Some microbiological problems with softlens solutions

Some microbiological problems with softlens solutions

Some Microbiological Problems with Soft lens Solutions R.E.M. Thompmn Dr. Thompson is Reader in Bacteriology and Head of Micro-Biology dept., The Midd...

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Some Microbiological Problems with Soft lens Solutions R.E.M. Thompmn Dr. Thompson is Reader in Bacteriology and Head of Micro-Biology dept., The Middlesex Hospital, London W.1. Solutions are used for a variety of purposes with soft contact lenses. They are used for cleaning, for lubrication and for disinfection. Clearly it is important that, whichever of these functions a solution Is designed to perform, no harm shall result to the wearer of the lenses as a result of its use. As a medical microbiologist, my major interest is the diagnosis and treatment of infection and perhaps most important of all the prevention of infection. In the case of contact lens solutions this deals with sterilization of the solutions by the manufacturer, maintenance of sterilization during use by the wearers and in the case of disinfecting solutions, the efficiency of the solutions in destroying micro organisms.

However, the process is not always suitable, perhaps the article to be sterilized is destroyed by heat, or not easily penetrated by steam, or its physical state is changed. In these circumstances some other method must be used. In the case of fluids the second choice is often filtration. This process removes g e r m s - - it does not destroy them. I t is much less reliable and for this reason requires much more thorough checks for sterility on the processed materials. The third possibility is by gamma irradiation. The source of irradiation is radioactive Cobalt (e°Co) and while the time of sterilization is dependant on the size of the Cobalt source, it is generally a lengthy process and has to be carded out under carefully controlled conditions in well screened plants to avoid any risks from escaping irradiation. The dose usually used for sterilization is 2.5 mega r a d s - - to be compared with a lethal dose for human beings of say 1500 rads. The point of this being that in general the smaller the target cell, the bigger the dose of irradiation that is required to destroy it and bacteria are much smaller than human tissue cells. While this is a very widely used method of sterilization it is worth recording that there is a bacteria, Micrococcus radiodurans which requires, 6.5 mega rads to destroy. Clearly then there is a possibility, however remote, of bacterial survival after processing. In general, contact lens solutions are sterilized by one of these methods or a combination of them. As an example of the latter, a fluid may be sterilized by autoclaving or filtration and then bottled into containers, often made of plastic, which have been irradiation sterilized. The filling of such containers with the presterilized fluid has to be performed aseptically to minimise the risk of recontamination. In practice this means that a careful control has to be kept on the environment in which the work is carded out as well as on the methods of work and the workers and their personal hygiene.

1. Sterilization o f the fluids The simplest definition of sterilization is a process that removes or destroys all living microbes, including all kinds of bacteria, viruses, fungi and protozoa. Sterilization is not an absolute condition and even with the most efficient methods known failures can occur (Fig. 1). In practice the most efficient method is

Bacterial Survival Curve 7

5 ......... . ..... 4

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t

0

i

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Log 10 3 survivors

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910

Time Fig. 1 Bacterial survival curve showing lag at beginning and end of exposure period to adverse agents.

Maintenance o f Sterility during Use It is at this point that one reaches the first problem that has a special bearing on soft contact lens solutions. In general solutions are packaged in multidose containers - - 110 ml being a common size for disinfecting solutions, 65 ml is common for

steam under pressure - - autoclaving - - where with the use of efficient, well maintained, machinery a very high probability of sterility can be guaranteed.

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wetting solutions and some cleaning solutions and 15 ml for other cleansers. All of these are designed for multiple use by the lens wearers. The problem is that there is a risk of contamination every time the container is opened, the extent of the risk being largely dependant on the care with which the container is handled. A common type of container is a plastic squeeze bottle with the outlet covered and thus protected by a well-fitting screw cap. Now if this is opened and care taken never to touch the protected nozzle under the cap, the contamination risk is very small. But if the nozzle is touched some bacteria, possibly a lot, will be introduced. Clearly in solutions which do not contain an antibacterial substance, this will mean that all subsequent withdrawals will contain some of these bacteria. It is of interest here to show you a list of organisms isolated from either contaminated lens cases or contaminated solutions received from soft lens wearers (Table I). These are mostly wet situation

