PATENT ABSTRACT
An anti-infective covering for an implantable medical device is described. The covering may be a polymeric boot that comprises an anti-infective agent in an amount effective to prevent an infection when implanted in a pocket of a patient. The boot is configured to snuggly engage at least a portion of the implantable medical device. The boot may contain a side hole that allows a housing of the implantable medical device to serve as a return electrode. The boot may be placed about the implantable medical device to render the device anti-infective.

PATENT DESCRIPTION
RELATED APPLICATIONS  
       [0001]     This application claims the benefit of priority of and is a Continuation-in-Part application of U.S. application Ser. No. 10/393,121, filed on 20 Mar. 2003 and published as US patent application No. 2004/0186528, which priority application is hereby incorporated herein by reference in its entirety. This application also claims the benefit of priority to U.S. Provisional Patent Application Ser. Nos. 60/529,461 and 60/529,424, both filed on Dec. 12, 2003, which provisional applications are hereby incorporated herein by reference in their entireties. 
     
    
     FIELD  
       [0002]     The present invention relates generally to implantable medical devices (IMDs).  
       BACKGROUND  
       [0003]     At present, a wide variety of IMDs are commercially released or proposed for clinical implantation that include a housing that is implanted subcutaneously and typically include elongated medical electrical leads or drug delivery catheters that extend from the subcutaneous site to other subcutaneous sites or deeper into the body to organs or other implantation sites. Typically, the IMD includes a battery-powered implantable pulse generator (IPG) that is coupled with electrical medical leads, a battery-powered implantable monitor that may or may not be coupled with electrical medical leads, a battery-powered drug pump coupled with a drug delivery catheter, etc. Such IMDs include implantable cardiac pacemakers, cardioverter/defibrillators having pacing capabilities, other electrical stimulators including spinal cord, deep brain, nerve, and muscle stimulators, drug delivery systems, cardiac and other physiologic monitors, cochlear implants, etc. Typically, the battery-powered component of the IMD is implanted subcutaneously at a surgically prepared site, referred to as a “pocket”. The surgical preparation and initial or replacement IMD implantations are conducted in a sterile field, and the IMD components are packaged in sterile containers or sterilized prior to introduction into the sterile field. However, despite these precautions, there always is a risk of introduction of microbes into the pocket. Surgeons therefore typically apply disinfectant or antiseptic agents to the skin at the surgical site prior to surgery (e.g., Chlorhexidine, Gluconate, Povidone-Iodine, Isopropyl Alcohol, Ethyl Alcohol), directly to the site before the incision is closed (e.g., gentamicin, vancomycin), and prescribe oral antibiotics for the patient to ingest during recovery (e.g., sefuroxin, gentamicin, rifamycin, vancomycin).  
         [0004]     Despite these precautions, infections do occur. In addition, once the pocket becomes infected, the infection can migrate along the lead or catheter to the, heart, brain, spinal canal or other location in which the lead or catheter is implanted. Such a migrating infection can become intractable and life-threatening, requiring removal of the IMD in the pocket and associated devices, such as leads and catheters. Removal of a chronically implanted lead or catheter can be difficult and dangerous. Aggressive systemic drug treatment is also provided to treat the infection. To prevent pocket infection and thus the ability of infection migration along a lead or catheter, there is a need to impart antimicrobial activity to the IMD residing in the pocket itself.  
         [0005]     There is long history of the actual or proposed use of antimicrobial agents coated on IMDs for prevention of infection. However, applying coatings to surfaces of IMDs intended for long-term implantation can be problematic because the coatings can degrade and slough away over time. This may be particularly problematic with IMDs configured to be implanted in the pocket, which IMDs may contain metallic surfaces. Such IMDs, e.g., such as neurostimulatory pulse generators, cardiac pacemakers, drug infusion pumps, and the like, containing metallic surfaces can be more difficult to coat than polymeric surfaces. As such, there is a need to impart antimicrobial activity to active IMDs residing in subcutaneous pockets, where the vehicle containing the antimicrobial activity can withstand long-term implantation.  
       SUMMARY  
       [0006]     Various embodiments of the invention are directed to providing a simple, effective and long lasting anti-microbial agent into the subcutaneous implantation pocket that is surgically prepared to receive an IMD. This may be accomplished by disposing about the IMD a covering comprising an anti-infective agent. The covering may be a boot, jacket, etc. The anti-infective agent is present on the surface of the covering or is eluted from the covering in an amount sufficient to prevent infection in a subcutaneous pocket into which the IMD is implanted. The covering may be conformed to the shape of the IMD implanted into the pocket and may be attached to or detached from the IMD. In an embodiment, the covering is a polymeric boot that fits around at least a portion of an outer housing of the IMD.  
         [0007]     Polymeric boots have been proven over long-term clinical use to not degrade significantly in the body despite the fact that they are relatively thin. Therefore, it is expected that anti-infective agent dispersed through the thin wall of the anti-microbial pad or boot component or other component will be beneficially present or released over time.  
         [0008]     By using coverings as described herein, as opposed to coatings, it is not necessary for manufacturers to commit to manufacturing and clinical buyers to stock redundant models of expensive IMDs, one model with the anti-infective polymeric component and one without the anti-microbial polymeric component. Once it is determined that an IMD having anti-infective properties is desired, the coating may be placed about the IMD by the manufacturer, the consumer, or the user.  
