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Section IV.   MOIST WOUND HEALING FOR THE BURN WOUND? Continued . . .

D ) Comparison of Antibacterial Safety and Stability Properties of Neomycin, Neosporin, Polymyxin and Sulfamylon Solutions on Wounds. 

A comparison of 5% Sulfamylon Solution with Double Antibiotic Solution for Grafts in Burns. Warden GD, MD, et al. Shriners Hospitals for Children, Cincinnati, OH

June 1998 marked the approval of Sulfamylon (mafenide acetate) 5% solution (SMS) by the FDA. This was preceded by many years of clinical use for microbial control in excised and grafted burn wounds under an Investigational New Drug exemption. 

The SMS IND study prospectively included those patients with large burns (28.9% Total Body Surface Area – TBSA), burns with known Pseudomonal colonization and burns exposed to the flora of other burn units. These patients were treated with SMS alternating with Double Antibiotic solution (DAB: Neomycin 40mg. + Polymyxin B 200,000 U/I) to fresh skin grafts. Smaller burns (9.7% TBSA) whose grafts were treated with DAB alone, were evaluated retrospectively for comparison. 438 patients were treated between 5/21/91 and 10/13/95, including 281 in the SMS/DAB (study) group and 157 in the DAB only (control) group. 

Treatment failure was defined as infectious graft loss or a change in topical treatment due to colonization with the potential for loss. Within the two treatment groups 11 DAB and 44 SMS patients had graft loss. These losses were significantly less in the SMS group by the Cochran-Mantel-Haenzel Boot Strap estimation of Odds Ratio, despite the fact that this group had significantly larger burns. A change in topical treatment was required for 7.6% of the DAB patients, but only 2% of the SMS patients. 

The cause for change in the latter group was generally the need to cover yeast or fungus. Microbial prevalence within each group was significantly different (p = 0.001) in the growth of any organism at day 5, with 76% of the DAB group having positive cultures versus only 54% of the SMS group. There were more positive cultures for Staph (p = 0.05) and Pseudomonas aeruginosa (p < 0.001) in the DAB group at day 5 than in the SMS group. Day 10 was significant for positive cultures in the DAB group (p=0.001). Gram negative organisms were also significantly higher in the DAB group at both day 5 (p< 0.001) and day 10 (p=0.001). Yeast and fungus were not controlled well by SMS in the very large burns. 

Significantly more yeast grew in the SMS group at day 2 (p=0.011) and day 5 (p< 0.001). Fungal growth was higher in the SMS group at days 2,5 and 10. In summary, this study was clearly biased against SMS with a larger burn size and higher mortality in this group. Despite the larger burns. 

SMS reduced the infectious graft loss compared to DAB. 

(J Burn Care Rehab 1999:20; 232)

Introduction: In an attempt to alternate topical agents and to individualize their use to specific burn wounds, Neosporin G.U. Irrigant is sometimes used as a wet dressing for second and third degree burn wounds. This study was designed to evaluate the combination of this solution with Nystatin to increase the broad spectrum coverage of the Neosporin to include antifungal activity.

Methodology: ATCC stock cultures and 2 burn wound isolates of each species of common burn wound pathogens were tested for antimicrobial susceptibility or resistance against 4 different concentrations of Nystatin (50,100, 150 and 200 units/ml) combined with Neosporin GU Irrigant. The antimicrobial activity was determined using the Holder Wet Disc Antimicrobial Solution Assay. Sterility was confirmed by broth culture.

Conclusion: Neosporin and nystatin can be combined and used as a burn wound dressing with antifungal activity with nystatin concentrations of 150 units/ml or more. Neosporin GU solution is not effective against Pseudomonas Enterococcus and Proteus mirabilis. However, this combination can broaden the spectrum of activity as a burn wound dressing for common skin flora (J Burn Care Rehab 1999:20:232.)

Sulfamylon (mafenide acetate 5%, Bertek, Inc) is often used with antifungal agents to enhance coverage of Candida, Aspergillus and other fungi. There are conflicting reports on the efficacy of these drug combinations. We studied efficacy of 5% mafedrine solution (MAF) with topical miconazole and nystatin, and systemic antifungal agents including amphotericin B (AMPHB), itraconazole and fluconazole in vitro.

Methods: MAF was combined with Micro-Guard (miconazole nitrate 2%) and Nystop (nystatin 100K USP U/gm) powders at standard concentration, 1:10 and 1:100 dilutions and plated on ATCC Calbicans and B subtilis. Zones of inhibition were measured at 24 and 48 hrs and compared with standards for each agent alone. Effects of 5%, 0.5% and 0.05% MAF on systemic antigungal agents were measured by sensitivity testing. Post controls were diluted to appropriate known tissue achievable levels. 2-fold dilutions of itraconazole and AMPHB were tested in presence of ATCCC albicans and 2 pt isolates of Aspergillus fumigatus.

