One antiseptic is safer and more efficacious than those used historically for treating surgical wounds

The Centers for Disease Control and Prevention (CDC) estimates that 27 million surgical procedures are performed each year in the United States, with an overall 2.8% surgical-site infection rate.1 Many of these surgical-site infections result in open wounds. It is not unusual for large wounds to remain open, to heal poorly, to be colonized with bacteria, and to remain infected for long periods.

The treatment of open wounds with topical agents that have broad-spectrum microbicidal activity is becoming increasingly important and desirable—especially before additional surgery can be done.2 Plastic surgeons are responsible for managing a significant percentage of colonized or infected open wounds.

The current treatment of many open wounds consists of operative debridement, parenteral antimicrobial agents, frequent dressing changes, and topically applied agents aimed at reducing microbial populations within the wound. The topical application of agents—other than sterile saline solution—on open wounds has remained controversial, as discussed below.

Typical Topical Agents

Saline is not antimicrobial, yet it is the only topical treatment used on most open or infected postoperative wounds. Treatment with saline alone significantly increases microbial titers, according to the report of a 1989 randomized emergency-department trial, in which contaminated traumatic open wounds were treated with sterile saline, povidone–iodine, or dry gauze.3 In that trial, the wounds were covered with gauze soaked with saline or povidone–iodine; for the control group, only dry gauze was used.

Quantitative cultures were run before and after treatment. The only significant trend was an increase in bacterial counts in the saline-soaked wounds after treatment (a 50-fold increase, compared to the controls). This effect was greater with higher initial levels of bacterial contamination. The group that was treated with saline had a higher wound-infection rate than the other groups.

Saline irrigation of open wounds is another common treatment. But irrigation as typically delivered—even with voluminous amounts of saline solution—removes little but surface contamination.4 Saline irrigation in the operating room (OR) should not be relied upon to completely reduce bacterial contamination, although it does remove debris, foreign material, and clots—all of which often contain bacteria—from surgical wounds.4

An in vitro study showed that saline irrigation reduced colony counts of Staphylococcus aureus, S. epidermidis, and Escherichia coli by 12%–56%. However, the reduction in colony numbers was not always statistically significant, and even when it was, the amount of reduction was not clinically significant.5

Chlorhexidine gluconate is the active ingredient in many antiseptic formulations, and it is used in dilute solutions for wound care. A 1988 study found little or no adverse impact to patients at concentrations of 0.05%–4%.6 The study also found that chlorhexidine gluconate does not appear to deter wound healing; its cytotoxic effect on fibroblasts in vitro does not exist in vivo. The study also showed that patients in the chlorhexidine gluconate group healed significantly faster than those in the saline-treated group.6

A 1992 burn-unit study found chlor­hexidine gluconate to be toxic to cultured human fibroblasts; thus, it recommended that chlorhexidine gluconate should not be used before making cultured skin grafts.7

In the United States, few formulations are available that can be used on open wounds. Most 4% chlor­hexidine gluconate formulations contain alcohol and detergents that can cause irritation, so they are not used on open wounds. Even so, dilutions of this formulation are widely used with positive results.

Acetic acid, which has an antimicrobial effect, has been used to treat open, infected wounds as long ago as 1778, during the American Revolution. Today, it is primarily used for wounds infected with Pseudomonas spp.8 Solutions of 0.25% acetic acid are estimated to decrease bacterial counts by only 20%.9 One in vitro trial showed that a 0.0025% solution (a factor of 100 less concentrated than the generally used dilution) of acetic acid lacked toxicity to fibroblasts but could inhibit only P. aeruginosa.10 

A 1985 comparison of the bactericidal and cytotoxic effects of serial dilutions of acetic acid showed that its cytotoxicity outweighed its bactericidal potency.11 Therefore, acetic acid is considered by many health care professionals to deter wound healing and should not be used. Moreover, its bactericidal ability is only selective.

Hypochlorite was first used to treat open wounds in France in 1825. In 1915, Dakin introduced a solution of 0.5% sodium hypochlorite that was used to disinfect open wounds during World War I.8 Now called Dakin solution, it is still used today, but its cytotoxicity makes it unsuitable for use in wound care.11 

However, bactericidal, noncytotoxic dilutions of sodium hypochlorite have been identified.10,11 McKenna and Lineaweaver showed 0.005% dilutions of sodium hypochlorite to be noncytotoxic yet bactericidal; such dilutions are 100 times less concentrated than the 0.5% solution that is commonly used in wounds. A study of capillary circulation of granulation tissue concluded that, “Hypochlorite solutions may be sufficiently toxic to preclude their clinical value.”12 

Iodine use on wounds was first reported in 1839. Iodine was used successfully during the US Civil War to treat open wounds. Molecular iodine can rapidly penetrate the cell walls of microorganisms; however, exactly how it kills living cells is not known.

