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PubMed2006

Systematic review: antimicrobial urinary catheters to prevent catheter-associated urinary tract infection in hospitalized patients.

BACKGROUND: The efficacy of antimicrobial urinary catheters in hospitalized patients is poorly defined. PURPOSE: To assess currently marketed antimicrobial urinary catheters for preventing catheter-associated urinary tract infection (UTI). DATA SOURCES: Electronic databases, conference proceedings, bibliographies, trialists, and catheter manufacturers (search dates, 1966 to June 2005). STUDY SELECTION: Randomized and quasi-randomized trials of nitrofurazone-coated or silver alloy-coated antimicrobial urinary catheter use for less than 30 days; no language restriction. DATA EXTRACTION: Study design, study sample, inclusion and exclusion criteria, allocation, blinding, UTI definition, ascertainment methods, and proportion developing symptomatic UTI (primary end point) or bacteriuria (secondary end point) were extracted by using a structured data collection instrument. DATA SYNTHESIS: Twelve qualifying trials (13,392 total participants or catheters) were identified. They compared nitrofurazone-coated silicone (n = 3) or silver-coated latex (n = 9) catheters with silicone or latex catheters. No study addressed symptomatic UTI. All trials suggested protection against bacteriuria with test catheter use. However, effect size varied considerably and postrandomization exclusions were very common. Effect size was greatest in trials of nitrofurazone-coated catheters (all post-1995) and in pre-1995 silver alloy-coated catheter trials and was smallest in post-1995 silver alloy-coated catheter trials. Control group bacteriuria rate, control catheter type (latex vs. silicone), and patient sample (urology vs. other) also predicted effect size. Few studies addressed secondary bloodstream infection, mortality, costs, or microbial resistance. Short-term adverse effects were minimal. LIMITATIONS: The study was limited by the number, size, and quality of studies and by lack of the following: intention-to-treat analyses, data on clinical end points, and trials comparing nitrofurazone-coated with silver alloy-coated catheters. CONCLUSIONS: According to fair-quality evidence, antimicrobial urinary catheters can prevent bacteriuria in hospitalized patients during short-term catheterization, depending on antimicrobial coating and several other variables. Older data probably lack current relevance. Cost implications and effect on infectious complications remain undefined.

Anti-Infective Agents, Urinary↗

PubMed1979

Action of nitrofurans on E. coli: mutation and induction and repair of daughter-strand gaps in DNA.

The antibacterial and mutagenic potency of 9 nitrofurans in "treat and plate" experiments varied over almost 5 orders of magnitude. The relative toxicities were as follows: FANFT greater than AF2 greater than ANFT greather than furazolidone greater than furagin greater than nitrofurantoin greater than nitrofurazone greater than methylnitrofuroate greater than nitrofuroic acid. In general, mutagenic activity paralleled toxicity. The compounds at concentrations corresponding to their LD50's, induced mutations at frequencies which ranged from 2.5/10(6) survivors for FANFT to 130/10(6) survivors for furagin (NF416). The observed differences in antibacterial and mutagenic activity are unlikely to be due to lack of activation of the weaker agents since the two most potent agents were reduced somewhat more slowly than many of the less active agents. The relative sensitivities to the antibacterial effects of AF2 of strains WP2, WP2 uvrA, CM561 (lexA) and CM571 (recA) were 1 : 1.6 : 3 : 7 and to nitrofurazone 1 : 1 : 25 : 50. The wvrA strain was 6--7-fold more mutable with both these agents than was WP2. No increase over the spontaneous mutation frequency was observed when recA or lexA strains were exposed to either AF2 or nitrofurazone in these experiments. When wild-type of wvrA bacteria containing nitrofuran-induced lesions replicated their DNA in drug-free medium in the presence of [3H]thymidine for 5 min, the label was found in low molecular weight DNA indicating that daughter-strand gaps were formed. During subsequent incubation in nonradioactive medium the molecular weight of the DNA increased to the control value. A recA strain (which was very sensitive to the lethal effects of AF2 and nitrofurazone) lacked the ability to repair daughter-strand gaps caused by nitrofuran-induced lesions.

DNA Repair↗

PubMed1964

INFECTION AND HEALING IN SUPERFICIAL WOUNDS. A COMPARATIVE CLINICAL STUDY OF TOPICAL TREATMENT METHODS.