Results: In the bioassay, the zones of inhibition test for antagonism when combining MAF with chemical and commercial grade nystatin and miconazole powders. Small diameter sizes indicate antagonism, and larger zones correlate with synergism. Equal diameter sizes indicate no effect. Combinations of MAF with miconazole and nystatin powders showed no clinically significant difference in zone sizes when tested against both B subtilis and C albicans. Although nystatin; MAF combination decreased zone age against C albicans, this was most likely related to poor solubility. In addition, the antibiotic sensitivity testing checked for antagonism by MAF on antifungal activity of miconazole, fluconazole, itraconazole, and AMPHB. MAF had no effect on activity of AMPHB and itranazole and AMPHB. MAF did not effect activity of AMPHB and itraconazole, and AMPHB. MAF did not affect activity of AMPHB and itraconazole toward ATCCC albicans and 2 pt isolates of A fumigatus. MAF increased MIC of fluconazole against ATCCC albicans from 0.25 to 0.5 mcg/ml, but these levels remained well below typical MIC’s of the organism.

Conclusion: MAF and selected antifungal agents showed no antagonism when combined. Our results may differ from previous studies because we used a powder formulation of nystatin; we suspect its sparingly soluble nature leavels low amounts of drug in solution to yield activity against C albicans.

We recommend MAF 5% solution with micronazole powder for broad topical coverage of burn wounds. (J Burn Care Rehab 2000:21;215)

Introduction: Sulfamylon solution 5% (SS) has been used as an adjunct to wound care after skin grafting for many years prior to its approval by the FDA for routine use. This is a summary of an IRB/FDA approved study of the safety of SS conducted in our burn center.

Methods: SS was used as a post-graft irrigant after Institutional Review Board approval to treat burn patients who underwent tangential excision and skin grafting. Records of this study were reviewed to assess safety. Via irrigation catheters placed at surgery, dressings were kept moist with SS solution until graft take and the interstices were closed. Nystatin Powder (10,000 u/ml) was added for fungal prophylaxis. The records of this study and recorded complications were resolved.

Conclusions: Utilizing a strict post graft wound care protocol, 5% Sulfamylon solution has a low complication rate as an adjunct to surgical debridement and grafting after burn injury. SS provides a moist antibacterial wound environment during and should be considered for wounds with a significant risk of wound infection. (J Burn Care Rehab 2000:21;214.)

The development of sophisticated antimicrobials has revolutionized burn care. In an attempt to alternate topical agents and individualize their use to specific burn wounds, a study using Neosporin GU irrigant (NGUI) in topical wound therapy was undertaken. Some issues raised in considering Neosporin were storage temperature and solution outdate. The purpose of this study was to assess the potency and stability of NGUI over time and at varied storage temperatures.

ATCC stock cultures of Pseudomonas aeruginosa (PSA), Escherichia coli, Enterococcus faecalis, Enterobacter cloacae, Staphylococcus aureus (HAS), Methicilllin Resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermis and 2 burn wound isolates of each species were tested for antimicrobial susceptibility/resistance and sterility over 16 weeks. The antimicrobial activity was determined using the Holder Wet Disc Antimicrobial Solution Assay. Sterility was confirmed by brother culture and testing was done weekly. The antibiotic solution was prepared in the manner and concentration used in clinical wound care and stored at 37, 25 and 4° C.

Sterility for all test solutions was maintained using standard laboratory sterile technique for the length of the study. Antimicrobial activity remained constant from strain to strain. Individual strain sensitivity patterns remained the same throughout the study. At 16 weeks the zones of inhibition had not changed and decreased potency was not noted. All isolates of Staphylococcus epidermis, Staphylococcus aureus, MRSA, Escherichia coli, and Enterobacter cloacae were sensitive to NGUI; while isolates of PSA and E. faecalis were resistant to NGUL. Storage temperature did not efficact potency. In conclusion, NGUI is a cost effective topical that can be used on the same patient after opening the container as long as sterile technique is used. NGUI maintains its efficacy and stability in storage where in an incubator, on the shelf, or in a refrigerator for a minimum period of 16 weeks. Proceed Amer Burn Assoc 1996:173;

Topical 5% Mafenide acetate suspension (MAS) has been shown to be effective in controlling microbial growth in the treatment of burn wounds. Concerns over time have been preparation procedures, storage temperature, sterility, stability and potency. The purpose of this study was to assess the stability and potency of 5% MAS over time and at varied storage temperatures.

ATCC stock cultures of Pseudomonas aeruginosa (PSA), Escherichia coli, Enterobacter cloacqae, Enterococcus faecalis, Staphylococcus aureus (HAS), Methicillin Resistant Staphylococcus aureus (MRSA), and Staphylococcus epidermis and 2 burn wound isolates of each species were tested for antimicrobial susceptivility/resistance and sterility over 16 weeks. The antimicrobial activity was determined using the Holder Wet Ldisc Antimicrobial Solution Assay. Sterility was confirmed by brother culture, and testing was done weekly. The antibiotic solution was prepared in the manner and concentration used in clinical wound care and stored at 37, 25 and 4° C.

Sterility for all test solutions was maintained using standard laboratory sterile technique for the length of the study. Antimicrobial activity varied from species to species and strain to strain, but individual strain sensitivity patterns remained constant throughout the study. PSA, HAS, E. faecalis and MRSA and their burn isolates were all sensitive to MAS. S. epi and both burn isolates were resistant, and E. coli was resistant with one isolate resistant and one sensitive. E. cloacae was sensitive with one isolate resistant and one sensitive to storage temperature. (efficacy was unaffected by storage temperature).

In conclusion, topical 5% MAS can be prepared in advance for use as a burn wound dressing; it can be stored in the incubator, on the shelf, or in the refrigerator for at least 16 weeks. This is a cost effective way to use 5% mafenide acetate suspension which does not jeopardize sterility, stability, or potency.

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