## 1 Introduction  
The skin is the body's largest organ, playing a fundamental role in several physiological processes. It contributes to functions such as vitamin D synthesis, hydration, and regulation of body temperature. Notably, it serves as a main defense against chemicals and pathogens, with the epidermis acting as the first line of protection [1]. Skin infections are among the most common pathologies found in community and hospital settings. They can range from limited superficial infections, mostly controlled by topical antibiotic treatments, to severe infections of deep tissues that can lead to death if the patient is not appropriately treated [2]. _Staphylococcus aureus_, a versatile bacterium living as a commensal in 30% of people [3], is one of the main causes of human bacterial infections worldwide and the most common agent in skin and soft tissue infections. Due to the emergence of methicillin-resistant isolates, it represents a significant public health problem [4]. At the same way, _S. epidermidis_ is a normal inhabitant of the healthy human skin and mucosal microbial communities and has emerged as a common cause of numerous nosocomial infections, mostly occurring in immuno-compromised hosts or patients with implanted medical devices [5]. Most clinical isolates of both _S. aureus_ and _S. epidermidis_ show the capacity to adhere to abiotic surfaces and to develop biofilms, complex and aggregated communities of microorganisms embedded in a self-producing matrix of extracellular polymeric substances [6]. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment in killing bacteria in biofilms [7]. Given this, undoubtedly, this microorganism represents a high-priority pathogen for developing new therapeutic strategies capable of eradicating both planktonic and sessile forms [8]. Among antimicrobial agents, natural products have been extensively explored to avoid the side effects of traditional antibiotics [9; 10]. _Pistacia lentiscus_ L. is a bush that plays an important role in the ecosystem of the Mediterranean maquis. It is a rustic, drought-resistant evergreen species and has been used for a long time in traditional medicine for the treatment of various kinds of diseases. Almost the whole plant, including the leaves, fruits, wood, and mastic resin, contains a variety of chemical constituents which are medicinally important [11]. Antioxidant, hepatoprotective, anticancer, anthelmintic, wound healing, hypotensive, antiarthritic and antimicrobial properties have been described [12]. Lentisk (_Pistacia lentiscus_) oil (LO) is obtained from _P. lentiscus_ berries and is able to promote the repair of skin lesions and inhibit lipid oxidation and depletion of antioxidant defense enzymes [13]. This oil was commonly used in topical treatment of burns, wounds and sores [14] and its antimicrobial activity has been reported [15]. Levofloxacin (LVX) is one of the ofloxacin isomers and a conformationally locked analog of nonfloxacin, from the third generation. It was less toxic and more potent than the other dextro form [16]. It is active against Gram-negative and Gram-positive bacteria and possesses significant activity against atypical pathogens, such as _Chlamydia_, _Mycoplasma_ and _Legionella_ species [17]. LVX is mainly used in respiratory, urinary tract, and soft-tissue infections due to its high renal elimination rate. The marketed products are for parenteral or oral administration and, due to their nearly complete absorption, both formulations may be interchangeable [18]. The fluoroquinolones levofloxacin, gatifloxacin, and moxifloxacin are FDA-approved for both complicated and uncomplicated skin infections. However, due to their broad-spectrum potency, they are commonly reserved for more serious infections. Additionally, levofloxacin is not typically the first choice for MRSA infections due to potential resistance [19].