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Staphylococcus Aureus Swabbing and Decolonization Before Neuromodulation Procedures: A Systematic Review and Meta-analysis

Open AccessPublished:October 02, 2022DOI:https://doi.org/10.1016/j.neurom.2022.07.013

      Abstract

      Introduction

      Staphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization.

      Materials and Methods

      A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR).

      Results

      Five observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09–0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I2 = 0.43%, τ2 = 0.00).

      Conclusions

      Preoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.

      Keywords

      Introduction

      The foremost bacterial cause of surgical-site infections (SSI) is Staphylococcus aureus (S aureus), contributing to approximately 30% of all SSIs.
      • Perl T.M.
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      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      Furthermore, almost two-thirds of implantable device infections are due to S aureus or coagulase-negative staphylococci.
      • Darouiche R.O.
      Treatment of infections associated with surgical implants.
      As such, endogenous colonization of S aureus has been associated with a two-to-nine times higher risk of SSI,
      • Perl T.M.
      • Cullen J.J.
      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      ,
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      • Verbrugh H.
      Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks.
      ,
      • Wenzel R.P.
      • Perl T.M.
      The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection.
      and it has been shown to be the most important risk factor for developing any SSI for patients receiving orthopedic implantation.
      • Kalmeijer M.D.
      • van Nieuwland-Bollen E.
      • Bogaers-Hofman D.
      • de Baere G.A.
      Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery.
      Given that more than 80% of health care–related S aureus infections are due to endogenous flora,
      • von Eiff C.
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      • Stammer H.
      • Peters G.
      Nasal carriage as a source of Staphylococcus aureus bacteremia.
      • Weinstein H.J.
      The relation between the nasal-staphylococcal-carrier state and the incidence of postoperative complications.
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      • et al.
      Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers.
      patients who develop S aureus SSI show a corresponding 80% to 85% match rate between the infected culture isolate and that colonizing the nares.
      • Kalmeijer M.D.
      • van Nieuwland-Bollen E.
      • Bogaers-Hofman D.
      • de Baere G.A.
      Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery.
      When considering approximately 30% of the general population carries S aureus
      • Perl T.M.
      • Cullen J.J.
      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      ,
      • Weinstein H.J.
      The relation between the nasal-staphylococcal-carrier state and the incidence of postoperative complications.
      and this associated proclivity for causing SSI, screening and decolonization protocols emerge as an important area of interest for the reduction of SSI. Common approaches used for S aureus decolonization include isolated or combinations of mupirocin nasal ointment, oral antibiotics, and chlorhexidine washes in conjunction with generalized hygiene.
      Randomized controlled trials (RCTs) have established the efficacy of S aureus nasal screening and subsequent decolonization for reducing rates of SSI.
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      ,
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections.
      A 2010 randomized, double-blind, placebo-controlled, multicenter study involving 917 patients by Bode et al
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      investigated whether preoperative identification of S aureus colonization through nasal swabbing followed by decolonization reduced the risk of S aureus infection. A 56% reduction in S aureus infection was observed for the cohort randomized to decolonization with mupirocin-chlorhexidine. A 2008 study by Hacek et al
      • Hacek D.M.
      • Robb W.J.
      • Paule S.M.
      • Kudrna J.C.
      • Stamos V.P.
      • Peterson L.R.
      Staphylococcus aureus nasal decolonization in joint replacement surgery reduces infection.
      implemented rapid nasal S aureus swabbing for 912 patients before orthopedic total joint procedures. Of those swabbed, 223 received positive screening results and were decolonized with mupirocin. A 75% reduction in S aureus SSI was found when compared with an historical control. The results of the study by Hacek et al are promising upon consideration that an S aureus screening and decolonization protocol was linked to decreases in SSI during orthopedic hip and joint implant operations. Further study on S aureus screening and decolonization is therefore warranted in the field of neuromodulation, which similarly uses implantable devices.
      Furthermore, this reduction in SSI has been shown to deliver substantial reductions in health care costs within the orthopedic literature.
      • Chen A.F.
      • Wessel C.B.
      • Rao N.
      Staphylococcus aureus screening and decolonization in orthopaedic surgery and reduction of surgical site infections.
      ,
      • van Rijen M.M.
      • Bode L.G.
      • Baak D.A.
      • Kluytmans J.A.
      • Vos M.C.
      Reduced costs for Staphylococcus aureus carriers treated prophylactically with mupirocin and chlorhexidine in cardiothoracic and orthopaedic surgery.
      Given that patients with S aureus SSI have a higher risk of death and increased median hospital costs than do uninfected surgical site patients,
      • Engemann J.J.
      • Carmeli Y.
      • Cosgrove S.E.
      • et al.
      Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.
      ,
      • Anderson D.J.
      • Kaye K.S.
      • Chen L.F.
      • et al.
      Clinical and financial outcomes due to methicillin resistant Staphylococcus aureus surgical site infection: a multi-center matched outcomes study.
      implementation of screening and decolonization protocols warrants further investigation.
      Neuromodulation commonly uses implantable devices, which are especially susceptible to S aureus. This necessitates extra vigilance in this patient population because S aureus can form biofilms on implantable equipment and devices.
      • Luan S.
      • Williams I.
      • Nikolic K.
      • Constandinou T.G.
      Neuromodulation: present and emerging methods.
      ,
      • Akhtar A.
      • Kadir H.
      • Chandran P.
      Surgical site infection risk following pre-operative MRSA detection in elective orthopaedic surgery.
      Thus, the failure to quickly detect these infections may result in complications such as pneumonia, septic shock, endocarditis, necrotizing fasciitis, bursitis, and death if explantation of this device is delayed or complicated.
      • Gofeld M.
      New horizons in neuromodulation.
      • Levy R.M.
      Centers of excellence for neuromodulation: a critical proposal.
      Canadian Agency for Drugs and Technologies in Health (CADTH)
      Pre-operative screening for methicillin-resistant Staphylococcus aureus (MRSA) infection: a review of the clinical-effectiveness and guidelines.
      • Green B.N.
      • Johnson C.D.
      • Egan J.T.
      • Rosenthal M.
      • Griffith E.A.
      • Evans M.W.
      Methicillin-resistant Staphylococcus aureus: an overview for manual therapists.
      Preventing these infections can improve patient outcomes, lower morbidity, lower mortality, and decrease costs.
      Therefore, in this study, the authors examine the utility of S aureus swabbing before neuromodulation procedures by performing a systematic search and meta-analysis of the published literature for all studies with patients who underwent nasal swabbing for S aureus. To our knowledge, this is the first review of this nature examining the effectiveness of preoperative S aureus swabbing conducted before deep brain stimulation (DBS), spinal cord stimulation (SCS), and intrathecal (IT) pump implantation procedures.