The comparative value of nitrofurazone-hydrocortisone cream, of saline solution soaks and of a dry method of care in preventing or curing surface infections was studied in 86 patients. Of a total of 117 discrete lesions treated, 59 were infected, most of these being chronically infected decubital ulcers in paraplegic patients. The other lesions were burns, avulsive and wringer injuries, orthopedic surgical wounds and various abrasions. Excellent results were obtained with the nitrofurazone-hydrocortisone cream in infected lesions: infection rapidly cleared in all 37 lesions treated although only 29 healed completely and promptly. Five lesions were improved, and in three instances healing was unduly delayed. Among 22 infected lesions treated twice daily with saline solution soaks, only five were cured, two improved, seven had delayed healing, and eight had no improvement. In the non-infected wounds, saline soaks or plain dry care after surgical debridement and hexachlorophene cleansing gave results generally more comparable to those obtained in similar cases treated with the nitrofurazone-hydrocortisone cream.

Administration, Topical↗

PubMed1978

Influence of antimicrobial agents on contamination and chlortetracycline production.

The possibility of shortening the thermal sterilization time for cultivating media was demonstrated in chlortetracycline fermentation with an industrial strain of Streptomyces aureofaciens. The medium was artificially contaminated with a mixture of eight strains of G+ and G- bacteria isolated from contaminated industrial fermentors, and the following chemical agents, either alone or in combination, were added: formaldehyde, phenol. dimethylformamide, p-aminosalicylic acid and nitrofurazone. Dimethylformamide was inhibitory even at 0.08%. formaldehyde concentrations higher than 0.05%, Nitrofurazone stimulated chlortetracycline production. The best combination was 0.01% formaldehyde added before, and 2.10-3% nitrofurazone added after short sterilization at 120 degrees C.

Aminosalicylic Acid↗

PubMed2004

Novel source of semicarbazide: levels of semicarbazide in cooked crayfish samples determined by LC/MS/MS.

Nitrofuran antibiotics were previously used in animal healthcare but are now prohibited. Semicarbazide is a breakdown product of 5-nitrofurazone and protein-bound semicarbazide is used as a marker residue for the illegal use of 5-nitrofurazone. However, the presence of the prohibited semicarbazide has been reported in some food items of animal origin. A novel observation is reported that semicarbazide can be detected in Finnish crayfish samples, i.e. crustacea, never medicated with nitrofurazone. The origin of the semicarbazide is presently unknown. Positive identification was undertaken by liquid chromatography coupled with tandem mass spectrometry detection. The level of semicarbazide was determined as the protein-bound form as well as the total amount of semicarbazide in the sample. The average levels of total semicarbazide and the protein-bound form were 4.2 and 0.5 ng g(-1) fresh crayfish meat, respectively. All the tested samples (n = 18) contained traces of semicarbazide, the highest amount being 12 ng g(-1) fresh crayfish meat.

Animals↗

PubMed1990

Electrochemical characteristics of nitroheterocyclic compounds of biological interest. V. Measurement and comparison of nitro radical lifetimes.

Using mixed aqueous/dimethylformamide solvents we have generated nitro radical anions by electrochemical reduction of nitroaromatic compounds. Six drugs have been examined: metronidazole, nitrofurazone, nifuroxime, chloramphenicol, M&B 4998 and 4(5)-nitroimidazole, chosen to represent a variety of ring structures and a range of reduction potentials. Analysis of the cyclic voltammetric response as a function of scan rate and dimethylformamide content yields information on the reactivity of RNO2.-. A kinetic analysis of the return-to-forward peak current ratio based on a theoretical treatment was employed. Second-order kinetics for the decay of RNO2.- for all six drugs examined was established. By extrapolation, first half-lives in purely aqueous media were found to increase in the order: nitrofurazone, nifuroxime, chloramphenicol, metronidazole and M&B 4998 (from 8.9 x 10(-2) seconds for nitrofurazone to 98s for M&B 4998 at a radical anion concentration of 1 x 10(-6) mol/dm3). Comparison with reduction potentials showed that as the lifetime of RNO2.- increased, the drug became progressively less electron-affinic (reduced at more negative potentials). The reactivity of RNO2.- was also examined in relation to the DNA damaging capability following electrochemical reduction of these nitroaromatic drugs.

