Simple and Effective Approach for Wound-Bed Preparation by Topical Citric Acid Application

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A wound heals by progression through various stages of inflammation, granulation tissue synthesis, collagen deposition and maturation, and epithelization.¹ The majority of acute wounds follow this organized pattern to achieve structural and functional stability. However, some acute wounds with large raw areas progress into chronic wounds refractory to conventional treatments. The presence of bacteria in significant numbers is one important reason a wound may not proceed through the healing trajectory.^2-4

In chronic wounds that do not respond to conventional therapies, wound bed preparation (WBP) is a structured approach to wound healing either by promoting natural healing or by facilitating alternative approaches such as skin grafting, dermal matrices, or other skin coverage products. Proper WBP is the first and most important step to achieve healing in chronic wounds.^3,5 Thus, WBP is a commonly used tool for assessing and treating chronic wounds. It is critical for successful wound closure by split-thickness skin grafting (STSG) because it establishes optimal physiological conditions and nourishes the graft, thereby preventing graft rejection.^3,5,6 WBP is needed to remove obstacles to healing and initiate the normal repair process. Debridement is the first step in WBP. Complementary approaches such as wound wash/irrigation, dressings with antiseptic solutions, topical antimicrobial agents, and systemic antibiotics are routinely used to reduce the burden of bacterial load and to augment WBP to make the skin grafting acceptable.^3,5-8 Honey has been reported to be effective in WBP in diabetic foot ulcers.⁹ The use of 3% citric acid has also been reported to provide effective WBP for wounds infected with multiple antibiotic-resistant bacterial pathogens, which are very difficult to eliminate from the infection site with conventional methods of treatment.¹⁰ The literature reveals that citric acid creates an acidic milieu that is unfavorable for growth of various microbes. Controlling infection results in early reduction of wound discharge, maintains a moist wound bed, and is known to facilitate early neovascularisation, fibroplasia, and neo-epithelization.^11,12

The present study evaluated the sole usage of 2% citric acid ointment for WBP of wounds infected with multiple antibiotic-resistant strains of bacterial pathogens that had proven refractory to conventional treatment approaches.

A total of 24 cases of chronic wounds with large raw areas (any ulcer/raw area ≥ 10 cm in length and/or width) were included for treatment with 2% citric acid ointment with the aim of WBP for STSG or healing by secondary intention (Table 1). None of the wounds had responded to conventional therapy (use of betadine, hydrogen peroxide, and Edinburgh University Solution of Lime with local antimicrobials like soframycin and mupirocin) after more than 3 weeks of treatment. Patients provided informed consent and the study followed ethical guidelines. The study’s endpoint was the appearance of healthy granulation tissue suitable for split-thickness skin grafting or healing by secondary intention.

A specimen of pus was obtained from each wound bed and processed for isolation and identification of causative bacteria using conventional aerobic culture techniques.¹³Antibiotic susceptibility testing of each isolate was carried out by a modified Kirby-Bauer disc diffusion method¹⁴ using ampicillin (10 µg), ciprofloxacin (5 µg), cephalexin (30 µg), gentamicin (10 µg), amikacin (30 µg), carbenicillin (100 µg), ceftazidime (30 µg), levofloxacin (5 µg), imipenem (10 µg), and meropenem (10 µg) discs. In addition, cefoxitin (30 µg) and linezolid (30 µg) were used for Staphylococcus aureus, and a piperacillin + tazobactam combination (100 µg + 10 µg) was used for Gram-negative bacteria.

Topical application of 2% citric acid ointment (prepared by triturating 2 g of citric acid in 100 g of 100% pure petroleum jelly as a base under sterile precautions) was applied over the wound bed after irrigating and cleaning the wound with normal saline. The citric acid ointment was applied once daily until healthy granulation tissue was clearly visible. No antibiotics were given during WBP, except in those patients showing systemic symptoms such as fever or toxemia.

