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At least 19 recordsLinked to original sources
PubMed1989

Evaluation of acetylator phenotype, renal function and serum sulfadiazine levels in patients with paracoccidioidomycosis treated with cotrimazine (a combination of sulfadiazine and trimethoprim).

The authors evaluated the relationships among renal function, acetylator phenotype and serum sulfadiazine levels in 22 patients with paracoccidioidomycosis treated with 1 tablet of cotrimazine (a combination of 820 mg sulfadiazine and 180 mg trimethoprim) administered orally every 12 hours. Fifteen patients (68.18%) presented free sulfadiazine levels above 50 micrograms/ml, 6(27.28%) presented serum levels above 40 micrograms/ml, and 1(4.54%), levels lower than 40 micrograms/ml, this being the patient in which treatment failed. The highest free sulfadiazine levels were obtained in slow acetylator patients with reduced renal function. One patient with neuroparacoccidioidomycosis presented free sulfadiazine levels in cerebrospinal fluid corresponding to 55% of the serum levels. Finally, the authors consider cotrimazine to be an important therapeutic alternative for neuroparacoccidioidomycosis and conclude that administration every 12 hours can provide therapeutic sulfadiazine levels. They also suggest that when the sulfadiazine-trimethoprim combination is used, the therapeutic levels of sulfadiazine should be above 40 micrograms/ml.

Acetyltransferases↗
PubMedDate not supplied

Comparative evaluation of zinc sulfadiazine and silver sulfadiazine in burn wound infection.

One percent silver sulfadiazine has been commonly used as a topical antimicrobial agent after a burn injury. Incidence of burn wound colonization by Staphylococcus aureus in patients treated with silver sulfadiazine has spurred research for other agents. A topical preparation that contains zinc and sulfadiazine (Zad-G) was evaluated for in vitro antibacterial spectrum and in vivo efficacy. Muscle biopsy specimens of rats treated with Zad-G appear to have fewer colonies of S. aureus than groups treated with silver sulfadiazine. Topical therapy with Zad-G for patients with burns was comfortable, reduced wound infection, and was comparable to therapy with silver sulfadiazine. A topical Zad-G preparation that contains zinc sulfadiazine appears to be an effective alternative to silver sulfadiazine in the treatment of burn wounds.

Administration, Topical↗
PubMed2005

Simultaneous determination of pyrimethamine, sulfadiazine and N-acetyl-sulfadiazine in plasma for monitoring infants in treatment of congenital toxoplasmosis.

A method for the simultaneous determination of pyrimethamine, sulfadiazine and its metabolite N-acetyl-sulfadiazine in small plasma samples from neonates in treatment for congenital toxoplasmosis has been developed. In this method only 25 microl of plasma is used and a simple sample preparation based on protein precipitation and centrifugation provides highly reliable data as the recovery is about 100% and the precision is good. The analysis is performed using high performance liquid chromatography with UV and mass spectrometric (MS) detection. Pyrimethamine was found to give a linear response using MS detection in the range 0.02-5 microg/ml. Sulfadiazine and its metabolite N-acetyl-sulfadiazine were preferably analysed by UV at 269 nm in the concentration ranges 0.2-200 microg/ml for sulfadiazine and 0.2-50 microg/ml for N-acetyl-sulfadiazine.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Comparison of silver sulfadiazine 1% with chlorhexidine digluconate 0.2% to silver sulfadiazine 1% alone in the prophylactic topical antibacterial treatment of burns.

Wound bacterial colonization in 118 patients treated with chlorhexidine digluconate 0.2% in silver sulfadiazine 1% applied daily to the burn wounds was compared to that of 135 comparable patients similarly treated with silver sulfadiazine 1%. With chlorhexidine digluconate 0.2% in silver sulfadiazine 1%, colonization by Staphylococcus aureus was less frequent (38%) than with silver sulfadiazine (54%, p = 0.016). No statistical difference was found for colonization by Enterococcus faecalis, Pseudomonas aeruginosa, or Enterobacter cloacae. Washing of the wounds of 65 patients with chlorhexidine gluconate 4% during daily dressing changes was associated with reduced wound colonization by S. aureus (35% versus 51%, p = 0.03) and P. aeruginosa (8% versus 16%, p = 0.08) when compared to the 188 washed with nonantibacterial soap. Chlorhexidine, whether added to the topical agent silver sulfadiazine (chlorhexidine digluconate 0.2%) or in the bath soap (chlorhexidine gluconate 4%), decreased colonization by S. aureus.

Administration, Topical↗
PubMed2004

Topical treatment of partial thickness burns by silver sulfadiazine plus hyaluronic acid compared to silver sulfadiazine alone: a double-blind, clinical study.