Chloramphenicol↗

PubMedDate not supplied

In vitro susceptibility testing of topical antimicrobial agents used in pediatric burn patients: comparison of two methods.

One hundred and seventy-seven bacterial isolates obtained from pediatric burn victims were tested for in vitro susceptibility against bacitracin, silver sulfadiazine, mafenide acetate, nitrofurazone, and mupirocin by two methods: standard microbroth dilution and Nathan's agar well diffusion (NAWD). Nitrofurazone had the broadest spectrum of activity. Mupirocin was the most potent agent against methicillin-susceptible Staphylococcus aureus. Silver sulfadiazine showed activity against gram-positive organisms and higher minimum inhibitory concentration (MIC) values, and smaller zone sizes were seen for methicillin-resistant S. aureus and gram-negative bacilli. Bacitracin showed activity against S. aureus and Streptococcus pyogenes by the microbroth method; activity could not be assessed by NAWD. Mafenide acetate had the highest MICs for all isolates tested. Correlation between methods for all isolates tested was best for mupirocin and nitrofurazone. NAWD was labor intensive and difficult to interpret; MIC method was easy to perform and reproducible. Clinical correlation is necessary to establish breakpoints for interpretation of test results.

Administration, Topical↗

PubMedDate not supplied

Effect of selected antibiotics and anticoccidials on Salmonella enteritidis cecal colonization and organ invasion in Leghorn chicks.

One-day-old leghorn chicks were placed in floor pens on previously used poultry litter (potentially providing exposure to normal chicken enteric flora) for 7 days and provided feed containing one of several antibiotics or anticoccidials. On day 7, all groups were challenged orally with an isolate of Salmonella enteritidis (10(6) colony-forming units) that was resistant to bacitracin, novobiocin, nalidixic acid, and nitrofurazone. All chicks were killed on day 13, and liver, spleen, and cecal tonsils were cultured. Dietary administration of novobiocin (0.385 g/kg) caused a significant increase (P < 0.05) in positive chick colonization rate (either liver and spleen or cecal tonsils) compared with the unmedicated controls. Similarly, chicks administered dietary nitrofurazone (0.3 g/kg) were infected with S. enteritidis at a significantly greater frequency than the unmedicated controls. A significant decrease in cecal volatile fatty acid concentration, previously shown to influence susceptibility to selected enteric pathogens, was observed in the novobiocin- and nitrofurazone-treated groups. Treatment with chlortetracycline (11.4 g/kg), monensin (0.91 g/kg), or nicarbazin (0.49 g/kg) had no effect on S. enteritidis invasion or colonization. Bacitracin (0.49 g/kg) significantly increased S. enteritidis cecal colonization rate when administered continuously throughout the study. These data support and extend previous investigations involving other salmonellae and indicate that selected antibiotics may increase the severity and frequency of S. enteritidis colonization and invasion rate in leghorn chicks.

Animals↗

PubMed1976

[The development of antibiotics resistance among Salmonella bacteria of animal origin in the Federal Republic of Germany and Berlin (West). 3rd Communication: 1972 Annual Report (author's transl)].

2273 Salmonella strains received from veterinary laboratories in the Federal Republic of Germany including Berlin (West) in 1972 were examined for their resistance against tetracyclines, ampicillin, chloramphenicol, kanamycin, nitrofurazone, and furazolidone. 13.3% of the strains studied were found to be resistant to one or more of these antibacterial substances. The proportion of resistant strains was 37.5% for S. typhimurium (excluding var. copenhagen), 3.1% for S. typhimurium var. copenhagen and 57% for S. panama. 79.8% of resistant strains were found to belong to these types. From 303 resistant strains found, resistance determinants were present in 87.4% to tetracyclines, in 37.2% to ampicillin, in 15.8% to chloramphenicol, in 4.6% to kanamycin, in 0.9% to furazolidone, and in 1.3% to nitrofurazone. 16 combinations of resistance determinants were found to occur 95.0% of strains transmitted resistance to E. coli K-12. A transmission of resistance determinants to furazolidone and nitrofurazone could not be demonstrated. Resistance patterns differed considerably from one serotype to another.

