WO1998031420A1

WO1998031420A1 - Antibacterial medical devices

Info

Publication number: WO1998031420A1
Application number: PCT/GB1998/000087
Authority: WO
Inventors: Thomas Stuart Jackson Elliott; Phillip Owen Byrne
Original assignee: Btg International Limited
Priority date: 1997-01-16
Filing date: 1998-01-12
Publication date: 1998-07-23
Also published as: EP1007149A1; JP2001508684A; GB9700875D0

Abstract

A catheter or other invasive/implant device (40) intended for relatively long term use, of the order of a day or more, in a patient's body is provided with an electric field generator to generate bactericidal H2O2 on and adjacent the device/body interface from available oxygen and water at a carbon cathode (48) connected in an electrical circuit (47, 50, 51). The field is preferably unidirectionally negative and also continuous and constant, but pulsatile, alternating and other field forms are possible. A surgical dressing may operate on the same principle.

Description

ANTIBACTERIAL MEDICAL DEVICES

This invention concerns a method of using medical devices intended for relatively long term use, of the order of a day or more, in a location extending on or at least partially within a patient's body, or in contact with an open wound, and extends to surgical dressings. Such devices include a variety of kinds, such as catheters, cannulae, shunts, specialised or surgical dressings and orthopaedic deployment in a temporary or permanent role. It is estimated that two-thirds of all patients admitted to hospital have such a device inserted or applied during their stay.

A fundamental problem associated with the use of such devices is that of infection. Infection in these circumstances is thought to involve the attachment of bacteria on the device surface which interfaces with the patient^'s body tissue and subsequent bacterial colonisation on and in the immediate vicinity of such surface. Treatment of such infections by antibiotics is costly, not always successful, and for example often necessitates catheter removal. This situation is discussed, for example, in an article entitled "Intravascular line associated infections - prospects for prevention" by Dr. T.S.J. Elliott, presented at a symposium on "New Perspectives on Staphylococcus Infections'^* held September 1986. Lancashire, and thereafter published in 1987 in a booklet under the latter title by Medicom (UK) Limited. It will be seen from this article that various proposals for combative measures have yet to be established as satisfactory.

An object of the present invention is to reduce this infection problem by way of a measure involving, in general terms, provision of the device with means to generate an electric field over its interface surface, which field acts to inhibit bacterial attachment and colonisation on and adjacent that surface. US Patent 5154165 is relevant, and the entire file is incorporated herein by reference.

According to the present invention, a method of generating hydrogen peroxide at a device applied to a body in the presence of water (for example implanted in. or placed on the surface of. or otherwise in contact with, a patient's body) comprises the steps of: providing a field-generating means comprising two electrodes and a separate power source producing a defined, or determinable. or discernible, or predetermined, current between said electrodes (thus generating a persistent negative electric field around said device or at least around one electrode thereof) for generating hydrogen peroxide at the negative electrode from oxygen and water; while said device is at least partially placed within a region containing both oxygen and water (for example within or on the surface of said body), generating hydrogen peroxide by reduction of the oxygen and water at the negative electrode upon connection of said power source, whereby bacterial activity in the body (for example the patient's body) at the device is inhibited, and/or bacteria at the device are killed by the hydrogen peroxide.

The concentration of dissolved oxygen in plasma, at 0.14 mmol/1, is amply aerobic. In another form of the invention the generating means comprises a conductor for or in connection with an electrical circuit, the conductor being supported by the device and the circuit being operable to generate the appropriate field by way of the conductor. The conductor can be supported as a coating over the device and so itself define the interface surface, or it can be embedded as a wire or other configuration within the device suitably, in this event, to follow the outer surface shape of the device. The current is preferably within the range 1-100 μA, and for many sites in the body is preferably 1-20 μA, such as 1-10 μA.

The electric field is preferably unidirectionally negative and is preferably continuously maintained in a substantially constant manner, but there is no reason to suppose that a pulsatile or otherwise varying negative field cannot be used to effect the desired action.