         [0009]     This summary of the invention has been presented here simply to point out some advantages over the prior art and is not intended to operate in any manner as a limitation on the interpretation of claims that are presented initially in the patent application and that are ultimately granted.  
         [0010]     These and other advantages will be more readily understood from the following detailed description, when considered in conjunction with the drawings.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0011]      FIG. 1  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s thoracic region, having a polymeric boot comprising an anti-infective agent fitted over the device.  
         [0012]      FIG. 2  is a plan view of the polymeric boot of  FIG. 1 .  
         [0013]      FIG. 3  is a side-cross-section view of the boot taken along lines  3 - 3  of  FIG. 2 .  
         [0014]      FIG. 4  is a top view of the boot of  FIG. 2 .  
         [0015]      FIG. 5  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s thoracic region, having a polymeric boot comprising an anti-infective agent fitted over the device and having a further boot fitted over or attached to the non-conducting side of the device.  
         [0016]      FIG. 6  is a schematic view of an implantable medical device including two modules implanted subcutaneously across the patient&#39;s thorax and tethered together, each module having a boot comprising an anti-infective agent fitted over the device.  
         [0017]      FIG. 7  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s abdominal region having a boot comprising an anti-infective agent fitted over the device.  
         [0018]      FIG. 8  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s abdominal region having a boot comprising an anti-infective agent fitted over the device.  
         [0019]      FIG. 9  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s pectoral region having a boot comprising an anti-infective agent fitted over the device.  
         [0020]      FIG. 10  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s pectoral region having a boot comprising an anti-infective agent fitted over the device.  
         [0021]      FIG. 11  is a schematic view of an implantable medical device implanted subcutaneously in a patient&#39;s pectoral region having a boot comprising an anti-infective agent fitted over the device.  
         [0022]      FIG. 12  is a schematic partial view of an exemplary implantable medical device depicting a connector header in partial cross-section and an exemplary lead connector assembly adapted to be fitted into a connector bore, wherein selected ones or all of polymeric components of the connector header and/or the lead connector assembly comprise an anti-infective agent.  
         [0023]      FIG. 13  is a perspective view of a subcutaneously implantable electrode wherein selected ones or all of the polymeric components of the electrode comprise an anti-infective agent. 
     
    
       [0024]     The drawings are not necessarily to scale.  
       DETAILED DESCRIPTION  
       [0025]     In the following detailed description, references are made to illustrative embodiments of methods and apparatus for carrying out the invention. It is understood that other embodiments can be utilized without departing from the scope of the invention.  
         [0000]     Anti-Infective Agents  
         [0026]     Any anti-infective agent may be incorporated in or on a covering configured to be disposed about an IMD. Preferably, the anti-infective agent is present in or on the covering, or may be eluted from the covering, in an amount sufficient to prevent an infection from forming in a pocket into which the IMD is implanted. It is also desirable that the anti-infective agent, in the concentration present in the covering, be nontoxic when implanted in the pocket. It will be understood that more than one anti-infective agent may be present in or on the covering. As used herein, “anti-infective agent” means an agent that prevents an infection. Anti-infective agents include agents that kill or inhibit the growth of a microbe or a population of microbes. Non-limiting examples of such agents include antibiotics and antiseptics.  
         [0027]     Any antibiotic suitable for use in a human may be used in accordance with various embodiments of the invention. As used herein, “antibiotic” means an antibacterial agent. The antibacterial agent may have bateriostatic and/or bacteriocidal activities. Nonlimiting examples of classes of antibiotics that may be used include tetracyclines (e.g. minocycline), rifamycins (e.g. rifampin), macrolides (e.g. erythromycin), penicillins (e.g. nafcillin), cephalosporins (e.g. cefazolin), other beta-lactam antibiotics (e.g. imipenem, aztreonam), aminoglycosides (e.g. gentamicin), chloramphenicol, sufonamides (e.g. sulfamethoxazole), glycopeptides (e.g. vancomycin), quinolones (e.g. ciprofloxacin), fusidic acid, trimethoprim, metronidazole, clindamycin, mupirocin, polyenes (e.g. amphotericin B), azoles (e.g. fluconazole) and beta-lactam inhibitors (e.g. sulbactam). Nonlimiting examples of specific antibiotics that may be used include minocycline, rifampin, erythromycin, nafcillin, cefazolin, imipenem, aztreonam, gentamicin, sulfamethoxazole, vancomycin, ciprofloxacin, trimethoprim, metronidazole, clindamycin, teicoplanin, mupirocin, azithromycin, clarithromycin, ofloxacin, lomefloxacin, norfloxacin, nalidixic acid, sparfloxacin, pefloxacin, amifloxacin, enoxacin, fleroxacin, temafloxacin, tosufloxacin, clinafloxacin, sulbactam, clavulanic acid, amphotericin B, fluconazole, itraconazole, ketoconazole, and nystatin. Other examples of antibiotics, such as those listed in Sakamoto et al., U.S. Pat. No. 4,642,104, which is herein incorporated by reference in its entirety, may also be used. One of ordinary skill in the art will recognize other antibiotics that may be used.  
