System and method for reducing catheter-associated infections

Abstract

Systems and methods are provided for irradiating a catheter to control against microbial migration. The method may include the steps of inserting a catheter into an orifice of a subject and irradiating the catheter with electromagnetic (EM) radiation using at least one EM radiation source. The at least one EM radiation sources may be embedded within the catheter or in a sheath configured to receive the catheter.

Description

System and Method for Reducing Catheter-Associated InfectionsCross Reference to Related Applications

[0001] The present application is based on, claims priority to, and incorporates herein by reference in its entirety for all purposes, US Provisional Application Serial No. 63 / 613,489, filed December 21, 2023.Statement Regarding Federally Sponsored Research

[0002] N / ABackground

[0003] Hospital acquired infections (HAIs) are a significant source of morbidity and mortality. One in 31 hospitalized patients has at least one HAI. HAI's are often caused by the presence of indwelling catheters, which can be of a variety of types including central venous catheters, urinary catheters, PICC lines, hemodialysis catheters, chemotherapy catheters of various types, endotracheal tubes, etc.

[0004] Urinary tract infection (UTI) is the most common form of HAI; this is because 15-25% of all hospitalized patients receive a urinary catheter. There are approximately 500,000 hospital acquired catheter associated UTIs (CAUTIs) in the US each year, at an additional cost of $4,694 - $29,743 per infection. Because Medicare and other health insurance companies no longer reimburse hospitals for HAIs, the result is an excess of $1 billion in costs borne directly by hospitals.

[0005] CAUTI is caused by migration of bacteria (most commonly E. Coli, but bacteria such as Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, and others are frequently indicated) from outside of the body into the urinary space. Specifically, bacteria can migrate from the patient’s perineum along the outside of the catheter toward the tip of the catheter located inside the bladder. Alternatively, bacterial migration can occur along the inner wall of the catheter. In this instance, the bacteria are thought to originate from contamination that occurs when the catheter’s connections (e.g., the connection to an external urine collection bag) are manipulated by the hands of medical personnel). In all cases, bacteria migrate along the catheter toward the catheter tip, where they form a biofilm. This ultimately leads to a urinary tract infection, which can involve the bladder alone or ascend further to affect the ureters and kidneys.

[0006] Traditionally, systemic antibiotics are used to treat CAUTIs. However, the increasingly prevalent phenomenon of antimicrobial resistance requires the development of increasingly sophisticated and expensive antibiotics. And in many instances, so-called “superbugs” are resistant to all available antibiotics. Additionally, antibiotics are used to treat infections once they become symptomatic, and it takes time for them to take effect against the existing infection.

[0007] Thus, there is a continuing need for new systems and methods to combat the challenge of HAIs.Summary

[0008] The present disclosure provides systems and methods for controlling or reducing HAIs and, particularly, catheter-associated infections. The present disclosure recognizes that bacterial infections associated with catheters are often caused by bacterial migration and the formation of biofilms that lead extend to ultimately create an infection in the body. With this recognition, the present disclosure further recognizes that killing all bacteria is neither necessary nor desirable. To the contrary, indiscriminate killing of bacteria, such as using antibiotics can be undesirable. Thus, rather than focus on killing bacteria or sterilizing catheters while deployed, the systems and methods provided herein are able to control against bacterial migration and, thereby, reduce or prevent bacterial infections associated with catheter placement.

[0009] In one non-limiting example, a catheter and / or catheter sheath system is provided that has light irradiating capabilities to control bacterial colonization and / or biofilm formation. By controlling against bacterial colonization and / or biofilm formation, the systems and methods provided herein can control against CAUTI or other infections.

[0010] According to an aspect of the present disclosure, a photonic irradiation system for controlling against microbial migration is described. The system comprises a catheter configured to be inserted into an orifice of a subject, wherein, when inserted into the orifice, the catheter extends from a proximal end extending outside the subject and a distal end arranged within the subject. The catheter comprises a wall with a length extending between the proximal end and the distal end, at least one lumen formed within the wall extending between the proximal and distal end, and at least one electromagnetic (EM) radiation source configured to irradiate at least a portion of the catheter with EM radiation having operational parameters configured to control microbial migration in a distal direction from the portion of the catheter.

