Biocompatible chitosan-pectin polyelectrolyte complex for simultaneous electrochemical determination of metronidazole and metribuzin.

Development of novel biocompatible sensor material suitable for modest, cost-effective, and rapid practical application is a demanding research interest in the field of electroanalytical chemistry. In this context, for the first time, we utilized biocompatible chitosan-pectin biopolyelectrolyte (CS-PC BPE) complex for the simultaneous electroreduction of an important antibiotic drug (metronidazole-MNZ) and herbicide (metribuzin-MTZ). This sensor reveals an attractive welfares such as simplicity, biocompatibility, and low production cost. Under optimized experimental conditions, the electroanalytical investigation confirmed that CS-PC BPE modified glassy carbon electrode (CS-PC BPE/GCE) was found to sense MNZ and MTZ in the nanomolar range. Moreover, as-prepared CS-PC BPE/GCE exhibited prominent selectivity, stability, and reproducibility. Additionally, the possible MNZ and MTZ sensing mechanism of CS-PC BPE/GCE have been discussed in detail. Lastly, real sample analysis was also carried out and revealed from several investigations that the CS-PC BPE/GCE is a good electrochemical sensor system for the detection of targeted analytes.

Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery.

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859 .

Uptake of metronidazole by human gingival fibroblasts.

BACKGROUND: Metronidazole is an important antimicrobial agent for the therapeutic management of periodontal diseases and dentoalveolar infections. As in other tissues, the metronidazole concentration in gingival crevicular fluid is about equal to the plasma level. Thus, we hypothesized that metronidazole is not actively transported into human gingival fibroblasts. METHODS: Using high performance liquid chromatography, the influences of extracellular metronidazole concentrations, temperature, pH, and inhibitors of transporters on the uptake of metronidazole by cultured human gingival fibroblasts were tested. RESULTS: Metronidazole was taken up rapidly by fibroblasts; the intracellular metronidazole concentration reached the extracellular level in 3 minutes at 37 degrees C and in 2 minutes at 4 degrees C. The uptake of metronidazole by human gingival fibroblasts was not saturable, and the intracellular metronidazole concentrations increased linearly with the extracellular level. Temperature and pH had no significant influence on the uptake of metronidazole by fibroblasts. Probenecid and adenine had no influence on the uptake of metronidazole by fibroblasts. These findings indicate that metronidazole uptake does not involve a transporter. Metronidazole bound rapidly to human gingival fibroblasts, but the cell-associated drug declined progressively until it reached a stable plateau in 15 minutes. CONCLUSIONS: Metronidazole rapidly entered human gingival fibroblasts via simple diffusion. Metronidazole easily reached the minimal inhibitory concentration in fibroblasts and gingiva. Given the fact that intracellular concentrations of metronidazole in other tissues and cells are also close to the plasma level, we speculate that metronidazole enters other tissues and cells via simple diffusion.

Metronidazole clearance: a one-sample method and influencing factors.

After 96 administrations of metronidazole to 36 subjects, it was found that the clearance could be determined from one plasma sample, the dose, and a volume of distribution estimated from sex, age, body weight, and height, without loss of precision and accuracy compared with conventional clearance determinations (r greater than 0.97). In 230 sample pairs the plasma and saliva concentrations of metronidazole were identical (r = 0.99). In 119 subjects the one-sample clearance of metronidazole was unimodally distributed. Body weight (r = 0.28) and the alcohol consumption (r = 0.23) correlated with the metronidazole clearance. In the same subjects the consumption of tobacco (r = 0.28), alcohol (r = -0.19), coffee/tea (r = 0.27), age (r = -0.24), and sex (r = 0.28) correlated with the antipyrine clearance. The clearances of metronidazole and antipyrine were correlated (r = 0.34). The differential influence of the environmental factors on the elimination rates supports differential metabolism of metronidazole and antipyrine.

[Antimicrobial chemoprevention in colorectal interventions: a single parenteral dose at the start of surgery is adequate]. / Antimikrobielle Chemoprophylaxe bei colorectalen Eingriffen: Parenterale Einmalgabe bei Operationsbeginn ausreichend.