      Materials and Methods

      Data Base Query

      This systematic review was performed using guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
      A systematic literature search was conducted in January 2022 by two independent researchers using the PubMed and Embase data bases to identify literature reporting rates of S aureus infection after a perioperative swab and/or decolonization protocol. The search terms used to query the data bases were (“staphylococcus aureus” OR “staph” OR “MRSA” OR “MSSA”) AND (“swabbing” OR “screen” OR “neuromodulation”) AND (“DBS” OR “spinal stimulation” OR “intrathecal baclofen” OR “intrathecal pump” OR “implant” OR neuromodulate”). Wildcard modifiers (“∗”) were added to the Boolean search terms, where appropriate, to broaden the search. Covidence (Headquarters Melbourne, Australia) was used for systematic review management software. After extraction of the data from the data bases, duplicate citations were removed.

      Screening

      Two authors independently assessed titles and abstracts of studies in accordance with the predetermined inclusion criteria and exclusion criteria of this study. Any discrepancies during the screening process were resolved by consensus among all authors. Relevant articles were then assessed through a full-text review after initial title and abstract screening. References of articles selected for inclusion were also scrutinized according to the inclusion and exclusion criteria for their suitability in this review.

      Selection Criteria

      Predetermined criteria were established for eventual inclusion in this study. The following inclusion/exclusion criteria were applied:
      • Primary studies of postoperative infection rates after neuromodulation procedures that used S aureus nasal swabbing and/or decolonization (excluding poster presentations, expert opinions, and case reports)
      • The study must have explicitly reported outcome data for postoperative infection rate in human patients
      • Implementation of a nasal swab and/or decolonization procedure to address infection risk by S aureus, ultimately providing comparative outcome data between a treatment and control
      • Full-text articles available in English. Any discrepancies were resolved through reaching a consensus among all authors.