Since its introduction into clinical practice in 1967 by Charles Fox Jr., silver sulfadiazine has been the gold standard for topical burn therapy. The addition to it of hyaluronic acid, which forms a substantial part of the human tissue intercellular matrix, is aimed at overcoming one of its very few disadvantages, i.e. prolongation of the wound re-epithelialization process. Since both hyaluronic acid and silver sulfadiazine have been used in therapy for decades and their efficacy is well documented, a topical treatment combining these two agents was formulated. The aim of the study was to investigate the efficacy and tolerability of a cream containing a hyaluronic acid/silver sulfadiazine fixed combination, compared with silver sulfadiazine cream alone, for the treatment of superficial and deep second-degree burns in a prospective, double-blind, controlled clinical study. The findings of the study confirmed that the association of the two compounds in a new topical treatment significantly reduced the healing time and significantly accelerated the reduction of local edema occurring shortly after injury. Furthermore, this new hyaluronic acid and silver sulfadiazine formulation has proven to have favorable antibacterial, anti-edematous and local analgesic effects, together with a clear stimulatory activity on the re-epithelialization process. This product may, therefore, significantly enrich the assortment of topical medications available for the treatment of burns and skin defects of other origin.

Administration, Topical↗
PubMed1995

Solubility of silver sulfadiazine in physiological media and relevance to treatment of thermal burns with silver sulfadiazine cream.

Silver sulfadiazine cream has been a standard treatment for burns over the past two decades. Although many studies have described the phenomenon of silver absorption from burn wounds treated with silver sulfadiazine, they failed to examine the chemistry underlying the absorption process: Silver chloride was assumed to form at the burn wound and absorption of silver was believed to be negligible. Here we have developed chemical model systems to investigate the interactions of silver sulfadiazine and silver chloride in direct contact with synthetic serum electrolyte solution (SSES), with SSES plus endogenous ligands or beef blood plasma, and with human serum. The results indicate that silver absorption from an acute burn site can be significant, because human serum is capable of solubilizing silver. This finding is of concern, given the potential for silver toxicity as a direct consequence of applying silver sulfadiazine to extensive burn wounds.

Absorption↗
PubMed1984

Prospective comparison of silver sulfadiazine 1 per cent plus chlorhexidine digluconate 0.2 per cent (Silvazine) and silver sulfadiazine 1 per cent (Flamazine) as prophylaxis against burn wound infection.

Patients with fresh full-thickness burn wounds were randomly assigned to receive wound treatment with daily applications of either 1 per cent silver sulfadiazine plus 0.2 per cent chlorhexidine digluconate cream (Silvazine) or 1 per cent silver sulfadiazine (Flamazine). Fifty-four patients treated with Silvazine were comparable to 67 treated with Flamazine with respect to extent and distribution of burn, age and all aspects of wound and associated treatment. Overall incidence of wound bacterial colonization was less in the Silvazine treated patients (65 per cent versus 88 per cent; P = 0.002). With Silvazine, wound colonization by Staphylococcus aureus was less (41 per cent versus 64 per cent; P = 0.01). Clinical wound infection with Staph, aureus developed in one Silvazine treated patient and five Flamazine treated patients (P = 0.16). Colonization by and infection due to all other organisms did not differ in the two groups. The incidence of graft failure was similar with both agents. In future increasing the concentration of chlorhexidine digluconate above 0.2 per cent might produce an improved prophylactic effect against Gram negative bacteria reported by other authors using the combined agent in in vitro and clinical trials. Silvazine was effective in reducing the incidence of Staph. aureus burn wound colonization without fostering supervening opportunistic infection.

Adolescent↗
PubMed2005

Second-degree burns: a comparative, multicenter, randomized trial of hyaluronic acid plus silver sulfadiazine vs. silver sulfadiazine alone.

AIMS: This multicenter, multinational, randomized, double-blind, controlled, parallel-group study, was designed to assess the efficacy and safety of a fixed combination topical medicinal product, containing 0.2% hyaluronic acid and 1% silver sulfadiazine (HA-SSD) (Connettivina Plus cream) versus 1% silver sulfadiazine cream alone (SSD), in the treatment of second-degree burns. METHODS: 111 adult patients (age 18-75 years) of both sexes, with IIa-degree (superficial) and IIb-degree (deep dermal) burns, were randomized to receive HA-SSD or SSD. Treatments (approximately 5 g/100 cm2) were applied once a day until the wounds healed, but for no longer than 4 weeks. Burns had to have occurred within 48 hours from the start of treatment, be caused by thermal injury, and be confined to the trunk and/or upper and lower extremities. RESULTS: Results showed that both the fixed combination HA-SSD, and SSD alone, were effective and well tolerated topical agents for the treatment of second-degree burns. All burns were healed except in one patient treated with SSD. It was also observed that the fixed combination HA-SSD caused a significantly more rapid re-epithelialization of burns, i.e. a shorter time to healing, than SSD alone. The difference recorded--4.5 days--was statistically significant (p = 0.0073). CONCLUSION: The observed shorter time to healing caused by the fixed combination is clinically relevant and further demonstrates the wound healing activity of HA.