         [0028]     It is desirable that the antibiotic(s) selected kill or inhibit the growth of one or more bacteria that are associated with infection following surgical implantation of a medical device. Such bacteria are recognized by those of ordinary skill in the art and include  Stapholcoccus aureus  and  Staphlococcus epidermis.  Preferably, the antibiotic(s) selected are effective against strains of bacteria that are resistant to one or more antibiotic.  
         [0029]     To enhance the likelihood that bacteria will be killed or inhibited, it may be desirable to combine one or more antibiotic. It may also be desirable to combine one or more antibiotic with one or more antiseptic. It will be recognized by one of ordinary skill in the art that antimicrobial agents having different mechanisms of action and/or different spectrums of action may be most effective in achieving such an effect. In a particular embodiment, a combination of rifampin and minocycline is used.  
         [0030]     Any antiseptic sutable for use in a human may be used in accordance with various embodiments of the invention. As used herein, “antiseptic” means an agent capable of killing or inhibiting the growth of one or more of bacteria, fungi, or viruses. Antiseptic includes disinfectants. Nonlimiting examples of antiseptics include hexachlorophene, cationic bisiguanides (i.e. chlorhexidine, cyclohexidine) iodine and iodophores (i.e. povidone-iodine), para-chloro-meta-xylenol, triclosan, furan medical preparations (i.e. nitrofurantoin, nitrofurazone), methenamine, aldehydes (glutaraldehyde, formaldehyde), silver sulfadiazine and alcohols. One of ordinary skill in the art will recognize other antiseptics.  
         [0031]     It is desirable that the antiseptic(s) selected kill or inhibit the growth of one or more microbe that are associated with infection following surgical implantation of a medical device. Such bacteria are recognized by those of ordinary skill in the art and include  Stapholcoccus aureus, Staphlococcus epidermis, Pseudomonus auruginosa,  and  Candidia.    
         [0032]     To enhance the likelihood that microbes will be killed or inhibited, it may be desirable to combine one or more antiseptics. It may also be desirable to combine one or more antiseptics with one or more antibiotics. It will be recognized by one of ordinary skill in the art that antimicrobial agents having different mechanisms of action and/or different spectrums of action may be most effective in achieving such an effect. In a particular embodiment, a combination of chlorohexidine and silver sulfadiazine is used.  
         [0033]     An anti-infective agent, such as an antibiotic or antiseptic, may be present in the covering at any concentration effective, either alone or in combination with another anti-infective agent, to prevent an infection within a pocket into which the covering is implanted. Generally, an antiseptic agent may be present in the covering at a range of between about 0.5% and about 20% by weight. For example, the anti-infective agent may be present in the covering at a range of between about 0.5% and about 15% by weight or between about 0.5% and about 10% by weight.  
         [0000]     Covering  
         [0034]     An embodiment of the invention provides a covering configured to be placed about at least a portion of an implantable medical device. The covering may be in the form of a boot, jacket, gauze, wrap and the like. The covering is formed of a polymeric material into or onto which an anti-infective agent is incorporated. Any polymeric material may be used. Preferably the polymeric material is biocompatible and is capable of presenting or eluting the anti-infective agent to the implant pocket in an amount effective to prevent an infection.  
         [0035]     Examples of suitable polymeric materials that may be used to form the covering include organic polymers such as silicones, polyamines, polystyrene, polyurethane, acrylates, polysilanes, polysulfone, methoxysilanes, and the like. Other polymers that may be utilized include polyolefins, polyisobutylene and ethylene-alphaolefin copolymers; acrylic polymers and copolymers, ethylene-covinylacetate, polybutylmethacrylate; vinyl halide polymers and copolymers, such as polyvinyl chloride; polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidene halides, such as polyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile, polyvinyl ketones; polyvinyl aromatics, such as polystyrene, polyvinyl esters, such as polyvinyl acetate; copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 and polycaprolactam; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxy resins; polyurethanes; rayon; rayon-triacetate; cellulose; cellulose acetate, cellulose butyrate; cellulose acetate butyrate; cellophane; cellulose nitrate; cellulose propionate; cellulose ethers; carboxymethyl cellulose; polyphenyleneoxide; and polytetrafluoroethylene (PTFE). In an embodiment the covering comprises silicone. In an embodiment, the covering comprises polyurethane.  
         [0036]     An anti-infective agent may be incorporated into or on the polymeric covering using any known or developed technique. For example, the anti-infective agent may be adhered to a surface of the covering, adsorbed into the covering, or compounded into the polymeric material that forms the covering. Accordingly, the anti-infective material may be embedded, coated, mixed or dispersed on or in the material of the covering. In various embodiments, the anti-infective agent may be incorporated into the polymeric covering as taught by U.S. Pat. Nos. 5,217,493 or 5,624,704.  
         [0037]     In an embodiment, the covering is a boot. The boot may be molded into a shape to conform to that of at least a portion of an IMD using known or developed techniques. The IMD may be an active IMD, such as a cardiac pacemaker, a cardioverter/defibrillators, a neurostimulator, a drug infusion pump, and the like.  
