). Endoscopy and culture were performed before treatment. Antimicrobial susceptibility was by agar dilution. H. pylori status was determined 6 weeks after the end of therapy using a (13)C-urea breath test., Results: The metronidazole, levofloxacin, tetracycline, and amoxicillin resistance rates were 85.3%, 40.2%, 1.1%, and 0.5%, respectively. The intention-to-treat and per-protocol (PP) eradication rates were 83% (95% confidence interval [CI]: 75.9-88.3%) and 88.1% (95% CI: 81.2-92.4%) (p = 0.22) for levofloxacin-bismuth (levo-bismuth) versus BMT quadruple, respectively, and PP rates were 85.4% (95% CI: 78.5-90.3%) and 90.6% (95% CI: 84.6-94.5%) (p = 0.18). Moderate and severe side effects were significantly higher with BMT quadruple than levo-bismuth (22.4% vs. 5%, p < 0.001) and higher in women (28.4%) than men (10.4%) in BMT quadruple therapy group (p = 0.015)., Conclusion: Increasing fluoroquinolone resistance has undermined levo-bismuth quadruple therapy making BMT quadruple therapy a better choice empiric second-line therapy for H. pylori infection. However, compliance was significantly higher with levo-bismuth quadruple therapy, especially among women.

Introduction: Preterm birth is the major cause of perinatal mortality and morbidity in high-income countries. The etiology of preterm birth is multifactorial but there is overwhelming evidence to implicate infection as a major cause. Abnormal genital tract flora in early pregnancy is predictive of preterm birth so it is logical to consider the use of antibiotics for the prevention of preterm birth., Areas Covered: Infection and antibiotics in the etiology, prediction and prevention of preterm birth., Expert Opinion: Antibiotics for the prevention of preterm birth have addressed different risk groups, diagnostic methods, degrees of abnormal flora, antibiotic dose regimens, routes of administration, host susceptibilities, host response, gestational age at time of treatment, outcome parameters and definitions of success and outcomes. To address this confusion, a number of systematic reviews/meta-analyses have been conducted but none has simultaneously addressed the optimal choice of agent, patient and timing of intervention. We conclude that inappropriate antibiotics used in inappropriate women at inappropriately late gestations do not reduce preterm birth. Conversely, a focused systematic review/meta-analysis, which targeted the use of clindamycin before 22 weeks gestation, in women with objective evidence of abnormal genital tract flora, demonstrated that clindamycin produced a significant decrease in late miscarriage and preterm birth.

Objective: Periodontitis is one of the most important chronic inflammatory dental diseases arising from the destructive actions caused by a variety of pathogenic organisms presented in the oral cavity. The aim of this study is the preparation and in vitro evaluation of films for the local treatment of periodontal pockets., Methods: The prepared films contained either metronidazole (Mtr), for its antimicrobial effect in periodontal diseases, using a mixture of polymers namely hydroxypropyl methyl cellulose, Carbopol 934 or locally applied Pentoxifylline (PTX), for its anti-inflammatory activity, using chitosan. All films were prepared using solvent casting technique and were evaluated for their physical characteristics, drug content uniformity, surface pH, swelling behavior, mechanical properties and in vitro release. Further characterization was done on the selected formulations using differential scanning calorimetry and scanning electron microscopy for surface structure. Clinical evaluation tests were also performed., Result: Appropriate physical characteristics and mechanical properties for most formulations and their suitability for periodontal application were observed. In vitro drug release from most films showed a burst release rate for both Mtr and PTX during the first 2 h after which the release rate was markedly decreased. Clinical trials on patients revealed the advantageous use of Mtr and PTX as an adjunct treatment with traditionally used dental techniques., Conclusion: The effectiveness of the co-therapy of either drug could add benefit in the eradication of chronic periodontal hazards.

