Prevention and Management of Intrathecal Drug Delivery and Spinal Cord Stimulation System Infections (2004)

FULLY implantable devices or drug–device combinations, such as intrathecal drug delivery (DD) systems and spinal cord stimulation (SCS) systems, increasingly are used for the treatment of chronic intractable pain. 1,2Another approved indication for intrathecal DD systems is the administration of intrathecal baclofen (ITB) to treat medically intractable spasticity of spinal or cerebral origin. 3–5Although patients with cancer, spinal cord injuries, or cerebral palsy have a reduced life expectancy, the majority of intrathecal drug administration devices—and nearly all SCS devices—are implanted in patients with painful non–cancer-related disorders that are associated with a normal life span. Therefore, long-term implantable devices used for the treatment of pain and spasticity should have a relatively benign safety record. 6,7Device-related infection is the most common, potentially reducible, serious adverse event associated with intrathecal DD or SCS devices.Reducing the number of implantable DD and SCS device infections is important for various reasons. One is that treatment of an established infection often involves temporary or permanent removal of the device, which causes cessation of drug or stimulation therapy. Therapy cessation (with or without eventual device replacement) increases the risks, discomfort, inconvenience, and expenses of patients who experience infectious complications. Abrupt cessation of intrathecal drug therapy may precipitate drug withdrawal symptoms and, in the case of ITB, can have fatal consequences. 8In rare cases, device-associated infections can progress to fatal sepsis, meningitis, or both.Available data indicate that implantable DD and SCS device infections share important features with other surgical site infections (SSIs), including those that affect cerebrospinal fluid (CSF) shunts and electrophysiologic cardiac devices such as implantable pacemakers and cardioverter–defibrillators (ICDs). Management of infections associated with DD and SCS systems typically involves administration of antibiotics and explantation of the devices. Measures that reduce the incidence of other SSIs also should reduce the infection rate associated with the implantation of SCS and intrathecal DD devices.The authors reviewed data pertaining to infections associated with DD and SCS. Sources of data included published 1and unpublished clinical study data, postmarket and medical device reporting (MDR) data, published meta-analyses, US Centers for Disease Control (CDC) guidelines and other selected publications about prevention of SSIs, 9,10and pertinent studies from the CSF shunt infection literature 11–42and from the ICD infection literature. 43–51Clinical study data included information about implanted DD and neurostimulation systems marketed by Medtronic, Inc. (Minneapolis, MN). Information regarding device-related infections was available from three monitored multicenter device studies (model 8709 catheter, SynchroMed®10-ml pump, and IsoMed®pump) and one monitored multicenter study of an investigational intrathecal drug. The 8709 catheter study results were published previously. 1Results of the two pump studies and one intrathecal drug study are unpublished to date.The postmarket and MDR data included information about implanted DD and neurostimulation systems reported to the device manufacturer (Medtronic, Inc.), information which is reported also to the US Food and Drug Administration. The DD and SCS infection data analyzed in this review were reported between September 1, 2000, and July 1, 2002. Because of confidentiality regulations and voluntary reporting practices, it was not possible to audit postmarket surveillance data by comparing the information voluntarily reported by health-care professionals, patients, or both to original medical records. Such limitations undoubtedly caused cases of DD or SCS device–related infections to go unreported.Reasons for considering DD and SCS devices together and for including a focused review of the recent CSF shunt and ICD infection literature include the following: Allowing for the differences in patient populations, underlying disease states, and other factors—CSF shunts and DD devices both involve catheterization of the subarachnoid space with a fluid-conduit system and, like SCS, involve tunneling a portion of the implanted system subcutaneously between two anatomical sites. Neurosurgeons implant and manage virtually all patients with CSF shunts and implant a substantial proportion of DD and SCS devices. In general, neurosurgeons use similar methods to minimize the occurrence of infections associated with each type of implant surgery. ICD and SCS devices are similar to each other in size and appearance but are smaller than DD pumps. ICD implantation also involves tunneling from one anatomical site to another. Infection is a frequent, serious, and potentially reducible complication associated with implantation of all of these devices (DD, SCS, CSF shunts, and ICD). Reported infection rates for the various devices are comparable. 