This invention relates to medical devices that are resistant to bacterial growth or encrustation such as a) urinary catheters and more particularly to urinary catheters constructed of a material which enables the urinary catheters to inhibit urease and to prevent calcium and magnesium phosphate deposits on the catheters and b) contact lenses, more particularly to extended wear lenses coated with a suitable material to enable the lenses to resist the adherence of microorganisms.
Urinary Catheters: Catheters are used in urological surgery and when other methods of managing urinary incontinence fail. These catheters are generally made from a nontoxic, non-irritating material which is flexible but which will withstand collapse. Ideally they should resist colonization by bacteria and encrustation by mineral deposits.
The most common materials used for the catheters are latex, plastic or silicone. All biomaterials, including the most recently tested polyurethane, polyurethane-carbon and silicone-carbon, become encrusted with mineral deposits to varying extents. The degree of encrustation formation on biomaterials exposed to urine is dependent upon the biomaterial, the length of urinary exposure, the presence of infection and the solute content of urine. Several independent studies (e.g. Hukins et al., 1989) of the scraped encrusted material have identified - two major salts, namely apatite Ca.sub.5 (PO.sub.4).sub.3 (OH) and struvite Mg NH.sub.4 PO.sub.4 6H.sub.2 O. A very small amount of brushite CaHPO.sub.4.2H.sub.2 O has also been identified. Apatite is precipitated from urine under alkaline conditions (pH=9.2) along with struvite. Brushite with a K.sub.sp of the order of 10.sup.-5 is not stable above pH=7; but is precipitated below 6.5.
The pH increase of urine occurs due to urease producing bacteria, that infect the urine. Urease catalyzes the hydrolysis of urea at an enormous rate (10.sup.14 times as fast as the spontaneous hydrolysis of urea which is not observable in neutral solution) producing ammonia, which in turn precipitates calcium phosphates.
Microbial heterogeneity and structural complexity of the biofilms observed on infected catheter materials by means of scanning and transmission electron microscopy reveal a variety of microflora. It appears that the adherent microcolonies of bacteria are much less susceptible than their planktonic counterparts to antibiotics because the extensive anionic matrix surrounding the cell appears to comprise an ion exchange barrier between charged antibiotic molecules and their cellular targets. Antibiotics should be reserved for symptomatic, febrile infections; otherwise their use produces a change in bacterial flora with the potential for producing resistance.
Bacteriurea in a catheterized patient indicates the urinary tract has become colonized or infected. Administration of anti-bacterials such as nitrofurantoin, methenamine, and naldixic acid are used in practice. Most of these are not very effective in alkaline urine, and to achieve a high concentration in urine, the patient has to be given enormous doses.
Catheter associated bacteriurea results from ascending bacterial colonization within glycocalyx enclosed biofilm on the inside and/or outside surfaces of the catheter and drainage systems. Urinary tract catheters made from a biomaterial that inhibits bacterial adherence and thus retards upstream colonization of bacteria may reduce acquired urinary tract infection (UTI). While hydrophilic surfaces show reduced protein adhesion, antibacterial surfaces offer better protection. Either a controlled release or an antibacterial immobilized on the surface should offer continuous protection against bacterial colonization. A silver oxide catheter is described in a publication by Shaeffer, A. J., Story, K. O., Johnson, S. M. in "Effect of silver oxide/Trichloroisocyanuric Acid Antimicrobial Urinary Drainage System on Catheter Associated Bactiurea", J. Urol., 39, 60 (1988). A recent clinical study on silver catheters reported by Johnson, J. R., Roberts, P. L., Olsen, R. J., Moyer, K. A., and Stanni, W. E. in "Silver Oxide Coated Catheters", J. Infect. Diseases, 162, 1145 (1990) ) indicated the prevention of UTI among women not receiving antimicrobials.
The other problem associated with catheters left in place for long periods of time is the encrustation due to the formation of calcium hydroxyapatite and struvite. Long-term urethral catheterization is frequently necessary for patients with intractable urinary incontinence or retention. This procedure is employed in as many as 16-28% of patients in various chronic care facilities. More than 50% could suffer from blockage of their catheters. This can cause incontinence due to urinary bypassing of the catheter or acute pain and discomfort associated with urinary infection. This is particularly distressing for patients being cared for in the community where professional help is not immediately available. In addition, the coarse irregular surface may result in pain and physical trauma when the catheter is removed increasing the risk of infection.