Indeed, it is not at present considered that the field should necessarily be unidirectionally negative. A field of alternating polarity can interfere with the ionic exchange process between the bacterial cell wall and surrounding medium and so act to inhibit colonisation between bursts of hydrogen peroxide generation. Moreover, an alternating field for this purpose need not necessarily be symmetrically cyclic, but can be asymmetrical.

Also, it is considered that the field of the invention can act against infection in other ways than bactericidal hydrogen peroxide production. For example, electroporation can be caused in cells subject to the field and this could facilitate the action of drugs and/or natural immune response mechanisms on bacteria in the vicinity of the device. Moreover to the extent that drugs, such as antibiotics, often exhibit a positive surface charge they can be beneficially attracted to and retained in the same vicinity.

The electrode, especially the negative electrode, and any conductive surface associated therewith that is intended for contact with or insertion into the body, may advantageously be non-metallic, e.g. of carbon or conductive polymer or may contain an organic matrix to facilitate production of H₂O₂, or chlorine or both, such as a conductive gel, possibly using additives or materials reducing the work function of the surface to facilitate said production and reduce overall energy consumption.

The invention also provides a surgical dressing for use as described above, and a surgical dressing comprising a flexible non-conducting material having a plurality of electrically separated non-metallic electrodes applied thereon.

The invention is now described by way of example with reference to the accompanying drawings, in which:-

Figures 1 -3 diagrammatically illustrate respectively different experiments conducted during development of the invention,

Figures 4 and 5 similarly illustrate, by way of example, respectively different forms of device according to the invention, and

Figure 6 illustrates a surgical dressing according to the invention, with a central negative electrode. In the experiment of Figure 1 a stainless steel wire 10 was located along a plastics cannula 11 with a free end portion of the wire being wound around the tip portion of the cannula to form an electrode 12. The other end of the wire 10 was connected to the negative terminal of a constant current generator 13, a further stainless steel wire 14 being connected to the positive terminal of the generator and extending to an "indifferent" electrode 15 at its free end. The cannula tip plus its electrode 12 was placed, with the indifferent electrode 15, in mutually spaced manner in a turbid aqueous broth 16 of

Staphylococcus epidermidis, at about 10⁷ cfu ml^"1, the broth being retained in aerobic conditions within the confines of an O-ring 17 mounted on a glass slide 18. The generator 13 was then operated to pass a small current of 1-10 or 1-100 μA between the electrodes for a period of 1 -1.5 hours. After such operation clear areas appeared around the cannula and its electrode, that is to say there were insufficient bacteria in this area to make it turbid, and there were no bacteria visible on the cannula surface. At the same time the broth closely around the indifferent electrode appeared more turbid than that further spaced. The clear areas coincided with where H₂O₂ was present having been electrochemically generated on the electrode 12 from available oxygen and water. For comparative purposes the same arrangement was set up and left for 1.5 hours without generator operation and, in the result, the broth remained evenly turbid.

In the experiment of Figure 2 the same arrangement of slide, O-ring and broth was used as in Figure 1 but with the other elements changed. In this case a D.C. source 20 had respective PVC insulated wires 21 and 22 connected to its terminals, the free end portions of these wires being located to pass through the broth in mutually spaced manner before securement to the slide with silicon sealant 23. Operation with the source applying a potential of about 100 V to the wires was considered effective to induce a small surface charge on the insulation surfaces of the wires. This charge was sufficient on the negative wire insulation to repel bacteria judged by the appearance of a clear zone in the broth around this wire.