1,2,4–6,11–51Despite the differences between DD and SCS devices and therapy, a review of the postmarket infection surveillance data presented in this article revealed similarities in most of the factors that were examined.The risks, prevention, and management of infections associated with implantable DD and SCS systems have not been explored in detail. In contrast, the CSF shunt and ICD infection literature is substantial. The CSF shunt infection literature contains reliable, high-level evidence regarding patient-related risk factors and methods to minimize the incidence of infection. Given the similarities among the various kinds of device-related infections, information from the medical literature and data from clinical trials and postmarket surveillance can be used to formulate general guidelines and recommendations for the prevention and management of DD and SCS infections.The diagnosis of an implantable device–related SSI is established definitively by identification or culture of microorganisms (most commonly bacteria) or both on specimens from a clinically suspect surgical wound or implant site. Clinical signs of wound infection can include fever, redness, swelling, pain, wound exudate, poor healing, or skin erosion at the implant site. Meningismus indicates CSF involvement. Most cases reported in the postmarket and clinical studies reviewed in this article met those strict criteria. However, the need to begin treatment of suspected infections that involved device components implanted within the spinal canal sometimes prompted physicians to begin antibiotic therapy, to remove devices without waiting for the results of cultures or stains, or both. It is possible that some device infections reported by clinicians and investigators were misdiagnosed (false–positives).The device-related infections that occurred in four DD device or drug–device clinical studies are summarized in table 1. The aggregate total period at risk for the occurrence and detection of an infection in those studies was 7,620.8 device-months. Limitations include different data collection periods in each study (mean follow-up varied from 6.4 to 14.1 months) and the fact that none of the studies specifically was designed to investigate device-related infections. Another limitation was that the diagnosis of an infection in each study did not have to meet all of the criteria defined in the previous section. However, all cases had clinical signs, bacteriologic evidence of infection, or both. In addition, the studies were mandated by the US Food and Drug Administration and were monitored in accordance with US Food and Drug Administration and international standards (table 1). 1Those features increase the likelihood that all device-related infections were identified and reported. The infection rates, based on the number of infections that occurred and the number of patients that were enrolled in each study, varied from 2.5 to 9.0% of implanted patients. The highest infection rate, 9%, occurred in the 10-ml SynchroMed®pump study. That study cohort consisted of pediatric patients with spasticity of cerebral origin, predominantly spastic cerebral palsy (n = 90 of 100 patients). The infection rate, occurred in the of intrathecal to treat all infections patients were reported in a total of patients infection infections reported in the various clinical studies The majority of infections in each study involved the pump site. The aggregate proportion of cases that were with or device removal also varied from to The investigators the to all or of the device in each The of cases and differences between the that predominantly involved the pump in each clinical study did not to be The available data also did not to the for site and device removal among the clinical trials were the or different of the patients of infections by the each study or period had or of drug withdrawal were differences between the 10-ml pump study cases the other three studies included a relatively proportion of infections within with those than from the 8709 1and studies were analyzed to differences in the rate of device-related implant by or at different the rate of device varied from to among and in those two were or differences in the device infection of the studies summarized in table information to underlying risk factors for device-related infection, and none were designed to patients to differences in the infection rate among the different or results of postmarket surveillance and MDR of infections that involved Medtronic, intrathecal DD devices and that were reported to the between September 1, 2000, and 1, are summarized in the of table Because of the limitations associated with postmarket the incidence of device-related infections not be or from these The in table to the proportion of cases that the or in each of the of DD cases had pain, had pain, and had and in the underlying diagnosis was not reported. of DD cases had or medical that may have the risk for an SSI (table risk factors were identified at the of the Information was most often by the or health-care sometimes from patients or Because of limitations data not be the limitations of postmarket data collection and did not to with the number of reported infections or with other factors that were of DD patients were and the pump was the most site of infection. of in of DD cases of cases with was reported in of Most did not the were or the most for of infections. cultures were of DD cases and and antibiotics to treat infections. to remove