Antibacterial and Wound-Healing Activities of Statistically Optimized Nitrofurazone- and Lidocaine-Loaded Silica Microspheres by the Box-Behnken Design.

In the current study, nitrofurazone- (NFZ) and lidocaine-loaded (LD) silica microspheres were fabricated to address pathological indications of skin infections. The microspheres were prepared by the sol-gel method applying the Box-Behnken design and evaluated for size distribution, morphology, zeta potential, physico-chemical compatibility, XRD, thermogravimetric analysis, antibacterial and cytotoxicity activities. The comparative in vitro drug release study of microspheres revealed a 30% release of NFZ and 33% of LD after 8 h. The microspheres showed 81% percentage yield (PY) and 71.9% entrapment efficiency. XRD patterns confirmed the entrapment of NFZ-LD in silica microspheres with a significant reduction in crystallinity of the drugs. Thermal and FTIR studies proved the absence of any profound interactions of the formulation ingredients. The smooth spherical microspheres had a -28 mV zeta potential and a 10-100 µm size distribution. In vitro antibacterial activities of the NFZ-LD microspheres showed an increased zone of inhibition compared to pure drug suspensions. The in vivo efficacy tested on rabbits showed a comparatively rapid wound healing with complete lack of skin irritation impact. The cytotoxicity studies revealed more acceptability of silica microspheres with negligible harm to cells. The study suggests that the NFZ- and LD-loaded silica microspheres would be an ideal system for accelerating and promoting rapid healing of various acute and chronic wounds.

Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi.

Hydroxymethylnitrofurazone (NFOH) is a therapeutic candidate for Chagas disease (CD). It has negligible hepatotoxicity in a murine model compared to the front-line drug benznidazole (BZN). Here, using Trypanosoma cruzi strains that express bioluminescent and/or fluorescent reporter proteins, we further investigated the in vitro and in vivo activity of NFOH to define whether the compound is trypanocidal or trypanostatic. The in vitro activity was assessed by exploiting the fluorescent reporter strain using wash-out assays and real-time microscopy. For animal experimentation, BALB/c mice were inoculated with the bioluminescent reporter strain and assessed by highly sensitive in vivo and ex vivo imaging. Cyclophosphamide treatment was used to promote parasite relapse in the chronic stage of infection. Our data show that NFOH acts by a trypanostatic mechanism, and that it is more active than BZN in vitro against the infectious trypomastigote form of Trypanosoma cruzi. We also found that it is more effective at curing experimental infections in the chronic stage, compared with the acute stage, a feature that it shares with BZN. Therefore, given its reduced toxicity, enhanced anti-trypomastigote activity, and curative properties, NFOH can be considered as a potential therapeutic option for Chagas disease, perhaps in combination with other trypanocidal agents.

Nitrofurazone repurposing towards design and synthesis of novel apoptotic-dependent anticancer and antimicrobial agents: Biological evaluation, kinetic studies and molecular modeling.

Drug repurposing has gained much attention as a cost-effective strategy that plays an exquisite role in identifying undescribed biological activities in clinical drugs. In the present work, we report the repurposing of the antibacterial drug nitrofurazone (NFZ) as a potential anticancer agent against CaCo-2, MDA-MB 231 and HepG-2 cancer cell lines. Novel series of nitrofurazone analogs were then designed considering the important pharmacologic features present in NFZ. Synthesis and biological evaluation of the target compounds revealed their promising anticancer activities endowed with antimicrobial potential and possessing better lipophilicity than NFZ. Compound 7, exclusively, inhibited the growth of all tested cancer cells more potently than NFZ with the least cytotoxicity against normal cells, displaying anti Gram-positive bacterial activities and antifungal potential. Analysis of the stereo-electronic properties of compound 7 via investigating the energies of HOMO, LUMO, HOMO-LUMO energy gap and MEP maps demonstrated its high reactivity and the expected molecular mechanism of action through reduction of the 5-nitrofuryl moiety. Data of the bioactivity studies indicated that the potent anticancer activity of 7 is mainly through increasing intracellular ROS levels and induction of apoptosis via significantly down-regulating the expression of Bcl-2 while up-regulating BAX, p53 and caspase 3 expression levels. Compound 7 potently inhibited the cellular expression levels of antioxidant enzymes GPx1 and GR compared to NFZ. Antioxidant enzymes kinetic studies and blind molecular docking simulations disclosed the mechanistic and structural aspects of the interaction between 7 and both GR and GPx1. Thus, the successful discovery of 7 as a potential dual anticancer-antimicrobial nitrofurazone analog might validate the applicability of drug repurposing strategy in unravelling the unrecognized bioactivity of the present conventional drugs, besides furnishing the way towards more optimization and development studies.