In the experiment of Figure 3 a petri dish 30 holding agar 31 was flooded with a broth of Staphylococcus epidermidis and allowed to dry such that about 10⁶ cfu bacteria were deposited, this being insufficient to give visible turbidity. Thereafter two pairs of hypodermic needles 32 were inserted in the agar in like mutually spaced manner to serve as electrodes. One such pair of electrodes was connected by wires 33 to respective terminals of a constant current source 34, while the other pair were left unconnected as control electrodes, and the dish incubated overnight at 37 °C with the source operating at about 10 μA. In the result the bacteria grew to form a confluent turbid lawn over the agar surface except for a clear zone 35 of about 3 mm diameter around the electrode connected to the source negative terminal, in which zone there was no bacterial growth.

The device of Figure 4 is a catheter 40 comprising an elongate tubular body 41 of plastics material. The distal end portion or tip has a rounded closed end 42, while the proximal end portion terminates in a socket 43 of Luer or other form. The catheter is of double lumen form, having a larger lumen 44 communicating the socket 43 with apertures 45 in the wall of the tip for fluid transmission through the catheter, and a smaller lumen 46 closed at its ends. A wire 47 extends through the smaller lumen 46 and at its ends penetrates the catheter wall in sealed manner. The distal end portion for entry into a patient has an external electrode coating 48 of metal, carbon or other conductive material connected with the adjacent end of wire 47 and at the proximal end portion the end of the wire is connected with an electrical terminal 49. In use the catheter will be connected by way of terminal 49 with the negative terminal of a constant current generator 50, suitably powered by a 1.5 V battery to generate an output of 1-10 μA, the generator having its positive terminal connected to a skin electrode 51 of conventional form, such as used in ECG monitoring and the like, for application to the patient. The device of Figure 5 is similar to that of Figure 4 except that in this case the distal electrode, denoted at 54, is embedded within the material of the catheter body to follow the outer surface shape of the body. This electrode is subjected to a potential of about 100 V by a battery-powered dc-to-dc converter having a current output limitation facility set no higher than 1 μA for patient safety in the event of breakdown of the catheter material insulation around the electrode during use.

In further experiments, intravascular catheters made of 15% carbon-impregnated polyurethane, with an external diameter of 2.3 mm, and which conducted electricity, were steam-sterilised at 100°C for 30 minutes, which did not disrupt the plastic polymers. The catheters were connected to a 9 V alkaline battery in series with a variable high stability carbon film resistor to generate a constant direct current of between 10 to 100 μA. In all experiments, flow of electric current was confirmed by placing an ammeter in series in the circuit.

Experiments were carried out with two clinical isolates: Staphylococcus epidermidis 983 and 811 and two type cultures: S. aureus NCIMB 6571 and S. epidermidis NCIMB 12721. The majority of the experiments were carried out with the type cultures.

Nutrient agar was prepared by adding agar of final concentration 1.5% w/v, to nutrient broth. Blood agar was prepared by supplementing Columbia agar with 7% defibrinated horse blood. For the investigation into the effect of electric current on bacteria attached to a catheter surface, a continuous culture broth for biofilm was used, consisting of glycerol, lO mM; (NH₄)₂SO₄ 6 mM; MgS0₄, 0.5 mM; KC1, 13.5 mM; KH₂PO₄, 28 mM; Na₂HPO₄, 72 mM; thiamine, 1 mg/1: biotin, 1.5 mg/l; peptone, 3 mg/1. The medium was buffered to pH 7.4. All media were sterilised by autoclaving at 121 °C for 15 minutes.