[0011] According to an aspect of the present disclosure, the at least one EM radiation source is embedded within the wall of the catheter.

[0012] According to an aspect of the present disclosure, the photonic irradiation system further includes a sheath including a channel, wherein the channel is configured to feed the catheter through the sheath.

[0013] According to an aspect of the present disclosure, the at least one EM radiation source is embedded within the sheath.

[0014] According to an aspect of the present disclosure, a method of irradiating a catheter to control against microbial migration is described. The method includes the steps of inserting a catheter into an orifice of a subject, wherein the catheter incudes a wall with a lumen formed therein, and irradiating the catheter with EM radiation using at least one EM radiation source.Brief Description of the Drawings

[0015] FIG. 1 shows a non-limiting example of a cross-section of catheter of the photonic catheter system according to aspects of the preset disclosure.

[0016] FIG. 2 shows a non-limiting example of a cross-section of a sheath around a standard catheter of the photonic catheter system according to aspects of the present disclosure.

[0017] FIG. 3A is a schematic of a non-limiting photonic irradiation system of a urinary catheter with a laser light source in female (left) and male (right) anatomies.

[0018] FIG. 3B is a cross section of the urinary catheter of FIG. 3 A, according to one non-limiting example of the present disclosure.

[0019] FIG. 3C is a cross section of the urinary catheter of FIG. 3A, according to one non-limiting example of the present disclosure.

[0020] FIG. 3D is a cross section of the urinary catheter of FIG. 3A, according to one non-limiting example of the present disclosure.

[0021] FIG. 3E is a schematic of a non-limiting photonic irradiation system of a urinary catheter with light emitting diode (LED) source(s) in female (left) and male (right) anatomies.

[0022] FIG. 3F is a cross section of the urinary catheter of FIG. 3E, according to one non-limiting example of the present disclosure.

[0023] FIG. 3G is a schematic of a non-limiting photonic irradiation system sheath of a urinary catheter with a laser light source in female (left) and male (right) anatomies.

[0024] FIG. 3H is a cross section of the urinary catheter and sheath of FIG. 3G, according to one non-limiting example of the present disclosure.

[0025] FIG. 31 a schematic of a non-limiting photonic irradiation system sheath of a urinary catheter with LED light source(s) in female (left) and male (right) anatomies.

[0026] FIG. 3 J is cross section of the urinary catheter and sheath of FIG. 31, according to one nonlimiting example of the present disclosure.

[0027] FIG. 4 shows non-limiting steps of irradiating a catheter with a photonic irradiation system wherein the EM radiation source is embedded in a catheter wall as described in FIG. 1.

[0028] FIG. 5 shows non-limiting step of irradiation a catheter with a photonic irradiation system wherein the EM radiation source is embedded in a sheath as described in FIG. 2.

[0029] FIG. 6A shows the migration of Proteus mirabilis on a portion of catheter tubing 1 h and 10 h after incubation without exposure to antimicrobial light.

[0030] FIG. 6B shows the migration of Proteus mirabilis on a portion of catheter tubing 1 h and 10 h after incubation with exposure to antimicrobial light at an irradiance of 1 mW / cm2and a duty cycle of 50%.

[0031] FIG. 7 shows an experimental setup of catheter tubing, a portion of which is wrapped in agar, and an optical fiber inserted inside the tube to irradiate the tube with antimicrobial light.

[0032] FIG. 8A shows the migration of Proteus mirabilis in agar wrapped around a portion of catheter tubing after Oh, 6h, and 12h without exposure to antimicrobial light.

[0033] FIG. 8B shows the migration of Proteus mirabilis in agar wrapped around a portion of catheter tubing after Oh, 6h, and 12h with exposure to antimicrobial light, such as the optical fiber of FIG. 7.

[0034] FIG. 8C shows the migration of Proteus mirabilis in agar wrapped around a portion of catheter tubing of FIG. 8 A and 8B from 12 h to 24 h, both without exposure to antimicrobial light.

[0035] FIG. 9 is a photograph of a duty-cycle experimental setup.

[0036] FIG. 10A is an image of the experimental setup of FIG. 9.

[0037] FIG. 10B is an image of the experimental setup of FIG. 9.