Amniotic membrane dressing versus nitrofurazone-impregnated dressing in the treatment of second-degree burn wounds: a randomized clinical trial.

INTRODUCTION: Both the amniotic membrane biologic dressing and nitrofurazone-impregnated dressing are treatment options for burn wounds. OBJECTIVE: To compare the efficacy of these treatments in healing second-degree burns, a randomized clinical trial was conducted among patients with second-degree burns who had no comorbidities or history of addiction and were referred to a burn center in Urmia, Iran, between December 2017 and September 2019. MATERIALS AND METHODS: Patients were randomly assigned to one of 2 study groups. Wounds were dressed in either amniotic membrane covered with moistened gauze/petrolatum or nitrofurazone-impregnated gauze. Comparative groups were matched according to percentage of burn (total body surface area). The dressing application occurred once daily in the nitrofurazone group and once weekly in the amniotic membrane group. The study was conducted until all wounds healed. The study outcomes included the infection rate of the wound, pain severity related to dressing changes, dressing change frequency, epithelialization rate, hospitalization length of stay, morphine use, and scarring. Data were collected in real time by the researcher via observation, interview, examination of the patient, and, eventually, completion of a checklist. Analyzed quantitative and qualitative variables were reported as mean ± standard deviation and percentage (frequency). RESULTS: Each group included 35 participants (24 men, 11 women; age, 20.05 ± 3.60 years in the amniotic dressing group; and 20 men, 15 women; age, 21.60 ± 2.02 years in the nitrofurazone-impregnated gauze group). Assessment was performed on days 1, 7, 14, and 30 from the initial treatment and at discharge. No significant difference was noted in the rate of infection between the 2 groups. Epithelialization was complete (100%) by day 7 in the amniotic membrane group, versus 77% in the nitrofurazone group. Pain following dressing application, length of hospitalization, morphine use, and scarring at day 14 were significantly lower (P < .05) in the amniotic membrane group. CONCLUSIONS: This study indicated that the use of amniotic membrane dressing improved factors key to healing in second-degree burn wounds compared with nitrofurazone-impregnated dressing. Further research with a larger sample is warranted.

Novel 5-Nitrofuran-Activating Reductase in Escherichia coli.

The global spread of multidrug-resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is the reconsideration of "old" antimicrobials, which remain effective after decades of use. Synthetic 5-nitrofurans such as furazolidone, nitrofurantoin, and nitrofurazone are such a class of antimicrobial drugs. Recent epidemiological data showed a very low prevalence of resistance to this antimicrobial class among clinical Escherichia coli isolates in various parts of the world, forecasting the increasing importance of its uses to battle antibiotic-resistant enterobacteria. However, although they have had a long history of clinical use, a detailed understanding of the 5-nitrofurans' mechanisms of action remains limited. Nitrofurans are known as prodrugs that are activated in E. coli by reduction catalyzed by two redundant nitroreductases, NfsA and NfsB. Furazolidone, nevertheless, retains relatively significant antibacterial activity in the nitroreductase-deficient ΔnfsA ΔnfsBE. coli strain, indicating the presence of additional activating enzymes and/or antibacterial activity of the unreduced form. Using genome sequencing, genetic, biochemical, and bioinformatic approaches, we discovered a novel 5-nitrofuran-activating enzyme, AhpF, in E. coli The discovery of a new nitrofuran-reducing enzyme opens new avenues for overcoming 5-nitrofuran resistance, such as designing nitrofuran analogues with higher affinity for AhpF or screening for adjuvants that enhance AhpF expression.

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation-A histopathological study.

Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- and long-term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti-T. cruzi agent.

Immediate tooth replantation: root canal filling for delayed initiation of endodontic treatment.

