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Home , Chronic wound

Role of topical antimicrobials in management

Georgina All contain microorganisms, and the host response to this is based on Gethin, PhD, RGN, HE Dip various factors, including the number of bacterial present and their Wound Care, virulence. Antimicrobial agents, including antiseptics, can be used to prevent the FFNMRCSI, Lecturer/ growth of microbial pathogens in critically colonised and locally infected wounds. Research This article explains the theory behind the bioburden continuum and gives Coordinator, Research recommendations on the best use of topical antimicrobials Centre, Faculty of Nursing Keywords: wound bioburden; topical antimicrobials; clinical signs of and Midwifery, Royal College of Surgeons in ound healing is a complex, mul- more bacterial species in up to 95% of chronic Ireland, Dublin, ti-stage process that is influenced wounds.7-9 However, more bacterial species have Ireland by many intrinsic and extrinsic been noted in larger wounds with a long dura- factors. The development of a tion, and there is a significantly greater chance wound infection negatively that an will fail to heal if four or more bacte- Wimpacts on this process, delaying healing. In some rial groups are present.8,10 Of note in many studies cases, the effects are life-threatening. The increas- is that Staphylococcus aureus and Pseudomonas aer- ing of chronic illness1 and thus of uginosa were the most common wound isolates8-10 chronic wounds, together with the emergence of and were present in both healing and non-heal- -resistant ,2,3 warrants further ing wounds.11 efforts to improve wound management practices Polymicrobial wounds thus contain several and prevent wound infection. This is an intricate potential pathogens, any one of which can cause field, primarily because of the issues associated infection. This delays healing, and the ensuing with nosocomial , wound colonisation morbidity and risk of mortality causes patients and , which are influenced by the health of great distress.12 the host and the characteristics of the microbes. The level of bacterial burden is defined by the presence of replicating microorganisms within a Bacteria in wounds wound, the bacterial load, the virulence of the Microorganisms are present in all chronic wounds microorganism and the host reaction.6 Schultz et and are acquired from the indigenous flora of the al.4 argued that the pathogenic species may be human host or from the external environment.4 much more important than the number of organ- Human infection is caused by four types of micro- isms within the chronic wound, while host sus- organisms: bacteria, fungi, and protozoa. ceptibility is probably the most important pre­ While a minor, acute healing wound may allow determinant of the risk of infection.13 time for only a relatively small number of contaminates to take residence, the continued Wound bioburden exposure of devitalised tissue in a slowly healing The concept of wound bioburden has been intro- chronic wound is likely to facilitate the colonisa- duced to describe the increased metabolic load tion and establishment of a wide variety of endog- imposed by multiplying bacteria in the wound enous microorganisms, and increase the likeli- bed, which are often present as multiple strains, hood of infection.5 and their ability to spread in tissues and produce However, the presence of microorganisms such toxins.3,14 This bioburden continuum represents a as bacteria does not necessarily indicate that an broad range of bacterial states, from that of wound infection has occurred or that it will lead to contamination through to infection. The terms impaired .6 This is supported by used to described the various stages in the con- studies that have reported the presence of one or tinuum are defined below:

j o u r n a l of wound care / AC T I VA h e a lt h ca r e S U P P l e M E N T 2 0 0 9  l Contamination — defined as the presence of associated with a surface, and are resistant to non-replicating microorganisms in the wound4 environmental stresses that can overwhelm a l Colonisation — defined as the presence of rep- lone bacterium.21 Biopsies of 16 acute and 50 licating organisms that are adhering to the chronic wounds showed that 60% of chronic wound but not causing to the host.4 Col- wound beds demonstrated definite biofilms onised wounds are characterised as those that compared with 6% of acute wounds.22 This are progressing normally with no necrotic tis- study concluded that chronic wounds showed sue and with limited slough that is usually thin evidence of biofilms significantly more often and mobile in depth and character.15 While the than acute wounds. wound may be progressing normally, there is no consensus on the impact of bacterial coloni- Antimicrobials sation on wound healing16 These are agents that either kill or inhibit the l Critical colonisation — there is no universally growth and division of microorganisms.23 They agreed definition of this. It is proposed that a include (which act on specific target wound is critically colonised when bacteria sites), antiseptics, and other agents causes a delay in healing.4 Kingsley and Jones (which act on multiple cellular target sites).23 further defined this term as a wound that is Antibiotics and antiseptics are defined below: indolent (not healing) despite seemingly appro- l Antibiotics — a chemical substance produced priate therapy.17 Non-healing can first be detect- by a microorganism that has the capacity, in ed when the wound margins fail to change. dilute solutions, to selectively inhibit the Such wounds are characterised as having growth (static) of, or to kill (cidal), other micro- increased , often with over 50% slough organisms23 at the base. There may be malodour but no cel- l Antiseptics — agents that destroy or inhibit lulitis. Bright friable that the growth of microorganisms in or on living bleeds easily, especially at dressing removal, tissue.24 They have a broad spectrum of activity may be present.4,17,18 Additionally, an unpleas- that includes bacteria, fungi, viruses, protozoa ant or putrid malodour may be accompanied and prions. Several categories exist, including by new areas of or breakdown in the alcohols (ethanol), anilides (triclocarban), wound base4 biguanides (chlorhexidine), bisphenols (tri- l Infection — this signifies microbial growth and closan), chlorine compounds, iodine com- the presence of replicating microorganisms pounds, silver compounds, peroxygens and within the wound, resulting in injury to the quaternary ammonium compounds.25 Com- host and the interruption of wound healing.4,19 monly used products in clinical practice today This occurs when virulence factors expressed by include povidine-iodine, chlorhexidine, alco- one or more microorganism in a wound out- hol, acetate, hydrogen peroxide, boric acid, compete the host’s natural immune system and silver nitrate, silver sulfadiazine and sodium the subsequent invasion and dissemination of hypochlorite.24 microorganisms in viable tissue provokes a series of local and systemic host responses.5 Host Identifying infection susceptibility is probably the most important The precise pathways to overt or ‘frank’ infection determinant of wound infection and is influ- of a wound are complex and involve a number of enced by various local and systemic factors.4,19 defined stages: following colonisation of a wound, This is illustrated in the following equation: immunocompetent individuals react immediately with an acute, innate, inflammatory response that Bacterial load x virulence leads to the ingress of phagocytic cells and blood Host resistance .26 When this response occurs in the early stages of wound healing, it serves to remove tissue l — created when a single-cell planktonic debris and detrimental microorganisms.26 In con- bacterium adheres to the surface of the wound trast, associated with wound infec- by attaching to the exposed tion involves the development of erythema, , proteins.20 Wound biofilms are polymicrobial raised local temperature and swelling.19 communities and do not comprise a particular Microbiological factors, such as the quantity, type or species of bacterial cell. They are held type and interaction of pathogens, act together together by extracellular polymeric substrates with host factors, such as immune responses and j o u r n a l of wound care / AC T I VA h e a lt h ca r e S U P P l e M E N T 2 0 0 9  tissue conditions, to predispose an individual to When to use infection. Importantly, infection is identified clin- While the is the governing ically based on signs and symptoms,27 thereby factor in the development of infection, the supporting the need for ongoing, purposeful reduction of bioburden, if achieved to a suffi- . cient degree and for a sufficient duration, can Cutting and Harding proposed that, in chronic enable the host defences to regain control.14 The wounds, additional signs and symptoms of infec- careful selection of topical antimicrobials agents tion beyond the well-established ones of pain, and their application at a correct dosage can help erythema and swelling, may be present and achieve these goals. These agents are intended to should be observed for. These additional signs and prevent ingress of microbes into the wound, pro- symptoms include: vide a barrier to cross-infection and prevent the l Friable granulation tissue progression from localised to overt infection. l Delayed healing Infection interrupts healing and extends the l Abnormal smell time to wound closure. Thus, preventing infec- l Discolouration tion prevents delayed healing. At worse, infec- l Unexpected pain or tenderness tion can result in sepsis and even . Indeed, l Pocketing at the wound base patients who acquire nosocomial wound infec- l Bridging of tions have significantly higher mortality rates l Wound breakdown. than those who do not.30 Gardner et al.28 assessed the validity of the clas- Vowden and Cooper23 suggested that use of sic signs of infection and formulated a list of 12 topical antimicrobials should be considered criteria specific to chronic wounds based on the when it is suspected that a wound is progressing work of Cutting and Harding.29 Their study iden- towards overt infection or an interruption in the tified that the 12 criteria indicated wound infec- healing process is observed. According to Bowl- tion more accurately than the classic signs alone. er,5 this occurs before infection when a wound is Increasing pain and wound breakdown had a pos- failing to heal but the clinical signs of infection itive predictive value of 1.00 — in other words, all are not apparent, such as when the wound is of the wounds with increasing pain or wound critically colonised. Application of topical anti- breakdown were infected, as confirmed by wound microbial agents at this stage is recommended to biopsy culture. redress the host-bacterial imbalance in favour of A study aiming to identify the clinical criteria the host.5,15 Fig 1 shows the stages at which topi- for wound infection, using a Delphi technique, cal antimicrobial agents may be recommended; involved 54 wound-care experts.18 It identified it considers the bacterial load and virulence, and that cellulitis, malodour, delayed healing or dete- takes account of the local and systemic resistance rioration were the clinical criteria for wound infec- to the development of infection.31 Antibiotics tion common to all wound types. Pain was an should be reserved for acute infections and their important indicator of infection, and was described choice based on both assessment and laboratory as increased pain, unexpected pain or change in sensitivity analysis. nature of pain.18 Other criteria that may assist with The selection of antimicrobial agents must be the early recognition of infection included: oede- influenced by the specificity and efficacy of the ma, increased exudate and the sudden appearance agent, its cytotoxicity to human cells, its poten- or increase in the amount of slough.18 tial to select resistant strains and its allergenici- ty.23 Further consideration should be given to the Topical antimicrobials condition of the wound bed, the size and shape The topical application of antimicrobials to a of the wound, level of exudate and severity of chronic wound will never affect the systemic fac- bacterial load. tors that contribute to its failure to heal.24 Evidence of the clinical efficacy of topical However, topical antimicrobials may be used antimicrobial agents is limited because of the wide to prevent wound infection in patients range of wound types, the diversity of products at high risk. Topical antimicrobials present advan- and differences in study outcomes.24 However, evi- tages over topical antibiotics as they do not cause dence from controlled trials is emerging that dem- the emergence of drug-resistant bacteria and have onstrates lower rates of infection in venous leg a broader antimicrobial spectrum and lower seni- ulcers when topical antimicrobials are used in con- tisation rates.24 junction with compression therapy.32,33

