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PubMedDate not supplied

Comparison of battlefield-expedient topical antimicrobial agents for the prevention of burn wound sepsis in a rat model.

Topical antimicrobial therapy has the potential to limit the mortality and morbidity of contaminated battlefield injuries. Many agents available are ill-suited for use on the battlefield; however, mafenide acetate solution (MAS) has known efficacy as a burn dressing adjunct, and previous work with mafenide as a direct chemotherapeutic has shown promise. A total of 71 male Sprague-Dawley rats underwent a 20% TBSA full-thickness scald. Wounds were inoculated with a solution containing 1 x 10 colony-forming units per milliliter of Pseudomonas aeruginosa 1244 (ATCC 27317). Treatments with 10% mafenide acetate cream (MAC), 5% MAS, 5% mafenide hydrochloride solution (MHS), and 4% chlorhexidine gluconate solution (CHG) were established. Agents were applied directly to the wound daily for 10 days. Animals were monitored for 21 days and euthanized if they manifested a moribund state as a result of sepsis. Survival to study completion in the negative control group (no treatment) was 25% (3/12). Survival in the positive control group (MAC) was 100%. None of the test agent groups demonstrated significant survival over the untreated controls; MAS resulted in 5/12 (42%) survival (P = .67), CHG in 4/12 (33%) survival (P = 1.0), and MHS resulted in 2/12 (17%) survival (P = 1.0). There were no significant differences in group weights on day 1. By day 6, all test agent groups were significantly underweight compared with the MAC group. This trend resolved as underweight animals died. We did not demonstrate significant prevention of wound sepsis with these agents as we used them. These techniques should not be substituted for established burn care. Aqueous direct topical antimicrobial agents have logistical advantages over creams and dressing soaks for field use, and the search for a battlefield-expedient agent for use at or near the point of wounding should continue.

Administration, Topical↗
PubMed1971

Inhibition of Pseudomonas aeruginosa by hyperbaric oxygen. I. Sulfonamide activity enhancement and reversal.

To elucidate an explanation for in vitro sulfonamide enhancement by high-pressure oxygen (HPO) and the reported absence of enhancement with in vivo therapy, Pseudomonas aeruginosa cultures were exposed to selected antifolate antimicrobials in the presence of 1.87 atm absolute of O(2) and compared with non-HPO treated controls. Under these conditions, HPO alone retarded growth. Trimethoprim, a non-sulfonamide which inhibits dihydrofolate reductase, was not bactericidal, nor did HPO enhance existent bacteriostatic activity. The sulfonamide, sulfisozazole, was not bactericidal, but HPO enhanced bacteriostatic activity twofold; bacteriostasis was mitigated in HPO-treated and control cultures by p-aminobenzoate but not by a mixture of compounds involved in folate-mediated "1-C" biosynthesis. Mafenide, a unique sulfonamide, at high concentrations with HPO, was synergistically bactericidal; non-HPO-treated cultures were bacteriostatically inhibited. Bacteriostatic activity of lower mafenide concentrations was also enhanced at least twofold by HPO. These inhibitory effects of mafenide, acting with or without HPO, were mitigated by the above mixture, but not by p-aminobenzoate. This may explain the lack of in vivo HPO-mafenide enhancement in burn-wound sepsis where exudates would contain such a mixture. Lastly, HPO itself was largely bactericidal at 2.87 atm absolute of O(2). This was reversed to various degrees by the above mixture, or its components, or by folic, folinic, or p-aminobenzoic acids. These in vitro interactions suggest HPO per se may act at the same site as some sulfonamides to inhibit folate synthesis (not primarily at the dihydrofolate reductase level), or coenzyme functions of folate, or both.

Aminobenzoates↗
PubMedDate not supplied

Topical Bactroban (mupirocin): efficacy in treating burn wounds infected with methicillin-resistant staphylococci.