Ampicillin↗

PubMed1976

[The development of antibiotics resistance among slamonella bacteria of animal origin in the Federal Republic of Germany and Berlin (West). 4th Communication: 1973 Annual Report (author's transl)].

2894 salmonella strains received from veterinary laboratories in the Federal Republic of Germany including Berlin (West) in 1973 were examined for their resistance against tetracyclines, ampicillin, chloramphenicol, kanamycin, nitrofurazone, and furazolidone. 24.4% of the strains studied were found to be resistant to one or more of these antibacterial substances. The proportion of resistant strains was 63.9% for S. typhimurium (excluding var. copenhagen), 6.5% for S. typhimurium var. copenhagen and 51% for S. panama. 81.3% of resistant strains were found to belong to these types. From 708 resistant strains found, resistance determinants were present in 92.9% to tetracyclines in 27.9% to ampicillin, in 22.0% to chloramphenicol, in 13.6% to kanamycin, in 1.4% to furazolidone, and in 1.7% to nitrofurazone. 20 combinations of resistance determinants were found to occur 90.9% of strains transmitted resistance to E. coli K-12. A transmission of resistance determinants to furazolidone and nitrofurazone could not be demonstrated. As in the preceding years, there was a clear difference of resistance patterns from one serotype to another.

Ampicillin↗

PubMed2003

Development of new hydroactive dressings based on chitosan membranes: characterization and in vivo behavior.

Different poly(vinyl alcohol) (PVA)/chitosan lactate (ChL)-blended hydrogels containing nitrofurazone as a local anti-infective drug were prepared by the phase-inversion technique. The swelling degree, surface free energy, mechanical properties, and nitrofurazone release of these membranes were determined. Blood compatibility of these systems was evaluated by the open-static platelet adhesion test with whole human blood. The results showed that water absorption into the PVA/ChL membranes slowed down, governed by the rate at which the dressing interacted with the physiological fluid. Swelling degree values up to 200% were observed. The rate of release of nitrofurazone seemed to depend on the ChL percentage on the blend as well as the pH of the solution. The surface free energy values were in the range of 20-30 dynes/cm, which was appropriate for a favorable interaction with blood. From the Young's module curve, it could be seen that elastic hydrogels were obtained with increment of ChL in the PVA/ChL blends. Values of platelet adhesion and whole blood clotting times for the PVA/ChL blends as well as the increase of ChL, which appears to reduce the fibrinogen adsorption on the PVA/ChL membranes, demonstrated that the blood compatibility of PVP/ChL blends is superior to that separated polymers. The results of in vivo experiments in rats were in very good agreement with these observations, suggesting that PVA/ChL may serve as a new type of potential wound-dressing material.

Bandages↗

PubMed1977

Cytotoxicity and DNA damage to mammalian cells by nitrofurans.

Nitrofurazone, nitrofurantoin, furazolidone, furaltadone and N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) were toxic to cultured mouse L cells. The extent of toxocity and the rate of reduction of nitrofurazone increased markedly as the oxygen content of the incubation medium was lowered. The toxic effect of nitrofurans was decreased by addition of serum and was much greater in phosphate-buffered saline containing glucose (PSG) than in medium. Damage to L cell DNA by nitrofurans increased as the oxygen concentration decreased from 21% to 0%. The concentration of nitrofurazone and duration of exposure also determined the number of DNA single-strand breaks. It is suggested that toxicity and DNA damage may result from the actions of toxic intermediates in the metabolic reduction of nitrofurans.

Cell Survival↗

PubMed1984

Metabolism of 1,8-dinitropyrene by Salmonella typhimurium.