This study was performed to obtain prolonged drug release with biodegradable in situ forming implants for the local delivery of metronidazole to periodontal pockets. The effect of polymer type (capped and uncapped PLGA), solvent type (water-miscible and water-immiscible) and the polymer/drug ratio on in vitro drug release studies were investigated. In situ implants with sustained metronidazole release and low initial burst consisted of capped PLGA and N-methyl-2-pyrolidone as solvent. Mucoadhesive polymers were incorporated into the in situ implants in order to modify the properties of the delivery systems towards longer residence times in vivo. Addition of the polymers changed the adhesiveness and increased the viscosity and drug release of the formulations. However, sustained drug release over 10 days was achievable. Biodegradable in situ forming implants are therefore an attractive delivery system to achieve prolonged release of metronidazole at periodontal therapy.

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.

Two 1% and one 0.75% metronidazole cream products were approved as bioequivalent products. These products were evaluated for their in vivo cutaneous penetration characteristics by dermatopharmacokinetic (DPK) and dermal microdialysis (DMD) sampling methodologies. The same three products were also evaluated for their rheological and in vitro drug release (IVR) properties. Structural differences were observed in the resulting flow curves. However, similar IVR profiles were obtained for the two topical semisolid dosage forms containing 1% metronidazole. For the lower strength product, a higher IVR rate was associated with the lower DPK profile. All three products exhibited similar values of area under the curve when investigated by DMD. This in vitro evaluation corroborated the divergent penetration characteristics found using in vivo methodologies.

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets., Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole., Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed., Results: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage., Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

The Society for Healthcare Epidemiology (SHEA) and the Infectious Diseases Society of America (IDSA) clinical practice guidelines for Clostridium difficile infection (CDI) help to define and make recommendations for the treatment of mild to moderate disease with metronidazole and severe disease with vancomycin. We retrospectively evaluated 285 patients who were initially treated with metronidazole and stratified them by severity of illness using the guideline criteria. We compared the outcomes in the 2 groups including the need to change therapy, recurrences, and 30-day all-cause mortality. There were no differences in recurrence rates based on severity of disease. From the multivariate analysis, severe CDI was predictive of 30-day all-cause mortality (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07-3.67, p = 0.03), after controlling for ICU stay prior to diagnosis (OR 2.94, 95% CI 1.60-5.41. p = 0.001), age (OR 1.02, 95% CI 1.004-1.05, p = 0.02), and the modified Charlson score (OR 1.31, 95% CI 1.14-1.49, p < 0.0001).

Objective: The aim of this study was to investigate various deformable liposomes for their potential application for the vaginal administration of metronidazole., Materials and Methods: Deformable liposomes composed of egg phosphatidylcholine (EPC) and various surfactants [sodium deoxycholate (SDCh), Tween 80 or Span 80] and conventional liposomes consisting of EPC and egg phosphatidylglycerol-sodium (EPG-Na) were prepared with and without metronidazole. Additionally, a freeze-thaw method was applied to both classes of vesicles (liposomes) containing the drug to improve its trapping capacity. All of the liposomes prepared were characterized and compared in terms of size, polydispersity, zeta potential, entrapment efficiency and their permeability on a Caco-2 cell monolayer., Results and Discussion: Conventional liposomes, both with and without metronidazole, were larger than the deformable vesicles. The presence of ethanol in the preparations of the elastic EPC/SDCh and EPC/Tween 80 liposomes was found to affect the particle size in terms of reducing this parameter. Different types of vesicles were compared for their trapping efficiency of metronidazole and the highest entrapment was observed with conventional liposomes. However, deformable EPC/SDCh liposomes were found to enhance the permeability of metronidazole more effectively than the conventional liposomes based on the in vitro model of the epithelial barrier., Conclusion: These preliminary data indicate that EPC/SDCh liposomes may have a promising future in vaginal delivery of metronidazole. Therefore, additional investigations on elastic vesicles and their incorporation in a suitable vehicle should be considered to further evaluate their applicability in vaginal drug delivery.