         [0038]     The remainder of this description may refer specifically to a silicone rubber boot  15 ,  215 ,  335 ,  340 , etc. into which an anti-microbial metal ion zeolite is compounded. However, it will be understood that any covering may be substituted for the boot  15  and that any anti-infective agent may be substituted for the metal ion zeolite.  
         [0039]     In an embodiment the covering is any covering as described herein, with the proviso that the anti-infective agent is not a metal ion zeolite.  
         [0040]     In an embodiment the covering is any covering as describe herein, with the proviso that if the anti-infective agent is a metal ion zeolite, then the metal zeolite is not compounded into the covering.  
         [0041]     In an embodiment of a detachable, elastic, boot  15  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be tatted over an IPG or monitor  50  implanted in patient  10  is depicted in  FIGS. 1-4 . The boot  15  has first and second major boot sides  20  and  25  joined by a mutual boot edge  30  defining a boot cavity  45 . A side opening  35  through major boot side  20  and an edge opening  40  through a segment of boot edge  30  are provided.  
         [0042]     The boot  15  is fitted over the housing  55  and connector block  60  of the exemplary IPG or monitor and inserted into a subcutaneous pocket  140  at a distance from the heart  100  as shown in  FIG. 1 . The fitted boot  15  provides the anti-microbial protection in the subcutaneous implantation pocket  140  while leaving at least a portion of the housing  55  of IPG/monitor  50  exposed through side opening  35 . Preferably, the size and shape of the side opening fits within a circle having a diameter of the zone of inhibition of the one or more anti-infective agents in or on the boot  15 . In an embodiment, the diameter of the zone of inhibition is determined at 30 days post-implantation. In an embodiment, the diameter of the zone of inhibition is determined at 90 days post-implantation. If such a sized and shaped side opening  35  is too small for its intended purposes, more than one side opening  35 , each having a size and shape fitting within a circle having a diameter of the zone of inhibition of the one or more anti-infective agents in or on the boot  15  may be employed.  
         [0043]     The IPG  50  depicted in  FIG. 1  as a ventricular pacemaker IPG or hemodynamic monitor that is coupled to a cardiac lead  70  extending from a connection with connector block  60  into the heart  100  through a conventional transvenous route. The cardiac lead comprises an active or cathodal pace/sense electrode  80  at the distal end of lead body and optionally comprises a pressure transducer  90  proximal to pace/sense electrode both disposed in this instance in the right ventricle  105  of heart  100 . The housing of IPG  50  is hermetically sealed and formed of a conductive metal that is electrically connected to pacing and/or sensing circuitry within housing  55  to function as an indifferent or anodal pace/sense electrode  85  that is exposed by side opening  35 .  
         [0044]     The housing  55  and connector block  60  of IPG/monitor  50  can take any shape known in the art, and that shape dictates the shape and dimensions of the boot  15 . The specifications and operating modes and other characteristics of the pacemaker IPG and the cardiac lead(s) coupled therewith can correspond to any of those known in the art. The monitor can correspond to the Medtronic® CHRONICLE® IHM (implantable hemodynamic monitor) that is coupled through a cardiac lead of the type described in commonly assigned U.S. Pat. No. 5,564,434 having capacitive blood pressure and temperature sensors as well as at least one EGM sense electrode.  
         [0045]     The IPG/monitor  50  is slipped through the side opening  35  and the connector block  60  is oriented to be exposed through the edge opening  40 . It will also be understood that the side opening  35  is necessary to expose the housing  55  for use as a remote indifferent stimulating and/or sensing electrode in either of a unipolar pacemaker IPG/monitor  50  or in a bipolar pacemaker IPG/monitor also having the capability of monitoring the far field EGM. The boot  15  having such a side opening  35  can still be efficaciously used over a typical bipolar pacemaker IPG/monitor not having such a far held sensing capability. These features of the boot  15  are applicable to the remaining boot embodiments illustrated in  FIGS. 5-10 .  
         [0046]     An embodiment of a detachable, elastic, boot  215  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over a rectilinear ICD IPG  250  implanted in patient  10  is depicted in  FIG. 5 . The boot  215  is also formed of first and second major boot sides joined by a mutual boot edge defining a side opening  235  through major boot side and an edge opening  240  through a segment of the boot edge.  
         [0047]     The boot  215  is fitted over the housing  255  and connector block  260  of the exemplary ICD IPG  250  and inserted into a subcutaneous pocket  140  at a distance from the heart  100  as shown in  FIG. 5 . The fitted boot  215  provides the anti-microbial protection in the subcutaneous implantation pocket  140  while leaving at least a portion of the housing  255  of ICD IPG  250  exposed through side opening  235 . The exposed portion of the housing  255  may be employed as one electrode.  
         [0048]     The ICD IPG  250  depicted in  FIG. 5  is coupled to an exemplary set of leads extending to pace/sense electrodes and electrodes. It will be understood that not all of the depicted leads and that other combinations of leads can be connected to the ICD IPG  250 . In this particular instance, a right ventricular (RV) lead  275  extends from a connection with connector block  260  into the right ventricle  105  of the heart  100  through a conventional transvenous route. The RV lead  275  comprises active or cathodal pace/sense electrode and fixation helix  280  at the distal end of the lead body, a more proximally located, ring-shaped, indifferent or anodal pace/sense electrode  285 , and an elongated electrode  290 . A coronary sinus (CS) lead  225  extends from a connection with connector block  260  to an elongated electrode  230  disposed in the coronary sinus or great vein  115  of the heart  100  through a conventional transvenous route.  