the devices or to the infections in of cases (table The majority of device infection and explantation occurred within The aggregate proportion of DD systems within the implantation was at at of cases without but in of cases, patients drug withdrawal symptoms as a of device removal and therapy One DD patient from and are not of published clinical studies of SCS devices that are to the for DD devices. The results of postmarket surveillance and MDR of infections that involved Medtronic, implantable SCS and that were reported to the between September 1, 2000, and July 1, are summarized in the of table SCS cases had pain, and had medical that may have at risk for an infection (table risk factors were identified in the as for DD was the case for DD clinical and postmarket data, did not to the number of reported infections or to be associated with other of patients were and the implantable or was the most site of infection. of SCS device also in a of cases of of cases with was reported in of SCS cases, the proportion reported for of was not also caused of SCS device and cultures were for of SCS patients and and antibiotics to treat infections. to or remove the SCS devices in of SCS The of SCS systems the was at at of SCS cases of patients fluid shunts share features with DD and SCS The devices are implanted by neurosurgeons who most use similar infection prevention and management for each type of implant surgery. and methods that are to reduce the incidence of and to manage CSF shunt infections also should to DD and SCS from a review of the CSF shunt literature that are pertinent to DD and SCS device infections are and in table possible shunt factors that not to implanted with DD or SCS systems were not of previous device or infections to increase the risk for infection that included an of than between or both. CSF the risk of infection in some but not in of the or experience and the of the implant factors which may be were in some studies not in antibiotic administration as a predominantly the infection rate in the or study period was relatively data from different studies were in the of antibiotics in shunt infection rates is to in a of the relatively infection study to the use of one antibiotic but a for may be administration of the antibiotic the skin the to increase the risk of infection. as the or and other management have not reduced shunt infection rates those were of a infection studies have a between shunt and infection rates, other studies was the case for implantable DD and SCS infections, most shunt infections occurred relatively implantation and were caused by The majority occurred within implantation in case and within implantation in published for of infections in was the most commonly identified the differences in patient populations, for device and medical of the share features that are to infection and management with DD and SCS devices. infection rates for varied from to associated with ICD infection rates included and in a than in a or both. were device than the most commonly were and treatment in most cases involved explantation of the system in with antibiotic to the infection without device removal or with device removal were associated with rates and studies have not infection rates antibiotic administration at the of device information from the most recent of SSI prevention guidelines published by the is summarized in table recommendations from a review of the CSF shunt literature and from postmarket surveillance data on DD and SCS device infections are included among the recommendations in table The original and a review to the of general and other surgical on and other factors not to the review are from the to patients with different or surgical infection or the results of device and drug–device clinical postmarket surveillance and MDR data, and literature regarding surgical cardiac device, and CSF shunt infections all the that DD and SCS system infections share features with other substantial of evidence and the use of at the incidence of such infections and also a for infection management delivery and SCS system infections to relatively predominantly involve the site device and are caused by specifically which from the skin of the patient or data that most DD and SCS system infections from surgical wound at the of device the postmarket data also that antibiotic in the of other is to device-related infections. However, the number of infectious be reduced by to the established of surgical that in the recent majority of DD and virtually all SCS are in patients and are to the of In most cases, is available to the guidelines and recommendations that are summarized in table However, patients or to the that and for surgery. patients with pain or intractable spasticity have underlying medical that be or implantation of DD devices. recommendations (table to and treat all infections and to in as as may be for patients with pain or spasticity who also have of the risk factors identified in table infection, poor or patient-related risk with can be by the of or both. However, the results of studies and trials were or not as as of the studies specifically DD or SCS device cases were included in the important that the of was that a majority of SSI were caused by different of than the that had the cases in which risk factors such as or be of the implantable