Iodine is used today in the form of an iodophor, in which the carrier of the iodine is an inert polymer. This type of delivery agent increases the solubility of iodine by means of a sustained-release reservoir of the halogen. When iodophors are diluted, the amount of free iodine in solution increases. Thus, it is very important to follow the directions for use of this microbicidal product, because as the amount of free iodine increases, so does cell toxicity.13 

A solution of 1% povidone–iodine is the dilution most commonly used for wound care. This dilution is considered by many researchers to be unsuitable for use in wounds because of its cytotoxicity.10,11 Mckenna and Lineaweaver found that a 0.001% dilution was not cytotoxic, but remained effective against some strains of bacteria. One clinical study found that absorption from povidone–iodine preparations after topical administration resulted in possible metabolic complications.14

Hydrogen peroxide was first used as a disinfectant by an English physician in 1858 and was marketed under the name Sanitas. The 3% solution was popular for use on wounds from about 1920 to 1950. Hydrogen peroxide kills bacteria by decomposing to hydroxy radicals. It is produced by living cells to protect the body from harm caused by bacteria.

Catalase, a cell enzyme, adequately protects cells from damage by regulating steady-state levels of metabolically produced hydrogen peroxide. This defense overwhelms concentrations of hydrogen peroxide used as a disinfectant on human tissues.15 Today, hydrogen peroxide has been generally abandoned for use in wounds because of its unfavorable results, and it is a better disinfectant on inanimate objects.

Ethyl alcohol (ethanol) has a long history of medical use. In 1903, it was shown that a 60%–70% solution was the most effective at killing bacteria, but no concentration is sporicidal.

Isopropyl alcohol has a slightly greater bactericidal action than does ethyl alcohol. Both alcohols are relatively nontoxic in topical applications, have a cleansing action, and evaporate readily. They are widely used preceding veni­punctures, hypodermic injections, finger sticks, and other procedures that break the intact skin; they are also used as a hand rinse.16 But generally, they are not used in open wounds.

Parenteral antibiotics are frequently applied directly to open wounds, even though their efficacy in this regard has not been established.17 The effectiveness of topical antibiotic irrigation has been shown in vitro and in the surgical research literature.4 The focus of that research has been on antibiotic irrigation in the OR.

Transferring the use of triple antibiotic irrigation from the OR to the care of open wounds has not been therapeutically beneficial. Moreover, the cost of producing topical antibiotic solutions is significant. Also of concern is the development of, and selection for, resistant organisms after the use of antibiotic topical treatments.17 

In summary, topical treatment of colonized or infected open wounds is not novel, and several agents have been used over the years. Saline, the most commonly used solution, has no microbicidal activity and has been shown to significantly increase bacterial counts.3,18 But the other topical agents (acetic acid, hypochlorite, iodine, hydrogen peroxide, and ethyl or isopropyl alcohol) tend to be toxic to healing tissues or ineffective in reducing bacterial counts.4,11,12,17 Parenteral antimicrobials have no established therapeutic benefit in the treatment of open wounds, and there is grave concern that their topical use is leading to the emergence of resistant organisms.

Our Preferred Antiseptic

A topical antiseptic used on open wounds should be nontoxic to healing tissues, should be indiscriminately microbicidal, should promote wound healing, and should not facilitate microbial resistance in the concentrations commonly used in health care settings. The antiseptic introduced for use on open wounds in 1995 in our institution has all of these attributes. It contains 3% p-chloro-m-xylenol and 3% phosholipid PTC as the active ingredients. The formulation, generically called PCMX-PL, is supplied commercially.

PCMX-PL exhibits broad activity against bacteria and fungi.2 Its mode of action is generalized cell-wall disruption and enzyme inactivation. A 30-second exposure to PCMX-PL results in a 6-log reduction (99.9%) of methicillin-sensitive and methicillin-resistant S. aureus (MRSA) and E. coli.2,19

Our experience with PCMX-PL since 1995 shows that it is associated with markedly improved outcomes for patients with complex, infected open wounds. The impetus to begin using it in our institution was a report from Everett et al in 1994 that showed a 59% first-year survival rate for pancreas-transplant recipients with open, deep infections.20 Since we began using it, we have noticed a significant improvement in overall survival for our own pancreas-transplant recipients with open, deep, complex infections.2 

Caring for Surgical Wounds

Our antimicrobial wound-care procedure (see the box on this page) was developed by the University of Minnesota Department of Surgery’s Surgical Infec­tious Disease Service, along with infection-control and wound-care professionals from the University of Minnesota Medical Center, Fairview. It was written to accommodate all types of open wounds, from the simple to the complex. Instituted in 2000, it is used widely within our hospital and for outpatients.