         [0049]     A further lead  265  extends subcutaneously from a connection with connector block  260  to a rectilinear, pad-shaped, electrode  270  disposed in a further subcutaneous pocket  140 ′ selected by the surgeon to optimally apply shock therapies between selected pairs of the electrodes  230 ,  255 ,  270 , and  290 .  
         [0050]     Typically the rectilinear electrode  270  is formed of a flexible silicone rubber or polyurethane pad supporting a electrode surface or array on one major side disposed toward heart  100  and a non-conductive side disposed toward the skin. A further detachable, elastic, boot  295  that is compounded of silicone rubber and the preferred anti-microbial metal ion neolith and molded in a shape to be fitted over the non-conductive major side of the rectilinear electrode  770  is shown in  FIG. 5 .  
         [0051]     The boot  295  can be affixed by sutures or other means to the silicone rubber or polyurethane pad to ensure that it does not move or detach from the non-conductive side within the pocket  140 ′.  
         [0052]     More recently, it has been proposed that all components of an ICD be implanted subcutaneously distributed between two or more electrode bearing; modules implanted in subcutaneous pockets  140 ,  140 ′ around the thorax to deliver shock therapies between them and through the heart. Such ICDs are disclosed in U.S. Pat. Nos. 5,255,692, 5,314,451, and 5,342,407 and in U.S. patent application Publication Nos. 2002/0042634 and 2002/0035377. Such an arrangement is depicted in  FIG. 6  wherein the ICD  300  comprises first and second schematically depicted, hermetically sealed ICD IPG modules  305  and  310  tethered together by a cable  315 .  
         [0053]     First and second electrodes  320  and  325  are supported on one side of the ICD IPG modules  305  and  310 , respectively, that are intended to be implanted in the subcutaneous pockets  140 ,  140 ′ facing the heart  100  and one another.  
         [0054]     The hermetically sealed ICD IPG module  305  encloses the electronic sensing, pacing, and circuitry, including the relatively bulky high voltage capacitors that are charged and discharged to deliver shocks, as well as a low voltage battery employed for powering the circuitry and the delivered pacing pulses. The second hermetically sealed ICD IPG module  310  encloses a relatively bulky high power battery as well as a switch to enable selective connection with the high voltage capacitor charging circuitry within the first ICD IPG module  305  in the manner described in the above referenced &#39;451 patent. The cable  315  encases conductors distributing power from the battery and exchanging signals and commands between circuitry in the first and second ICD IPG modules  305  and  310 .  
         [0055]     First and second detachable, elastic, boots  335  and  340  that are each compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the respective first and second ICD IPG modules  305  and  310  implanted in patient  10  are also depicted in  FIG. 6 . The boots  335  and  340  have openings  345  and  350  in the major sides thereof that expose the first and second respective electrodes  320  and  325 .  
         [0056]     The first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  are preferably implanted subcutaneously in posterior and anterior positions through a single skin incision intermediate the illustrated posterior and anterior positions. Tunneling tools would be employed to displace the tissue and advance the first and second hermetically sealed housings to the depicted sites or other selected sites around the thorax. Tissue adhesive may be employed to secure the first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  at the sites and prevent migration. Alternatively, the sites may be exposed through minimal surgical exposures, and the first and second hermetically sealed ICD IPG modules  305  and  310  bearing the first and second detachable, elastic, boots  335  and  340  can be sutured at the sites through the boots  335  and  340  to prevent migration.  
         [0057]     Therapeutic administration of pain suppressing electrical stimulation into the intraspinal space, that is to either the epidural space or to the intrathecal space, is also known in the art as illustrated in  FIG. 7 . Three meningeal sheaths that are continuous with those which encapsulate the brain within the enclosure by the vertebral canal for the spinal cord by the bones of the vertebrae surround the spinal cord. The outermost of these three meningeal sheaths is the dura matter, a dense, fibrous membrane which anteriorally is separated from the periosteum of the vertebral by the epidural space. Posterior to the dura matter is the subdural space. The subdural space surrounds the second of the three meningeal sheaths, the arachnoid membrane, which surround the spinal cord. The arachnoid membrane is separated from the third meningeal sheath, the pia mater, by the subarachnoid or intrathecal space. The subarachnoid space is filled with CSF. Underlying the pia mater is the spinal cord. Thus the progression proceeding inwards or in posterior manner from the vertebra is the epidural space, dura mater, subdural space, arachnoid membrane, intrathecal space, pia matter and spinal cord.  
         [0058]     An exemplary spinal cord stimulation (SCS) system  400  comprising a neurostimulator SCS IPG  450 , an SCS lead  410 , and a detachable, elastic, boot  415  that is each compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the neurostimulator IPG  450  is depicted implanted in patient  10  in  FIG. 7 . The neurostimulator IPG  450  may comprise the Medtronic® Itrel® 3, Synergy™ or Synergy Versitrel™ neurostimulator, and the SCS lead  410  may comprise the Medtronic® Pisces Z Quad lead.  