Bacterial antimicrobial susceptibility predictors such as the minimal inhibitory concentration (MIC) assay and Nathans Agar Well Diffusion (NAWD) assay provide essential information relevant to the therapeutic approach in burn-wound sepsis. The susceptibilities of 68 gram-positive burn-wound isolates were tested against topical Bactroban (mupirocin) (Beecham Laboratories, Bristol, Tenn.) and compared with other topical antimicrobials such as mafenide acetate, silver sulfadiazine, and bacitracin/neomycin/polymyxin (BNP). Topical susceptibility data were obtained with a modification of NAWD assay. Bactroban's antimicrobial activity was greater than that of mafenide acetate (100% vs 97%), and significantly greater than that of silver sulfadiazine and that of BNP (p less than 0.001). Of the 68 isolates that were susceptible to Bactroban, 51 were predominately methicillin-resistant staphylococci (MRSA). Bactroban showed in vitro activity against 71% of the 85 gram-negative isolates tested. Mafenide acetate showed activity against 89% of these isolates, a significant difference compared with Bactroban (p less than 0.02). In general, no significant difference was found between the activities of Bactroban and silver sulfadiazine against the gram-negative isolates. The activities of mafenide acetate and silver sulfadiazine against isolates of Pseudomonas aeruginosa were significantly greater than that of Bactroban (p less than 0.05). Bactroban may be used in the treatment of documented staphylococcal burn-wound infections. On the basis of the in vitro data, 13 patients with MRSA burn-wound infections susceptible to Bactroban were evaluated. Quantitative wound biopsies were employed to determine the efficacy of this therapeutic approach. The outcome of these infections was correctly predicted by the NAWD assay in 92.3% of the patients treated (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1988

Comparison of standard and chlorhexidine-derivative topical antibacterial agents on the infected burned rat wound.

The effect of daily treatment with three current topical antibacterial agents and four experimental formulations of chlorhexidine was evaluated after 1 week in rats with full thickness burns. The burn was seeded with 1 x 10(8) colony forming units (CFU) of a strain of P. aeruginosa isolated from the infected wound of a burn patient. Mafenide acetate resulted in the lowest incidence of muscle invasion and yielded the lowest mean eschar and muscle concentrations. Mafenide acetate, gentamicin, and chlorhexidine diphosphanilate (0.5 per cent) had lower mean eschar and muscle concentrations than silver sulphadiazine 1 per cent alone. Addition of chlorhexidine digluconate (0.5 per cent or 1.0 per cent) to silver sulphadiazine reduced mean eschar concentrations but not muscle concentrations compared to silver sulphadiazine alone. All treatments effectively suppressed systemic invasion of lung and blood and prevented death compared with controls. Mafenide acetate, gentamicin sulphate and chlorhexidine disphosphanilate 0.5 per cent were most effective against this patient strain of P. aeruginosa.

Administration, Topical↗
PubMed1980

[In-vitro efficacy of topical antibiotics on bacteria from burns].

The influence of topical antimicrobial agents on bacterial growth was determined with an agar diffusion technique. 349 isolates were tested with mafenide acetate and silver sulfadiazine, 226 isolates were tested with povidone iodine. None of these agents was likewise effective against all organisms of the same bacterial strain. The inhibition of growth by mafenide acetate and silver sulfadiazine demonstrated dose-response. 26 to 40% of the tested grampositive cocci were inhibited by mafenide acetate, whereas the growth of about 26 to 90% of gramnegative rods was effected by silver sulfadiazine, with the exception of proteus species (9%). Both agents influenced the growth of pseudomonas (40 to 65%). The results obtained with povidone iodine led to the consideration that the agar diffusion method might not be suitable for testing this drug.

Anti-Bacterial Agents↗
PubMed1994

Comparison of the effects of commonly used wound agents on epithelialization and neovascularization.