[0038] FIG. 10C is an image of the experimental setup of FIG. 9.

[0039] FIG. 10D is an image of the experimental setup of FIG. 9.

[0040] FIG. 11 is a series of photographs of a portion of tubing inoculated with Proteus mirabilis subjected to different duty cycles of aBL irradiation 1, 6, 11, 16, and 19 h after inoculation.

[0041] FIG. 12 is a series of photographs of a portion of tubing inoculated with Proteus mirabilis subjected to different duty cycles of aBL irradiation 36 h and 38 h after inoculation.

[0042] FIG. 13A is a plot of bioluminescence signal measured at 1 hour after inoculation.

[0043] FIG. 13B is a plot of bioluminescence signal measured at 6 hours after inoculation.

[0044] FIG. 13C is a plot of bioluminescence signal measured at 11 hours after inoculation.

[0045] FIG. 13D is a plot of bioluminescence signal measured at 16 hours after inoculation.

[0046] FIG. 13E is a plot of bioluminescence signal measured at 18 hours after inoculation.

[0047] FIG. 13F is a plot of bioluminescence signal measured at 19 hours after inoculation.Detailed Description

[0048] The present disclosure recognizes that bacterial infections associated with catheters are often caused by bacterial migration and the formation of biofdms that lead extend to ultimately create an infection in the body. Light irradiation may be used in some clinical applications to sterilize the surface of catheters. However, the present disclosure recognizes that light-based sterilization approaches may not be suitable for use when the catheter is deployed in vivo. For example, specific wavelengths in the ultraviolet spectrum are known to cause harmful effects to human tissue (e.g., cancer) and can degrade many natural and synthetic polymers. Common forms of UV radiation known to destroy harmful microorganisms include UVA (315 to 400 nm), UVB (280 to 315 nm) and UVC (100 to 280 nm) radiation. However, all forms of UV light can also produce DNA damage in mammalian cells and are potentially harmful to the tissues being penetrated by the catheter. A clear link exists between chronic exposure to UV light and skin cancer resulting from UV-induced damage to DNA.

[0049] Thus, the present disclosure further recognizes that killing all bacteria is neither necessary nor desirable. To the contrary, indiscriminate killing of bacteria, such as using antibiotics or UV light can be undesirable for the reasons described above. Thus, rather than focus on killing bacteria or sterilizing catheters while deployed, the systems and methods provided herein are able to control against bacterial migration and, thereby, reduce or prevent bacterial infections associated with catheter placement. That is, the present disclosure distinguishes between “controlling migration,” which means that the bacteria may continue to live, but be limited against moving to a new location, as opposed to sterilization, which just kills bacteria and does not exert any control on the bacteria, with respect to migration or otherwise.

[0050] The present disclosure recognizes that some irradiances of antimicrobial blue light (aBL) may be used to control bacterial migration, including, in vivo. As one, non-limiting example, a light of X = 290-470 nm or 390 - 470 nm or other ranges therein may be used to control against and, even prevent over a given time period, bacterial migration, especially along the surface of a catheter when the catheter is designed or adapted in the manner described herein. In fact, when properly designed as described herein, the need for relatively small irradiance over a small area is able to control or prevent bacterial migration (and hence prevent bacterial colonization and biofilm formation and prevent CAUTI) enables development of low-cost, portable, and even disposable devices. In one non-limiting example, the irradiance may be 1 mW / cm2or lower. In another nonlimiting example, the irradiance may be 0.5 mW / cm2or lower. In a preferred embodiment, the irradiance may be 0.55 mW / cm2. Further, aBL is a non-pharmacologic treatment, and development of bacterial resistance to aBL has not been demonstrated.

[0051] As will be described in greater detail below, the catheters of the photonic irradiation system can include a thin, flexible tube having an optically transparent or partially transparent wall; and an EM radiation source can be configured and arranged to emit light through the catheter of the photonic system, which may be antimicrobial light (aBL).

[0052] In a non-limiting example, aBL that is safe to expose to human tissue, visible spectrum light from 290-470 nm in wavelength may be used. This wavelength of light controls against and / or prevents the migration of bacteria and formation of biofilm of the inner and outer surfaces of the catheter as well as within the urethra.