The likelihood that a surgical wound will become infected is determined by three factors:

• the inoculum size and the type of contaminating microorganisms;

• the host’s defenses; and

• the extent of wounding (including the amount of time in the OR).21 

It has been well-established that the risk of wound infection increases with high microbial titers. Wounds contaminated with more than 100,000 microbes per gram of tissue frequently become infected, as shown in experimental and clinical trials.22 By using PCMX-PL on open wounds that require a surgical procedure, we decrease the inoculum size of the colonizing or infecting microorganisms and decrease the risk of infection.

Multiple environmental studies have shown that microorganisms that colonize or infect an open wound can be cultured from all areas of the patient’s room and from the hands and clothing of health care workers.23,24 When hospitalized patients’ wounds become colonized with multidrug-resistant bacteria, such as MRSA, 11%–38% of them will become infected.25 

Patients infected with multidrug-resistant bacteria have significantly increased morbidity and mortality.26,27 Therefore, it is beneficial to attain a significant log reduction of bacteria colonizing or infecting an open wound by using a topical antiseptic such as PCMX-PL. Doing so will lower the risk of bacterial contamination on the pa­tients’ skin and in the hospital environment, and it will prevent the spread of microorganisms from colonized open wounds.

The use of antiseptics becomes increasingly important as reports of multidrug-resistant microorganisms in hospital environments and the community become more prevalent.28–30 Our institution’s antimicrobial-resistant bacteria rates compare favorably to those reported by the National Nosocomial Surveillance System.31 The use of topical antiseptics, including PCMX-PL, as an adjunct treatment of open wounds plays an important role in preventing the spread of multidrug-resistant microorganisms. Their use is an important addition to the CDC’s campaign to prevent antimicrobial resistance.32  PSP

Catherine L. Statz, RN, BSN, MPH, performs surgical wound-infection surveillance for the Surgical Infectious Disease service at the University of Minnesota Department of Surgery in Minneapolis. She can be reached at (612) 626-3151 or statz001@umn.edu.

Acknowledgment

I wish to thank Mary E. Knatterud, PhD, for her editorial assistance.

References

 1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999;20: 250–278.

 2. Grubbs BC, Statz CL, Johnson EM, Uknis ME, Lee JT, Dunn DL. Salvage therapy of open, infected surgical wounds: A retrospective review using Techni-Care. Surg Infect. 2000;1:109–114.

 3. Lammers RL, Fourre M, Callaham ML, Boone T. Effect of povidone–iodine and saline soaking on bacterial counts in acute, traumatic, contaminated wounds. Ann Emerg Med. 1990;19:709–714.

 4. Dirschl D, Wilson F. Topical antibiotic irrigation in the prophylaxis of operative wound infections in orthopedic surgery. Orthop Clin North Am. 1991;22: 19–426.

 5. Benjamin J, Volz R. Efficacy of a topical antibiotic irrigant in decreasing or eliminating bacterial contamination in surgical wounds. Clin Orthop Related Res. 1984;184:114–117.

 6. Denton GW. Chlorhexidine. In: Block SS, ed. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia & London: Lea & Febiger; 1991: 274–289.

 7. Damour O, Hua SZ, Lasne F, Villain M, Rousselle P, Collombel C. Cytotoxicity evaluation of antiseptics and antibiotics on cultured human fibroblasts and keratinocytes. Burns. 1992;18:479–485.

 8. Block SS. Historical review. In: Block SS, ed. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia & London: Lea & Febiger; 1991: 3–17.

 9. Robson MC. Differential diagnosis and treatment of infected wounds. Paper presented at: Wound Institute General Conference; May 16, 1995; Tampa, Fla.

10. McKenna PJ, Lehr GS, Welling RE. Antiseptic effectiveness with fibroblast preservation. Ann Plast Surg. 1991;27:265–268.

11. Lineaweaver W, Howard R, Sourey D, et al. Topical antimicrobial toxicity. Arch Surg. 1985;129:267–270.

12. Brennan S, Leaper D. The effect of antiseptics on the healing wound: A study using the rabbit ear chamber. Br J Surg. 1985;72:780–782.

13. Gottardi W. Iodine and iodine compounds. In: Block SS, ed. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia & London: Lea & Febiger; 1991:152–166.

14. Dela Cruz F, Brown DH, Leiken JB, et al. Iodine absorption after topical administration. West J Med. 1987;146:43–45.

15. Block SS. Peroxygen compounds. In: Block SS, ed. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia & London: Lea & Febiger; 1991: 167–181.