Three colonies obtained from cultures on nutrient agar slopes were inoculated into 5 ml of nutrient broth. The resulting bacterial suspension was then incubated at 37 °C for 2 hours. A 4 μl sample of the staphylococcal suspension (ca. 10⁵ cells) was inoculated onto the surface of a nutrient agar plate. Three nutrient agar plates were prepared for each bacterium studied. Two carbon catheters (2.5 cm long), were placed perpendicularly in one nutrient agar plate. The carbon catheters were then connected to an electrical device which generated 10 μA DC via external leads with one catheter acting as a cathode and the other as anode. The agar plate was then incubated at 37 °C, in air for 16 hours. The second agar plate was flooded with 0.5 ml of a freshly prepared catalase solution which had 1500 units of activity (one unit decomposes 1.0 μmole of H₂0₂ per minute at pH 7.0 at 25 °C at 10.3 mM H₂0₂). This agar plate was then left at room temperature for up to 5 minutes to allow the catalase to be absorbed by the agar. Two catheters were then placed perpendicularly in the agar, and electric current of 10 μA was applied as described above. This plate was then incubated at 37 °C, in air, for 16 hours. The final agar plate of the set was placed in an anaerobic cabinet with an atmosphere of 10% CO₂, 10% H₂ and 80% N₂ at 37 °C. After 10 minutes, two catheters were placed in the nutrient agar plate and connected to one electrical device as described above. The plate was then incubated under these conditions for 16 hours.

Following incubation, catheters were removed from the plates and the diameters of any zones of inhibition around the catheter insertion sites into the agar were measured with a vernier calliper. The diameter was taken as the total distance between the outer edge of the inhibition zone with the centre of the catheter acting as the mid-point. The staphylococcal strains were tested on six separate occasions.

To quantify the effect of catalase on the inhibition zone, various amounts of the enzyme were dissolved in phosphate buffered saline (PBS) and added to 20 ml molten nutrient agar that had been cooled to 44 °C (final concentration of catalase ranged from 50 to 2500 units/ml agar). After thorough mixing, the plates were allowed to set, 4 μl of staphylococcal suspension prepared as above was then spread onto each plate. Two carbon catheters were perpendicularly placed in the agar and connected to the electrical device which generated 10 μA DC. All plates were incubated in air, at 37°C for 16 hours. After the catheters were removed, the diameter of inhibition zone was measured. S. a reus NCIMB 6571 and S. epidermidis NCIMB 12721 were tested six times at each concentration of catalase. Four μl of staphylococcal suspension were spread onto each of five nutrient agar plates. Two catheters were then placed in each nutrient agar plate as described above. An electrical device which generated 10 μA was connected to the catheters of one of the five plates and was then incubated in air, at 37 °C. Another plate with the two catheters connected to an electrical device which generated 10 μA was placed in an anaerobic container. A palladium, vanadium, iridium or vallidium catalyst pack and a Gas Generating Kit. Campylobacter System (Oxiod BR 60) which was prepared according to the manufacturer^'s instructions were immediately placed in the container which was then sealed and incubated at 37 °C. Microaerophilic condition (approximately 5% oxygen) was achieved within 30 minutes. The remaining three nutrient agar plates with the catheters were placed in an anaerobic cabinet. An electrical device which generated either 10, 75 or 100 μA DC was then connected to the catheters of each plate via external leads. All 5 nutrient agar plates were incubated for 16 hours and then the diameter of the inhibition zone measured as described above. S. aureus NCIMB 6571 and S. epidermidis NCIMB 12721 were each tested six times. After measuring the diameter of the inhibition zone, an indicator strip to detect H₂0₂ was placed on the nutrient agar within the inhibition zone. The strip contained a peroxide which transfers oxygen from a peroxide or a hydroperoxide group to an organic redox indicator. The indicator is then converted to a blue-coloured oxidation product which can be visually detected. The strip measures between 0.5 to 25.0 mg/1 hydrogen peroxide semi-quantitatively. The presence of hydrogen peroxide less than 0.5 mg/1 was indicated by the presence of blue colour on the reaction area.