device can the size and to minimize the likelihood of long-term erosion the skin and other have been previously. an pump with a smaller and may be for the pediatric patient than the pump implanted in that reduce the incidence of wound and infection include or of the patient for surgical and or of or and of pump on the or to such factors can in device which may to on the surgical the for wound or infection. the of the therapy are one may to with device implantation in patients the potentially risk of infection with the the or SSI guidelines did not management factors that were in some studies of CSF shunt infection of the studies that the of at which an was the likelihood that an infection However, two studies that from the of a to reduce the shunt infection to a incidence of infection of devices is implantation is in a than in a and as of a infection to be and on cord stimulation device implantation nearly involve to or and some of DD devices use It based on that use of is physicians should the within the at the of the should to reduce the for of the surgical and implantable devices.The of antibiotics in the CSF shunt and ICD literature. the available evidence indicates that it is to antibiotics for DD and SCS implantation The antibiotic should be selected to the experience and of the in the antibiotic of that are for most infections. In general, a of an antibiotic skin should be within the skin or antibiotics or both may be in cases, in patients with drug or previous infections with data not the use of of the surgical with and are important of surgical are in the of device data indicate a of or other available the of a relatively incidence of surgical in a recent study, use of and some of or surgical may reduce the incidence of device infections. surgical to the implantable device with surgical not with to minimize device include the of devices and components that the number of or implant of surgical to the implanted and the of in with of space are among CSF shunt and DD or SCS is at the pump or may to infection, or are data that indicate the used to the the likelihood of or the incidence of infection. The results of one in and in study of various that can The was to the of the similar was in an in study in the of the and have a for the most the DD pump and SCS of an the on wound of an may reduce the incidence of skin erosion or wound the of the implantable have published a of the implantation for use in or patients with spasticity who are for therapy. of the pump in a than the may some of wound or skin the event that wound skin or CSF DD is and medical and surgical is data regarding the likelihood of one to a DD or SCS implant with treatment of CSF shunt infection most often explantation of the and the ICD infection literature indicates that treatment that to the implanted device and clinical experience that wound and, antibiotic administration are most to be as as possible in the clinical device often is the period in the and the is not of a of the surgical may reduce the likelihood of wound should the and should not be that with device The and of the may with as as the of the surgical or DD system infections in pediatric patients with spasticity of cerebral data are and information from the 10-ml SynchroMed®pump study that patient-related risk factors may such to both and infections. In pediatric patients with spasticity of cerebral had potentially associated with device infections, including or infection, poor and or use of the relatively 10-ml pump in that study did not infections. the reported infections, involved the pump occurred and the other three occurred between and device implantation (table were not on the use of implant in that study, it that have reduced the infection should the use of smaller devices and to infectious risk factors that may be in pediatric spasticity patients. risk for device infection in the 10-ml pump study was that an number of patients had temporary intrathecal for use with pump systems to an of administration permanent device Such may have caused of the surgical site or CSF the implant patients with pain and underlying or infectious also may be at risk for device-related infections. such for device the therapy is to or the of strict to the recommendations to and treat all infections and to in as as may not be possible or In in the case of spastic or with therapy may to or the skin or infectious risk may to SCS which the majority of stimulation marketed in the Medtronic, surveillance data revealed that the aggregate total proportion of site site infections was of reported SCS device infections with of reported DD device infections. Such of should not be of limitations that include of the data and differences between the data However, implantation of stimulation involves the and the to stimulation different device or that is and than implantation of intrathecal In most SCS are or are to implanted SCS and to of of therapy for a permanent device a The and of the implantation the use of a or a period that for or and the need for a implant all to the spinal and infections in SCS patients. of the potentially temporary SCS the period and of the on the of the the of the temporary or are to those the permanent or or both be implanted at the site used for the temporary a between removal of the system and implantation of the permanent