The effectivity in reducing septic complications after colorectal operations of oral 1 g Neomycin plus 0.25 g Metronidazol t.i.d. on the last preoperative day vs. intravenous single dose 5 g Mezlocillin plus 0.5 g Metronidazole was tested by sequential medical plan. There was no statistically significant difference between both chemoprophylaxis groups (p = 0.10). It is concluded that the intravenous chemoprophylaxis should be preferred because of the lowest dosage and therefore the fewest side-effects.

[Accumulation of metronidazole in tumors during whole-body hyperthermia induced by Sulfazin]. / Nakoplenie metronidazola v opukholi pri obshchei gipertermii, vyzvannoi sul'fazinom.

A study was made of metronidazole accumulation in the blood of animals and tumorous tissues of Pliss lymphosarcoma after the total moderate hyperthermia caused by subcutaneous injection of the pyrogenic drug sulfadiazine. Metronidazole concentration in the blood and tumors of hyperthermized animals was 2-3 times as high as in those of the control animals. A time shift of the maximum values of metronidazole accumulation occurred in hyperthermia. Under normal conditions the peak of accumulation was observed 2 h after the administration of the radiosensitizer whereas in hyperthermia depending on its duration it could develop 1 h earlier. Thus the total moderate hyperthermia served as a favorable background for raising metronidazole concentration in tumor opening up prospects for potentiating the radiosensitizing effect of metronidazole and perhaps some other means in the utilization of small nontoxic doses of the drug.

[Radiosensitization with metronidazole. Pharmacocinetical comparison by means of blood level curves after administration of "metronidazol" in the form of tablets, suppositories, and enemas (author's transl)]. / Strahlensensibilisierung mit Metronidazol. Pharmakokinetischer Vergleich an Hand von Blutspiegelkurven nach Verabreichung von Metronidazol in Form von Tabletten, Suppositorien und Klistier.

Severe acute gastrointestinal side-effects following high oral doses of metronidazole (6 g/m2) could be avoided by a combined oral and rectal application. With tablets and an enema (1 g metronidazole/2 ml) in a ratio 1:4 and an increased dosage of 10 g/m2, maximal serum concentrations of about 200 micrograms/ml are obtained like after an oral dosage of 6 g/m2. The maximal radiosensitizing effect on hypoxic tumor cells is seen five hours after oral application and seven hours after the combined oro-rectal application. No longterm toxicity was found following six high doses of metronidazole.

Effect of antibiotics on the prevention of experimental Bacteroides fragilis endocarditis.

The relative efficacy of single doses of antibiotics in modifying the development of Bacteroides fragilis subsp. fragilis endocarditis was studied in an experimental model. Antibiotics were administered 0.5 h before intravenous injection of B. fragilis subsp. fragilis into rabbits prepared by insertion of a polyethylene catheter into the left side of the heart; 48 h later, intracardiac vegetations were excised and cultured anaerobically. B. fragilis was recovered from 92% of untreated animals. After a single dose of procaine penicillin G (250 mg/kg intramuscularly), 80% of the animals remained infected. Chloramphenicol (30 mg/kg), carbenicillin (50 mg/kg), and metronidazole (10 mg/kg) were also ineffective (76, 80, and 75% infected, respectively). Cefamandole (30 mg/kg), cefoxitin (30 mg/kg), and erythromycin (30 mg/kg) were significantly more active (50, 55, and 45% infected, respectively), as were higher doses of carbenicillin. Clindamycin (50 mg/kg) was the most effective regimen (11% infected). At present, the relevance of these results to the therapy of serious B. fragilis infections is not known, but this model may prove useful in the evaluation of the prevention of B. fragilis subsp. fragilis bacteremia.

Metronidazole retention enema in the management of severe intestinal amoebiasis.

Metronidazole is a drug of proven efficacy in amoebiasis; however its use is restricted in patients who cannot take the drug by mouth, because of severe complications of the disease. Preliminary studies in eight control subjects show that rapid absorption and high serum levels are achieved after rectal administration of 2 gm. of metronidazole in 200 ml. of normal saline. Six patients with severe intestinal amoebiasis treated with metronidazole retention enema are presented, and they illustrate the efficacy of the new method of therapy. The efficacy of metronidazole in anaerobic bacteriodes infection and its proven amoebicidal effcet also indicate the possible use of the metronidazole retention enema technique in bowel preparation for colonic surgery in developing countries.