The objective of the present investigation was to develop and evaluate physiological environment responsive periodontal drug delivery system (PERPDDS) for local delivery of metronidazole benzoate. Poly-ϵ-caprolactone an in situ precipitating polymer was used in combination with, carbopol 934P, a pH simulative polymer to develop PERPDDS. The prepared PERPDDS was evaluated for various parameters such as in vitro gelling capacity, viscosity, rheology, compatibility study, and in vitro diffusion study. A 3(2) full factorial design was used to investigate the influence of formulation variables. Drug release data from all formulations were fitted to different kinetic models and the korsemeyer-peppas model was found the best fit model. The value of diffusional exponent (n) was in between 0.3283 and 0.3979 indicating purely fickian diffusion release mechanism. Increasing the concentration of each polymeric component increases viscosity, and time for 50% and 90% drug release was observed and graphically represented by the surface response and contour plots.

The aim of this study was to evaluate the physical properties, chemical structure and bioactivity of sol-gel processed oxide (SiO(2)-CaO-P(2)O(5)) composites used as controlled release materials for Metronidazole-drug applied in periodontal disease treatment. The obtained composite materials were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), the Brunauer-Emmet-Teller (BET) technique and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug over time. Using tetramethoxysilane (TMOS) as a precursor of silica matrix and calcium nitrate tetrahydrate (Ca(NO(3))(2) 4H(2)O), triethyl phosphite (P(OC(2)H(5))(3)) as precursors of CaO and P(2)O(5) respectively, xerogels with different morphology and physical properties were obtained. The applied modifications improved also the bioactivity and changed the profile of the drug release. Based on the presented results of this study, it may be concluded that applied xerogel matrices could be promising candidates for the formulation in local delivery systems.

Clostridium difficile colitis infection is on the rise and is considerably increasing the duration of hospital stay, as well as healthcare costs. The management of C. difficile colitis has become more challenging with the increasing failure of therapeutic response to metronidazole and oral vancomycin. Tigecycline is a new glycylcycline that has shown in vitro activity against C. difficile. We report herein a case of C. difficile colitis that failed to improve on a combination of metronidazole and oral vancomycin. The patient subsequently developed a surgical abdomen secondary to refractory C. difficile colitis, but was successfully treated with a combination of rifaximin and tigecycline after she refused to undergo surgical treatment.

Objective: The aim of this study is to develop, characterize and evaluate (in vitro and in vivo) a novel colon-targeted bioadhesive microsphere (BAM) containing metronidazole (MTZ)., Methods: BAMs are prepared using Assam Bora rice starch as a natural bioadhesive polymer by a double emulsion solvent evaporation method., Results: The prepared microspheres showed a uniform spherical shape, with excellent retention time. The in vitro drug release study of the optimized formulations, in different physiological environments, confirmed the insignificant release of metronidazole in the physiological conditions of the stomach (10 - 12.5%) and small intestine (< 25%). Further, fast and major drug release in cecal content (> 90) indicated that the release of the drug was unaffected by the hostile environment of the gastrointestinal tract (GIT). In vitro bacterial inhibition studies illustrated that MTZ loaded BAMs, inhibiting metronidazole-sensitive Bacteroides fragilis and selected BAMs (F1 - F7), have an equivalent or higher zone of inhibition than the marketed formulation. An in vivo organ distribution study of MTZ revealed that Assam Bora rice starch-based microspheres were relatively intact in the upper part of GIT, and the drug was released only after reaching the colon, owing to the microbial degradation of Assam Bora rice starch by microflora residing in the colon., Conclusion: MTZ release patterns exhibited slow and extended release over longer periods of time, which shows the potential of Assam Bora rice starch microspheres as a drug carrier for an effective colon-targeted delivery system.

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.

