This chapter will provide an overview of antiseptic agents used to irrigate wounds for the prevention or treatment of orthopaedic infections, including their mechanism of action, spectrum of microbicidal activity, safety including potential adverse effects, efficacy in eliminating infective pathogens, and efficacy against established biofilm. Some of the common irrigation solutions include acetic acid, bacitracin and polymyxin, chlorhexidine, dilute povidone-iodine (PI), sodium hypochlorite, and hydrogen peroxide. The current guidelines for prevention of surgical site infection (SSI) from the Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and International Consensus Meeting (ICM) on orthopaedic infections only recognize sterile dilute PI as the most optimal irrigation solution. PI, sodium hypochlorite, and hydrogen peroxide provide the broadest range of antimicrobial coverage. Chlorhexidine, PI, and hydrogen peroxide may be useful in eradicating biofilm. The addition of antibiotics to irrigation solutions is not recommended as it does not confer any benefit and may further contribute to emergence of antibiotic resistant pathogens. While severe adverse effects are uncommon, cases of anaphylaxis with chlorhexidine and oxygen emboli with the use of hydrogen peroxide have been reported.
3 Irrigation Solutions for Orthopaedic Infections
Practical Tips
Dilute povidone-iodine (PI) solution, at a concentration of 0.35%, may be a preferred surgical irrigant given its broad spectrum of antimicrobial activity and efficacy.
Addition of antibiotics to irrigation solution have not demonstrated increased efficacy in preventing infection and may contribute to antibiotic resistance.
Broad antimicrobial coverage can be achieved with PI, sodium hypochlorite, and hydrogen peroxide.
PI, chlorhexidine, and hydrogen peroxide have demonstrated efficacy in reducing biofilm.
3.1 Acetic Acid
3.1.1 Overview of Antiseptic Agents Mechanism of Action
Acetic acid (AA) is a weak organic acid that has long been used in the treatment of infections and is used in bladder irrigation and otitis externa. 1 Weak acids are thought to have cytotoxic effects by disrupting the proton gradients that are required for synthesis of adenosine triphosphate (ATP) by bacteria and fungi (▶ Table 3.1). 2
Spectrum of Antimicrobial Activity
AA has demonstrated antimicrobial activity against gram-positive and gram-negative organisms, both in the free-floating (planktonic) and biofilm states, as well as fungal species. 3 , 4 Exposure to a 6% solution of AA for 30 minutes has been shown to be effective against Actinobacteria and Mycobacterium tuberculosis. 5
Safety and Adverse Effects
AA is considered harmless to tissues at concentrations of 5% or less, but may impair wound healing at concentration as low as 0.25%. 3 , 6 At concentrations greater than 10%, AA can be damaging to tissues and potentially corrosive to metals, although the metals commonly used for orthopaedic implants are resistant to these corrosive effects. 3 , 7 Hypersensitivity to AA solutions has not been documented in the literature.
3.1.2 Efficacy as Surgical Wound Irrigant
Prophylactic Use
No studies have assessed irrigation with AA as a prophylactic measure to reduce risk of infection.