The aim of this study is to evaluate the action of paramonochlorophenol associated with Furacin followed by calcium hydroxide (CH) dressing in the control of inflammatory root resorption in cases of immediate tooth replantation with delayed endodontic treatment. A total of 28 incisors of 3 male dogs were extracted and replanted after 15 minutes, and randomly divided into 3 groups: Group I (n = 8) - endodontic treatment was performed before the extraction and replantation; Group II (n = 10) - endodontic treatment was performed 30 days after replantation and the root canal was filled with CH dressing; Group III (n = 10) - endodontic treatment was performed 30 days after replantation and root canals received temporary medication of paramonochlorophenol-Furacin followed by CH dressing. The animals were euthanized 90 days after replantation. The histomorphological events analyzed at the epithelial reattachment site were the intensity and extent of acute and chronic inflammatory processes, periodontal ligament (PDL) organization, the intensity and extent of acute and chronic inflammatory processes in the PDL space, root resorption, bone tissue, and ankylosis. Data were submitted to the Wilcoxon Signed Ranks Test for group comparison (α = 5%). In Groups I, II and III the periodontal ligament was regenerated and most of the resorption areas were repaired by newly formed cementum. The depth and extent of root resorption were significantly higher in Group II than in Group III. The use of paramonochlorophenol-furacin followed by CH dressing was more effective in controlling inflammatory root resorption after immediate tooth replantation.

Immediate tooth replantation: root canal filling for delayed initiation of endodontic treatment

Abstract The aim of this study is to evaluate the action of paramonochlorophenol associated with Furacin followed by calcium hydroxide (CH) dressing in the control of inflammatory root resorption in cases of immediate tooth replantation with delayed endodontic treatment. A total of 28 incisors of 3 male dogs were extracted and replanted after 15 minutes, and randomly divided into 3 groups: Group I (n = 8) - endodontic treatment was performed before the extraction and replantation; Group II (n = 10) - endodontic treatment was performed 30 days after replantation and the root canal was filled with CH dressing; Group III (n = 10) - endodontic treatment was performed 30 days after replantation and root canals received temporary medication of paramonochlorophenol-Furacin followed by CH dressing. The animals were euthanized 90 days after replantation. The histomorphological events analyzed at the epithelial reattachment site were the intensity and extent of acute and chronic inflammatory processes, periodontal ligament (PDL) organization, the intensity and extent of acute and chronic inflammatory processes in the PDL space, root resorption, bone tissue, and ankylosis. Data were submitted to the Wilcoxon Signed Ranks Test for group comparison (α = 5%). In Groups I, II and III the periodontal ligament was regenerated and most of the resorption areas were repaired by newly formed cementum. The depth and extent of root resorption were significantly higher in Group II than in Group III. The use of paramonochlorophenol-furacin followed by CH dressing was more effective in controlling inflammatory root resorption after immediate tooth replantation.

Evaluation of Antimicrobial Durability and Anti-Biofilm Effects in Urinary Catheters Against Enterococcus faecalis Clinical Isolates and Reference Strains.

BACKGROUND: Enterococcus faecalis, Escherichia coli, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans biofilms are major causes of catheter-associated urinary tract infections. Antimicrobial-coated or impregnated urinary catheters are seen as a possible way to prevent these infections. AIMS: To determine the biofilm-forming ability of 89 E. faecalis isolates from urinary tract infections and to compare several urinary catheters for antimicrobial durability and the inhibitory effects on biofilm formation of different laboratory strains and clinical isolates of E. faecalis. STUDY DESIGN: In vitro experimental study. METHODS: The biofilm forming ability of E. faecalis isolates was determined by the crystal violet staining and plate counting methods. For comparison of urinary catheters, biofilms of 45 E. faecalis isolates from the catheter samples of hospitalized patients and five laboratory strains of E. coli ATCC25922, S. epidermidis ATCC35984, P. aeruginosa ATCC27853, E. faecalis ATCC29212 and C. albicans ATCC90028 were formed on the catheters in 24-well tissue culture plates. Scanning electron microscopy analysis was performed to observe biofilms. RESULTS: All 89 E. faecalis isolates were found to be biofilm positive. Nitrofurazone-impregnated catheters significantly reduced the cell counts of E. faecalis isolates and completely inhibited the formation of P. aeruginosa and S. epidermidis biofilms compared with the others. Regarding reduction of biofilm cell counts, a hydrophilic-coated catheter was more effective against P. aeruginosa, whereas a silver-coated catheter was found to be more effective against S. epidermidis. The nitrofurazone-impregnated catheter had the best antimicrobial durability. CONCLUSION: Urine isolates of E. faecalis had considerable ability with respect to biofilm formation. The nitrofurazone-impregnated catheter was the most effective against all tested bacteria; however, the effect of a hydrophilic or silver-coated catheter depends on the species present in it.