Background: Topical antifungals comprising imidazole derivatives have been used for the treatment of rosacea previously, owing to their anti-inflammatory activities. Terbinafine, an antifungal agent belongs to allylamine group, has also anti-inflammatory effects. Currently, there are only a few unpublished studies, in which terbinafine has been used systemically for rosacea treatment., Aims: In this single-blind, 8-week study, we investigated the potential efficacy and safety of terbinafine 1% cream for the treatment of mild and moderate papulopustular rosacea, and compared the results with those of 0.75% metronidazole gel., Patients/methods: Forty patients, 30 females and 10 males, with papulopustular rosacea were enrolled into the study between 2006 and 2007 years. Twenty of the patients were instructed to apply 1% terbinafine cream, whereas others patients of the study population were instructed to use 0.75% metronidazole gel. A total of 32 patients completed the study. Pre-treatment and post-treatment total severity score (TSS) of the disease were determined by assessing the severity of erythema/telangiectasia, and the number of papules/pustules of the whole face. The overall response rates, differences of pre-/post-treatment scores of each criterium and the percentages of the decrease in TSS of the study groups were compared statistically., Results: There was no statistically significant difference between the groups in terms of age, sex, and disease duration (P = 0.937, 1.000, and 0.055, respectively). No significant difference was found between the mean post-treatment TSSs of the two groups (P = 0.605). The percentage of clearance assessed by the differences between pre-treatment and post-treatment TSSs was 55% in terbinafine group, although the percentage was 45% in metronidazole group, with no statistically significant difference between the groups (P = 0.496). Local side effects including erythema, pruritus, and burning were mild and transient in both groups, with similar frequencies (P = 0.101)., Conclusion: This preliminary study suggests that 1% terbinafine cream is an effective and safe treatment for papulopustular rosacea, and can be an option for patients who cannot tolerate other modalities.

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 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 (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., Conclusions: The pharmacokinetic profile of metronidazole did not change at the different time points assessed during pregnancy.

In the present investigation metronidazole-loaded alginate beads consisting of calcium silicate as a porous carrier or NaHCO(3) as a gas-forming agent were prepared for local eradication of Helicobacter Pylori. Gelation method was used for preparation of conventional sodium alginate beads. Drug entrapment efficiency, drug loading, floating properties, drug release, crystallinity and release kinetic as well as morphology of the prepared beads were assessed. The silicate based beads showed slower release pattern, compared to the gas-forming beads due to network structure strengthening effect of the calcium silicate. Furthermore, the gas-forming-based beads had shorter initial buoyancy lag time, owing to the fact that the NaHCO(3) produced larger pores than those of silicate treated ones. Drug entrapment efficiency ranged between 61.7 and 93.1% for the prepared formulations. The maximum value of drug loading for gas-forming and silicate-based beads were 66.64% and 34.97%, respectively. Kinetically, release pattern of metronidazole in simulated gastric fluid from the beads fitted best to Reciprocal powered time, Weibull and log-probability models with the respect overall mean percentage error values of 4.50, 5.30 and 7.76. By and large, these systems can float in the gastric condition and control the drug release from the beads.

Background: Seborrhoeic dermatitis is a common, chronic, papulosquamous dermatosis. Treatment of seborrhoeic dermatitis includes topical treatments such as corticosteroids, antifungals, metronidazole and pimecrolimus., Objective: This study aimed to compare and contrast the efficacy and tolerability of pimecrolimus cream 1%, methylprednisolone aceponate 0.1% cream and metronidazole 0.75% gel topical treatments in the treatment of facial seborrhoeic dermatitis., Methods: The study included a total of 64 (32 males and 32 females) consecutive patients with facial seborrhoeic dermatitis. Patients were randomized into three equal groups. One group applied pimecrolimus 1% cream, another group applied methylprednisolone aceponate 0.1% cream, and the third group applied metronidazole 0.75% gel to their facial lesions twice daily for 8 weeks. Assessment of the disease severity was performed at baseline and at weeks 2, 4, and 8. Clinical measures assessed were erythema, scaling and pruritus, which were evaluated using a four-point scale (0-3)., Results: Of the 64 patients, 17 (80%) in the metronidazole group, 21 (100%) in the pimecrolimus group and 22 (100%) in the methylprednisolone aceponate group completed the study. Four patients in the metronidazole group left the study. All of the therapeutic agents were found to be effective; however, the efficacy of pimecrolimus was higher than those of metronidazole and methylprednisolone (p < 0.05). When side effects associated with pimecrolimus and metronidazole were compared, the latter was found to be associated with more side effects (p < 0.05)., Conclusions: We suggest pimecrolimus to be a therapeutic option for seborrhoeic dermatitis cases that show an unfavourable response to methylprednisolone aceponate.