         [0059]     Therapeutic administration of stimulation of the sacral nerves to control bladder function or treat sexual dysfunction is also alternatively illustrated in  FIG. 7  by the sacral nerve stimulation lead  420  depicted in dotted lines extending from the neurostimulator IPG  450  and detachable, elastic, boot  415  into a foramen of the sacrum. In this case, the neurostimulator IPG  450  may comprise the Medtronic® InterStim® Neurostimulator Model 3023. In one embodiment, a sacral nerve stimulation lead  420  bearing one or a plurality of distal stimulation electrodes are percutaneously implanted through the dorsum and the sacral foremen of the sacral segment S 3  for purposes of selectively stimulating the S 3  sacral nerve. The distal electrode(s) is positioned using a hollow spinal needle through a foremen (a singular foramina) in the sacrum. The electrode is secured by suturing the lead body in place, and the lead body is tunneled subcutaneously to the implant site of the neurostimulator IPG  450  within the boot  415 .  
         [0060]     The detachable, elastic, boot  415  corresponds to the detachable, elastic, boot described above with respect to  FIGS. 1-4 . It will be understood that the actual shape of such commercially available neurostimulator IPGs may differ from the exemplary shape of neurostimulator IPG  450  shown in  FIG. 7 , and that boot  415  is molded to conform to the actual shape. Again, the boot  415  has a major side opening  435  exposing the housing  455  of the IPG  450  that can function as an indifferent stimulation electrode in conjunction with a stimulation electrode or electrodes along the distal end segment of the SCS lead  410  disposed within the intraspinal space and obscured from view. The boot  415  also has an edge opening  440  enabling access to the connector block  460 .  
         [0061]     Therapeutic administration of pain suppression or therapeutic drugs into the intraspinal space as also known in the prior art is illustrated in  FIG. 8 . Administration of a drug directly to the intrathecal space can be by either spinal tap injection or by catheterization.  
         [0062]     Intrathecal drug administration can avoid the inactivation of some drugs when taken orally as well and the systemic effects of oral or intravenous administration. Additionally, intrathecal administration permits use of an effective dose that is only a fraction of the effective dose required by oral or parenteral administration. Furthermore the intrathecal space is generally wide enough to accommodate a small catheter, thereby enabling chronic drug delivery systems. Thus, it is known to treat spasticity by intrathecal administration of baclofen. Additionally, it is known to combine intrathecal administration of baclofen with intramuscular injections of botulinum toxin for the adjunct effect of intramuscular botulinum for reduced muscle spasticity. Furthermore, it is known to treat pain by intraspinal administration of the opioids morphine and fentanyl. A drug pump is required because the antinociceptive or antispasmodic drugs in current use have a short duration of activity and must therefore be frequently re-administered, which re-administration is not practically carried out by daily spinal tap injections. The drug pump is surgically placed under the skin of the patient&#39;s abdomen. One end of a catheter is connected to the pump, and the other end of the catheter is threaded into a CSF filled subarachnoid or intrathecal space in the patient&#39;s spinal cord. The implanted drug pump can be programmed for continuous or intermittent infusion of the drug through the intrathecally located catheter.  
         [0063]     Thus a fully implantable intrathecal drug delivery system  500 , e.g., the Medtronic® SynchroMed® EL Infusion System, comprising a programmable SynchroMed® drug pump  550  and a drug delivery catheter  510 , is depicted in  FIG. 8 .  
         [0064]     A detachable, elastic, boot  515  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the drug pump  550  is depicted implanted in patient  10  in  FIG. 7 . Again, the boot  515  has a major side opening  535  in this case exposing a drug fill port  555  for percutaneously refilling a drug chamber within the drug pump  550  in a manner well known in the art. The boot  515  also has an edge opening  540  enabling access to the connector block  560  that the drug delivery catheter  510  is attached to.  
         [0065]     The drug pump  550  and boot  515  encasing the drug pump  550  are implanted just under the skin of the abdomen in a prepared subcutaneous pocket  140  so that the drug fill port is oriented outward to enable access to the drug fill port  555 .  
         [0066]     Turning to  FIG. 9 , it schematically illustrates the delivery of Medtronic® Activa® Tremor Control Therapy or Parkinson&#39;s Control Therapy to a patient  10  for controlling essential tremors and those associated with Parkinson&#39;s disease. The Activate Therapy is delivered by an deep brain stimulator similar to a cardiac pacemaker, that uses mild electrical stimulation delivered by electrodes implanted in the brain to block the brain signals that cause tremor.  
         [0067]     The Activa® Tremor Control System stimulates targeted cells in the thalamus the brain&#39;s message relay center—via electrodes that are surgically implanted in the brain and connected to a neurostimulator IPG implanted near the collarbone. In the treatment of Parkinson&#39;s tremors, the electrodes are located at the subthalamic nucleus (STN) or globus pallidus interna (GPI) that control movement and muscle function. A lead with tiny electrodes is surgically implanted at these sites in the brain and connected by an extension that lies under the skin to a neurostimulator IPG implanted near the collarbone. The electrical stimulation can be non-invasively adjusted to meet each patient&#39;s needs.  
         [0068]     The implanted components of the Activa® System  600  depicted in FIG. 9  include the Medtronic® Itrel® II Model 7424 neurostimulator IPG  650 , a DBS™ lead  670  and an extension  610  that connects the lead  670  to the neurostimulator IPG  650 .  