[0053] The photonic irradiation system is used on a patient and a therapeutic amount of light is administered to control against microbial migration on the surface of the catheter and within the urethra, thereby reducing the risk of infection to the patient. The system may be configured for use in cardiovascular, neurovascular, neurological, renal, urological, oncologic, gastrointestinal, spinal, peripheral intervention, endoscopic, patient-monitoring, surgical, interventional radiology, respiratory, wound management, ophthalmic or any other health application, and may be indwelling or temporary.

[0054] In a non-limiting example, light may be administered for the duration of use or another time period. For example, the duty cycle may range from 25% to 100%. Because of the antimicrobial properties of irradiation, the risk of bacterial infection through the use of the catheter is reduced.

[0055] In a non-limiting example, the sub-mW irradiation can be used to control against the migration of bacteria on the surface of the catheter and within the urethra. For example, the catheter may be irradiated with at least one EM radiation source emitting light with an irradiance of 1 mW / cm2or less. In a preferred embodiment, the irradiation is 0.55 mW / cm2. By contrast, sterilization configured to kill the bacteria requires a minimum irradiation of 100 mW / cm2. By requiring lower power needs to control against migration, and thereby reducing bacterial infection, a sub-mW irradiation system may be more cost-effective to produce and more widely available for different clinical settings.

[0056] As used herein, a “catheter” is a medical device that includes a flexible shaft, which contains one or more lumens, and which may be inserted into a subject for introduction of fluids, for removal of fluids, or both.

[0057] Referring to FIG. 1, an example of a cross-section of a catheter of the photonic irradiation system is shown. The catheter wall 102 is made of a flexible and optically transparent material. The catheter wall 102 may include an inflation lumen 104 for inflating a balloon (not shown) in order to secure the catheter within the bladder and to provide symmetrical positioning of the catheter within the urethra. Catheter wall 102 further includes a main lumen 106 for fluid passage. A plurality of lumens 108 are also embedded within the catheter wall 102 for one or more fibers.

[0058] FIG. 2 shows an example of a cross-section of a sheath of the photonic irradiation system. The sheath 203 is a tube with a channel 204 through which a catheter 202 is fed. The catheter 202 may be any standard catheter or the catheter as depicted in FIG. 1. The sheath 203 includes a plurality of lumens 208 embedded therein. In a non-limiting embodiment, the sheath 203 may cover a portion of the total length of the catheter.

[0059] The lumens 108 and 208 may include one or more EM radiation sources to allow for irradiation of the inner and outer surfaces of the catheter, as well as the surrounding tissue of a subject. In a non-limiting example, the EM radiation sources include optical fibers connected laser sources and LEDs.

[0060] In a non-limiting example wherein the EM radiation sources are embedded in the catheter wall 102, the EM radiation sources may span the length of the catheter, may be discretely distributed along the length of the catheter, or may be placed at one or more discrete locations along the length of the catheter. In one non-limiting example, the EM radiation source is placed along the length of the catheter that coincides with the opening of an orifice of the subject, such asthe urinary meatus, thereby providing targeted irradiation at the border of a non-sterile (i.e., external skin surface) and sterile (i.e., urethra) environment.

[0061] FIG. 3A shows a non-limiting example of a photonic irradiation system used in a urinary catheter. The catheter 302 is configured to be inserted into an orifice of a subject, wherein, when inserted into the orifice, the catheter extends from a proximal end extending outside the subjected and a distal end arranged within the subject. A wall with a length extends between the proximal and distal end. Further, an EM radiation source is configured to irradiate at least a portion of the catheter with EM radiation having operational parameters configured to control microbial migration in a distal direction 301 from the portion of the catheter.

[0062] In a non-limiting example, the catheter 302 may be made of transparent material to radiate the inner and outer surfaces of the catheter 302 itself as well as the surrounding tissue. A cross section 305 of the catheter tube 302 is shown in FIGS. 3B-D. The wall of catheter 302 may include lumens 308 for passing optical fibers along the length of the catheter 302.