Earlier work has shown that many nitroaromatic and nitroheterocyclic compounds are directly 'activated' to their ultimate mutagenic forms through the action of bacterial nitroreductase enzymes. However, in the case of 1,8-dinitropyrene (DNP) and certain other nitroarenes the pathway of activation is more complex and neither the identity of the ultimate mutagens nor the nature of the DNA adducts formed are known. We now show that Salmonella typhimurium strains TA98 and TA1538, which are sensitive to DNP and have wild type nitroreductase complements, do metabolize DNP to 1-amino-8-nitropyrene (ANP) and 1,8- diaminopyrene (DAP) but that these compounds are much weaker mutagens than DNP. These two strains (TA98 and TA1538) contain two separable components of nitroreductase activity as determined using nitrofurazone as the substrate. The major component, at least, is capable of reducing both 1-nitropyrene (NP) and DNP although the rates are much lower than with nitrofurazone. TA98NR , a mutant of TA98 that is resistant to nitrofurazone and NP but not to DNP, lacked the major nitroreductase but retained two minor components. In contrast, a mutant ( DNP6 ) which is resistant to DNP (but not to NP) contained a full complement of nitroreductases. When the metabolism of [3H]DNP by crude extracts of TA98 was re-examined, previously undetected metabolites were found. These were more polar than DAP and ANP and were also seen when TA98NR was used as the source of enzyme. These metabolites were not formed when enzymes from TA98DNP6 or TA98NR / DNP6 were used. This work supports the notion that some enzymic activity other than (or in addition to) nitroreductase is required for the activation of DNP and that the new polar metabolites may be related to this process.

Chromatography, High Pressure Liquid↗

PubMed2005

Effect of low-level laser therapy on the healing of second-degree burns in rats: a histological and microbiological study.

This paper presents the results of a study on the effects of two different doses of low-level laser therapy on healing of deep second-degree burns. Sixty rats were randomly allocated to one of four groups. A deep second-degree burn was inflicted in each rat. In the control group burns remained untreated; in two laser treated groups the burns were irradiated daily with low-level helium-neon laser with energy densities of 1.2 and 2.4 J/cm2, respectively. In the fourth group the burns were treated topically with 0.2% nitrofurazone cream every day. The response to treatments was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at Day 15. The number of macrophages at day 16, and the depth of new epidermis at day 30, was significantly less in the laser treated groups in comparison with control and nitrofurazone treated groups (P=0.000). Staphylococcus epidermidis was found in the 70% of rat wounds in the laser treated groups in comparison with 100% of rats in the control group. S. aureus was found in the 40% rat wounds in the nitrofurazone treated group, but there was not found in the wounds of laser treated, and control groups. It is concluded that low-level laser therapy of deep second-degree burn caused significant decrease in the number of macrophage and depth of new epidermis. In addition, it decreased incidence of S. epidermidis and S. aureus.

Animals↗

PubMed1961

Observations on the production of pyrogenic substances by rabbit and human leucocytes.

1. The mechanism of release of a pyrogen from leucocytes has been studied in cells obtained from sterile rabbit peritoneal exudates and from rabbit blood. Attempts were made to induce human leucocytes-from blood-to release a pyrogen. 2. Rabbit leucocytes, kept below 4 degrees C., were not pyrogenic and did not release any pyrogen when disintegrated. Incubating such cells, in various media, at 37 degrees C. led to the formation of a pyrogen which was heat-labile. The maximum yield was attained after 1(1/2) hours' incubation. 3. The formation of rabbit leucocytic pyrogen was prevented by freezing and thawing the leucocytes, by heating them to 56 degrees C. for half an hour before incubation, and by ageing them in the cold. 4. Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) prevents the formation of leucocytic pyrogen when given by mouth to the cell-donor animals, or when added to leucocytes in intro. 5. Leucocytes from rabbit blood formed leucocytic pyrogen, on incubation in saline, and this formation was also inhibited by nitrofurazone. 6. No leucocytic pyrogen was released from human leucocytes subjected to mechanical, osmotic, or thermal damage, and it was not formed when the cells were incubated in saline. 7. The source of rabbit leucocytic pyrogen, the action of nitrofurazone on leucocytes, and the supposed role of leucocytic pyrogen in fever are discussed.

Animals↗

PubMedDate not supplied

Delivery and activity of antimicrobial drugs released from human fibrin sealant.