The results of investigating mechanisms of bactericidal activity of electricity by the zone inhibition test were as follows :-

In the majority of experiments, there was no zone of inl ibition around the anode with all the staphylococcal strains tested. On a few occasions, a rim (<1 mm width) of clear area around the catheter-agar interface was observed. The diameter of the inhibition zone produced around the cathode in air, in air with catalase and in anaerobic condition without catalase is shown in Table I. The diameter of the inhibition zone in air for all staphylococcal strains was similar (mean 10.2-11.5 mm). Addition of catalase to the agar reduced the zone size for the three strains of S. epidermidis and there was no inhibition zone with S. aureus NCIMB 6571. When the zone of inhibition tests were carried out in anaerobic conditions (gaseous oxygen concentration <0.1%), there was no inhibition zone around the cathode for any of the organisms tested.

Considering now the effect of various concentrations of catalase on the diameter of the inhibition zone, it was found that addition of catalase as low as 50 units/ml agar significantly reduced the zone size (pO.Ol , Wilcoxon Signed Rank Test) as compared to control. When S. epidermidis NCIMB 12721 was tested, increasing the amount of catalase from 50 to 2,500 units/ml agar did not reduce the diameter of the inhibition zone any further nor eliminate it completely. With S. aureus NCIMB 6571, increasing the amount of catalase reduced the inhibition zone gradually, but still did not eliminate the inhibition zone completely even at the highest concentration (2,500 units/ml agar) of the enzyme.

The diameter of the inhibition zone around the cathode was reduced as oxygen concentration decreased as under micro conditions (Table II). When the zone of inhibition tests were carried out in anaerobic condition, no inhibition zone was formed around the cathode and the organisms grew up to the catheter-agar interface. Increasing the electric current to 100 μA did not alter this effect. However, the absence of oxygen had no influence on the activity of the anode. In addition, as the amperage increased under anaerobic conditions, the zone size similarly increased.

Hydrogen peroxide was detected in the agar within the inhibition zone around the cathode only. It is supposed that the overall reaction O₂ + 2e + 2H₂0 → H₂0₂ + 20H^", more correctly rendered as O₂ + 2e + 2H⁺ → H₂0₂, occurs at the cathode. The need for oxygen, and the need for a source of hydrogen ion such as water, can be seen. The concentration of H₂O₂ was up to 20 mg/1 (0.59 mmol/1) at the catheter-agar interface and gradually diminished over a 2-3 mm distance from the catheter surface. Within the zone of inhibition in the agar with added catalase, hydrogen peroxide was not detected. After the application of 10 μA DC, hydrogen peroxide was detected only in the broth associated with the cathode. It was detected qualitatively by indicator strip after 4 hours of application of electric current and increased to 5-10 mg/1 (0.15-0.30 mmol/1) after 16 hours. The influence of anaerobic conditions on the antibacterial activity of electric current on organisms attached to a catheter surface was now considered. Ten μA DC is known to be bactericidal to organisms attached to the surface of an electroconducting catheter when the test was carried out in aerobic conditions. Therefore, if the activity of electric current applied to the organisms attached on the catheter surface were to be examined under anaerobic conditions, any bactericidal activity present at the cathode would indicate that mechanisms other than electrolysis are involved. When the activity of electric current (10 μA DC) on organisms attached to catheter surfaces was carried out in anaerobic conditions, the mean viable count (241 cfu/cm length of catheter), on the cathodal catheter surface was reduced. This was significantly lower (n = 4, p<0.01) than the control catheter and the field catheter since both viable counts were > 1,000 cfu/cm length catheter. The dissolved oxygen concentration in the broth was 0.1 mg/1 and no H₂O₂ was detected by the indicator strip.