Objective: To compare the effectiveness of single dose ceftriaxone versus multiple doses of ampiclox, gentamicin, and metronidazole to prevent infectious morbidity at elective cesarean section., Methods: This was a randomized clinical trial involving 200 pregnant women who had an elective cesarean section for various reasons during the study period. Outcome measures included endometritis, urinary tract infections, febrile morbidities, wound infections, duration of hospital stay, and cost of antibiotic therapy. Data were managed using SPSS., Results: There was no statistically significant difference in the mean duration of hospital stay between the two groups, but a significant statistical difference was found in the mean cost of antibiotic treatment ($15 for the combination and $9 for ceftriaxone; p = 0.000), with the group of patients taking a single dose of ceftriaxone (ROPHEX) having a lower mean cost of treatment than those taking a combination of ampiclox, gentamicin, and metronidazole. The study groups did not differ significantly in the incidence of endometritis (14% versus 15%), urinary tract infection (11% versus 15%), wound infections (7% versus 8%), febrile morbidity (7% versus 6%), and peritonitis (0% versus 0%)., Conclusion: Single dose ceftriaxone was as effective as a combination of ampiclox, gentamicin, and metronidazole in preventing post-elective cesarean section complications.

The effect of sodium bicarbonate (SB) on the swelling behavior and the sustained release of floating systems was studied with varied proportions of this excipient and metronidazole. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. Under in vitro dissolution conditions, the addition of SB to metronidazole sustained-release tablets modifies the matrix hydration volume, increasing at the beginning, reaching a maximum, and then declining. Pure Carbopol matrices show a rapid hydration with a limited further effect of the SB and metronidazole loads. Methocel show a significant increase of the apparent hydration volume due to SB addition with no further notable change due to metronidazole load. Increasing the metronidazole load reduces the floating time of Carbopol matrices while no effect on Methocel matrices could be observed within 8 hours dissolution. Matrices show increasing release constant values (k) as the metronidazole load increases. Methocel matrices release the drug 10% to 15% faster than Carbopol matrices. SB increases the cumulative amount of drug released from Methocel but not that releasing from Carbopol. These results are attributed to the intrinsic polymer properties, the barrier effect of CO(2) bubbles, and the matrix volume expansion produced after addition of SB.

A prospective, randomized, double-blind study was designed to compare Clostridium difficile immune whey (CDIW) with metronidazole for treatment of laboratory-confirmed, recurrent, mild to moderate episodes of Clostridium difficile-associated diarrhoea (CDAD). CDIW was manufactured by immunization of cows in their gestation period with inactivated C. difficile vaccine. The resulting colostrum was processed, immunoglubulins were concentrated and the end-product containing high titres of C. difficile immunoglobulin was used as CDIW. 20 patients received metronidazole at a dosage of 400 mg t.i.d. and 18 patients CDIW 200 ml t.i.d. The study was interrupted early because of the bankruptcy of the sponsor. After 14 d of treatment, all 20 (100%) of 20 patients had responded to metronidazole therapy, compared with 16 (89%) of 18 who had received CDIW. 70 d after the beginning of treatment, sustained responses were observed in 11 (55%) of 20 patients receiving metronidazole and 10 (56%) of 18 patients treated with CDIW. In this preliminary study CDIW was as effective as metronidazole in the prevention of CDAD recurrences and it was well tolerated.