         [0069]     The lead  670  is implanted using a stereotactic headframe designed to keep the head stationary and help guide the surgeon in the placement of the lead  670  into the brain  130  to dispose the electrodes  680  at the desired site  135 . The brain  130  and the placement of the lead  670  is imaged using CT (computed tomography) or MRI (magnetic resonance imaging) equipment. The Model 3387 DBS™ lead, with a plurality of widely spaced electrodes, and the Model 3389 DBS™ lead, with a plurality of narrowly spaced electrodes, provide physician options for precise placement and stimulation selectivity. Other components of the Activate System  60  include a neurostimulator control magnet, neurological test stimulator, physician programmer, lead frame kits, and Memory Mod software cartridge.  
         [0070]     A detachable, elastic, boot  615  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector block of the neurostimulator IPG  650  is depicted implanted in patient  10  in  FIG. 9 . Again, the boot  615  has a major side opening  635  and an edge opening  640  enabling access to the connector block  660  that the lead extension  610  is attached to. The neurostimulator IPG  650  and boot  615  encasing the neurostimulator IPG  650   d  are implanted just under the skin of the upper thorax in a prepared subcutaneous pocket  140 . The exposed surface of the bipolar neurostimulator housing  655  can be employed as a stimulation electrode in this instance.  
         [0071]     An implantable infusion pump (IIP) comprising an implantable drug pump and: catheter is disclosed in commonly assigned U.S. Pat. Nos. 5,643,207 and 5,782,798 for dispensing pancreatic polypeptide blockers and other drugs that decrease sensations of hunger and increase satiety into particular sites in the brain through a distal catheter segment that is implanted through the skull and extends to the specific sites. The delivery of other appetite influencing drugs directly into the brain for increasing appetite to treat anorexia is also proposed in the &#39;207 patent. The drug that is dispensed from the infusion pump coupled to the catheter through the catheter lumen and into the brain is expected to induce or increase the feeling of satiety to treat: obesity by reducing caloric intake or to increase feelings of hunger to treat anorexia by increasing caloric intake. The system of the &#39;798 patent can also be employed to apply electrical stimulation to the brain through catheter borne electrodes and conductors to increase feelings of satiety to treat obesity or to decrease feelings of satiety to treat anorexia presumably either with or without delivery of the identified drugs.  
         [0072]     Such an implantable deep brain drug delivery system  700  is depicted in  FIG. 10  comprising an implantable drug pump  750  and catheter  710  for dispensing pancreatic polypeptide blockers and other drugs that decrease sensations of hunger and increase satiety through catheter ports  780  into a particular site  135  in the brain through a distal catheter segment  770  that is implanted through the skull and extends to the specific site  135 . The implantable drug pump  750  can comprise a programmable SynchroMed® drug pump  750 . A detachable, elastic, boot  715  that is compounded of silicone rubber and the preferred anti-microbial metal ion zeolite and molded in a shape to be fitted over the housing and connector of the drug pump  750  is depicted implanted in patient  10  in  FIG. 10 . Again, the boot  715  has a major side opening  735  in this case exposing a drug fill port  755  for percutaneously refilling a drug chamber within the drug pump  750  in a manner well known in the art. The boot  715  also has an edge opening  740  enabling access to the connector block  760  that the drug delivery catheter  710  is attached to. The drug pump  750  and boot  715  encasing the drug pump  750  are implanted just under the skin of the thorax in a prepared subcutaneous pocket  140  so that the drug fill port is oriented outward to enable access to the drug fill port  755 .  
         [0073]     An implantable EGM monitor for recording the cardiac electrogram from electrodes remote from the heart is disclosed in commonly assigned U.S. Pat. No. 5,331,966 and PCT publication WO 98/02209 and is embodied in the Medtronic® REVEAL® Model 9526 Insertable Loop Recorder having spaced housing EGM electrodes employed with a Model 6191 patient activator and a Model 9790 programmer. Such implantable monitors when implanted in patients suffering from cardiac arrhythmias or heart failure accumulate date and time stamped data that can be of use in determining the condition of the heart over an extended period of time and while the patient is engaged in daily activities. A wide variety of other IMDs have been proposed to monitor many other physiologic conditions as set forth in U.S. Pat. No. 6,221,011.  
         [0074]     Therefore, a REVEAL® Insertable Loop Recorder  850  is depicted in  FIG. 11  implanted in a subcutaneous pocket  140  in the thorax of patient  10 . The Insertable Loop Recorder  850  comprises a hermetically sealed housing  855  enclosing the monitoring circuitry, battery, telemetry antenna, and other components and a header  860  that supports a sense electrode  810  coupled to the a sense amplifier via a feedthrough extending through the housing  855  and has a pair of suture holes extending through it. An electrically un-insulated portion of the housing  855  that is coupled with the sense amplifier provides a second sense electrode  820 . A detachable, elastic, boot  815  that is compounded of silicone rubber and the preferred anti microbial metal ion zeolite and molded in a shape to be fitted over at least the housing  855 . Again, the boot  815  has a major side opening  835  exposing the sense electrode  820  and an edge opening  840  enabling insertion of the housing  855  into the boot  815 .  