16. Larson EL, Morton HE. Alcohols. In: Block SS, ed. Disinfection, Sterilization, and Preservation. 4th ed. Philadelphia & London: Lea & Febiger; 1991: 191–203.

17. Leaper D. Prophylactic and therapeutic role of antibodies in wound care. Am J Surg 1994;167:15S–20S.

18. Angeras MH, Brandberg A, Falk A, Seeman T. Comparison between sterile saline and tap water for the cleaning of acute traumatic soft tissue wounds. Eur J Surg. 1992;158:347–350.

19. Smith K. Ferro Corporation (US). Antimicrobial testing of scrub formulation, per cent bacterial reduction [TSR: 90-117]. Bedford, OH: Ferro Corp, 1990.

20. Everett JE, Wahoff DC, Statz CL, et al. Characterization and impact of wound infection after pancreas transplantation. Arch Surg. 1994;129:1316–1317.

21. Dunn DL. Postoperative surgical wound infection. In: JL Cameron, ed. Current Surgical Therapy. 5th ed. St Louis: Mosby-Year Book Inc; 1994:937–942.

22. Heggers JP, Robson MC. Quantitative Bacteriology: Its Role in the Armamentarium of the Surgeon. CRC Press: Boca Raton, Fla; 1991.

23. Boyce JM, Potter-Bynoe G, Chenevert C, King T. Environmental contamination due to methicillin-resistant Staphylococcus aureus: Possible infection control implications. Infect Control Hosp Epidemiol. 1997;18:622–627.

24. Herrero IA, Issa NC, Patel R. Nosocomial spread of linezolid-ressistant, vancomycin-resistant Enterococcus faecium. N Engl J Med. 2002;346:867–869.

25. Safdar N, Maki DG. The commonality of risk factors for nosocomial colonization and infection with antimicrobial-resistant Staphylococcus aureus, Enterococcus, gram-negative bacilli, Clostridium difficile, and Candida. Ann Intern Med. 2002;136:834–844.

26. Engemann JJ, Carmeli Y, Cosgrove SE, et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection. Clin Infect Dis. 2003;36: 592–598.

27. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus—Minnesota and North Dakota, 1997–1999. MMWR Morb Mortal Wkly Rep. 1999;48: 707–710.

28. Methicillin-resistant Staphylococcus aureus infections among competitive sports participants—Colorado, Indiana, Pennsylvania, and Loa Angeles County, 2000–2003. MMWR Morb Mortal Wkly Rep. 2003;52:793–795.

29. Staphylococcus aureus resistant to vancomycin—United States, 2002. MMWR Morb Mortal Wkly Rep. 2002;51: 565–567.

30. Public health dispatch: Vancomycin-resistant Staphylococcus aureus—Pennsylvania, 2002. MMWR Morb Mortal Wkly Rep. 2002;51:902.

31. National nosocomial infections surveillance (NNIS) system report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. 2004;32:470–485.

32. CDC’s campaign to prevent antimicrobial resistance in health-care settings. MMWR Morb Mortal Wkly Rep. 2002;51:343.

An Antimicrobial Wound-Care Procedure

1) Cleanse the entire wound with full-strength antiseptic PCMX-PL in a gentle scrubbing motion (or gently apply to the entire wound) with a sterile cotton-tipped or gauze sponge applicator. Leave on the wound for 2minutes or less. For large affected areas, be sure to coat the entire area.

2) Irrigate the wound with sufficient sterile normal saline using a large syringe to remove all visible PCMX-PL and as much necrotic tissue and drainage as possible. Use 150–1,000 mL of normal saline, depending on the size of the wound. If the physician approves, the patient can irrigate the wound in the shower instead. Rinse well.

With any wound, a soft-tip IV catheter (16- or 18-gauge) at­tached to a large Luer-lock syringe or irrigation cap on a saline pour bottle is strongly recommended. Either of these items adds water pressure to help debride the wound.

With a large wound, a suction setup is also strongly recommended to efficiently collect the irrigant. With a very large, deep-tunneling wound, a red Robinson catheter may be helpful for irrigating.

3) Especially with complex or problematic wounds, spray the entire wound with benzethonium chloride 0.1% antimicrobial wound cleanser after irrigating.

4) Loosely pack the open wound with an appropriate dressing (for example, bandages or gauze soaked with saline or a gel dressing). Be sure to maintain dry skin around the open wound.

5) During one or two dressing changes per day, clean the wound using full-strength PCMX-PL. When the wound appears to be healthy and free of infection, the physician may decrease PCMX-PL use to once per day.