Implications for Implantable Pain Therapies: Staphylococcus Aureus Colonization
Cite as: Keith A, Provenzano D, Kilgore J. Implications for implantable pain therapies: staphylococcus aureus colonization. ASRA Pain Medicine News 2022;47. https://doi.org/10.52211/asra020123.008
The Problem: Surgical Site Infections
Surgical site infections (SSIs) from spinal cord stimulation (SCS) trials and implants are associated with substantial clinical, economic, and humanistic costs.1,2 The United States Closed Claims Project database recently identified infection as the most common damaging event associated with implantable pain therapies.3 Infection rates for SCS surgical procedures have ranged from 1%-10% with a large U.S. payer database of greater than 6,000 patients demonstrating a 3% SCS-related infection rate within 12 months of implantation.1,4
The economic costs of SCS-related infections are also high with incremental annual healthcare expenditures for infected initial and replacement SCS patients estimated at approximately $60,000 USD (Initial implant: $59,716; 95% CI: $48,965 – $69,480).5 The humanistic costs are substantial with a majority of patients requiring surgical explants and less than 30% undergoing a reimplant.5 Patients who do not undergo surgical explant of an infected device are at risk for severe infectious complications, such as meningitis, abscess formation, osteomyelitis, in-hospital mortality, or permanent disability due to paralysis.2 Therefore, further advancement in understanding mitigation strategies to limit the risk of SCS device SSIs is warranted.
The Culprit: Staphylococcus aureus
Staphylococcus aureus (S. aureus) accounts for approximately 30% of nosocomial infections.6 Furthermore, S. aureus is the major bacterial species associated with > 80% of SCS-related infections.7,8 Staphylococcus aureus is a gram-positive bacterium with both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. S. aureus infections on implanted SCS devices are associated with biofilm formation that assists in circumventing host immune-mediated clearance and contains biofilm matrices that may be impermeable to certain antibiotics.9,10 Unfortunately, patients can be S. aureus transient, intermittent, or persistent carriers with associated specific anatomical reservoirs including the oropharynx, axillae, groin, perineurium, and neck which increase patient risk of SSI from 2 to 9 times.6,9,11 In addition, a majority of the sources of S. aureus infections are endogenous to the patient with the isolate of S. aureus infections in the wound matching the isolates found in the nares > 80% of the time.6,12
Since MSSA colonization is also a modifiable surgical site infection risk factor, consideration should be given to preoperative screening for both MRSA and MSSA.
The specific S. aureus carriage rate of a population varies based on population characteristics and geographic location with MSSA and MRSA prevalence rates ranging from 20% to 36% and 0.6% to 6%, respectively.9,12,13 Staphylococcus aureus colonization rates have been investigated for specific interventional fields, including cardiology, orthopedics, and spine surgery with S. aureus prevalence rates greater than 20%.14-19 While S. aureus prevalence rates for these surgical fields have been well established in the literature, until recently, limited published data existed on S. aureus prevalence rates in SCS surgical patient populations.
A recent study, however, determined the prevalence of S. aureus colonization for SCS patients as well as sought to identify specific at-risk patient populations.20 Following ethics approval, the authors employed a retrospective review of electronic medical records and operative reports to identify SCS trial and implant surgical patients.
Preoperative characteristics, such as age at the time of procedure, body mass index (BMI), and medical comorbidities, including, but not limited to, diabetes, smoking, obesity, and previous history of SSIs, were identified for each patient. Advanced age was defined as patients ≥ 65 years old. Obesity was defined as patients with a BMI ≥ 30.0 kg/m2.
All (100%) patients were screened for MRSA, and 98.3% were screened for MSSA. In patients undergoing SCS surgical procedures, 23.3% of patients were preoperatively colonized with S. aureus, according to the following classification: 20.2% were positive for MSSA and 4.3% were positive for MRSA. Notably, MSSA carriage was detected at a rate nearly five times that of MRSA. The prevalence rates for S. aureus and, more specifically, MSSA in SCS surgical patients are comparable to the results reported in the literature of the aforementioned surgical fields.14-19 Due to the decreased prevalence of MRSA compared to MSSA, MRSA screening alone would have failed to identify >90% of S. aureus colonized patients with only MSSA carrier status. Since MSSA colonization is also a modifiable SSI risk factor, consideration should be given to preoperative screening for both MRSA and MSSA.
