Effects on antibiotic resistance of Staphylococcus epidermidis following adhesion to polymethylmethacrylate and to silicone surfaces
Introduction
A frequent cause of implant failure is bacterial infection. Accidental contamination during surgery can expose the implant to risks of microbial colonisation and subsequent infection. Some evidence suggests that a material surface could have an influence on the interactions with bacteria. Local inhibitory effects on the immune system due to release of active chemical substances from the implant surface could favour bacteria eluding host defense systems. It is also known that bacterial strains involved in clinically significant infections can possess adhesins receptors. These receptors bind to specific extra-cellular proteins such as collagen and fibrinogen, and can be used to selectively adhere to the proteinaceous layer adsorbed onto biomaterials, achieving a better anchoring of the bacterial cells on the material surface. Furthermore, bacteria strains often encountered in clinical situation produce a polysaccharide based matrix referred to as slime. The capability of producing slime is considered by different authors to be a virulence factor, able to provide bacteria with an additional mechanism of adhesion and, even more, with a coating protective from host defenses and somehow related to antibiotic drug therapy resistance.
Staphylococci are considered as the most important pathogens of prosthetic infections, thus contributing to the majority of hospital acquired bacteremias [1], [2]. Over the last decades, both Staphylococcus aureus and Staphylococcus epidermidis have accumulated multiple resistance determinants. The onset of antibiotic-resistance in staphylococci has been ascribed to the positive selective pressure carried on by the large clinical handling of broad-spectrum antibiotics. In periprosthesis infections, bacterial adhesion to the surface of artificial materials is considered the fundamental mechanism of virulence [3], [4]. Clinically, the available antibiotic therapies are usually ineffective, because of antibiotic resistance of the adherent biofilm bacteria [5]. Also in vitro studies have revealed an increase of the antibiotic resistance in connection with bacterial adhesion to some biomedical polymers [6], [7]. It can be conceived that the biomaterial, acting as a substratum for the bacterial adherence leads to a selection, among the whole contaminant bacterial population, of variants endowed with more marked adhesive properties as well as with increased resistance towards antibiotics.
In the present study, the susceptibility to penicillin, erythromycin, clindamycin, cefamandole, imipenem, vancomycin, ciprofloxacin, ampicillin, cefazolin, trimethoprim–sulfamethoxazole, chloramphenicol, amikacin and netilmicin has been evaluated in a methicillin-, gentamicin- and tobramycin-resistant Staphylococcus epidermidis strain from an infected prosthesis following in vitro adhesion to polymethylmethacrylate (PMMA) and to silicone elastomer. The two polymers were selected because of their recurrent use in clinical applications. PMMA finds large use in many applications particularly in the orthopaedic field as bone cement and in ophthalmology as artificial intraocular lenses [8], while silicone elastomer is employed in a wide range of surgical applications [9], i.e. as scleral buckles for retinal surgery, in bone reconstruction/correction, in plastic surgery, as tissue expander, coating of pacemakers, catheters and so on. Both polymers are known as materials prone to bacterial adhesion.
The susceptibility to antibiotics both of adherent bacteria and of bacteria which, although exposed to the same materials, had not undergone adhesion, has been investigated by means of plate antibiogram according to Kirby–Bauer method [10] and in accordance with the guidelines of the National Committee for Clinical Laboratory Standards [11]. The bacterial growth inhibition area around each antibiotic disk was measured using an image analyser, which allows optimised detection of small variations in antibiotic susceptibility.
Section snippets
Materials
The two test materials were 1 mm-thick smooth sheets, respectively, of polymethylmethacrylate (Good Fellow Advanced Materials, Cambridge, UK) and of silicone elastomer (medical grade Silastic® Elastomer sheet, Dow Corning Corporation, USA). Square specimens of both materials with an exposed area of 200 mm2 were used in the assay for bacterial adherence. The Api-Staph test for microbial identification was purchased from Biomérieux, France. All the antibiotics, the Trypticase Soy Broth (TSB)
Results
For each material 31 experiments in triplicate have been carried out. Table 1 shows the values of the diameters of the growth inhibition areas of the bacteria adhered to PMMA in comparison with the diameters of growth inhibition areas of non-adhered bacteria. The table shows also the percent difference between the mean values of adherent and non-adherent bacteria and the significance of the difference (t Student's test).
In the case of the cells which had been placed in contact with PMMA, the
Discussion
In recent years Staphylococcus epidermidis has emerged, together with Staphylococcus aureus, as a frequent etiologic agent of infections associated with indwelling medical devices [3], [16], [17]. The enlightenment of the pathogenetic mechanisms of the biomaterial-associated infections is the necessary premise for the adoption by clinicians of efficacious prophylactic and therapeutic measures [18], [19], [20], [21], [22].
Recent researches have provided evidence for an association between the
Acknowledgements
This work was supported by Italian Ministry of Health grant SVE 4-ICS/RF98-610 (“Interaction between opportunistic bacteria and biomaterials”).
The technical assistance of Daniela Cavedagna is gratefully acknowledged. We are also grateful to Chiara Vescovini and Roberta Rambaldi for their skilled assistance in preparing the manuscript.
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