Design, synthesis and antitrypanosomal activity of some nitrofurazone 1,2,4-triazolic bioisosteric analogues.

Chagas disease, caused by Trypanosoma cruzi, is a parasitosis that predominates in Latin America. It is estimated that 25 million people are under the risk of infection and, in 2008, more than 10 thousand deaths were registered. The only two drugs available in the therapeutics, nifurtimox and benznidazole, showed to be more effective in the acute phase of the disease. However, there is no standard treatment protocol effective for the chronic phase. Nitrofurazone (NF), an antimicrobial drug, has activity against T. cruzi, although being toxic. Considering the need for new antichagasic drugs, the existence of promising new therapeutic targets, as 14α-sterol demethylase and cruzain, and employing the bioisosterism and molecular hybridization approaches, four novel compounds were synthesized, characterized by melting point range, elemental analysis, IR and NMR spectroscopy. The compounds were tested against T. cruzi amastigotes in infected U2OS cells. All compounds showed selectivity towards T. cruzi and showed trypanomicidal activity in low micromolar range. The compound 3 showed potency similar to benznidazole, but lower efficacy. These results highlight the importance of the 1,2,4-triazole, thiosemicarbazonic and nitro group moieties for designing new efficient compounds, potentially for the chronic phase of Chagas disease.

Automated In-Injector Derivatization Combined with High-Performance Liquid Chromatography-Fluorescence Detection for the Determination of Semicarbazide in Fish and Bread Samples.

Semicarbazide (1) is a widespread genotoxic food contaminant originating as a metabolic byproduct of the antibiotic nitrofurazone used in fish farming or as a thermal degradation product of the common flour additive azodicarbonamide. The goal of this study is to develop a simple and sensitive high-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method for the detection of compound 1 in food products. In comparison to existing methods for the determination of compound 1, the reported method combining online precolumn derivatization and HPLC-FLD is less labor-intensive, produces higher sample throughput, and does not require the use of expensive analytical instruments. After validation of accuracy and precision, this method was applied to determine the amount of compound 1 in fish and bread samples. Comparative studies using an established liquid chromatography coupled with tandem mass spectrometry method did not yield systematically different results, indicating that the developed HPLC-FLD method is accurate and suitable for the determination of compound 1 in fish and bread samples.

Synthesis of gelatin nano/submicron particles by binary nonsolvent aided coacervation (BNAC) method.

A newly developed modified coacervation method is utilized to synthesize gelatin nano/submicron particles (GN/SPs) as a drug carrier. Binary nonsolvent aided coacervation (BNAC) method is a modified single step coacervation method, which has yielded approximately a threefold lower particle size and higher average yield in terms of weight percentage of around 94% in comparison to the conventional phase separation methods. In this study 0.5% (w/v) gelatin aqueous solution with a binary nonsolvent system of acetone and ethanol was used. Nanoparticle synthesis was optimized with respect to nonsolvent system type and pH. pH7 has resulted a minimum particle size of 55.67 (±43.74) nm in anhydrous medium along with a swollen particle size of 776nm (±38.57) in aqueous medium with a zeta potential of (-16.3±3.51) mV in aqueous medium. Swelling ratio of 13.95 confirms the crosslinked hydrogel nature of the particles. Furthermore, drug loading efficiency of the gelatin particles prepared at 7pH was observed with nitrofurazone as the model drug. Results of drug release study indicate the potential use of GN/SPs as drug loading matrix for wound management such as burn wound management.

Effects of nitrofurazone on correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue.

PURPOSE: To evaluate the effects of nitrofurazone on the correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue in rats. METHODS: A defect in the abdominal wall was created and corrected with polypropylene mesh in 20 rats. They were randomly distributed into four groups: control, fibrous mesh, nitrofurazone and nitrofurazone dip in the mesh. Euthanasia was performed in 21 post-operative days. The healing process was analyzed regarding the meshes and macroscopic and microscopic aspects. RESULTS: All animals had adhesions. However, no statistically significant difference (p>0.05) when compared between groups. Similarly microscopic analysis, in which there was no statistical significance level for the evaluated parameters such as mono and polymorphonuclear lymphocytes, granuloma, fibrosis, necrosis and collagen proliferation. CONCLUSION: There was no significant effect on the abdominal wall defect repair with polypropylene mesh surrounded by fibrous tissue when dipped in nitrofurazone 2%.