Table 1 shows the patient demographic data and wound characteristics. Nine patients had non-healing ulcers and 6 patients had a post-traumatic wound with infection and delayed healing. A total of 32 strains from 24 patients were isolated. Staphylococcus aureus (12, 37.5%) was the most common isolate, followed by Pseudomonas aeruginosa (8, 25.0%), Escherichia coli (5, 15.6%), Klebsiella spp. (3, 9.4%), and others in decreasing order of frequency. The majority of isolates were found to be resistant to multiple antibiotics (Table 1). Application of 2% citric acid ointment resulted in the formation of healthy granulation tissue in all cases after 3 to 20 applications (Table 1, Figures 1 and 2).


 

The ultimate aim of wound management in large raw areas is to prepare them for grafting by removing the barriers that hinder the formation of healthy granulation tissue. Infection is the single most important obstacle in WBP, because it does not allow wounds to granulate.¹⁵ In a chronic wound, elimination of pathogens and infection management is a matter of concern because of safety and efficacy issues related to topical antiseptic agents and the inability of systemic antimicrobial agents to reach adequate levels in chronic granulation tissue. Studies suggest that many antiseptic agents—including iodine, chlorhexidine, hydrogen peroxide, alcohol, silver sulfadiazine, mafenide acetate, sodium hypochlorite (Dakin’s solution), polyhexamethylene biguanide chloride, acetic acid, and even povidone iodine—are toxic to the cells involved in the wound healing process. These agents interfere with healing by slowing down the process of epithelization.^16-24 In chronic wounds, poor and unhealthy granulation results in inadequate levels of antibiotics; thus, the systemic administration of antibiotics is ineffective against the bioburden in chronic wounds.²⁵ Topical use of growth factors has shown promising results in controlled environments, but long-term effects and cost are areas of concern.²⁶

The use of citric acid has been reported to be effective in the management of a variety of chronic wounds, including those caused by multiple antibiotic-resistant strains of bacteria.^27-30A concentration of 3% citric acid ointment has been found to be effective in WBP in orthopedic patients after road traffic accidents.¹⁰ On a trial-and-error basis, the authors of the present study started the application of 2% citric acid ointment in the first case in this series. Surprisingly, that wound granulated very well after only 3 applications. This prompted the use of 2% citric acid ointment for wound management in subsequent patients with large raw areas in this study. Some patients had additional comorbidities such as diabetes, leprosy, snakebite, and necrotizing fasciitis. Many wounds were infected with multiple antibiotic-resistant strains of bacterial pathogens. In the present study, 2% citric acid ointment provided effective outcomes with favorable WBP in all patients, despite comorbidities and antibiotic resistance. Favorable granulation tissue was noted with 3 to 20 applications, thereby contributing to shorter hospital stays and lower costs. No local toxicity was noted.

This is an observational descriptive study. The small sample size and absence of a control group are the only limitations in this study.

In this study, 2% citric acid ointment was highly effective in controlling infections—an important barrier to wound healing—and promoting the formation of healthy granulation. Given the safety and efficacy issues associated with conventional topical antiseptics, these observations highlight the role of citric acid as a safe, effective, and economical option with no local toxicity.

Authors: Rajendra Malu, MS; Geetkumar Hajgude, MS; Abhijit S. Rayate, MS; Kaustubh Jaiswal, MBBS; Arunkumar Rao, MS; and Basavraj Nagoba, PhD

Affiliation: MIMSR Medical College, Latur, India

Correspondence: Basavraj S. Nagoba, PhD; MIMSR Medical College, Latur – 413 531 (M.S.) India; dr_bsnagoba@yahoo.com        

Disclosure: The authors have no financial or other conflicts of interest to disclose.

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics statement: The patients in this manuscript gave written informed consent for publication of their case details and photos. The authors have maintained confidentiality and dignity of the patient throughout the work for this study. The Institutional Ethics Committee approved the study presentation and publication.