there will be no more to kill any subsequent contaminants. Now in the case of hard contact lenses the solutions used may be of sufficient strength to kill large numbers of bacteria. Antiseptics at such concentrations may be used because hard lenses do not absorb so that a simple rinse will remove all the antiseptic so that none will be transferred to the eye. With soft contact lenses the situation is different because the materials which these lenses are made of not only absorb water and small molecule substances dissolved in the water, but they also concentrate certain chemicals. This presents two problems or at least two aspects of the same problem. Firstly an absorbed antiseptic will not be removed by a simple rinse, absorption is a relatively slow diffusion into the substance of the lens and removal is an equally slow process of diffusion. Secondly concentration by absorption may be very difficult to reverse, indeed in some circumstances may be largely irreversible. In both cases antiseptic is liable to be transferred to the eye in unacceptable concentrations with the risk of causing damage. In practice these two problems work against each other. That is to say the solution is formulated from antiseptics - - single or in combination w that do not concentrate in the lens material and in strengths which will not be harmful to the eye. So far so good, but the low concentrations used have low bacterial killing capacities which means that casual contamination by the users may very quickly exhaust this capacity with the result that the preparation can no longer fulfil its proper function of destroying bacteria on contaminated lenses. Indeed the antibacterial solution may contain living multiplying bacteria. There are two possible solutions to this problem, three if you postulate the possibility of some unknown, non-toxic, non concentratable, non absorbed antiseptic turning up. The solutions are either changing to single dose containers or improved education in aseptic techniques for the wearers. I will not enter into the various objections to single dose containers since, while highly relevant, they are non microbiological.

E S C H E R I C H I A COLI K L E B S I E L L A SPP. P S E U D O M O N A S SPP. SERRATIA MARCESSENS STAPHYLOCOCCUS ALBUS Table I

Bacterial species commonly isolated from contaminated soft lens solutions.

STAPHYLOCOCCUS ALBUS STAPHYLOCOCCUS AUREUS DIPHTHEROIDS MICROCOCCI Table II

Bacterial species isolated from conjunctival swabs from non-infected eyes.

species, that is to say they live and multiply in water and require very little in the way of added organic material for multiplication. You would find all of these quite commonly in the home environment in such things as, sink taps, flower vases, dish cloths in fact any wet situation and you will realise from this it is very easy to get them on the hands and very easy to transfer them to another wet situation. You will note from Table II that it is a very different list from the organisms that are usually isolated from conjunctival swabs taken from healthy or at any rate apparantly uninfected eyes. These latter are organisms usually found on skin and not found in the kind of wet situation mentioned earlier. In the case of disinfectant solutions you might well ask whether such contamination matters since the antibacterial agent will deal with it. It is here that the problem becomes important. Any antiseptic solution will kill or inhibit a fixed number of bacteria and no more. This is because in destroying a bacteria some of the antiseptic is used up and when it is all used up

Antiseptics in c o m m o n

use

The antiseptics which are most commonly used for disinfecting soft lenses are shown in Table III. ANTISEPTICS COMMONLY INCORPORATED INTO SOFT LENS SOLUTIONS ( C O N C E N T R A T I O N S USED IN C O M M E R C I A L PREPARATIONS) CHLORBUTOL 0.3 - - 0.5% THIOMERSAL 0.001 - - 0.004% C H L O R H E X I D I N E 0,0025 - - 0.006% Table III Antiseptics most commonly used in soft lens solutions with the range of concentrations most usually employed.

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Chlorbutol is a weak antiseptic used at a concentration of 0.5% as a preservative in injections and eye drops. In these circumstances it is expected to deal with small chance contaminations and would not be expected to be suitable for coping with a large contamination and certainly unsuitable as a sterilisant. Also it has certain other rather undesirable properties. It diffuses through certain plastics and solutions stored in plastic containers might rapidly lose potency on this account. It is denatured by gamma irradiation and it is appreciably decomposed by autoclaving - - all this means that filtration is the only available method of sterilization. Chlorhexidine is a diguanide antiseptic widely used in medicine for disinfection of skin and mucus membranes. Preparations containing as much as 3% are used on the intact skin and are among the most effective agents available. On mucus membranes much lower concentrations are used as a rule, for example a 0.02% solution is instilled into the bladder by some urologists to prevent bacterial contamination during instrumentation. This you will note is of the order of four times as concentrated as anything available for soft lens decontamination. Yet it is a fact that solutions of this strength will allow the survival of some bacteria, even pathogenic species - - Mitchell and Hayward' in 1966 reported urinary tract infections in seven children following its use, here the offending organism was a species of Pseudomonas. My point in quoting this is to underline the ease with which an infection could be transferred to an eye by a lens treated with a contaminated solution. Thiomersal is a mercury containing a compound that is bacteriostatic. This brings us to an important point. Antibacterial agents whether they be antibiotics or antiseptics can be divided into two categories, those that are bacteriostatic and those which are bactericidal. The former act by inhibiting multiplication of but not killing bacteria, the latter by killing. You will understand with this in mind that bacteriostatic agents by themselves cannot disinfect because there will always be riving bacterial survivors of the process. They are often used alone as preservatives acting in exactly the same way as a domestic refrigerator, by preventing bacterial multiplication. When they are used for disinfection purposes, as they are in some lens solutions, they are combined with other antibacterials. The most usual of combinations is with chlorhexidine. Ethylene diamine tetra-acetic acid or E D T A is a common constituent of our solutions. Its antibacterial effect is minimal, it acts by c h e l a t i n g - forming complexes with - - certain metals, notably Calcium. It may help other antiseptics by making trace metals, some of which are essential for bacterial growth and nutrition, relatively inaccessible to bacteria and thus at least slow bacterial growth. Benzalkonium chloride is an example of a