[0063] In a non-limiting example, one or more radiation directors is embedded within the wall of the catheter 302 to direct the EM radiation to an exterior or interior surface of the wall to control microbial migration in a distal direction 301 from at least a portion of the catheter. As used herein, the term “radiation director” describes any means of changing the direction or propagation of EM radiation. In a non-limiting example, a radiation director includes an etching 306 to scatter light from the optical fiber(s) (FIG. 3C). Alternatively, the optical fibers may be etched to provide light scattering. Another example of a radiation director is shown in FIG. 3D, wherein the catheter 302 includes a coating 307 on at least one of the outer and inner surface for total internal reflection of light along the length of the catheter. In a non-limiting example, the etching 306 and coating 307 may be embedded within the wall at a location along the length of the catheter. For example, the location is configured to coincide with the opening of the orifice of the subject when the catheter 302 is inserted into the orifice. Alternatively, the etching 306 or coating 307 is embedded in the wall along the length of the catheter 302. Further, one or more radiation directors may be embedded in the wall at one or more discrete locations along the length of the catheter 302.

[0064] Referring again to FIG. 3A, the catheter 302 may be inserted into a patient’s urethra 312. However, the photonic irradiation system used herein is not limited to urinary catheterization and may be used in, but is not limited to, cardiac and vascular catheterization or laparoscopic procedures. In FIG. 3A, the distal end of the catheter 302 is inserted into the bladder 314 of thepatient. In a non-limiting example, the optical fibers are connected to a laser source 316. In a nonlimiting example, the laser source emits aBL at a wavelength between 290-470 nm.

[0065] In a non-limiting example, FIG. 3E shows an alternative photonic irradiation device. FIG. 3F shows the cross section 305 of catheter 302. In this example, the catheter 302 includes one or more LEDs 309 embedded in the walls of the catheter 302. For example, a location for one or more LEDS 309 is configured to coincide with the opening of the orifice of the subject when the catheter 302 is inserted into the orifice. Alternatively, the one or more LEDs 309 are embedded in the wall along the length of the catheter 302. Further, one or more LEDS 309 may be embedded in the wall at one or more discrete locations along the length of the catheter 302. The LEDs may be powered by an external power source 318. Alternatively, the power source may be embedded in the wall of catheter 302 (not shown). The power source 318 may be a battery or AC electrical outlet. In a non-limiting example, the LED emits aBL at a wavelength between 290-470 nm. The catheter 302 of FIGS. 3E-3F may further include radiation directors as previously described.

[0066] In another non-limiting example, FIG. 3G shows photonic irradiation systems wherein one or more EM radiation sources are embedded or associated with sheath 303. FIG. 3H shows the cross section 305 of catheter 302 and sheath 303.. The catheter 302 may be catheter 102 of FIG. 1, any of the catheters in FIGS. 3B-3D and 3F, or any commercial catheter. With respect to FIGS. 3G-3H, the sheath 303 axially surrounds the catheter 302. As illustrated, the sheath 303 covers a portion of the catheter 302 at the opening of the orifice, such as the urinary meatus, of the patient. Alternatively, one or more sheaths 303 may be positioned at discrete locations along the catheter 302 or a single sheath 303 may extend the length of the catheter 302.

[0067] The sheath 303 may also include radiation directors embedded therein, as previously described.

[0068] In FIG. 3H, the sheath 303 includes openings 310 for housing optical fibers. As previously described, the optical fibers may be etched for light scattering. Alternatively, one or more of the sheaths 303 and the catheter 302 may be etched for light scattering. As shown in FIG. 3G, the optical fibers in the sheath 303 are connected to a laser source 316.

[0069] In an alternative embodiment shown in FIG. 31 the sheath 303 includes one or more LEDs 311 embedded therein. FIG. 3 J shows cross section 305 of catheter 302 and sheath 303. The catheter 302 may be catheter 102 of FIG. 1, any of the catheters in FIGS. 3B-3D and 3F, or any commercial catheter. As described previously, the LED(s) 311 may be connected to an externalpower source 318, such as a battery or wall outlet. As described for the embodiment of FIGS. 3G- 3H, one or more sheaths 303 of FIG. 3J may be positioned at discrete locations along the catheter 302 or a single sheath 303 may extend the length of the catheter 302.