Engraftment and healing of native or cultured skin grafts depend on adherence, vascularization, and control of microbial contamination in the wound bed. Fibrin sealant is a biocompatible polymer that may be used to promote skin engraftment by serving as a delivery vehicle for antimicrobial drugs. Human fibrin sealant (25 mg/ml) was polymerized with antibacterial agents (mupirocin [32 micrograms/ml], nitrofurazone [0.02% wt/vol], polymyxin B [400 U/ml], or norfloxacin [20 micrograms/ml]) on nitrocellulose (nc) backing and was prepared as 6 mm diameter discs with skin punches. Discs (n = 6) were applied in the Wet Disc Assay to clinical isolates of Staphylococcus aureus (mupirocin, nitrofurazone) or Pseudomonas aeruginosa (polymyxin B, norfloxacin). Controls included drug applied to 6 mm paper discs (25 microliter) and nitrocellulose discs submerged in each drug, blotted, and applied to bacterial cultures on agar in petri dishes. Data were expressed as zone of clearing (mm diameter +/- SEM) after overnight incubation at 35 degrees C. Significant differences (ANOVA and Turkey's test, p < 0.05) were found for each drug released from the disc of fibrin sealant compared with other vehicles. Release from filter paper discs compared with nitrocellulose was significant for nitrofurazone and norfloxacin. Serial transfer of fibrin discs to fresh bacterial cultures after 24 hours showed no zones of clearing. The data show that fibrin sealant releases topical drugs with no inhibition of antimicrobial activity on burn organisms. Greater zones of clearing from fibrin sealant may result from passive fluid retention or from active binding to fibrin followed by protease digestion by burn organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

PubMed1977

[The development of antibiotics resistance among Salmonella bacteria of animal origin in the Federal Republic of Germany and Berlin (West). 5th communication: 1974 Annual report (author's transl)].

2713 salmonella strains having been isolated by veterinary laboratories in the Federal Republic of Germany including West Berlin in 1974 were tested for resistance to tetracyclines, ampicillin, chloramphenicol, kanamycin, gentamycin, furazolidone, nitrofurazone, and trimethoprim. 21.7% of the strains tested were resistant to one or several of the antibacterially effective substances examined. The proportion of the resistant strains amounted to 52% for S. typhimurium and 4.7% for S. typhimurium var. copenhagen, 16.8% for S. enteritidis, and 22.1% for S. panama, 85.1% of all resistant strains belonged to these types. Out of 589 resistant strains found, resistance determinants were present in 93.7% to tetracyclines, 34.6% to ampicillin, 32.4% to chloramphenicol, 25.3% to kanamycin, 3.4% to furazolidone, and 0.5% to nitrofurazone. 1 strain of S. typhimurium var. copenhagen had a transmissible determinant of resistance to trimethoprim. No strain was resistant to gentamycin. 93.4% of the strains transmitted resistance determinants to E. coli K-12. A transmission of resisance to furazolidone and nitrofurazone could not be demonstrated. The serotypes were exhibiting clear-cut differences in their resistances patterns.

Animals↗

PubMed1980

Formation and excision of nitrofuran-DNA adducts in Escherichia coli.

When Escherichia coli were incubated with the strong mutagen 2[14C]2-amino-4-(5-nitro-2 furyl)-thiazole (ANFT) radioactivity became tightly and presumably covalently bound to DNA. Hydrolysis of the DNA with nucleases yielded low molecular weight radioactive material. The bound radioactivity was associated with at least two functionally and chemically distinct adducts. One of these was rapidly removed in uvr+ E. coli while the other was more persistent. Analysis of enzymatic hydrolysates on a Dowex AG 50W-X4 column showed that the 'excisable adducts' were chromatographically different from most of the persistent ones. ANFT caused daughter-strand gaps when the DNA of treated cells was replicated, provided this DNA contained excisable adducts. In situations where removal of these adducts was complete no gaps were found in newly synthesized DNA. 3-[14C]2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (AF2) (another strongly mutagenic nitrofuran) became bound to the DNA of E. coli WP2 uvrA to a slightly greater extent than did [14C]ANFT. In contrast, [14C]nitrofurazone (the semicarbazide of 5-nitro-2-furaldehyde) a much weaker mutagen, gave considerably less binding. With AF2 and ANFT there was roughly the same relation between the amount of adduct formed and the subsequent yield of daughter strand gaps when the DNA replicated while with nitrofurazone the yield of gaps per adduct was somewhat lower. Incubation in vitro of [14C]ANFT with DNA in the presence of an E. coli nitrofuran reductase preparation also resulted in the binding of 14C to DNA.

DNA, Bacterial↗