BACKGROUND: The primary effect sought with most topical wound therapy is antimicrobial. Topical wound agents are thought to promote normal healing by protecting the wound from infection. In this study, we examined the effect of six commonly used topical wound agents (bacitracin, sodium hypochlorite, silver nitrate, silver sulfadiazine, mafenide acetate, and povidone-iodine) on epithelialization and neovascularization in noninfected wounds. For this study, a new wound model was used in which direct visualization and quantification of wound epithelialization and neovascularization were carried out throughout the entire healing process. STUDY DESIGN: We measured the effect which 500 U per g of bacitracin, 0.25 percent of sodium hypochlorite, 0.5 percent silver nitrate, 1 percent silver sulfadiazine, 8.5 percent mafenide acetate, and 10 percent povodione-iodine had on the rate of wound epithelialization and neovascularization. The agents were applied topically to 99 circular full-thickness wounds (2.25 mm diameter, 0.125 mm depth) created on the dorsum of male hairless mouse ears. This model enabled us to visualize and measure directly wound epithelialization and neovascularization repeatedly throughout healing, using intravital video microscopy and computerized digitized planimetry. RESULTS: Control wounds and wounds treated with silver sulfadiazine (n = 18) and mafenide acetate (n = 14) epithelialized in 7.2 +/- 0.7, 7.1 +/- 0.3, and 7.3 +/- 0.3 days, respectively. This was significantly (p < 0.01) faster than the wounds treated with povidone-iodine (n = 10), sodium hypochlorite, (n = 8), and bacitracin (n = 13). Wounds treated with povidone-iodine epithelialized the slowest (11.8 +/- 0.55 days). Wound neovascularization was completed most rapidly in the groups treated with povidone-iodine and silver sulfadiazine (15.0 +/- 0.4 and 15.3 +/- 0.7 days, respectively). This was significantly (p < 0.05) faster than wounds treated with silver nitrate (n = 15), which neovascularized in 18.4 +/- 0.56 days. One-half of the wounds treated with sodium hypochlorite (eight of 16) did not epithelialize or neovascularize. CONCLUSIONS: The various antimicrobial agents studied in our in vivo model affect wound epithelialization and neovascularization differently. These effects on these two very important aspects of healing should be taken into consideration when indicating a specific agent for treatment of different types of wounds.

Animals↗
PubMed2004

Photosystem II associated carbonic anhydrase activity in higher plants is situated in core complex.

The thylakoid membrane containing photosystem II (PSII membranes) from pea and wheat leaves catalyzed the reaction of CO2 hydration with low rate, which increased after their incubation either with Triton X-100, up to Triton/chlorophyll ratio 1:1, or 1 M CaCl2. The presence of the inhibitor of CAs, p-aminomethylbenzensulfonamide (mafenide), at the start line in the course of electrophoresis of PSII membranes solubilized by n-dodecyl-beta-maltoside (DM) decreased the amount of PSII core complex in the gel. The elution of PSII core complex from the column with immobilized mafenide occurred only either by mafenide or another inhibitor of CAs, ethoxyzolamide. The above results led to a conclusion that membrane-bound CA activity associated with PSII is situated in the core complex.

Carbonic Anhydrases↗
PubMed1983

Retrospective analysis of plasmid patterns in a study of burn unit outbreaks of infection due to Enterobacter cloacae.

To evaluate the usefulness of plasmid pattern analysis as an epidemiologic tool and to determine the mechanism of resistance to silver sulfadiazine and mafenide acetate, silver sulfadiazine-resistant, mafenide acetate-resistant Enterobacter cloacae isolates from a 1976 outbreak of infections in a burn unit (group I) were analyzed retrospectively. These strains were compared with various E cloacae isolates (groups II-V), including E cloacae isolates from a more recent (1982) burn unit outbreak (group V). Agarose gel electrophoresis (AGE) of DNA isolated from "epidemic" strains of E cloacae revealed a uniform pattern of four plasmid DNA bands, ranging in molecular size from 66 to 2 megadaltons. No such plasmid pattern was seen in silver sulfadiazine-, mafenide acetate-susceptible isolates of E cloacae in groups II, III, and V. Analysis of non-E cloacae coisolates suggested that silver sulfadiazine resistance was associated with the 55-megadalton plasmid. Plasmid pattern analysis easily separated "epidemic" E cloacae isolated in 1976 from those isolated in 1982.