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, beta-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations.

Large-scale chemoprevention of peptic ulcer disease and gastric cancer through eradication of Helicobacter pylori would expose large population groups to antibiotics, which raises concerns about possible dissemination of antibiotic resistance. The objective of this cohort study was to determine whether a triple therapy, containing omeprazole, clarithromycin, and metronidazole, of H. pylori infection increases the prevalence of macrolide resistance in the normal microbiota. 85 patients with a peptic ulcer disease with verified H. pylori infection and 12 dyspeptic patients without positive findings upon endoscopy were included. Minimal inhibitory concentrations of clarithromycin for Staphylococcus, Streptococcus, Enterococcus and Bacteroides spp. were determined from samples taken before and after treatment, and 1 y later. Before treatment, macrolide resistance was observed in 11%, 31%, 9% and 11% of the staphylococci, streptococci, enterococci and Bacteroides, respectively. The number of resistant isolates remained elevated after 1 y, most notably for staphylococci and streptococci. No development of persistent resistance was detected in the untreated control group. Triple therapy including clarithromycin leads to persistent macrolide resistance in the normal microbiota. A prevalent pool of resistance genes in the normal microbiota constitutes an ecological hazard that needs to be considered before global treatment programmes for eradication of H. pylori are implemented.

Introduction: Rosacea is a common and chronic disorder characterized by flushing, erythema, papules, pustules, and telangiectasia on the central part of the face. Because the facial skin of individuals with rosacea is particularly sensitive, irritants can trigger a worsening of the signs and symptoms of the disease. This enhanced sensitivity is thought to be linked to a deficient stratum corneum barrier function., Materials and Methods: In the present study, 20 individuals receiving twice-daily applications of metronidazole 0.75% gel for at least 15 days applied a gentle non-irritating moisturizing cream (Cetaphil Moisturizing Cream) twice daily for 15 days on one half of the face; the other side remained treated with metronidazole only and served as the control., Results: Clinical assessments, confirmed by biophysical measurements (electrical capacitance, transepidermal water loss (TEWL), and lactic acid stinging test), provided evidence that the moisturizer contributed to the restoration of the skin barrier: skin dryness, roughness and desquamation were much improved and skin sensitivity was significantly reduced. Skin properties and skin discomfort were also greatly enhanced and the patients were very satisfied with the product., Conclusions: It can thus be concluded that in the management of rosacea, basic skin care regimens, including daily use of a therapeutic moisturizer, offer optimal benefits.

In vitro dissolution of metronidazole from sustained release floating tablets was studied with varied proportions of sodium bicarbonate (SB) and Pharmatose DCL 11. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. The variables studied include the matrices' release profile, hydration volume, and floating behavior. All Methocel matrices floated more than 8 h with SB proportions up to 24%, while Carbopol matrices floated more than 8 h with SB proportions only up to 12%. Matrices' hydration increased with time until reaching a peak and declining thereafter. Methocel matrices showed greater hydration volumes and greater drug dissolution compared to Carbopol matrices. After adding increasing quantities of Pharmatose to matrices containing 12% SB, hydration volume decreased while dissolution increased. These results were attributed to water-filled pores that formed following the Pharmatose dissolution and to reduced polymer proportions. Carbopol matrices showed greater susceptibility to the added Pharmatose, becoming more erodible and releasing higher quantities of metronidazole. The greater Carbopol susceptibility to added Pharmatose was attributed to its faster hydration. Methocel matrices hydrate rapidly only at the surface, delaying hydration and Pharmatose dissolution.