j o u r n a l of wound care / AC T I VA h e a lt h ca r e S U P P l e M E N T 2 0 0 9  Host resistance

Bacteria (load x virulence)

Topical antiseptic agents

Systemic antibiotics and topical antiseptic agents

Fig 1. Diagrammatic illustration of when to administer topical antiseptics and/or systemic antibiotics31

Early studies supported the use of topical anti- showing signs of healing, it is advisable to change microbials in critically colonised wounds.34 The the choice of dressing to reflect the needs of the use of antimicrobial dressing on these wounds, wound. However, host systemic factors that lower which did not have clinical signs of infection, resistance to infection, such as poor tissue per- accelerated healing with decreased exudate in fusion due to ischaemia, drug therapies or diabe- many patients and resulted in an improvement in tes, may be ongoing. In such cases, continued use surface semiquantitative bacterial swab results. A of topical antimicrobial agents may be justified. further case series of 126 patients with chronic wounds demonstrated a reduction in clinical signs Assessing the wound bed of infection and a statistically significant reduc- Ongoing assessment and documentation will help tion in exudate levels when antimicrobial dress- to identify the early signs of infection. Based on ings were used (p<0.001).35 previous studies and the European Wound Man- Systematic reviews provide the most powerful agement Association position documents, there evidence on antimicrobials. A systematic review are two key elements that should be routinely of antibiotics and antiseptics in venous leg ulcers monitored in wound assessment: pain and wound reported that when cadexomer iodine was com- size.37,38 Validated pain assessment tools that are pared with standard care the pooled estimate easy to use and suitable for both adults and chil- from two trials for frequency of complete healing dren are available.39 A variety of wound measure- at 4–6 weeks indicated significantly higher heal- ment tools are also available, and a review by ing rates for cadexomer iodine (RR 6.72, 95% CI Flanagan,40 supported by further studies on venous 1.56 to 28.95).36 and diabetic ulcers, have found that failure of chronic wounds to reduce in size by 30% over four When to stop weeks is an indicator of poor healing.41,42 There is no definitive guidance on when to stop using topical antimicrobial agents. However, ongo- Conclusion ing wound assessment should identify if the fac- The prevention and treatment of infection is still tors that promoted their initial use are still persist- a major concern, both in wound care and health ing within the wound bed. Once the infection or care in general. The use of topical antimicrobial critical colonisation is reduced and the wound is agents in wound management can contribute to j o u r n a l of wound care / AC T I VA h e a lt h ca r e S U P P l e M E N T 2 0 0 9  this, and their choice should be based on compre- 14 Warriner, R., Burrell, R. Infection and the chronic wound: a focus on silver. Adv Skin Wound Care 2005;18 (Suppl. 1): 2-12. hensive assessment of the patient and wound. 15 Sibbald, G. Topical antimicrobials. Ostomy Wound Manage 2003; 49: When the host’s ability to resist infection is (Suppl.) 5, 14-18. reduced and the bacterial load is increasing, topi- 16 Penhallow, K. A review of studies that examine the impact of infection on the normal wound-healing process. J Wound Care 2005; 14: 3, 123-126. cal agents can help prevent the progression from 17 Kingsley, A., Jones, V. Diagnosing wound infection: the use of C-reactive colonisation to infection. . Wounds UK 2008; 4: 4, 32-46. 18 Cutting, K., White, R., Mahoney, P., Harding, K. Clinical identification of wound infection: a Delphi approach. In: Clane, S., (ed.) EWMA position Document: Identifying Criteria for Wound Infection. MEP, 2005. Key points 19 Cooper, R. Understanding wound infection: Position Document. In: 1. Regular wound assessment should identify early Cutting K, Gilchrist B, Gottrup F, Leaper D, Vowden P, editors. European Wound Management Association, Position Document: Identifying criteria signs of wound infection. This includes for wound infection: position document. MEP, 2005. measurement of wound size and assessment of 20 Wolcott, R., Rhoads, D. A study of biofilm-based wound management in pain, signs of delayed healing, increasing subjects with critical limb ischaemia. J Wound Care 2008; 17: 4, 145-155. 