Wound healing is an intricate process with many factors that can lead to delays in healing. Bacterial presence in wounds can be an important cause of problems in patients with chronic wounds.19 The presence of bacteria in chronic wounds occurs in varying degrees, from asymptomatic contamination to colonization to local infection, increasing to invasive infection and septicemia.20 It is the interaction between the patient and the bacteria present in the chronic wound that determines the degree of healing or infection, and therefore the need for treatment.3,21,22
Numerous studies have shown the most common bacterium present in chronic and acute wounds is S. aureus.12,23 Over recent past decades, there has been a disturbing trend toward increasing antibiotic resistance of MRSA, accounting for up to 75% of S. aureus isolates.11,23 MRSA is now in many US healthcare facilities and communities. In 2003, Pan et al24 retrospectively reviewed 295 San Francisco County jail inmate health records that showed 74% of S. aureus isolates obtained were MRSA. This correlates with Valencia et al’s12 2004 retrospective review of patients at a Miami, Florida inpatient dermatology unit, showing MRSA to be present in 36 out of 48 patients’ (75%) S. aureus isolates from leg ulcers.
A prospective study in Copenhagen23 found S. aureus to be the most common isolated bacterium (93.5%) in chronic venous ulcers. The current in vitro study examined multiple strains of MRSA and MSSA, including the MRSA USA300 strain. Currently, USA300 is the most common strain of MRSA isolated in the US and persists in community populations in at least 16 states.25-28 Other strains examined in the current study are commonly used in testing the effectiveness of antimicrobial hand-washing formulations (MRSA 33591, MSSA 6538). MSSA 6538 also is used in a wide variety of commercial testing, including filtration efficiency testing, media testing, and antimicrobial and antiseptic testing. MSSA 14776 is used in World Health Organization International studies to standardize antibiotic sensitivity disks.
The in vitro effectiveness of the topical antimicrobials evaluated in this study correlates with the known antibiotic susceptibilities of the strains evaluated. For example, MRSA 33593 and MRSA 700699, which are known to be resistant to gentamicin, had inhibition zone areas of nearly zero, not significantly different from that of the petrolatum control. Furthermore, the results seen in this in vitro study also correlate with the reputation of S. aureus’ remarkable ability and history of decreasing susceptibility to antibiotics with increasing exposure. The results from this study are in agreement with those of the in vitro study by Suzuki et al,29 where the USA300 strain was found to be resistant to TAO. The newer antibiotics — mupirocin and retapamulin — used in this study had significantly and far larger areas of bacterial growth inhibition than TAO, which has been in use for many years. Furthermore, the use of mupirocin and retapamulin is not as common as TAO in the US because they are restricted — ie, controlled agents requiring a prescription to acquire and use. Suzuki et al29 also concluded that TAO resistance occurs to a greater degree in MRSA strains in the US where TAO is widely used. This is in contrast to MRSA strains in Japan where the use of TAO and its components is not widespread.
The greater sensitivity exhibited in this study by these eight strains of S. aureus to mupirocin and retapamulin is consistent with less exposure of these strains to these antimicrobials. Bacterial growth inhibition to these common topical antimicrobials occurred regardless of methicillin susceptibility. This would be expected, given the unique and different mechanisms of action of each antimicrobial agent from that of methicillin.
The ability of infections to slow the healing of both acute and chronic wounds, prolong hospital stays, and increase morbidity and the cost of these wounds is well known.30-33 In a retrospective study31 of 51 patients (17 colonized with MRSA, 34 control), patients with MRSA had longer hospital stays and increased incidence of negative post op outcomes compared to patients without MRSA. A prospective study32 of 59 venous ulcer patients found S. aureus was present in 94.9% of ulcers, compared to 5.1% of patients who were S. aureus free, significantly delaying time to healing. A summary of the literature contained in an in vitro study of the effectiveness of silver-containing products against bacteria33 underscores the role of infection on increased patient debilitation and healthcare costs.
Some antimicrobial agents such as iodine in aqueous solution are rapidly consumed in the wound milieu, while the presence of increasingly resistant bacteria may render topical antibiotics in low concentrations ineffective.34-37 A review36 of their role, particularly in diabetic foot ulcers, suggests biofilms pose greater challenges to the effectiveness of topical antimicrobials in chronic wounds; primarily, it is difficult for the antimicrobial to penetrate the biofilm in a sufficient concentration to kill bacteria.
The data from the current in vitro study indicate the bacterial growth of both MRSA and MSSA is more affected by mupirocin and retapamulin than by TAO and gentamicin. Judicious use of all of these agents is needed to reduce the likelihood for the development of resistance. Perhaps the use of these common topical antibiotics that can be delivered in a sustained fashion in conjunction with a topical antiseptics, and subsequently have an immediate effect on bacteria, may be more effective against bacteria.36 This combination may prevent the development of resistance to the antibiotic agent. Furthermore, the antiseptic may disrupt the biofilm and allow greater penetration of the antibiotic, while also having a bactericidal action against a bacterium such as MRSA.31,33
Whether acute or chronic, superficial or deep, skin wounds that are critically colonized with bacteria require diligent wound care to prevent the progression of colonization to varying degrees of infection. Cleansing, debridement, and the use of topical agents and antimicrobials may be needed as important elements in managing acute and chronic wounds.