Objective: Sulphate-reducing bacteria (SRB) have been implicated in the aetiology of ulcerative colitis. Sulphide produced from reduction of sulphate by SRB is highly toxic to colonocytes and can impair their metabolic function. The aim of this study was to investigate the modulation of the colonic bacterial flora using metronidazole and the prebiotic oligofructose on the concentration and activity of SRB., Material and Methods: Healthy volunteers were randomly allocated to take metronidazole (5 days), oligofructose (12 days) or both metronidazole (5 days) and oligofructose (12 days). At days 0, 5, 12 and 19, stool samples were cultured, and their pH measured; concentrations of sulphate, hydrogen sulphide, short-chain fatty acids (SCFAs) were measured and the sulphate reduction rates (SRRs) determined., Results: In SRB-positive volunteers (n=16) faecal SRB concentrations fell with metronidazole (95% CI, 2.19, 3.36 p<0.0001) even when combined with oligofructose (95% CI 2.32, 4.01 p<0.0001). Faecal anaerobe concentrations fell with metronidazole and bifidobacterial concentrations rose with oligofructose irrespective of SRB status. Faecal SRRs fell with metronidazole irrespective of the presence of faecal SRB (95% CI 29.0, 56.1 p<0.0001). No changes in faecal sulphate concentrations were seen. Faecal hydrogen sulphide concentrations fell with oligofructose in SRB-positive volunteers (95% CI 0.14, 0.53 p=0.002). Faecal SCFA concentrations fell with metronidazole (-103.7, -19.6, p=0.007) and rose with oligofructose (9.9, 83.1 p=0.016)., Conclusions: The study shows that metronidazole, but not oligofructose, reduced the concentration and activity of faecal SRB. This reduction had no impact on faecal concentrations of sulphate and hydrogen sulphide, suggesting that other methods of hydrogen sulphide production are more important. Oligofructose causes a reduction in faecal hydrogen sulphide, and an increase in SCFA concentrations may thus have a therapeutic role in patients with ulcerative colitis.

Dika nut mucilage obtained from the nuts of Irvingia gabonensis (O'Rorke) Bail (family Irvingiaceae) has been evaluated as a binding agent in metronidazole tablet formulations in comparison with gelatin BP. The compressional properties of metronidazole formulations were analyzed using density measurements and the Heckel equations as assessment parameters, whereas the mechanical properties of the tablets were assessed using the tensile strength (T), brittle fracture index (BFI), and the friability of the tablets. The drug release properties of the tablets were assessed using disintegration and dissolution times of the tablets. The results obtained indicate that formulations containing dika nut mucilage as binding agent show faster onset of plastic deformation under compression pressure than those containing gelatin. The tensile strength of the tablets increased with increase in concentration of the binding agents, whereas the BFI and friability values decreased. Furthermore, tablets containing dika nut mucilage generally showed lower tensile strength but higher brittleness and friability than those containing gelatin. The results also showed that tablets containing dika nut mucilage generally showed higher disintegration and dissolution times than those containing gelatin BP. The results suggest that dika nut mucilage could be useful in achieving various tablet strength and drug release properties.

Granulomatous cheilitis (GC) is a chronic edema which frequently affects the upper lip due to granulomatous inflammation. Its etiology is currently unknown. This rare disease is generally accompanied by Melkersson-Rosenthal syndrome (MRS), characterized by scrotal tongue, orofacial edema and facial paralysis. However, it is also known to develop only with orofacial edema. Granulomatous cheilitis is a difficult disease to treat because of recurrences. There are contradictory reports about the results of treatment without surgical intervention and the rates of recurrence. Our case was a 57-year-old female patient who was characterized by orofacial edema only. The edema and erythema had persisted for 1 year before admission. In the present case, application of intralesional corticosteroid treatment as a total of three injections over 3 consecutive months (one injection per month) and the accompanying metronidazole treatment brought about successful results. No recurrence was observed in the follow-up.