Burns↗
PubMedDate not supplied

Cytotoxicity to human leukocytes by topical antimicrobial agents used for burn care.

We tested two topical antimicrobial agents (TAAs), silver sulfadiazine and mafenide acetate, to determine their cytotoxic effects when human lymphocytes and neutrophils were incubated with the agents in vitro for 30 minutes. Dilute concentrations of both TAAs markedly inhibited neutrophil respiratory burst activity and mitogen-stimulated lymphocyte proliferation (p < 0.05). The components of silver sulfadiazine (silver and sulfadiazine) were separately tested, and each component inhibited both neutrophil and lymphocyte functions. Mafenide acetate markedly decreased intracellular Ca+2 flux in lymphocytes. The effects of the TAAs were partially reversed when cells were washed and resuspended in medium after they were exposed in vitro to the TAAs. Commonly used TAAs may contribute to local immune dysfunction in the patient with burns. Because evidence suggests that T lymphocytes may participate in wound healing, prolonged treatment with TAAs may also effect certain aspects of wound healing.

Burns↗
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

Comparative evaluation of the antimicrobial activity of ACTICOAT antimicrobial barrier dressing.

This study evaluated the antimicrobial activity of ACTICOAT Antimicrobial Barrier Dressing (Westaim Biomedical Corp, Fort Saskatchewan, Alberta, Canada), a silver-coated wound dressing, and compared it with silver nitrate, silver sulfadiazine, and mafenide acetate. The minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), zone of inhibition, and killing curves were determined with 5 clinically relevant bacteria. The data indicate that ACTICOAT silver had the lowest MIC and MBC and generated similar zones of inhibition to silver nitrate and silver sulfadiazine. Viable bacteria were undetectable 30 minutes after inoculation with the dressing, whereas it took 2 to 4 hours for silver nitrate and silver sulfadazine to achieve the same result. Mafenide acetate generated the biggest zones of inhibition, but it had the highest MICs and MBCs, and a significant number of bacteria still survived after 6 hours of treatment. The results suggest that ACTICOAT Antimicrobial Barrier Dressing has better antimicrobial performance than either of the existing silver-based products. ACTICOAT dressing killed the bacteria that were tested much faster, which is a very important characteristic for a wound dressing acting as a barrier to invasive infection to have. The study also suggests that a single susceptibility test such as a MIC or zone of inhibition test does not provide a comprehensive profile of antimicrobial activity of a topical antimicrobial agent or dressing. A combination of tests is desirable.

Anti-Infective Agents, Local↗
PubMed1993

Inhibition of wound contraction by topical antimicrobials.

Spontaneous wound healing occurs partly by wound contraction, a process that requires intact functioning fibroblasts, and collagen production. Disruption of fibroblasts by the topical antimicrobials, silver sulfadiazine and mafenide acetate has been demonstrated in vitro. An acute rat wound model was used to show that wound contraction in vivo is significantly impeded by silver sulfadiazine and mafenide acetate.

Administration, Topical↗
PubMed1990

Current treatment recommendations for topical burn therapy.

Infections in burn patients continue to be the primary source of morbidity and mortality. Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients. The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection. In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections. At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens. In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control. Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis. However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use. Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations. The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time.

Administration, Topical↗
PubMed1986

[Antibacterial activity of a number of preparations and their combination with a proteolytic enzyme against the microflora of burn and surgical wounds].

Antibacterial activity of antibiotics (azlocillin, tobramycin and piperacillin), antiseptics (metacid, chlorhexidine and quinosoline) and some other drugs (dioxidine and mafenide acetate) against the main representatives of the burn and surgical wound microflora, i. e. Staphylococcus, P. aeruginosa, Proteus, Providencia, Serratia, Klebsiella and E. coli was studied. Tobramycin and piperacillin were highly active against P. aeruginosa, Staphylococcus and Proteus. It was shown that in the presence of terrilytin, a proteolytic enzyme the activity of the combinations of chlorhexidine with dioxidine or mafenide acetate against all microorganisms occurring in burn and surgical wounds markedly increased.