Adjuvants, Immunologic↗
PubMed2001

An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns.

Sixty patients with moderate and severe burns were randomly assigned to receive topical silver sulfadiazine (SSD) alone (n=30) or SSD combined with cerium nitrate (SSD-CN) (n=30). There were four deaths in the SSD group and one in the SSD-CN group; more patients with higher risk severity survived in the SSD-CN group. Wound infection did not differ significantly between the groups. The rate of re-epithelialization of partial thickness burns was faster by 8 days in the SSD-CN group. The relatively dry shell-like eschar of the SSD-CN-treated burn allowed planned excisions with immediate autologous grafting and the tissue beneath was ready to accept grafting 11 days earlier than in the SSD group (p=0.03). This resulted in a significantly shorter hospital stay for those in the SSD-CN group than in the SSD group (23.3 vs. 30.7 days; p=0.03) with consequent cost savings. A higher incidence of transient stinging pain was reported with application of SSD-CN, but this was effectively managed with analgesics where necessary. The results of this study confirm the greater efficacy of SSD-CN in the treatment of burns patients.

Administration, Topical↗
PubMed2006

Development and validation of an immunochromatographic assay for rapid detection of sulfadiazine in eggs and chickens.

A rapid immunochromatographic assay (ICA) was developed and validated for the detection of sulfadiazine in eggs and chickens. Based on the competitive reaction mechanism, the competitor of sulfadiazine (sulfadiazine-BSA conjugate) was immobilized to the defined detection zone on a nitrocellulose membrane which acted as the capture reagent, and the monoclonal antibody against sulfadiazine was conjugated to colloidal gold particles which served as the detection reagent for the preparation of the immunochromatographic strips to test sulfadiazine. With this method, the semi-quantitative detection of sulfadiazine was accomplished in less than 15min, with high sensitivity to sulfadiazine (5ng/g) and low cross-reactivities with other sulfonamides. With experimental egg and chicken samples spiked with sulfadiazine at concentrations of 10, 20, and 100ng/g, recoveries were demonstrated to be from 71% to 97% in egg samples and 71% to 95% in chicken samples. This method was compared with the enzyme-linked immunosorbent assay by testing 52 egg samples from the animal experiment, and compared with the high-performance liquid chromatographic method by testing 56 chicken samples, with an agreement rate of 100% for both comparisons, by using the maximum allowed residue of sulfadiazine (i.e. 100ng/g) as the cut-off level as set by the European Union and China. The accuracy of ICA was also confirmed in an initial study with marketed egg and chicken samples. In conclusion, the method is rapid and accurate for the detection of sulfadiazine in eggs and chickens.

Animals↗
PubMed1977

Topical chemotherapy for burns using cerium salts and silver sulfadiazine.

These experimental data indicate that cerium compounds exert a measurable antimicrobial action in vitro. In vivo the simultaneous use of cerium sulfadiazine and silver sulfadiazine was more effective than silver sulfadiazine alone or the combination of cerous nitrate and silver sulfadiazine. When cerous nitrate was used clically, gram-positive bacteria predominated. In contrast, wounds exposed to silver salts alone harbor a predominately gram-negative flora. The combination of cerous nitrate and silver sulfadiazine appears to provide a broad spectrum inhibitory to both types of organisms. It is apparent that a sampling problem exists in any attempt to monitor wounds that may exceed a square meter in extent. These bacteriologic data pertain only to the surface flora. The need to culture tissue samples of burn wounds has been emphasized. Our experience, however, is that invasion of deep tissue without dense surface colonization, greater than 10(5), is infrequent. Furthermore, fragments of eschar were submitted regularly for culture; those results confirmed the surface culture findins. The characteristic yellow-green color of cerium nitrate treated eschars may results from oxidation of trivalent cerium to yellow ceric ions. Free silver and sulfadiazine ions are available also in small amounts because of limited ionization of the highly insoluble silver sulfadiazine. This might promote the in vivo formation of cerous sulfadiazine and would provide a continuous source of ionic cerium for microbial inhibition. The modification of silver sulfadiazine cream by incorporating cerous nitrate into it strikingly enhances its topical antiseptic effect in burn wounds without increasing toxicity.