Effects of nitrofurazone on correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue

PURPOSE:Toevaluate the effects of nitrofurazone on the correction of abdominal wall defect treated with polypropylene mesh involved by fibrous tissue in rats.METHODS: A defect in the abdominal wall was created and corrected with polypropylene mesh in 20 rats. They were randomly distributed into four groups: control, fibrous mesh, nitrofurazone and nitrofurazone dip in the mesh. Euthanasia was performed in 21 post-operative days. The healing process was analyzed regarding the meshes and macroscopic and microscopic aspects.RESULTS:All animals had adhesions. However, no statistically significant difference (p>0.05) when compared between groups. Similarly microscopic analysis, in which there was no statistical significance level for the evaluated parameters such as mono and polymorphonuclear lymphocytes, granuloma, fibrosis, necrosis and collagen proliferation.CONCLUSION:There was no significant effect on the abdominal wall defect repair with polypropylene mesh surrounded by fibrous tissue when dipped in nitrofurazone 2%.

Why semicarbazide (SEM) is not an appropriate marker for the usage of nitrofurazone on agricultural animals.

A comprehensive global database on semicarbazide (SEM) in foodstuffs and food ingredients is presented, with over 4000 data collected in foods such as seafood (crustaceans, fish powders), meat (beef, chicken powders), dairy products (e.g. raw milk, milk powders, whey, sweet buttermilk powder, caseinate, yoghurt, cheese), honey and other ingredients. The results provide evidence that the presence of SEM in certain dairy ingredients (whey, milk protein concentrates) is a by-product of chemical reactions taking place during the manufacturing process. Of the dairy ingredients tested (c. 2000 samples), 5.3% showed traces of SEM > 0.5 µg/kg. The highest incidence of SEM-positive samples in the dairy category were whey (powders, liquid) and milk protein concentrates (35% positive), with up to 13 µg/kg measured in a whey powder. Sweet buttermilk powder and caseinate followed, with 27% and 9.3% positives, respectively. SEM was not detected in raw milk, or in yoghurt or cheese. Of the crustacean products (shrimp and prawn powders) tested, 44% were positive for SEM, the highest value measured at 284 µg/kg. Fish powders revealed an unexpectedly high incidence of positive samples (25%); in this case, fraudulent addition of shellfish shells or carry-over during processing cannot be excluded. Overall, the data provide new insights into the occurrence of SEM (for dairy products and fish powders), substantially strengthening the arguments that SEM in certain food categories is not a conclusive marker of the use of the illegal antibiotic nitrofurazone.

Point mutations in Escherichia coli DNA pol V that confer resistance to non-cognate DNA damage also alter protein-protein interactions.

Y-family DNA polymerases are important for conferring cellular resistance to DNA damaging agents in part due to their specialized ability to copy damaged DNA. The Escherichia coli Y-family DNA polymerases are encoded by the umuDC and dinB genes. UmuC and the cleaved form of UmuD, UmuD', form UmuD'2C (pol V), which is able to bypass UV photoproducts such as cyclobutane pyrimidine dimers and 6-4 thymine-thymine dimers, whereas DinB is specialized to copy N(2)-dG adducts, such as N(2)-furfuryl-dG. To better understand this inherent specificity, we used hydroxylamine to generate a random library of UmuC variants from which we then selected those with the ability to confer survival to nitrofurazone (NFZ), which is believed to cause N(2)-furfuryl-dG lesions. We tested the ability of three of the selected UmuC variants, A9V, H282P, and T412I, to bypass N(2)-furfuryl-dG in vitro, and discovered that pol V containing UmuC A9V has overall modestly better primer extension activity than WT pol V, whereas the UmuC T412I and UmuC H282P mutations result in much lower primer extension efficiency. Upon further characterization, we found that the ability of the UmuC variant A9V to render cells UV-mutable is dependent on the proper length of the arm of UmuD'. Cells harboring UmuC variants T412I and H282P show enhanced cleavage of UmuD to form UmuD', which, together with our other observations, suggests that this may be due to a disruption of a direct interaction between UmuC and UmuD. Thus, we find that protein interactions as well as protein conformation appear to be crucial for resistance to specific types of DNA damage.