[0070] In one non-limiting example, as illustrated in FIGS. 3G and 31, the photonic irradiation system included in the sheath 303 is placed at the opening of the orifice of a subject, specifically the urinary meatus. In a non-limiting example, a sterile catheter is fed through the sheath 303 that is posited at the opening of the urethra thereby providing targeted irradiation at the border of a non-sterile (i.e., external skin surface) and sterile (i.e., urethra) environment. The one or more EM radiation sources may be activated to irradiate the catheter as it passes through the sheath and further up the urethra to reach the bladder. Once positioned, the EM radiation sources in the sheath may be further activated continuously or at a duty cycle as low as 25% to control against microbial migration from outside of the urethra into and up the urethra. The location of the irradiation source acts as a barrier to bacteria, so as to stop or slow bacteria from migrating in a distal direction up the surface of the catheter and urethra.

[0071] Any of the components of the photonic irradiation system described by FIGS. 3A-3J may be used with one another and interchanged with one another. In other words, unless a specific combination is required for proper operation, the components of the irradiation system may be modified.

[0072] Referring to FIG. 4, a non-limiting example of a method 400 for using the irradiation system with the EM radiation source embedded in the catheter wall is described. At step 402, the catheter is inserted into an orifice of a patient. The catheter may be any one of the catheters described previously. The orifice may be a natural opening or surgically created opening. At step 404, the catheter is optionally adjusted to position one or more EM radiation sources at the opening of the orifice. In a non-limiting example, the one or more EM radiation source may be embedded in the wall of the catheter as described above. In a non-limiting example, the position of the one or more EM radiation source coincides with the urinary meatus. At step 406, the catheter is irradiated using one or more EM radiation sources. The EM radiation source emits light at a predetermined wavelength, irradiation level, and duty cycle. In a non-limiting example, the wavelength may range from 290 - 470 nm, the irradiation level may be < 1 mW / cm2, and the duty cycle may be > 25%. For example, the duty cycle may be 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or any number therebetween.

[0073] Referring to FIG. 5, a non-limiting example of a method 500 for using the irradiation system with the EM radiation source embedded in the sheath is described. At step 502, the sheath is inserted at the opening of the orifice of a subject. The sheath may be any one of the sheaths described preciously. In a non-limiting example, the orifice is the opening of the urethra, and the sheath is placed at the barrier between the non-sterile (i.e., external skin surface) and sterile (i.e., urethra) environments. In a non-limiting example, the sheath may extend from a proximal position located outside the subject to a distal position located inside the subject. Alternatively, the sheath may extend from a proximal position located outside the subject to a distal position at the opening of the orifice. In another example, the sheath may extend from a proximal position at the opening of the orifice to a distal position located inside the subject. At step 504, one or more EM radiation sources in the sheath may be activated before inserting the feeding a catheter through the sheath and into the orifice at step 506. Alternatively, activating the one or more EM radiation source at step 504 may occur after the catheter has been fed through the sheath into the orifice at step 506. For example, the sterile catheter is inserted through the sheath into the orifice while the EM radiation source is not activated. At step 508, the one or more EM radiation sources irradiate at least a portion of the catheter. The one or more EM radiation sources may emit a predetermined wavelength, irradiation level, and duty cycle. In a non-limiting example, the wavelength may range from 290 - 470 nm, the irradiation level may be < 1 mW / cm2, and the duty cycle may be > 25%. For example, the duty cycle may be 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, or any number therebetween.

[0074] Any methods disclosed herein may comprise one or more steps or actions for performing the described method. The method steps and / or actions may be interchanged with one another. In other words, unless a specific order of steps or actions is required for proper operation of the embodiment, the order and / or use of specific steps and / or actions may be modified.

[0075] Referring to FIGS. 6A-6B, a non-limiting example of the effectiveness of aBL on microbial migration is shown. FIG. 6A shows a piece of catheter tubing incubated with Proteus nrirabilis 1 h and 10 h after incubation without any exposure to aBL irradiation. Bacteria migrated to cover a larger area of the catheter tubing between the 1 h and 10 h timepoints. By comparison, FIG. 6B shows a piece of catheter tubing incubated with Proteus mirabilis 1 h and 10 h after incubation with exposure to intermittent aBL at 1 mW / cm2and a duty cycle of 50%. The bacteria did not spread to other areas of the catheter tubing.