Administration, Topical↗
PubMed2003

Comparison of a liquid chromatographic method with ultraviolet and ion-trap tandem mass spectrometric detection for the simultaneous determination of sulfadiazine and trimethoprim in plasma from dogs.

A method for the simultaneous determination of sulfadiazine and trimethoprim in plasma from Beagle dogs was developed and validated. Samples were deproteinized with acetonitrile and extracted with ethyl acetate. Sulfachloropyridazine and ormethoprim were used as internal standards for the sulfadiazine and trimethoprim analysis, respectively. The chromatography was carried out both on an LC-UV (liquid chromatography-ultraviolet detection) and ion-trap LC-MS(n) (liquid chromatography-mass spectrometric detection) instrument, operating in the positive APCI mode (atmospheric pressure chemical ionization). The purpose of this work was to compare the quantification results of both methods. Both the LC-UV and LC-MS-MS methods were validated for their linearity, accuracy, precision, limit of detection and limit of quantification, according to the requirements defined by the European Community. Calibration curves using plasma fortified between 0.1 and 1 microg/ml of sulfadiazine, 0.1 and 2 microg/ml of trimethoprim, 1 and 20 microg/ml of sulfadiazine showed a good linear correlation (r> or =0.9990, goodness-of-fit< or =8.4%). The results for the accuracy and precision at 1 microg/ml of sulfadiazine and trimethoprim and at 20 microg/ml of sulfadiazine fell within the ranges specified. The limits of quantification of both methods were 0.1 microg/ml. The limits of detection were 0.019 microg/ml of sulfadiazine and 0.024 microg/ml of trimethoprim for the LC-UV method, and 0.020 microg/ml of sulfadiazine and 0.062 microg/ml of trimethoprim for the LC-MS-MS method. The methods have been successfully applied in a pharmacokinetic study to determine the drug concentrations in plasma samples from dogs. A good correlation between the results of both methods was observed (R=0.9724, slope=1.0239, intercept=-0.2080 microg/ml for sulfadiazine and R=0.9357, slope=1.0433, intercept=0.0325 microg/ml for trimethoprim). The precision of both methods was also tested on the results of the same samples using an F-test (alpha=0.05), indicating that both methods did not differ in precision.

Animals↗
PubMed2005

Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms involved in sulfadiazine metabolism.

Sulfadiazine hydroxylamine has been postulated to be the mediator of the greatly increased rates of adverse reactions to sulfadiazine experienced by people with human immunodeficiency virus infection. Therefore, we investigated the in vitro human cytochrome P450 (P450) and N-arylamine acetyltransferase (detoxification) metabolism of sulfadiazine. Formation of both the hydroxylamine and 4-hydroxy sulfadiazine was NADPH-dependent in human liver microsomes (HLM). The average K(m) (+/-S.D.) and V(max) in HLM (n = 3) for hydroxylamine formation was 5.7 +/- 2.2 mM and 185 +/- 142 pmol/min/mg, respectively. Significant (p < 0.05) inhibition by selective P450 isoform inhibitor sulfaphenazole (2.1 microM; CYP2C9) indicated a role for CYP2C9 in the formation of the hydroxylamine. Hydroxylamine formation correlated strongly with tolbutamide 4-hydroxylation (CYP2C8/9) in HLM (r = 0.76, p < or = 0.004, n = 12). Fluconazole (CYP2C9/19 and CYP3A4 inhibitor at clinical concentrations) inhibited hydroxylamine formation, with one-enzyme model K(i) estimates ranging from 9 to 40 microM. Acetylation of sulfadiazine in human liver cytosol (HLC) correlated strongly with NAT2 activity as measured by sulfamethazine N-acetylation (r = 0.92, p < 0.001, n = 12). The average K(m) (+/-S.D.) and V(max) in HLC (n = 3) was 3.1 +/- 1.7 mM and 221.8 +/- 132.3 pmol/min/mg, respectively. The polymorphic acetylation of sulfadiazine may predispose slow acetylator patients to adverse reactions to sulfadiazine. On the basis of our K(i) estimates, clinical fluconazole concentrations of 25 microM would produce decreases of 40 to 70% in hepatic-mediated hydroxylamine production. Therefore, we predict that fluconazole may prove useful in the clinic as an in vivo inhibitor of sulfadiazine hydroxylamine formation to suppress adverse reactions to this drug.

Antiprotozoal Agents↗