Use in Irrigation and Debridement of Infection and Efficacy against Biofilm
Due to the inability of other irrigation solutions to completely eradicate biofilms, several studies have evaluated AA irrigation during debridement when treating orthopaedic infections. Exposure of tissues to a 3% AA solution for 20 minutes has been shown to be safe and only very low concentrations (0.19%) are required to inhibit bacterial growth. 8 While three studies have assessed the efficacy of AA in eradicating biofilm, two of these studies had clinically unfeasible exposure times of 180 minutes and 24 hours. 7 , 9 The third, most recent study found that concentrations of 15% AA for 10 minutes and 11% AA for 20 minutes were required to eradicate 99.9% of colony-forming units (CFUs), which defines the minimum biofilm-eradicating concentration (MBEC). These concentrations are above the safety threshold of 5%, 7 suggesting that AA is not effective in eradicating biofilm. However, at the maximal clinically acceptable concentration of 5%, AA was able to eradicate 96.1% of CFUs following 20 minutes of exposure, so AA may still have a role in treating orthopaedic infections, albeit likely not as sole therapy. 3
3.2 Bacitracin and Polymyxin
3.2.1 Overview of Antiseptic Agent
Mechanism of Action
Bacitracin comprises a mixture of cyclic polypeptides that have both bacteriostatic and bactericidal properties. It works by inhibiting cell wall synthesis and certain bacterial enzymes. 10 Polymyxin B is also a mixture of polypeptides that increase cell membrane permeability leading to cell death. 11
Spectrum of Antimicrobial Activity
Bacitracin is mostly effective against gram-positive organisms, predominantly staphylococcal species, but Neisseria species have also shown susceptibility, while polymyxin B provides gram-negative coverage. 10 , 11 Several common pathogenic organisms, including Staphylococcus aureus, Escherichia coli, Streptococcus pneumonia, and Enterococcus faecalis, have been reported to be resistant to these agents. 12 , 13
Safety and Adverse Effects
At clinical doses, the combination of bacitracin and polymyxin has been shown to inhibit replication and function of both fibroblasts and keratinocytes, suggesting that they may impair wound healing. 6 Patients may develop hypersensitivity to bacitracin and polymyxin, which most often only presents with mild local symptoms, but cases of anaphylaxis have been described in the literature. 14 Bacitracin is known to cause nephrotoxicity when delivered through the intramuscular route, but toxicity resulting from topical use has not been reported. 10 Increasing resistance to both antibacterial agents have been described in the literature. 15
3.2.2 Efficacy as a Surgical Wound Irrigant
Prophylactic Use
Early studies provided evidence that diluted topical antibiotics in irrigation solution reduced the risk of surgical site infections (SSIs). Commonly, the two antibiotics are added to irrigation solution to obtain a concentration of 0.05 mg polymyxin B and 50 units of bacitracin per milliliter. 16 However, recent evidence has determined that the addition of antibiotics to irrigation solutions has not demonstrated any benefit for preventing SSIs. 17 , 18 Additionally, unlike antiseptic agents, resistance to antibiotics is an issue of continued growing concern, in which the misuse of antibiotics has been cited as a significant contributing factor. 19
Use in Irrigation and Debridement of Infection and Efficacy against Biofilm
Irrigation with topical antibiotics is unlikely to be beneficial for treating orthopaedic infections. Exposure to triple topical antibiotics, namely bacitracin, polymyxin B, and gentamicin, for up to 10 minutes demonstrated no effect in eradicating biofilm. 20
3.3 Dilute Povidone-Iodine (PI)
3.3.1 Overview of Antiseptic Agent
Mechanism of Action
PI consists of iodine conjugated to polyvinylpyrrolidone, increasing the aqueous solubility of iodine. Free iodine is released into solution at a concentration of 1%, which in turn oxidizes and deactivates nucleotides, proteins, and fatty acids found in the cell membrane and cytosol. 21 , 22
Spectrum of Antimicrobial Activity
By this mechanism, PI has microbicidal effects on a broad spectrum of microorganisms including bacteria, both gram-positive and gram-negative, certain viruses, fungi, spores, and less common pathogens. Antimicrobial effects can occur within 30 seconds of exposure and have demonstrated efficacy against several drug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). No evidence of developed resistance to PI has been documented in the literature. 21 , 23
Safety and Adverse Effects
In vitro studies and case reports have raised concerns regarding safety of PI, highlighting potential cytotoxic effects on chondrocytes, osteoblasts, fibroblasts, and keratinocytes as well as the potential for metabolic disturbances. 6 , 24 , 25 , 26 None of these potential adverse effects have been substantiated in the several randomized-controlled trials evaluating irrigation of surgical wounds with PI. 27 , 28 , 29 , 30 , 31 True allergies to PI are uncommon, with a prevalence of 0.4%, and severe allergic reactions, such as anaphylaxis, are exceedingly rare. 32 The results of three previous studies suggest that PI in combination with chlorhexidine provides greater efficacy than either antiseptic alone. However, it is not yet known if these compounds may react to form harmful products. 33 Iodide ion is known to react with hypochlorite to form either iodine or triiodide ion, 34 and the in vivo effects of that combination are currently unknown. It is also unknown if other potentially harmful compounds may form from mixing NaOCl with PI. Hydrogen peroxide does not appear to react with PI in solution. 33 PI is available in both sterile and nonsterile preparations. Reports of iatrogenic infections from contaminated nonsterile PI solutions have been documented in the literature. 35 Therefore, it is recommended to only use sterile PI for surgical procedures, while nonsterile PI should be reserved for cleansing of intact skin.
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