         [0075]     The boot  815  may be shaped to extend over at least the portions of the header  860  having the suture holes to enable using the same sutures to secure the boot to the Insertable Loop Recorder  850  and the Insertable Loop Recorder  850  to subcutaneous tissue.  
         [0076]     Thus, a variety of subcutaneously implanted IMDs have been described having a variety of uses and shapes that are implanted in subcutaneous pockets  140 ,  140 ′ and over which a detachable anti-microbial component characterized as a pad or boot that fits around at least a portion of an outer housing of the IMD is placed. The: subcutaneous site is advantageously protected from microbial growth and infections of the types described above by inclusion of the anti-microbial polymeric component that is exposed to body fluids in the pockets  140 ,  140 ′ that is compounded of an antibiotic zeolite that elutes silver ions in concentrations exhibiting anti-microbial activity over a substantial period of time of implantation. In these embodiments depicted in  FIGS. 1-11 , the anti-microbial component is physically attached to the IMD by fitting it over the IMD. It will be understood that the anti-microbial component can be molded to conform to the shape of any IMD adapted to be: implanted subcutaneously that is presently available or may become available in the future, e.g., gastric stimulators and drug pumps, insulin delivery drug pumps, and other body organ, muscle or nerve stimulators and drug delivery devices that are specifically identified herein. It will be further understood that an otherwise detachable anti-microbial component can be rendered substantially un-detachable by adhering the component to the IMD using, e.g., a medically acceptable adhesive.  
         [0077]     In an embodiment, the anti-microbial component comprises a permanently attached portion of any of the above-identified IMDs that are implanted into the prepared subcutaneous pocket  140 . For example, a schematic partial view of an exemplary IPG/monitor  950  depicting the connector header  960  in partial cross section and an exemplary lead connector assembly  915  of an electrical medical lead  910  adapted to be fitted into a connector bore  965 , is depicted in  FIG. 12 . Bipolar lead  910  is depicted having a connector assembly  915  of conventional bipolar design comprising a connector pin  920  and a connector ring  930  adapted to fit a pin receptacle contact  925  and a ring receptacle contact of schematically depicted connector header  960 . Elastic polymeric sealing rings  940  and  945  are located adjacent to the connector pin  920  and connector ring  930 . Distal portion  985  of the lead connector assembly  915  coupled to the elongated lead body  990  is disposed outside the connector bore  965  when the more proximal portion of the lead connector assembly  915  is fully inserted within the connector bore  965 . Elastic bands  970  and  980  encircle the connector bore opening and a suture can be applied to tighten them against the elastic portion of the connector assembly between the sealing rings  945  and the distal portion  955 . The particular configurations of the connector elements  925  and  935 , the feedthroughs and wire connections, and any setscrews or other fasteners that are encased within the molded polymeric header body  975  for making secure electrical connections can take any of the known configurations and are not important to the practice of the present invention and are not depicted. The depicted IPG/monitor  950  is exemplary of any of the IPG/monitors and components thereof 50, 250, 305-310, 450, and 650, although the number of connector elements of the lead connector assembly and the connector header and their specific configurations may vary widely.  
         [0078]     Selected ones or all of the polymeric components of the IPG connector header  975  and/or the lead connector assembly  915  are compounded with metal ion zeolite as indicated by the cross-hatching in  FIG. 12  in accordance with a further embodiment of the invention. Usually, the lead connector assembly  915  is separately formed and attached to the lead body  990  in manufacture, so it is convenient to mold the polymeric lead connector assembly parts from silicone rubber or polyurethane compounded with the metal ion zeolite. The anti-microbial silver ions can thereby be eluted from the connector header body  975  and/or from the elastic band  970  and or from the lead connector portion  985  that is disposed outside the connector bore  965 . The anti microbial silver ions can also be eluted from the sealing rings  940  and  945  if they become wet with body fluids over chronic implantation to inhibit any microbial activity within the connector bore/connector assembly interface.  
         [0079]      FIG. 13  is a perspective view of a subcutaneously implantable electrode, e.g., electrode  275  wherein selected ones or all of the polymeric components of the electrode  275  are compounded with metal ion zeolite in accordance with a further embodiment of the invention. In particular, all or portions of the silicone rubber or polyurethane pad  220  can be molded with the metal ion zeolite as indicated by the cross-hatching in  FIG. 13 . Again, the silicone rubber or polyurethane pad  220  is separately formed and attached to the lead body of lead  265  in manufacture, so it is convenient to mold the polymeric pad as a single part or as multiple parts, depending on the design, from silicone rubber or polyurethane compounded with the metal ion zeolite.  
         [0080]     Similarly, the polymeric header  860  of the implantable monitor  800 , for example, the subcutaneously tunneled cable  315 , for example, between subcutaneously implanted IMD components, and the polymeric component of the catheter connectors  560  and  760  with the implantable drug pumps  500  and  700 , for example, can be molded from polymers compounded with metal ion zeolite.  
         [0081]     All patents and publications referenced herein are hereby incorporated by reference in their entireties.  
         [0082]     It will be understood that certain of the above-described structures, functions and operations of the above-described preferred embodiments are not necessary to practice the present invention and are included in the description simply for completeness of an exemplary embodiment or embodiments.