Various approaches for colon targeted drug delivery have been studied over the last decade including, pro-drugs, timed-released systems, coating of pH-dependant polymer and the use of polysaccharides. In the present work, a novel formulation consisting of cross-linked microspheres of guar gum has been investigated for colon-targeted delivery of metronidazole. An emulsification method involving the dispersion of aqueous solution of guar gum in castor oil was used to prepare spherical microspheres. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Placebo microspheres exhibited a smooth surface while the incorporation of drug imparted a slight roughness to the surface texture. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The in vitro drug release studies were performed in simulated gastric fluid for 2 h and intestinal fluid for 3 h, which revealed that the drug was retained comfortably inside the microspheres and that only 15.27+/-0.56% of the drug was released in 5 h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat cecal contents, which showed improved drug release. Moreover, to induce the enzymes that specifically act on guar gum, the rats were treated with 1 ml of 1% w/v dispersion of guar gum for 2, 4 and 6 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of cecal matter. A marked improvement in the drug release was observed in presence of cecal matter obtained after induction when compared to those without induction. In vitro release studies exhibited 31.23+/-1.49% drug release in 24 h in dissolution medium without rat cecal matter. However, the incorporation of 4% w/v cecal matter obtained after 6 days of enzymes induction increased the drug release to 96.24+/-4.77%.

Due to the development and release of newer topical formulations, the diagnosis and treatment of rosacea has received renewed attention over the past 3-5 years both in the literature and at medical symposia. Rosacea is a very common facial dermatosis. In the US, rosacea is estimated to affect > 14 million people, predominantly adults with approximately 60% of cases diagnosed before the age of 50. A frustrating aspect of the disease is its inherent chronicity punctuated with periods of exacerbation and relative remission. A variety of subtypes have been identified which correlate with clinical presentation. Although the pathogenesis of rosacea is poorly understood, multiple topical agents are available. The efficacy of topical therapy for rosacea relates primarily to reduction in inflammatory lesions (papules, pustules), decreased intensity of erythema, a reduction in the number and intensity of flares and amelioration of symptoms, which may include stinging, pruritus and burning. The list of main topical agents utilised for the treatment of rosacea include metronidazole, sulfacetamide-sulfur, azelaic acid and topical antibiotics (clindamycin, erythromycin). Depending on the severity at initial presentation, topical therapy may be combined with systemic antibiotic therapy (e.g., oral tetracycline derivative). Newer therapeutic choices primarily involve improved vehicle formulations, which demonstrate favourable skin tolerability and cosmetic elegance.

The focus of the article is on a generic approach to prediction of a healing process based on automatic measurement and modelling of mechanical disease indicators. As a specific example the healing process after treatment of advanced periodontitis is characterised and predicted based on measurement of tooth mobility (TM). For the measurement a new mechatronic instrument was developed that includes a pneumatically driven probe with incorporated sensors of tooth displacement and loading force. TM is measured by a computer controlled data acquisition system and predicted by a non-parametric regression. Similarly as in the characterisation of technical processes, a measured sample is described by TM time series detected on a particular patient, while the regression is determined by a set of samples obtained from a group of patients following periodontal therapy. The influence of surgical access therapy and systemic administration of metronidazole as an adjunct to the mechanical treatment is demonstrated. For this purpose the average changes of tooth mobility are determined on variously treated subgroups. A new method of healing process prediction is demonstrated and its performance is described by a prediction quality.

Vaginal suppository formulations of metronidazole were prepared using six different bases as Witepsol H15, Cremao, Ovucire WL2944, Ovucire WL3264, PEG 1500, PEG 6000. Three different dissolution methods were used to evaluate the in vitro drug release from the suppositories. The diffusion studies were performed through synthetic (cellophane) and natural membrane (rabbit vagina), but the drug did not show good permeation characteristics from natural membrane. Ovucire WL3264 suppositories of metronidazole labeled with 99mTc (Tecnetium-99m) were used for the vaginal absorption and biodistribution studies in the rabbits. Scintigraphic images were collected after vaginal administration of the labeled suppositories using SPECT gamma fitted with a low energy, high-resolution parallel hole collimator. The labeled drug showed high biodistribution in urine beside vaginal site. The results of this study suggested that the Ovucire WL3264 suppository of metronidazole prepared for vaginal infections could also be effective in the urinary infections.