An in vivo comparison of commonly used topical antimicrobials on skin graft healing after full-thickness burn injury.

Topical antimicrobials are frequently used for local control of infections in burn patients. It has been postulated that these agents retard wound healing. There are limited data about the effects of topical antimicrobial agents on skin graft healing. In this study, we aimed to evaluate the effects of nitrofurazone, 1% silver sulfadiazine, and povidone-iodine on skin graft healing. Forty male rats were used in this study. A meshed skin graft, placed on an excised burn wound, was used as a model to compare topical agents with a control group. Skin graft survival rates, closure of meshed graft interstices (based on physical parameters, namely epithelialization and wound contraction), and histological changes were analyzed. Graft take was more than 85% in all groups. There was no difference between the mean values of the percent graft survival for each group (P > .05). Epithelialization occurred significantly earlier in animals in the nitrofurazone group (P < .05). There was no significant difference between groups in wound contraction rates (P >.05). There was no histological difference between the biopsy specimens of skin grafts. In specimens obtained from the interstices of the meshed graft, no significant differences were found among the groups regarding the wound healing parameters (P > .05). We found that nitrofurazone, silver sulfadiazine, and povidone-iodine had no negative effect on graft healing and take in noncontaminated burn wounds.

Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.

The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics.

Cost effectiveness of antimicrobial catheters for adults requiring short-term catheterisation in hospital.

Catheter-associated urinary tract infection (CAUTI) is the second most common cause of hospital-acquired infection. A number of strategies have been put forward to prevent CAUTI, including the use of antimicrobial catheters. We aimed to assess whether the use of either a nitrofurazone-impregnated or a silver alloy-coated catheter was cost-effective compared with standard polytetrafluoroethylene (PTFE)-coated catheters. A decision-analytic model using data from a clinical trial conducted in the United Kingdom was used to calculate the incremental cost per quality-adjusted life-year (QALY). We assumed that differences in costs and QALYs were driven by difference in risk of acquiring a CAUTI. Routine use of nitrofurazone-impregnated catheters was, on average, £7 (€9) less costly than use of the standard catheter over 6 wk. There was a >70% chance that use of nitrofurazone catheters would be cost saving and an 84% chance that the incremental cost per QALY would be less than £30 000 (€36 851; a commonly used threshold for society's willingness to pay). Silver alloy-coated catheters were very unlikely to be cost-effective. The model's prediction, although associated with uncertainty, was that nitrofurazone-impregnated catheters may be cost-effective in the UK National Health System or a similar setting.

Development and characterization of a gel formulation integrating microencapsulated nitrofurazone.

Nitrofurazone (NTZ) is usually employed in the topical treatment of infected wounds and lesions of both skin and mucosa. Microencapsulation is a process utilized in the incorporation of active ingredients within polymers aiming at, among other objectives, the prolonged release of pharmaceutical compounds and protection from atmospheric agents (viz. moisture, light, heat and/or oxidation). With the goal of utilizing the microparticles containing encapsulated NTZ in pharmaceutical formulations, one prepared microparticles containing NTZ via ionotropic gelation of sodium alginate. The microparticles were characterized via scanning electron microscopy analyses, Fourier transform infrared spectroscopy (FTIR) analyses, via determination of encapsulation efficiency, and via thermal analyses (both TGA and DSC). The final gel formulation was also characterized rheologically. The extrusion/solidification technique employed to obtain the calcium alginate microparticles with encapsulated NTZ was found to be adequate, and produced an NTZ encapsulation efficiency of ca. 97.8% ± 1.1%. The calcium alginate microparticles thus obtained, with encapsulated NTZ, exhibited an oval shape and hydrodynamic diameters between 500 µm and 800 µm. From the thermal analyses performed, together with information from the infrared spectra, one may conclude that NTZ did not strongly bind to the polymer, which may be favorable for the release of the active ingredient. From the results obtained in the present research effort, one may conclude that the microparticles produced possess the potential to be utilized as carriers for NTZ in pharmaceutical formulations such as gels, ointments, and solutions.