**1. Introduction**

Among the top five human infections requiring medical treatment is dermatitis [1]. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains such as methicillin-resistant *Staphylococcus aureus* (MRSA) [2] and *Candida* sp. [3]. In recent decades, given the poor innovation in the discovery of new antimicrobials and the frequency of recalcitrant skin infections, the need for innovative anti-infective therapeutics is becoming more and more urgent. In this field, grea<sup>t</sup> interest in the last 20 years has been focused on the potential of natural products.

**Citation:** Di Vito, M.; Smolka, A.; Proto, M.R.; Barbanti, L.; Gelmini, F.; Napoli, E.; Bellardi, M.G.; Mattarelli, P.; Beretta, G.; Sanguinetti, M.; et al. Is the Antimicrobial Activity of Hydrolates Lower than That of Essential Oils?. *Antibiotics* **2021**, *10*, 88. https://doi.org/10.3390/ antibiotics10010088

Received: 14 November 2020 Accepted: 15 January 2021 Published: 18 January 2021

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In recent years, there has been growing interest in natural products obtained from aromatic plant distillation: essential oils (EOs) and hydrolates (Hys). As such, there are many scientific articles about the effectiveness of EOs in various contexts: antimicrobials, immunomodulatory, antioxidants, anti-inflammatory, pain-relievers, etc., but there is little evidence on the activities of Hys.

Official Pharmacopoeias well define the two natural products. The EO is considered to be a complex odorous product obtained by steam distillation, hydro-distillation, or by the dry distillation of a plant, some of its parts, or, in the case of OEs obtained from *Citrus* spp., through appropriate mechanical cold processes [4]. Similarly, starting from 2012, the French Pharmacopoeia defines the Hy as a product obtained through the distillation of different parts of aromatic plants, which separates from the essential oil at the end of the distillation [5].

While they originate from the same process, the two distillation products are quite different in terms of chemical composition and effectiveness.

EOs are hydrophobic mixtures mainly characterized by terpene molecules that, on the contrary, are extremely diluted in Hys. In fact, the Hys are hydrophilic solutions characterized, up to a maximum of 1 g/L, by the terpene components present in the corresponding EO [6]. Furthermore, in the Hy, the relative ratio of each terpenic molecule will be conditioned by its hydrophilic characteristics. Owing to this, the major components of an EO may not be the same that is present in the corresponding Hy.

Due to the high oxicity of many terpene compounds [7], essential oils require special warnings when used *per os* or in topical applications [8]. On the contrary, Hys resulting from dilution of terpenic solutions are less toxic and can be used more easily for the same applications.

However, only few studies have been carried out on EOs and Hys obtained from the same distillation process in order to compare their chemical composition [9–11], or study some of their activities such as psychopharmacological and anti-cancer activities [12,13], or larvicidal and nematodicidal ones [14,15]. Our group participated in these early investigations, assessing the chemical composition and the antimicrobial activity of the EO and Hy obtained from *Monarda citriodora* in a recent research. The study showed that, to achieve the same inhibitory effect of EO, a higher volume of Hy was necessary; however, in this volume, the concentration of active components was lower than that present in the corresponding EO, i.e., the EO from the same plant source [16]. Therefore, data indicate a higher likelihood for the active compounds isolated from *M. citriodora* Hy to be more active in the aqueous phase, because they can more easily reach their target, or because they are not contrasted with antagonistic compounds present only in the OE.

Given this background and in view of improving the knowledge on Hy potential uses, the first aim of this study was to evaluate the antimicrobial activity of six EOs and the companion Hys isolated from the same aromatic plant cultivated in Italy, towards fungal and bacterial strains potentially pathogenic for human skin. The following microorganisms isolated from patients with skin infections included the following. Six bacteria: methicillin-resistant *Staphylococcus aureus* (MRSA), methicillin- susceptible *Staphylococcus aureus* (MSSA), *Streptococcus pyogenes*, vancomycin-resistant enterococci (VRE) *Enterococcus faecalis* and *Enterococcus faecium*. Four drug-resistant yeasts: *Candida albicans*, *Candida parapsilosis*, *Candida glabrata* and *Candida tropicalis*. Five dermatophytes: *Trichophyton soudanense*, *Trichophyton tonsurans*, *Trichophyton rubrum*, *Trichophyton violaceum* and *Microsporum canis*. The second aim was to compare the relative concentration of active volatiles present in EOs and Hys obtained from the same plant by using the volatiles' conversion factor (CF).
