Simple and Effective Approach for Treating Non-healing Ulcers After a Snakebite

Abstract: The aim of this study was to develop a simple and effective approach for the treatment of snakebite ulcers using citric acid as the sole antimicrobial agent. Fifty-two (52) cases of snakebite ulcers that had not responded to conventional antibiotic therapy and local wound care were investigated for culture and susceptibility using swabs collected from the ulcers. Staphylococcus aureus (30.69%) and Pseudomonas aeruginosa (21.78%) were the most common isolates. Ciprofloxacin (61.38%) and amikacin (56.43%) were found to be most effective antimicrobial agents. Determination of susceptibility to citric acid showed MIC in the range of 500–2500 µg/mL. Topical application of citric acid ointment resulted in complete healing in 50 (96.15%) cases. Two cases (3.85%) showed healthy granulation, but wound closure required skin grafting because of large, raw areas. Results indicate that citric acid is the best alternative for effective management of snakebite ulcers.   Development of nonhealing ulcers following a snakebite is very common in patients who survive the bite. The severity of symptoms depends on the venom’s potency. Swelling of the bitten part and spreading cellulitis are the common manifestations. In the event of recovery, surviving patients may develop necrosis of the skin, muscles, tendons, and even bones. Various secondary infections leading to suppuration and gangrene may necessitate amputation.^1,2 To avoid further complications, it becomes obligatory to take proper care of local suppurative lesions infected secondarily by a variety of bacteria.   Topical use of citric acid for the treatment of various chronic wound infections has been reported.^3–6 In the present study, an attempt was made to treat snakebite ulcers using 3% citric acid as the sole topical antimicrobial agent. Methods   Fifty-two cases of snakebite ulcers (37 viper bites and 15 cobra bites) that were unresponsive to conventional antibiotic therapy (one antibiotic from aminoglycosides group [gentamicin or amikacin] another from cephalosporin [ceftazidime or ceftriaxone], or fluoroquinolones group [ciprofloxacin and metronidazole]) and had undergone local wound care for more than 1 month were included in the study. A swab culture was collected and processed using standard technique to confirm infection.⁷ Bacteria were isolated in significant numbers to confirm infection, which was defined as confluent growth on primary and secondary streaking, or a minimum of 100 colonies.   The susceptibility of each isolate was studied using the Kirby-Bauer disc diffusion method.⁸ Minimum inhibitory concentration (MIC) to citric acid was determined by broth dilution.⁹ The 3% citric acid ointment was prepared by mechanically mixing with white soft paraffin (100% pure petroleum jelly), acting as the inert vehicle, and was applied after thoroughly debriding the ulcers. Citric acid ointment was applied once daily until the ulcer healed completely or showed formation of healthy granulation tissue. Antibiotics were not administered except in two cases where systemic symptoms (ie, fever and toxicity) and rapidly spreading cellulitis were present. Skin grafting was performed in two cases after healthy granulation tissue had formed.

Results

  Culture studies revealed that S aureus (30.69%) was the most common isolate followed by P aeruginosa (21.78%), E coli (14.85%), and other bacteria in decreasing order of frequency. Ciprofloxacin (61.38%) followed by amikacin (56.43%) were the most effective antimicrobial agents in vitro. Ampicillin (11.88%) was the least effective antimicrobial agent (Table 1). Citric acid inhibited all bacterial isolates. The MIC of citric acid in vitro ranged from 500–2500 µg/mL against different clinical isolates. P aeruginosa was the most susceptible (MIC: 500–1000 µg/mL) and Klebsiella spp. was the least susceptible (MIC: 2000–2500 µg/mL). Other bacteria (ie, S aureus) had MIC ranging from 900–1000 µg/mL; however, E coli (MIC: 1500–2000 µg/mL), Proteus spp., and Citrobacter spp. had MICs ranging from 1000–1500 µg/mL. Application of citric acid to snakebite ulcers resulted in either complete healing or formation of healthy granulation tissue and elimination of pathogens from infection sites (Figures 1–4). Out of 52 cases of snakebite ulcers, 50 (96.15%) cases healed completely and were treated successfully in 16 to 43 applications of 3% citric acid; however, in two cases (3.85%) wound closure was done by skin grafting because of large, raw areas.

Discussion

  Citric acid has been used as topical agent for effective management of a variety of chronic wound infections.^3–6 Based on the excellent results of citric acid in the management of a variety of chronic wounds, an attempt was made to use citric acid as a topical agent in the management of snakebite ulcers. Topical application of 3% citric acid ointment in 52 cases was effective and eliminated bacterial pathogens from the infected sites.   The citric acid has antibacterial activity as indicated by microbiological studies and by rapid clearing of infected surfaces. The reason for this antibacterial activity may be lowering of pH that makes an environment unfavorable for growth and multiplication of bacterial pathogens at infection site. Citric acid also enhances epithelization, which is a major factor in successful wound healing. Citric acid keeps the wound surface moist and prevents wound desiccation, thus reducing necrosis. Histological studies showed that it increases vascularity, which helps to remove dead tissue and makes the wound healthier.¹⁰ As a result of these actions, there is increased epithelial cell migration from surrounding skin, which enhances epithelization. In the present study citric acid was found to be nontoxic and active against a broad range of bacterial pathogens including those that were resistant to multiple antibiotics. Thus, it was highly effective and shares many characteristics and advantages of the ideal topical agent.

Conclusion

  These results show that citric acid treatment is a simple, reliable, nontoxic, and economical approach for effective management of snakebite ulcers and the best alternative when the management of snakebite ulcers is a matter of great concern.

References

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