We believe that this invention is the first to exploit an electric current as low as 10 μA, when applied to a multi-ion solution, to electrolyse ions in the solution such as to produce the antibacterial substance hydrogen peroxide at the cathode. As the current is increased (at 100 μA), generation of hydrogen peroxide (+0.68 V) at the cathode and production of chlorine (+1.4 V) at the anode take place concurrently. It is possible that other bactericidal substances such as H0₂, ozone, OC1 are also produced. These reaction products can be controlled by the current. Other studies have previously used metallic electrodes to demonstrate the inhibitory effects of electric current on micro-organisms (Blenkinsopp et al., 1992. Costerron et al, 1994). However, electrolysis takes place even at low amperage level. Note that if metallic electrodes had been used in this description of the invention, they would have interfered with the process. Particularly they can corrode and affect the bactericidal activity of electric current. Free hydrogen peroxide, as generated according to the invention, eventually decomposes to harmless oxygen and water. This novel method of preventing catheter related infections delivers the antibacterial hydrogen peroxide to specific sites where it is most needed with no build-up of harmful reaction products from the H₂O₂. Similarly, the technique can be used to prevent wounds from becoming infected or to control infections under a surgical dressing.

Table 1. Zones of inhibition produced around the cathode under aerobic and anaerobic conditions with or without catalase. The catalase (1500 units in total) was spread over the nutrient agar plate.

Zone diam.¹ (mm): mean±S.D.,n=6

Notes:

1. the zone of inhibition was measured from edge to edge across the centre of the catheter and the external diameter of the catheter was 2.3 mm

2. no zone of inhibition observed, as the bacteria grew up to catheter-agar interface

3. significantly different from the control, p<0.01, Wilcoxon Signed Rank Test

4. no zone of inhibition observed (n=3) and mean =4.0 mm (n=3) Table II. Zone of inhibition produced under different atmospheric conditions

Zone diameter¹ (mean ± 1 S.D., mm; n=6)

Note:

1. the zone of inhibition was measured from edge to edge through the centre of the catheter and the external diameter of the catheter was 2.3 mm

2. oxygen concentrations under different conditions were: aerobic = 20.9%, microaerophilic = ca. 5%, anaerobic = 0.1%

3. significantly different from control, p<0.01, Wilcoxon Signed Rank test 4. no zone of inliibition observed, as the bacteria grew up to the catheter-agar interface

Turning to Figure 6, a surgical dressing is^" shown according to the invention. In the dressing, a substrate 2 of flexible non-conducting material is provided as a backing for the dressing. The material may for example be of a woven fabric or a thin plastics film.

On the substrate 2, an electrode 1 is fabricated of conducting gel (as for example used in heart monitors) coated by conventional techniques onto the substrate 2.

Overlying the electrode 1 is a dressing fabric 4 which may itself be arranged for contacting a patient's body or may have a supplementary layer suitable for such contacting. The dressing fabric 4 carries a coating of (normally the same) conducting gel forming a second electrode 1. The gel or the fabric 4 may be hygroscopic so as to absorb neighbouring liquid to provide liquid (normally aqueous) communication between the electrodes 1, providing conductivity and a source of H₂O₂. To prevent the gel from contacting an open wound, the gel may have a supplementary absorbent dressing placed on it as necessary in use. The gel preferably incorporates substances which lower the work function of the dressing (so as to encourage H₂O₂ formation).

The electrodes 1 are connected via respective connecting leads 3 to an external electric power source, and the geometrical form of the final assembly is such as to optimise and direct the electric field produced by passage of controlled current. Figure 6 shows a simple two-electrode arrangement, but other more complex electrode configurations for specific uses may be desirable, for example multiple electrode dressings may be required. Referring again to Figure 6, for H₂O₂ production the central electrode 1 (i.e. that on "top^" of the drawing, and closer to the patient's skin) would essentially be made negative with respect to the outer electrode 1 and because the central electrode could be in contact with a wound it may be covered with a water absorbing surgical coating or fabric. In the presence of saline, chlorine may be produced by electrolysis through the electrodes, and may be beneficial to wound protection.

Alternatively, metallised electrodes (e.g. of aluminium) may be applied side-by-side on a single layer combining the functions of the substrate 2 and the fabric 4. The electrodes may be of the same or different substances.

