Chronic wound infections: the role of Pseudomonas aeruginosa and Staphylococcus aureus Expert Rev. Anti Infect. Ther. Early online, 1–9 (2015) Raffaele Serra* 1,2 , Raffaele Grande 2 , Lucia Butrico 2 , Alessio Rossi 3 , Ugo Francesco Settimio 2 , Benedetto Caroleo 2 , Bruno Amato 1,4 , Luca Gallelli 5 and Stefano de Franciscis 1,2 1 Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, Headquarters: University Magna Græcia of Catanzaro, Viale Europa 88100 Catanzaro, Italy 2 Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy 3 Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy 4 Department of General, Geriatric, Oncologic Surgery and Advanced Technologies, University of Naples “Federico II”, Naples, Italy 5 Department of Health Sciences, University of Catanzaro, Catanzaro, Italy *Author for correspondence: Tel.: +390 961 364 7380 rserra@unicz.it Chronic leg ulcers affect 1–2% of the general population and are related to increased morbidity and health costs. Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacteria isolated from chronic wounds. They can express virulence factors and surface proteins affecting wound healing. The co-infection of S. aureus and P. aeruginosa is more virulent than single infection. In particular, S. aureus and P. aeruginosa have both intrinsic and acquired antibiotic resistance, making clinical management of infection a real challenge, particularly in patients with comorbidity. Therefore, a correct and prompt diagnosis of chronic wound infection requires a detailed knowledge of skin bacterial flora. This is a necessary prerequisite for tailored pharmacological treatment, improving symptoms, and reducing side effects and antibiotic resistance. KEYWORDS: antibiotics . chronic leg ulcers . chronic wounds . Pseudomonas aeruginosa . Staphylococcus aureus Background Chronic leg ulcers (CLUs) affect 1–2% of people worldwide. They are a major cause of prolonged morbidity, with frequent delay in healing and a high recurrence rate [1]. CLUs are prevalent, especially in the elderly (over 65 years of age), and are responsible for increased costs of diagnosis, treatment, nursing care and reha- bilitation [2]. Chronic venous ulcers (CVUs) are the most common type of CLUs (70% of cases). Arterial ulcers account for another 5–10%. The majority of diabetic ulcers have a neuropathic basis, and about 60% have an ischemic component. Mixed venous and arte- rial ulcers constitute 15–30% of all CVUs [3–6]. Physiologically, wound healing process is related to an interaction between keratinocytes, fibroblasts, Langerhans cells and endothelial cells [7], and it is characterized by hemostasis, inflammation, proliferation and remodeling [8]. In chronic wound, activated leukocytes release cytolytic enzymes, for example, matrix metallo- proteinases (MMPs) [9–15], free oxygen radicals and inflammatory mediators, inducing an imbalance between pathological local factors and integrity of immune defenses [16]. This promotes colonization of both Gram-positive and Gram-negative bacteria [17], particularly Staphylococcus, Enterococcus, Enterobacter, Pseu- domonas and Finegoldia [1,18,19]. CVUs are complicated by Staphylococcus aureus (found in 93.5% of evaluated ulcers), Enterococcus faecalis (71.7%), Pseudomonas aeruginosa (52.2%), coagulase-negative staphylococci (45.7%), Proteus spp. (41.3%) and anaerobic bacterial (39.1%) infections [20]. In diabetic and arterial foot lesions, Gram-positive aerobic cocci grow in 59% of cultures (24% are colonized by S. aureus) while Gram-negative aerobes grow in 35% of cultures (frequently Escherichia coli and Proteus mirabilis) [21,22]. S. aureus and P. aeruginosa represent the most common agents isolated from CLUs, often as a biofilm resistant to antimicrobial therapy [1,23,24]. S. aureus is usually detected in the top layer of wounds, while P. aeruginosa is localized in the deepest region of wound bed. S. aureus is a common opportunistic patho- gen [25] which is highly sensitive to several antibiotics (methicillin sensitive), even though, informahealthcare.com 10.1586/14787210.2015.1023291 Ó 2015 Informa UK Ltd ISSN 1478-7210 1 Review Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by 94.162.169.31 on 03/09/15 For personal use only.