Previous population-based studies and related surgical field studies on S. aureus colonization rates have identified specific patient characteristics and comorbidities, including diabetes, increased age, smoking, previous long-term care facility occupancy, renal insufficiency, and immunosuppression, as risk factors for S. aureus colonization.21,22 Aside from these few studies, patient risk factors for nasal S. aureus colonization remain largely unknown in surgical patient populations, specifically in the field of neuromodulation.
Provenzano et al.20, however, performed an analysis of independent patient characteristics that revealed anxiety and hypothyroidism as the only conditions that significantly increased the odds of MRSA and MSSA colonization, respectively. Thus, although previous research in other surgical fields and population-based studies have identified patient characteristics and comorbidities as risk factors for S. aureus colonization, the results presented in this study did not identify meaningful patient characteristics or comorbidities to limit or heighten the need for patient risk factor-targeted S. aureus screening. Interestingly, S. aureus colonization was not associated with a previous history of S. aureus SSI or S. aureus non-SSI skin infections.
Strategies for Mitigating Infection
Perioperative methods have been deployed in S. aureus carrier patients to mitigate the risk of infection. One method involves preoperative screening for S. aureus colonization, including both MSSA and MRSA, followed by appropriate decolonization of individuals with positive carrier status. In joint replacement and lumbar spine surgical fields, screening and decolonization have been shown to significantly reduce the incidence of SSIs.6,9,11,14-17,23-27
One study examined the efficacy of a screening and decolonization protocol to reduce surgical site infection in elective total joint arthroplasty patients. In this study, 9,690 patients were screened for MRSA and MSSA with nasal swabs before elective joint arthroplasty surgery. All patients with positive nares colonization were treated with mupirocin nasal treatment and chlorhexidine gluconate showers for 5 days before surgery. MRSA patients received vancomycin preoperatively and were placed in contact isolation. All elective arthroplasty patients used chlorhexidine gluconate antiseptic cloths the evening prior to and the day of surgery. The authors showed that the addition of MRSA and/or MSSA nares screening along with a perioperative decolonization protocol resulted in a decreased SSI rate by 69%.26
Another study examined the efficacy of a very similar protocol in patients undergoing total joint, spine, or sports medicine surgical procedures. In this study, 7,019 patients having an elective surgical procedure were screened for MRSA before surgery using nasal swabs. Those who were colonized for MRSA were treated with intranasal mupirocin and chlorhexidine body washes for 5 days before surgery (including the morning of surgery). The authors of this study demonstrated an 81% reduction of total SSIs for patients who had undergone the decolonization protocol.27
Despite the potential for severe morbidity and mortality due to S. aureus SSIs, recent survey studies have reported a relatively slow adoption rate of preoperative swabbing protocols in the field of pain medicine. Specifically, approximately only 11%-18% of surveyed physicians utilized preoperative nasal swabbing for MSSA. In addition, for the limited cases in which MSSA screening occurred, 44% of surveyed physicians did not implement any clinical care changes following a positive MSSA screen result. Only 25%-31% of surveyed physicians preoperatively swabbed surgical patients for MRSA. A lesser, but still considerable, 14.4% of physicians reported that they did not make any clinical changes following a positive MRSA test result. 28,29
It should be noted, however, that routine use of decolonization agents, including mupirocin and chlorhexidine, has not been shown to be effective in individuals who are not S. aureus colonized.6 Additionally, antimicrobial stewardship should be employed since widespread use of chlorhexidine and mupirocin has led to resistance and the potential for cross resistance with antibiotics.30-32 Foremost, antimicrobial resistance can be attributed to increased efflux pump activity in resistant S. aureus isolates. 33 Specifically, strains of S. aureus exposed to high concentrations of mupirocin have shown increased expression of several transporters including NorA and MepA, which are multidrug resistance efflux pumps with ciprofloxacin and chlorhexidine as substrates, respectively.31
Cost Effectiveness of Preoperative Screening and Antibiotic Resistance
Multiple studies in other surgical specialties have demonstrated the clinical and cost effectiveness of presurgical screening for S. aureus and the use of targeted decolonization to reduce the risk of SSI.6,9,11,14-17,23-27,34,35 Specifically, presurgical screening for MSSA has demonstrated clinical effectiveness by reducing MSSA SSIs and cost effectiveness as it resulted in significant savings when compared to the costs associated with infection.