Administration, Topical↗
PubMed1991

Effects of topical antimicrobial agents on the human neutrophil respiratory burst.

The neutrophil oxidative burst plays an important role in killing intracellular microorganisms. We studied the effects of topical antimicrobial agents on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated oxidative burst of human peripheral blood neutrophils, using a flow cytometric assay. Mafenide acetate, sulfadiazine silver, gentamicin sulfate, neomycin sulfate-polymyxin B sulfate (Neosporin GU irrigant), acetic acid, amphotericin B, and povidone-iodine inhibited the neutrophil oxidative burst at or below clinical concentrations, while 0.25% modified diluted sodium hypochlorite (Dakin's) solution caused cell death. Bacitracin-polymyxin B sulfate (Polysporin) greatly augmented the respiratory burst; this effect was due to the bacitracin component. Diluted gentamicin and acetic acid also augmented intracellular hydrogen peroxide production, but to a lesser extent than Polysporin. Inhibition of the respiratory burst of neutrophils might be considered when these agents are used for topical wound care, although clinical correlates of these effects have not been determined.

Acetates↗
PubMed1986

Chondritis of the burned ear: a preventable complication.

Chondritis may occur in up to 25 percent of burned ears and commonly follows a superficial partial-thickness injury. The onset is usually insidious and often delayed. Prevention is the key, as the treatment of an established infection frequently leads to disastrous consequences. Herein, we have reviewed 136 consecutive inpatients with burns of the ear. The burned ear was managed by careful, twice daily washing with minimal debridement, frequent application of mafenide acetate, and avoidance of pressure on the affected ear. Exposed cartilage was treated in the same manner, with surgical debridement of grossly nonviable tissue followed by skin grafting as necessary. There were no cases of chondritis in the series. Recognition of the potential for chondritis in any burn of the ear underscores the need for careful wound management, even for relatively minor injuries. The extreme difficulty of prospectively identifying the ear that will become infected coupled with the risks associated with more aggressive methods of prevention make these methods unwarranted.

Adolescent↗
PubMed1989

In vitro toxicity of topical antimicrobial agents to human fibroblasts.

Topical antimicrobial agents are essential to optimal burn care. However, exposure of WI-38 human diploid fibroblasts (ATCC CCL 75) and fresh donor human dermal fibroblasts to silver sulfadiazine and mafenide acetate results in a significant reduction in cell proliferation, as determined by hemocytometer cell counts and total matrix protein assays, within 48 hr of exposure. Changes in cellular morphology and progressive deterioration of cytoplasmic organelles and the nucleus are seen with phase-contrast microscopy and transmission electron microscopy. These findings may explain the clinical observation of delayed wound healing after the use of topical antimicrobial agents.

Anti-Infective Agents, Local↗
PubMed1990

Cytotoxicity to cultured human keratinocytes of topical antimicrobial agents.

Cultured skin grafts administered clinically for closure of burn wounds may be contacted by topically applied antimicrobial agents. A study was performed to assess whether commonly used topical antimicrobial agents are toxic to cultured human keratinocytes (HK) in vitro. Serum-free MCDB 153 culture medium containing Neosporin G.U. irrigant (Neomycin, 40 micrograms/ml-polymyxin B sulfate, 200 units/ml) and a standard tissue culture antimicrobial agent of penicillin (10,000 units/ml)-streptomycin (10,000 micrograms/ml)-amphotericin B (25 micrograms/ml) had no effect on the keratinocyte growth rates when compared to standard MCDB 153 medium without antibiotics. Medium containing Sulfamylon (mafenide acetate, 0.85%), Polysporin (polymyxin B sulfate, 1 x 10(4) units/ml-bacitracin, 500 units/ml), gentamicin sulfate (0.1%), modified Dakins solution (25%), and acetic acid (0.25%) all showed statistically significant (P less than 0.01) decreases in keratinocyte growth rates. This data suggests that commonly applied antimicrobials may not be appropriate for cultured grafts in the concentrations that are used clinically.

Acetates↗