Removal of deposits by acidic solution (citric acid-magnesium oxide) has been shown to dissolve encrustation in vitro and is now used extensively in practice. Frequent irrigation could result in the damage of the mucus in the bladder.
The patent literature abounds with patents on indwelling urinary catheter systems aimed at preventing urinary tract infection. These are mechanical devices with appropriate valve fittings to keep the drainage open at the same time preventing ascending infection. U.S. Pat. Nos. 4,946,449 issued to Richard Davis and 4,878,901 issued to Hans Ernst Sachse are two typical examples. However, these do not have any prevention methods for encrustation. In general, mechanical systems are complicated and do not provide adequate protection from infection. U.S. Pat. No. 4,932,948 issued to Kernes et al., discloses the use of a funnel shaped insert at the end of the urinary catheter that serves as a reservoir to antimicrobial agents. The antimicrobial agent is simply mixed with the ethylene/vinyl acetate polymer during the fabrication of the funnel. The catheter surface itself does not carry any antimicrobial nor is it capable of preventing encrustation. U.S. Pat. No. 4,579,554 issued to Jacob Glassman discloses a design that provides for irrigation of the catheter tube. Frequent irrigation, however, could result in the damage of the mucus in the bladder.
U.S. Pat. No. 4,642,104 issued to Sakamoto et al., teaches the use of polymers carrying multicarboxyl, amino or sulfonic acid group capable of binding antibiotics through ion exchange. The ion exchange groups are chemically introduced into the molecules of the inside and outside wall of the urethral catheter by hydrolysis of certain functionalities that are present in the polymer that is coated on the surface of the catheter. Cationic antibiotics such as polymyxins or soap preparations such as benzalkonium chloride or benzethionium chloride, cyclohexidine or povidine-iodine remain on the surface due to the electrostatic binding.
U.S. Pat. No. 4,950,256 issued to Luther et al., teaches the use of an intravascular catheter comprising a cannula for insertion into a vascular system of a patient. This catheter is coated with a hydrophilic polyurethane-polyene composition for binding antithrombogenic materials and cationic polymyxin antibiotics. Luther et al., show that the absorption of the polymyxins into the hydrophilic polyurethane can be controlled by varying the initial concentrations. The authors describe this as a time release intravascular catheter. The present invention differs from that of Luther et al., by virtue of the immobilization of polymyxin through a binding action with the dianionic diaminopropanol tetraacetic acid (DPTA) groups.
Contact Lenses: Infective ulcerative keratitis is one of the most severe hazards of hydrogel extended wear soft contact lenses (SCLs). The extent of bacterial adherence varies with the nature of the base materials, protein deposits and surface charges. While the mechanism of adhesion and colonization of bacteria on SCLs is not well understood, the influence of adsorbed proteins has been implicated. Recently it was reported ("Pseudomonas attachment to low-water and high-water and non-ionic, new and rabbit worn soft contact lenses", Brussel et al, Investigative Ophthalmology and Visual Science, 32, 657, 1991) that both new and worn SCLs can bind amounts of p. aeruginosa that could potentially produce bacterial keratitis.
SCLs in the eye are readily coated with tear proteins, mucus and lipids (Tripathy et al., "Lens Spoilage in Contact Lenses", in The CLAO guide to basic and applied clinical practice", Dabecies O. H. Jr. (Ed), Grune and Stratton Inc., Orlando Fla., 1984). P. aeruginosa is the responsible microorganism in up to two thirds of the reported cases of extended wear SCL associated infectious keratitis. The extended wear contact lens induces corneal hypoxia, microtrauma and tear film destruction that weaken corneal defense.
It is therefore a principal object of the present invention to provide a catheter for use in urological surgery or for managing urinary incontinence which inhibits the build up of encrustation on the surface of the catheter.
Another object of the present invention is to provide a catheter for use in urological surgery or for managing urinary incontinence which causes a lower risk of infection than known catheters.
It is yet another object of the present invention to provide a coating for contact lenses, particularly of the extended wear type, which inhibits the adhesion of harmful bacteria on the lens surface.