In another alternative, the substrate 2 and the fabric 4 as shown in Figure 6 are one and the same, with the outer electrode 1 being exactly as drawn, i.e. a ring around the inner electrode with an insulated lead 3, rather than being a continuous layer behind (and shielded by an intervening layer from) the inner electrode. Thus, the electrodes may be on the face of the dressing opposite to that which is to be applied to the body, or on that face of the dressing which is to be applied facing the body, or one or some on each face. A supplementary dressing may be provided in the latter two cases, between the electrode and the patient's body, and may be porous or absorbent to allow the generated hydrogen peroxide to be effective. It will be understood that the dressing of Figure 6, and the variants thereof as described, will, when connected to an electric power source, generate H₂O₂ from available oxygen and water as described in connection with the earlier Figures. Where a chloride salt is present, chlorine may be generated from the salt in the presence of water.

Claims

CLAIMS :-

1. A method of generating hydrogen peroxide at a device applied to a body in the presence of water, comprising the steps of: providing a field-generating means comprising two electrodes and a separate power source producing a current between said electrodes for generating hydrogen peroxide at the negative electrode from oxygen and water; and while said device is at least partially placed within a region containing oxygen, generating hydrogen peroxide by reduction of the oxygen and water at the negative electrode upon connection of said power source, whereby bacterial activity in the body at the device is inhibited and/or bacteria at the device are killed by the hydrogen peroxide.

2. A method according to Claim 1, wherein one of said electrodes forms at least part of the outer surface of said device to define said interface.

3. A method according to Claim 1 , wherein one of said electrodes is embedded in said device to follow at least part of the outer surface shape thereof.

4. A method according to Claim 1 , wherein said field is unidirectionally negative.

5. A method according to Claim 4, wherein said field is continuously maintained in a subsequently constant manner.

6. A method according to Claim 4, wherein said field is pulsatile.

7. A method according to Claim 1, wherein one of said electrodes is intimately connected with said device and the other of said electrodes is connected with said device remotely by way of said power source, said method comprising: placing said one electrode within said body together with said device to generate said field, and placing said other electrode on the skin of said body.

8. A method according to Claim 7, wherein said power source is a battery having negative and positive terminals and said one and other electrodes are respectively connected to said terminals.

9. A method according to any preceding claim, wherein the negative electrode transmits a current of from 1-100 ╬╝A.

10. A method according to Claim 9, wherein said current is 1-20 ╬╝A.

11. A method according to any preceding claim, wherein the electrode and any associated conductive surface within the body is non-metallic.

12. A method according to Claim 11 , wherein the electrode is of carbon or a conductive polymer or contains an organic matrix.

13. A method according to Claim 12, wherein the electrode is of a conductive gel.

14. A surgical dressing for use in a method according to any preceding claim.

15. A surgical dressing comprising a flexible non-conducting material having a plurality of electrically separated non-metallic electrodes applied thereon.

16. A dressing according to Claim 14 or 15, wherein the electrodes are on the face of the material opposite to that which is to be applied to the body.

17. A dressing according to Claim 14 or 15, wherein the electrodes are on that face of the material which is to be applied facing the body.

18. A dressing according to Claim 14 or 15, wherein one or more electrodes are on that face of the dressing which is to be applied facing the body and the remaining electrode(s) is (are) on the opposite face.

19. A dressing according to Claim 17 or 18, further comprising a supplementary dressing covering the electrode(s) which is(are) to face the body.

20. A dressing according to Claim 19, wherein the supplementary dressing is absorbent or porous.

21. A dressing according to any of Claims 14 to 20, further comprising electric connecting leads to the electrodes to facilitate connection of the electrodes to an external power source.

22. A dressing according to any of Claims 14 to 21, wherein at least one of the electrodes is of a conductive gel containing a substance which lowers the work function of the dressing.

23. A dressing according to any of Claims 14 to 22, modified in that in the presence of a chloride and water, chlorine is generated.

24. A method according to any of Claims 14 to 22, wherein chlorine is generated at the counter electrode to that whereat hydrogen peroxide is generated.