The ongoing battle against multi-resistant strains: In-vitro inhibition of hospital-acquired MRSA, VRE, Pseudomonas, ESBL E. coli and Klebsiella species in the presence of plant-derived antiseptic oils

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Abstract

The fight against hospital-acquired infections involving antibiotic-resistant microorganisms has become of critical concern to surgeons worldwide.

In addition to the development of new effective antibiotic chemotherapy, exploration of ‘forgotten’ topical antibacterial agents from the pre-antibiotic era has recently gained new attention. We report the promising efficacy of plant-derived antiseptic oils used in traditional aboriginal and south-east Asian treatments such as Lemongrass, Eucalyptus and Tea Tree Oil in the inhibition of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multi-resistant Pseudomonas aeruginosa, ESBL-producing Escherichia coli and Klebsiella pneumoniae in the in-vitro setting.

Large consistent zones of inhibition were observed for all three plant-derived oils tested in an agar diffusion test. The commonly used antibacterial agents chlorhexidine 0.1%, and ethanol (70%), and standard olive oil consistently demonstrated notably lower or no efficacy in regard to growth inhibition of strains. Notably, Lemongrass oil proved to be particularly active against gram-positive bacteria, while Tea Tree oil showed superior inhibition of gram-negative microorganisms.

As proven in vitro, plant-derived antiseptic oils may represent a promising and affordable topical agent to support surgical treatment against multi-resistant and hospital-acquired infections.

Introduction

The fight against hospital-acquired infections involving antibiotic-resistant microorganisms has become of critical concern to surgeons and clinicians worldwide. In maxillofacial surgery particularly units with critical care patients are increasingly affected by this fact. Worse, the World Health Organization has stated that international medical community is gradually losing this battle, and the world may even be on the brink of a ‘post-antibiotic era’.

Since its emergence in 1988, the incidence of nosocomial infection with vancomycin-resistant Enterococcus (VRE) has increased remarkably throughout the developed world and has affected surgical treatment outcomes. Enterococcus, once considered a pathogen of minimal clinical importance on a surgical ward, has thus now emerged as a rapidly growing cause of morbidity in the immunosuppressed patient, causing urinary tract infection, endocarditis, bacteraemia and sepsis (Courvalin, 2006; Willems and Bonten, 2007). Vancomycin resistance is growing, and VRE is becoming endemic in an increasing number of intensive care facilities worldwide (McGeer and Low, 2000). This rapid spread, combined with the limited therapeutic options available to the clinician in treating VRE, is fast becoming a cause of major concern.

In response, a number of pharmacological approaches have been attempted, with mixed success. Many surgeons and physicians have encouraged the withholding of overpowering broad-spectrum antibiotics as a first-line treatment as long as possible in order to delay the development of multi-resistance (Warnke et al., 2008). The novel antibiotic ‘linezolid’, introduced in 2000, was hoped to act as a solid bulwark against the steady spread of VRE. However, despite its early promise, resistant clinical isolates were discovered as early as 2002 and the incidence of infection due to resistant strains has been increasing across western Europe (Auckland et al., 2002).

Equally notable is methicillin-resistant Staphylococcus aureus (MRSA). MRSA drastically increases patient morbidity, and often requires multiple admissions, thereby exposing other vulnerable patients (MacKinnon and Allen, 2000). In many surgical units and hospital wards, this has created a requirement for isolation and sterilization of facilities and instruments used for these patients during their hospital stay. Some hospitals may refuse admission to patients carrying multi-resistant pathogens thereby compromising the affected patient's ability to access appropriate health care. Furthermore, infection with MRSA has been shown to significantly lower both the quality of life and self-esteem of patients (Theaker et al., 2001).

Among the gram-negative pathogens, strains of multi-resistant Pseudomonas aeruginosa and extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae has become a worldwide serious problem in the hospital setting, limiting the therapeutic options and surgical treatment dramatically (Paterson, 2001). Multi-resistant invasive oral infection is rare, but if it occurs is has been shown to be of particular consequence, requiring prompt diagnosis, extensive and often aggressive surgical debridement and long-term antibiotic therapy (Ghanem et al., 2011; Lorenzini et al., 2011).