[0076] FIG. 7 shows a non-limiting experimental setup wherein a portion of catheter tubing is partially wrapped in agar and exposed to aBL using an optical fiber inserted within the catheter tubing.

[0077] FIGS. 8A-8C show a similar setup as described above for FIGS. 6A-6B using the EM radiation source shown in FIG. 7. In this non-limiting example, a portion of the catheter tubing is wrapped in agar. FIG. 8 A shows the migration of Proteus mirabilis 0 h, 6 h, and 12 h after incubation without exposure to aBL irradiation. The bacteria migrated and spread across the agar. By comparison, FIG. 8B shows a piece of catheter tubing with a portion wrapped in agar and incubated with Proteus mirabilis at 0 h, 6 h, and 12 h after incubation with exposure to intermittent aBL at 1 mW / cm2and a duty cycle of 50%. The bacteria were contained and migrated across a smaller area compared to FIG. 6A. FIG. 6C shows the catheter tubing setups of FIGS. 8A-8B from 12 h - 24 h, both unexposed to aBL irradiation.

[0078] Referring to FIG. 9, an experimental set-up is shown to determine duty cycle and aBL irradiation intensity. In this example, a silicone urinary catheter was cut in half longitudinally and the “lumen” was filled with agarose. The catheter was placed into a 6 x 6 cm square petri dish with markings at 1 cm intervals. An inoculum of 106organisms of a bioluminescent strain of Proteus mirabilis was placed at the second marking. An area of the tubing between the fourth and fifth markings is exposed to aBL. The center of illumination is 2.5 cm from the inoculum and irradiance at this location is 1 mW / cm2. Example irradiation equipment setup for FIG. 9 is shown in FIGS. 10A-10D.

[0079] FIG. 11 shows the results of the experimental set-up of FIGS. 9 and 10A-10D after 0 hours, 1 hour, 6 hours, 11 hours, 16 hours, 19 hours, and 29 hours after inoculation. One petri dish was not exposed to any aBL irradiation. A second petri dish was exposed to aBL with a 25 % duty cycle (aBL turned on for 15 minutes of each hour). A third petri dish was exposed to aBL with a 50% duty cycle (aBL turned on for 30 minutes of each hour). A fourth petri dish was exposed to aBL with a 100% duty cycle (aBL turned on continuously).

[0080] FIG. 12 shows the results of the experimental set-up of FIGS. 9 and 10A-10D after 36 and 38 hours. One petri dish was not exposed to any aBL irradiation. A second petri dish was exposed to aBL with a 25 % duty cycle (aBL turned on for 15 minutes of each hour). A third petri dish was exposed to aBL with a 50% duty cycle (aBL turned on for 30 minutes of each hour). A fourth petri dish was exposed to aBL with a 100% duty cycle (aBL turned on continuously).

[0081] FIGS. 13A-13F show the results of the experimental setup of FIGS. 9-11 . Bioluminescence signal was measured at 1 h, 6 h, 11 h, 16 h, 18 h, and 19 h after inoculation. FIGS. 13A-13F depict evolution of the signal for the experiments with 25% duty cycle, 50% duty cycle, and no aBL exposure. In each figure, the envelope of aBL is depicted as well (relevant only for the 25% and 50% duty cycle experiments).

[0082] In FIG. 13 A, 1 hour after inoculation, bioluminescence signal appears as a “spike” around the area of inoculation. In Fig. 13B, 6 hours after inoculation, bioluminescence signal begins to “spread” or “widen” as the bacteria migrate or move. Eleven hours after inoculation (FIG. 13C), as bacteria migrate or move, bioluminescence signal broadens further. In FIG. 13D, 16 hours after inoculation, bioluminescence signal continues to broaden. The illuminated samples (25% duty cycle, 50% duty cycle) encroach into the envelope of the blue light exposure. In FIG. 13E, 8 hours after inoculation, there is continued encroachment of bacteria into the area of blue light exposure, but no migration beyond irradiance of approximately 0.55 mW / cm2. In FIG. 13F, 19 hours after inoculation, the “dark” sample, which is not exposed to aBL, continues to migrate or move along the plate. Both the 25% duty cycle and the 50% duty cycle samples remain stationary - they do not migrate into the area of aBL exposure greater than approximately 0.55 mW / cm2.