quaternary ammonium antiseptic. Members of this family have detergent properties so that they are good cleansers and antibacterial properties which can be quite strikingly active as in the present example. They are used in some hard lens disinfecting solutions and you will note that even at the lowest concentration (0.004%) used they are efficient. However other properties possessed by this family make them quite unsuitable for use with soft lenses. The particular properties that are unfortunate are firstly that they very easily absorb onto any surface and secondly they are very easily concentrated in soft lens materials and do not easily release the drug on rinsing. This results in concentrations harmful to eye tissues being present on lenses treated with these agents. For hard lenses the problem is much less since the material does not absorb and concentrate the agent so that rinsing will largely remove it. I include benzalkonium here to demonstrate that one of the major difficulties in the chemical disinfection of soft lenses is that properties of the lens material rules this out and many other active agents which otherwise could be used successfuUy, as indeed benzalkonium is used for hard lenses. The antiseptic activity of these agents in commonly used concentrations is shown in Tables IV, V, and VI. Ps. AERUGINOSA 1 5 M 3 0 M 1H 2 H CHLORBUTOL (0.5%) T H I O M E R S A L (0.004%) C H L O R H E X I D I N E (0.004%) BENZALKONIUM CHLORIDE

+ + +

+ + +

+

4H

8H

+

(0.oo4%) Table IV

Antiseptic action against Ps. aeruginosa. STAPH. AUREUS

CHLORBUTOL (0.5%) T H I O M E R S A L (0.004%) CHLORHEXIDINE(0.004%) BENZALKONIUM CHLORIDE

(0.004%)

Table V

1 5 M 3 0 M 1H 2 H + + + + + + + + + + + +

4H + + +

8H + + +

+

Antiseptic action against Staph. aureus. CANDIDA ALBICANS

CHLORBUTOL (0.5%) T H I O M E R S A L (0.004%) C H L O R H E X I D I N E (0.004%) BENZALKONIUM CHLORIDE

1 5 M 3 0 M 1H + + + + + + + + +

2H + + +

4H +

8H +

+

+

(0.oo4%) Table VI

Antiseptic action against Candida albicans.

The organisms used are standard reference strains of staphylococcus aureus, Pseudomonas aeruginosa and candida albicans. Chosen, I speculate here, because staphylococci commonly cause infections around the eye. Ps.aeruginosa is a wet situation organism that commonly contaminates solutions and is potentially

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pathogenic and C.albicans because it is a fungus and again a common contaminant. The bacterial challenge is one million riving organisms per millilitre of antiseptic. This is a very severe challenge for antiseptics at such low concentrations and a challenge which you will see cannot be met by any of the soft lens antiseptics acting alone. I stress this last point that in these tests based on the work of Norton 2 and his co-workers (1974) these are simple antiseptics not commercially available combinations. This challenge is severe even for the most active of the commercially available formulations and I can say without any fear of contradiction that there is no available solution that could withstand a repeated challenge of this magnitude. However, I think I must make it clear to you that such a challenge would be easily met by many antiseptics used for other purposes such as for example skin disinfection and furthermore would be met in minutes if not in seconds rather as here in hours. These results take me back to the dangers of contamination by the users of these solutions. It is very easy for untrained or careless users to repeatedly contaminate these solutions with the result as I have already pointed out that the solution has no remaining antibacterial activity and indeed may be an actively growing bacterial culture. I have confined my comments to a handfuU of the most commonly used antiseptics. There are various others used for the same purposes but in general all are less active antibacterials. I think you realise that as a bacteriologist I regard all the available solutions

for soft lenses (at any rate all that I have had the opportunity of examining) as at the best very poor when taken in the context of the very low concentrations at which they have. to be used. Other common factors which interfere with antiseptic action do exist; dirt and particularly proteinaceous soil interferes with all antiseptic fiction and the presence of such material on lenses will inevitably lessen the antiseptic activity of your solutions. In many ways I am amazed that eye infections are not far more commonly attributable to soft contact lenses, and I suspect that we should be very thankful for the extremely efficient natural anti-infection mechanisms of the human eye.

References 1. 2.

Mitchell, R. G. & Hayward, A. C. - - (1966) Lancet i, 980 Norton, D. A . , Davies, D. J. G., Richardson, N. E., Meakin, B. J. and Keall, A. (1974). J. Pharm. Pharmac. 26,841

This paper was delivered to the B. C.L.A. at the Royal Society of Medicine, London, in March 1979 Address for further correspondence:Dr. R. E. M. Thompson, The School of Pathology, The Middlesex Hospital Medical School, Riding House Street, London WIP 7LD.

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