SCS system may reduce the risk of of the In addition, the permanent of SCS a implant removal of the temporary should be by a on the from the the it from the of the stimulation DD or SCS can infection it to that of other methods to patients at the of implantation and cases with infections at the of diagnosis or The the of among various and and the fact that most infections are from the surgical that surveillance among at different guidelines a of and case methods to and the results of surveillance can to often to infection rate and the results to of the implant The DD device infection rate among the clinical studies reviewed in this in the study, may be a which to the results at data for DD and SCS systems, as as for CSF shunts and cardiac indicate that treatment of most infections involved antibiotics or and removal of the implanted devices. treatment an established DD or SCS device–related infection and The for CSF shunts and data were available in review of DD and SCS infections to or a reported infections were with device removal or without device cases may a among to or may the of involvement. cases in which shunt infections or cardiac device infections have been without device However, the rates and the highest rates for ICD infections occurred in patients without device of for treatment of ICD infections was similar to or than that treatment included device the possible of or skin without infection, removal of all device components and administration of antibiotics is of therapy, and the to include an antibiotic on the and the clinical of each In the event that device explantation is the intrathecal drug device removal or administration of or both may be to or treat or is but may in with the implantation or the of long-term therapy with intrathecal of intrathecal therapy the pump to be at that can from to an for the drug to and or for the to with skin of the may be the period to the of skin the of a that may of and to the diagnosis of in patients with implanted intrathecal DD systems, the of a chronic intrathecal catheter not to have on CSF or or and intrathecal drug including all marketed by Medtronic, a in the fluid between the drug and the catheter However, the fluid from the catheter to the spinal canal that have that from the should not on the of a to or infections for of the DD device infections in and implantation of devices that such all of the infections in table included also involved one or and the case of in table have been implant than or within the drug may the and it to the In cases of CSF infection the of antibiotics to the other in a pump been a in the medical literature. use of the and antibiotic to be most or the of the pump of treatment is of the with which been reported in the of other or device involvement. also should that antibiotic the CSF the pump not other potentially such as the the or the catheter DD or SCS data are available on which to recommendations for of device treatment of a previous infection. Most patients with CSF shunt infections implantation of a shunt system within of of antibiotic therapy, the infection based on clinical and regarding the ICD an infection. of antibiotic therapy explantation of an ICD been associated with a risk of other investigators have a of ICD and SCS devices are not is not as as for CSF shunts and Most physicians on the of and implantation of a DD or SCS system at without signs of the of antibiotic therapy. the recommendations that a device should not be implanted the infection is and signs of infection fever, have of it is based on surgical clinical and that of a DD or SCS system should at a site that was not involved in the original infection. In a review of patients who device explantation to treat a of ICD infections, the occurred of a device the or may be in the That also causes the catheter or to a different the the catheter or may be the spinal canal at a different than the and recommendations in this article may to other kinds of implantable devices and to SCS or DD devices the one patient in a study had DD systems of a infection. the clinical studies and data in this involved marketed by Medtronic, and of these to other devices or to of other may not limitations from the of cases in postmarket surveillance and from the fact that the clinical studies in this article were not designed to investigate device-related infections. The cardiac device and CSF shunt infection literature about risk factors and to reduce the incidence of device-related infections. CSF shunt devices and patients, and ICD systems and cardiac patients in important from DD or SCS devices and patients. the CSF shunt infection literature it is both and that the in infections may be to in with the highest infection or may not be in with an infection antibiotic and other undoubtedly SSI and management to device may include the of stimulation drug administration and other system for CSF and other in surgical and also may to the of the delivery and SCS device–related infections are potentially and treatment of established infections is and the incidence of such infections should be reduced to the in the may involve patient with underlying risk Given the relatively in which DD and SCS are studies of infection are not to be from the available data that the most of to published guidelines and recommendations that to SSIs in