21 Wolcott, R., Rhoads, D., Dowd, S. Biofilms and chronic wound exudate, malodour and erythema. inflammation. J Wound Care 2008;17: 8, 333-341. 22 James, G., Swogger, E., Wolcott, R. Biofilms in chronic wounds. Wound 2. Topical antimicrobials may be used when early Repair Regen 2008; 16: 1, 37-44. signs of infection are identified or in wounds 23 Vowden, P., Cooper, R. An integrated approach to managing wound infection. EWMA Position Document: management of wound infection with high bacterial load. 2006: 2-6. 24 Drosou, A., Falabella, A., Kirsner, R. Antiseptics on Wounds: an area of 3. The choice of antimicrobial should be based on controversy. Wounds 2003; 15: 5, 149-166. 25 McDonnell, G., Russell, A. Antiseptics and disinfectants: activity, action wound characteristics, size, exudate, evidence of and resistance. Clin Microbiology Reviews 1999; 12: 1, 147-149. efficacy, cost-benefit and patient acceptability. 26 White, R. Wound infection-associated pain. J Wound Care 2009; 18: 6, 245-249. 27 Armstrong, D., Lipsky, B. Diabetic foot infections: stepwise medical and 4. Follow manufacturers’ instructions in the surgical management. Inter Wound J 2004; 1; 2: 123-132. application of topical antimicrobials. 28 Gardner, S., Frantz, R., Doebbeling, B. The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen 2001; 9: 3, 178-186. 29 Cutting, K.F., Harding, K.G. Criteria for identifying wound infection. J References Wound Care 1994; 3: 4, 198-201. 1 Department of Health and Children. Health in Ireland: Key trends 2007. 30 Young, M., Washer, L., Malani, P. Surgical site infection in older adults: Department of Health and Children, Ireland, 2007. epidemiology and management. Drugs Aging 2008; 25: 399-414. 2 McDonald, P., Mitchell, E., Johnson, H. et al. Epidemiology of MRSA: the 31 Sibbald, R., Willaimson, D., Orsted, H. et al. Preparing the wound bed: North/South study of MRSA in Ireland 1999. J Hosp Infection 2003; 54: , bacterial balance and moisture balance. Ostomy Wound 2,130-134. Manage 1999; 46: 14-35. 3 Leaper, D. Silver dressings: their role in wound management. Inter Wound 32 Hansson, C. The effects of cadexomer iodine paste in the treatment of J 2006; 3: 4, 282-293. venous leg ulcers compared with hydrocolloid dressing and paraffin gauze 4 Schultz, G., Sibbald, G., Falanga, V. et al. : a dressing. Cadexomer Iodine Study Group. Inter J Dermatol 1998; 37: 5, systematic approach to wound management. Wound Repair Regen 390-396. 2003; 11: 1-28. 33 Gethin, G., Cowman, S. Manuka honey vs Hydrogel, a prospective, open 5 Bowler, P.G., Duerden, B.I., Armstrong, D.G. Wound microbiology and label, multicentre randomised controlled trial to compare desloughing associated approaches to wound management. Clin Microbiol Rev 2001; efficacy and healing outcomes in venous ulcers. J Clin Nurs 2009; 18: 3, 14: 2, 244-269. 466-474. 6. Dow, G., Browne, A., Sibbald, R.G. Infection in chronic wounds; 34 Sibbald, G., Browne, A., Coutts, P., Queen, D. Screening evaluation of an controversies in diagnosis and treatment. Ostomy Wound Manage 1999; ionized nanocrystalline silver dressing in chronic wound care. Ostomy 45: 8, 23-40. Wound Manage 2001; 47: 38-42. 7 Tammelin, A., Lindholm, C., Hambraeus, A. Chronic ulcers and antibiotic 35 Kotz, P., Fisher, J., McCluskey, P. et al. Use of a new silver barrier dressing, treatment. J Wound Care 1998; 7: 9, 435-437. Allevyn Ag in exuding chronic wounds. Int Wound J 2009; 6: 3, 186-194. 8 Trengove, N., Stacy, M., McGechie, D., Mata, S. Qualitative bacteriology 36 O’Meara, S.M., Al-Kurdi, D., Ovington, L. 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j o u r n a l of wound care / AC T I VA h e a lt h ca r e S U P P l e M E N T 2 0 0 9