[0083] While specific embodiments and applications of the present invention have been illustrated and described, it is to be understood that the invention is not limited to the precise configuration and components disclosed herein. Various modifications, changes, and variations which will be apparent to those skilled in the art may be made in the arrangement, operation, and details of the methods and systems of the present invention disclosed herein without departing from the spirit and scope of the invention.

Claims

Claims1. A photonic irradiation system for controlling against microbial migration, the system comprising: a catheter configured to be inserted into an orifice of a subject, wherein, when inserted into the orifice, the catheter extends from a proximal end extending outside the subject and a distal end arranged within the subject, and wherein the catheter comprises: a wall with a length extending between the proximal end and the distal end; at least one lumen formed within the wall extending between the proximal and distal end; and at least one electromagnetic (EM) radiation source configured to irradiate at least a portion of the catheter with EM radiation having operational parameters configured to control microbial migration in a distal direction from the portion of the catheter.

2. The photonic irradiation system of claim 1, further comprising one or more radiation directors embedded within the wall of the catheter to direct the EM radiation to an exterior or interior surface of the wall to control microbial migration in the distal direction from the portion of the catheter.

3. The photonic irradiation system of claim 2, wherein the one or more radiation directors includes an etching embedded within the wall at one or more locations along the length of the catheter.

4. The photonic irradiation system of claim 2, wherein the one or more radiation directors is embedded within the wall at one or more locations along the length of the catheter configured to coincide with an opening of the orifice of the subject when the catheter is inserted into the orifice.

5. The photonic irradiation system of claim 1, wherein the at least one EM radiation source is embedded within the wall of the catheter.

6. The photonic irradiation system of claim 1, further comprising a sheath including a channel, wherein the channel is configured to feed the catheter through the sheath.

7. A photonic irradiation system of claim 6, wherein the sheath includes at least one radiation director embedded therein.

8. The photonic irradiation system of claim 6, wherein the sheath is configured to be placed at an opening of the orifice.

9. The photonic irradiation system of claim 6, wherein the at least on EM radiation source is embedded within the sheath.

10. The photonic irradiation system of claim 1, wherein the at least one EM radiation source includes one of a laser or a light emitting diode (LED).

11. The photonic irradiation system of claim 1, wherein the at least one EM radiation source emits a wavelength of light ranging from 290-470 nm.

12. The photonic irradiation system of claim 1, wherein the at least one EM radiation source includes a battery configured to power the EM radiation source.

13. The photonic irradiation system of claim 1, wherein the wall includes an optically transparent material.

14. The photonic irradiation system of claim 1, wherein the at least one EM radiation source emits a light with an irradiance of 1 mW / cm2or less.

15. A method of irradiating a catheter to control against microbial migration, the method including the steps of: inserting a catheter into an orifice of a subject, wherein the catheter includes a wall with a lumen formed therein; and irradiating at least a portion of the catheter with electromagnetic (EM) radiation using at least one EM radiation source.

16. The method of claim 15, wherein the at least one EM radiation source is embedded within the wall at one or more locations along a length of the catheter.

17. The method of claim 16, wherein the at least one EM radiation source is embedded within the wall at one or more locations along the length of the catheter coinciding with an opening of the orifice of the subject.

18. The method of claim 15, further including inserting a sheath at an opening of the orifice of the subject; and feeding the catheter through a channel in the sheath into the orifice of the subject.

19. The method of claim 18, wherein the at least one EM radiation source is embedded within the sheath.

20. The method of claim 15, wherein the at least one EM radiation source is an optical fiber, a laser, or a light emitting diode (LED).

21. The method of claim 15, wherein the at least one EM radiation is at a wavelength of light ranging from 290-470 nm.

22. The method of claim 15, wherein irradiating the catheter with EM radiation is emitted with an irradiance of 1 mW / cm2or less.

23. The method claim 15, wherein irradiating the catheter with EM radiation is emitted using a 50% duty cycle.

24. The method of claim 15, wherein the at least one EM radiation source is electrically connected to and powered by a battery.

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