Staphylococcus aureus is a gram-positive bacterium that accounts for approximately 30% of nosocomial infections and is associated with > 80% of SCS-related infections.6-8 The propensity for S. aureus biofilm formation as well as prevalence rates greater than 20% estimated in other surgical fields warrant further advancement in understanding mitigation strategies to limit the risk of SCS device SSIs.9,10,12-19 For the field of neuromodulation, a comparable S. aureus prevalence rate was reported with 25% of patients undergoing SCS surgical procedures screening positive for S. aureus.20 Furthermore, the study identified MSSA carriage in approximately 20% of preoperatively screened SCS surgical patients, a rate nearly five times that of MRSA. Notably, the authors reported that MRSA screening alone would have failed to identify > 90% of S. aureus colonized patients with only MSSA carrier status. Since limited patient characteristics were associated with greater risk for S. aureus colonization and MSSA carriage was identified at a much greater rate than MRSA, the results suggests that the field of neuromodulation should consider preoperative decolonization when appropriate as well as screening of all patients for both MRSA and MSSA to mitigate the risk of infection.
Alexander D. Keith is a recent graduate of Washington & Jefferson College and former research intern with Pain Diagnostics and Interventional Care.
David A. Provenzano, MD, (@DProvenzano) is the president of Pain Diagnostics and Interventional Care in Sewickley, PA.
Dr. Provenzano has consulted for Avanos, Boston Scientific, Medtronic, Nevro, and SI Bone. Pain Diagnostics and Interventional
Care received research support from Avanos, Medtronic, Nevro, Stimgenics, and Abbott.
Jason S. Kilgore, PhD, is a professor of biology at Washington & Jefferson College in Washington, PA.
- Deer TR, Provenzano DA, Hanes M, et al. The Neurostimulation Appropriateness Consensus Committee (NACC) Recommendations for Infection Prevention and Management. Neuromodulation 2017;20(1):31-50. https://doi.org/10.1016/j.neurom.2021.10.013
- Goel V, Kumar V, Agrawal SN, et al. Outcomes associated with infection of chronic pain spinal implantable electronic devices: insights from a nationwide inpatient sample study. Neuromodulation 2020;24(1):126-34. https://doi.org/10.1111/ner.13263
- Fitzgibbon DR, Stephens LS, Posner KL, et al. Injury and liability associated with implantable devices for chronic pain. Anesthesiology 2016;124:1384-93. https://doi.org/10.1097/ALN.0000000000001122
- Falowski SM, Provenzano DA, Xia Y, et al. Spinal cord stimulation infection rate and risk factors: results from a United States payer database. Neuromodulation 2019;22(2):179-89. https://doi.org/10.1111/ner.12843
- Provenzano DA, Falowski SM, Xia Y, et al. Spinal cord stimulation infection rate and incremental annual expenditures: results from a United States payer database. Neuromodulation 2019;22(3):302-10. https://doi.org/10.1111/ner.12843
- Perl TM, Cullen JJ, Wenzel RP, et al. Intranasal mupirocin to prevent postoperative staphylococcus aureus infections. N Engl J Med 2002;346(24):1871-7. https://doi.org/10.1056/NEJMoa003069
- Bendel MA, O'Brien T, Hoelzer BC, et al. Spinal cord stimulator related infections: findings from a multicenter retrospective analysis of 2737 implants. Neuromodulation 2017;20(6):553-7. https://doi.org/10.1111/ner.12609.