Carriage of highly resistant bacterial strains thus has clear financial, epidemiological and even psychological implications. In our maxillofacial surgery units we found that complex elective surgery for patients in urgent need of treatment, who were carriers of multi-resistant strains, had to be postponed until the contamination was cleared. The multifaceted consequences for the patients, their relatives or employers together with the effects on clinical efficiency and patient waiting lists are often enormous.

There is mounting international evidence supporting the use of plant-derived antiseptic oils against pathogenic microorganisms (Shapiro et al., 1994; Larrondo et al., 1995; Maudsley and Kerr, 1999; Warnke et al., 2004; Fisher and Phillips, 2009; Warnke et al., 2009). Further, both clinical and in vitro studies have demonstrated potent bactericidal properties of essential oils, including efficacy against antibiotic-resistant strains (Harkenthal et al., 1999; Peana et al., 1999; Sherry et al., 2001; Halcon and Milkus, 2004; Fisher and Phillips, 2009; Warnke et al., 2009).

We have previously reported on significant clinical utility of plant-derived essential oils. This included significant reduction in malodour caused by tumour ulceration and promotion of ulcer healing and slight re-epithelisation in maxillofacial and head and neck cancer patients (Warnke et al., 2004, 2005, 2006), as well as promotion of healing in MRSA osteomyelitis via injection of essential oils (Sherry et al., 2001). In 2009, we tested a large number of essential oils for antimicrobial properties in vitro and proved the significant efficacy of a small subset against clinical MRSA isolates from surgical wards and critical Candida kruzei strains (Warnke et al., 2009).

After those preliminary findings our aim was now to evaluate the antibacterial efficacy of three selected essential oils with proven antimicrobial properties (Warnke et al., 2009) on a wider range of clinical isolates of typically hospital-acquired pathogens frequently found on surgical wards: methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), multi-resistant P. aeruginosa, ESBL-producing E. coli and K. pneumoniae.

Section snippets

Test group – essential oils

The following oils were selected for analysis: Lemongrass oil, Eucalyptus oil, and Tea Tree oil. The oils were provided by Felton Grimwade & Bosisto's Pty Ltd, FGB, Melbourne, Australia. All oils were non-diluted and not chemically altered by any solvent or processing.

Control group – oils and antiseptics

The antibacterial effects of essential oils were compared with those of undiluted household olive oil as well as the commonly used clinical antiseptics ethanol (70%) and chlorhexidine (0.1%).

Bacterial strains

Clinical isolates of 5 different

Results

Test group: All three essential oils tested showed good bactericidal activity against VRE, MRSA, ESBL-producing E. coli and K. pneumoniae strains, while only Tea Tree oil showed notable activity against multi-resistant (MR) P. aeruginosa strains. Lemongrass oil demonstrated the largest zones of inhibition out of all the substances against VRE (13–18 mm) and MRSA (20–29 mm), yet showed relatively moderate inhibition against E. coli ESBL strains (2–13 mm) and poor inhibition against MR

Discussion

For thousands of years, the therapeutic properties of essential oils have been recognized by Australian aboriginals, who used Tea Tree poultices to treat a variety of infections, wounds and insect bites. Tea Tree oils were soon adopted by the colonial settlers and were marketed as a medicinal germicidal from the early 20th century.

In this study, the susceptibility of a wide range of clinical isolates of surgically relevant hospital-acquired multi-resistant bacteria to essential oils was proven

Conclusion

VRE, MRSA, MR P. aeruginosa, ESBL-producing E. coli and Klebsiella pneumonia are all susceptible to a range of plant-derived oils. We suggest that such oils may be a promising force as supportive topical treatment in the case of stubborn and multi-resistant hospital-acquired infections in the clinical setting.

Conflict of interest

The authors declare no conflict of interest.

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