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The Role Of Antibiotics and Antiseptics In Wound Healing

Wound infection is a leading cause of delayed wound healing in chronic wounds. In general, almost all wounds are colonized by bacteria and pathogens to some extent. However, the presence of bacteria in the wound bed does not necessarily imply wound infection. [1] Antimicrobial agents have historically been used to reduce the bacterial burden in chronic wounds. The emergence of antibiotic-resistant organisms has recently created a controversy regarding the indiscriminate use of antimicrobial agents in wound care. 

How Infection Interferes With Wound Healing

Before considering the role of antimicrobial agents in wound healing, wound care specialists and podiatrists need to consider the role of infection in delaying wound healing. 

When the growth of pathogens in the wound exceeds a certain limit, it can result in the invasion of deep tissues and the development of infections like cellulitis, osteomyelitis, and sepsis. [2] As a result of microbial invasion in the wound, neutrophils are recruited to the wound site which releases proteolytic enzymes causing further tissue damage. [3] There is also an increase in the inflammatory mediators in the wound site which results in vasoconstriction and thrombosis, contributing to a hypoxic wound environment which is a known contributor to delayed wound healing. 

Wound infection also interferes with the proliferation phase of wound healing through excessive stimulation of macrophages by bacterial toxins. This in turn leads to increased angiogenesis at the wound site, which results in fragile, edematous granulation tissue. Despite the increased deposition of collagen in infected wounds, there is also an increased breakdown of collagen and diminished proliferation of epithelial cells. [4] Wound contraction is also affected by bacterial infection. All of these effects collectively delay wound healing, which highlights the importance of the early identification and treatment of wound infection. 

Antibiotic Usage In Wound Care

The application of antibiotic therapy in wound care is currently regarded as controversial. Topical antibiotics have historically been used for the prophylaxis of postoperative wounds. However recent evidence suggests that the topical antibiotics do not have any substantial effect on wound healing, and might contribute to the development of multidrug-resistant (MDR) organisms.  Furthermore, there's also a risk of hypersensitivity reactions with the use of antibiotics. [5]

Current guidelines recommend the use of antibiotics for high-risk wounds and in the presence of clinical wound infection. Due to the lack of specific criteria for infection identification, wound care specialists and podiatrists need to rely on their clinical judgment for an antibiotic prescription. The clinical signs and symptoms of wound infection can include local signs such as cellulitis, purulence, malodor, or wet gangrene. Systemic signs of infection include fever, hypertension, hyperglycemia, and altered mental status. [6]

A microbiological sample should be obtained from the wound before initiating antibiotic therapy. Contaminated wounds should be treated with co-amoxiclav. However, in case the patient is allergic to penicillin, erythromycin combined with metronidazole can be a viable alternative. For clean wounds, flucloxacillin should be used. The antibiotics should be administered either orally or intravenously. [7]

Antiseptic Usage In Wound Management 

In contrast to antibiotics that specifically target a particular pathogen, antiseptics can target multiple microorganisms and therefore have a broader spectrum of activity. The antiseptic solutions are applied topically and help to reduce wound bioburden which is critical in promoting wound healing. Due to the lower resistance rates associated with antiseptics, they have emerged as a popular antimicrobial treatment for wound care. [8] The following are the commonly available antiseptic agents:

  • Iodine: By providing a moist wound environment, cadexomer iodine can stimulate wound healing. [9] It is also an effective antimicrobial agent, targeting both gram-positive and gram-negative bacteria. It has been found to improve wound healing rates but should only be used for the short term. 
  • Polyhexanide: It is now one of the most commonly used antiseptics in wound care due to its low cytotoxicity. The antiseptic activity of polyhexanide does not interfere with wound epithelialization and is superior in efficacy to iodine-based antiseptics. Polyhexanide has also been found to be effective in the successful eradication of Methicillin-Resistant Staph Aureus (MRSA). [10]
  • Silver-based agents: Silver is toxic to bacteria and is used by wound care specialists to decrease the bacterial burden in the wounds. However, despite the documented toxic effect of silver on bacterial activity, silver-based products are not significantly effective compared to other wound care methods in improving wound healing. In addition, silver is highly toxic to fibroblasts and keratinocytes so its use should be limited. [11]

References:

  1. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clinical microbiology reviews. 2001 Apr 1;14(2):244-69.
  2. Tarnuzzer RW, Schultz GS. Biochemical analysis of acute and chronic wound environments. Wound Repair and Regeneration. 1996 Jul;4(3):321-5.
  3. Ninnemann JL, editor. Traumatic injury: infection and other immunologic sequelae. University Park Press; 1983.
  4. Bucknall TE. The effect of local infection upon wound healing: an experimental study. Journal of British Surgery. 1980 Dec;67(12):851-5.
  5. Draelos ZD, Rizer RL, Trookman NS. A comparison of postprocedural wound care treatments: do antibiotic-based ointments improve outcomes?. Journal of the American Academy of Dermatology. 2011 Mar 1;64(3):S23-9.
  6. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clinical infectious diseases. 2012 Jun 15;54(12):e132-73.
  7. Laceration - NICE CKS, January 2021 
  8. Thomas GW, Rael LT, Bar-Or R, Shimonkevitz R, Mains CW, Slone DS, Craun ML, Bar-Or D. Mechanisms of delayed wound healing by commonly used antiseptics. Journal of Trauma and Acute Care Surgery. 2009 Jan 1;66(1):82-91.
  9. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clinical infectious diseases. 2009 Nov 15;49(10):1541-9.
  10. Rietkötter J, Körber A, Grabbe S, Dissemond J. Eradication of methicillin-resistant Staphylococcus aureus in a chronic wound by a new polyhexanide hydrogel. Journal of the European Academy of Dermatology and Venereology: JEADV. 2007 Nov 1;21(10):1416-7.
  11. Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on burn wound infection control and healing: review of the literature. burns. 2007 Mar 1;33(2):139-48.