- Follett KA, Boortz-Marx RL, Drake JM, et al. Prevention and management of intrathecal drug delivery and spinal cord stimulation system infections. Anesthesiology 2004;100(6):1582-94. https://doi.org/10.1097/00000542-200406000-00034
- Weiser MC, Moucha CS. The current state of screening and decolonization for the prevention of staphylococcus aureus surgical site infection after total hip and knee arthroplasty. J Bone Joint Surg Am 2015;97(17):1449-58. https://doi.org/10.2106/JBJS.N.01114
- Otto M. Staphylococcal biofilms. Microbiol Spectr 2018;6(4):10.1128/microbiolspec.GPP3-0023-2018. https://doi.org/10.1128/microbiolspec.GPP3-0023-2018
- Senn L, Basset P, Nahimana I, et al. Which anatomical sites should be sampled for screening of methicillin-resistant staphylococcus aureus carriage by culture or by rapid PCR test? Clin Microbiol Infect 2012;18(2):E31-3. https://doi.org/10.1111/j.1469-0691.2011.03724.x
- Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev 1997;10(3):505-20. https://doi.org/10.1128/CMR.10.3.505
- Weinstein HJ. The relation between the nasal-staphylococcal-carrier state and the incidence of postoperative complications. N Engl J Med. 1959;260(26):1303-8. https://doi.org/10.1056/NEJM195906252602601
- Higgins M, Bommireddy R, Shivji F, et al. Impact of MSSA screening on rates of surgical site infection following lumbar spine surgery. Eur Spine J 2018;27(10):2457-62. https://doi.org/10.1007/s00586-018-5705-y
- Rao N, Cannella B, Crossett LS, et al. A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections. Clin Orthop Relat Res 2008;466(6):1343-8. https://doi.org/10.1007/s11999-008-0225-4
- Rao N, Cannella BA, Crossett LS, et al. Preoperative screening/decolonization for staphylococcus aureus to prevent orthopedic surgical site infection prospective cohort study with 2-year follow-up. J Arthroplasty 2011; 26:1501-7. https://doi.org/10.1016/j.arth.2011.03.014
- Ribau AI, Collins JE, Chen AF, et al. Is preoperative staphylococcus aureus screening and decolonization effective at reducing surgical site infection in patients undergoing orthopedic surgery? a systematic review and meta-analysis with a special focus on elective total joint arthroplasty. J Arthroplasty 2021;36(2):752-766.e6. https://doi.org/10.1016/j.arth.2020.08.014.
- Neidhart S, Zaatreh S, Klinder A, et al. Predictors of colonization with Staphylococcus species among patients scheduled for cardiac and orthopedic interventions at tertiary care hospitals in north-eastern Germany-a prevalence screening study. Eur J Clin Microbiol Infect Dis 2018;37(4):633-41. https://doi.org/
- Pongbangli N, Oniem N, Chaiwarith R, Nantsupawat T, Phrommintikul A, Wongcharoen W. Prevalence of Staphylococcus aureus nasal carriage and surgical site infection rate among patients undergoing elective cardiac surgery. Int J Infect Dis 2021;106:409-14. https://doi.org/10.1007/s10096-017-3154-x
- Provenzano DA, Keith AD, Kilgore JS. Prevalence of staphylococcus aureus colonization in spinal cord stimulator surgical procedures. Neuromodulation 2022; S1094-7159(22)00684-5. https://doi.org/10.1016/j.neurom.2022.04.048
- Graham PL, 3rd, Lin SX, Larson EL. A U.S. population-based survey of staphylococcus aureus colonization. Ann Intern Med 2006;144(5):318-25. https://doi.org/10.7326/0003-4819-144-5-200603070-00006
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