      Data Extraction and Qualitative Assessment

      Independent and blinded reviewers extracted data from the eligible studies. Extraction variables included authorship, study duration, location, study design, patient number, treatment arms, decontamination protocol, swabbing schedule, infection rate, follow-up, and type of neuromodulation procedure. The primary outcome was postoperative infection rate between the two treatment arms. The secondary outcome was colonization rate. Eligible studies were assessed for risk of bias and inclusion in this study by two investigators with the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Cohort Studies.
      • Munn Z.
      • Moola S.
      • Riitano D.
      • Lisy K.
      The development of a critical appraisal tool for use in systematic reviews addressing questions of prevalence.

      Statistical Analysis

      The primary and secondary outcomes were presented using descriptive statistics in the forms of counts and percentages. In addition, meta-analysis was performed using the “metafor” package in R (version 4.1.2; R Foundation for Statistical Computing, Vienna, Austria) through Rstudio (build 443). Odds ratios (ORs) and pooled 95% CIs in a random-effects model were computed to assess for the effect of swabbing and decolonization on the primary outcome. Heterogeneity was quantified using the I2 statistic, where I2 ≥ 75.00% indicated substantial heterogeneity, with p < 0.05 defined as the threshold for statistical significance. The τ2 value was estimated using the restricted maximum likelihood method. Funnel plots were produced to assess for publication bias.

      Results

      Systematic Search

      In total, 172 articles were identified through the literature search (Fig. 1). After duplicates were removed, 105 articles remained. The 105 articles were then screened for project relevancy, and 91 were removed because they did not relate. The 14 full-text articles were then assessed: nine were excluded after evaluation, and five were selected for final inclusion.
      Figure thumbnail gr1
      Figure 1Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram.

      Study Characteristics

      All the included studies were prospective cohort studies using retrospective cohorts for control comparison (Table 1). Two studies were performed in the United States, with the other three being in the United Kingdom, Belgium, and France. Type of neuromodulation included DBS in two studies, SCS in two studies, IT baclofen in one study, and sacral neuromodulation in one study. Studies were conducted over an average of 6.6 ± 3.8 years (including follow-up), with the oldest study beginning in 2002 and the latest concluding in 2019. The total number of patients included averaged 393 ± 183 (minimum: 171, maximum: 688). The proportion of patients receiving intervention compared with the total number of patients studied ranged from 0.35:1 to 0.83:1. Two studies reported data on patient age, with a mean age of 49.6 ± 15.0 years. Minimum follow-up was a minimum of one week and a maximum of one year. Three of five studies (60%) used preoperative nasal swabbing, and all five used a decolonization protocol. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and decolonization) group, respectively. Overall infection rates were observed at 6.86% and 0.95% in the control and intervention groups, respectively (Table 2). Infection rates per study are displayed in Figure 2. Overall, 537 patients were swabbed preoperatively: of these, 91 were only swabbed for methicillin-resistant Staphylococcus aureus positive (MRSA+) colonization. When tested for, MRSA+ colonization was 9.1%.
      Table 1Characteristics of Comparative Cohort Studies Implementing Preoperative Staphylococcus Aureus Screening and/or Decolonization.
      StudyCountryDurationTotal patientsPatients in interventionAge, years, mean (SD)Minimum follow-upNeuromodulationNasal swabDecolonization
      Hill et al,
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      2020
      USA2011–20194633831 wkSacral neuromodulationYY
      Arocho-Quinones et al,
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      2019
      USA2013–201768835650 (7)12 moSCS, DBS, IT pumpNY
      Yusuf et al,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      2017
      Belgium2014–2016410161SCSNY
      Lefebvre et al,
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      2016
      France2008–2015182631 moDBSYY
      Pepper et al,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      2016
      UK2002–20141719148 (20)9 moDBSYY
      N, no; Y, yes.
      Table 2Experimental Parameters of Studies Using S Aureus Screening and/or Decolonization With Outcome Data.
      StudyControlInterventionRate ofAdditional notes
      Screen (location, time)
      Detection method was performed via microbial cultures.
      Decolonization protocolColonization n (%)Infection
      AntimicrobialScheduleControl n (%)Intervention n (%)p Value
      Hill et al,
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.


      2020
      No decolonizationY (nasal, N/A)Nasal mupirocin 2%

      IV vancomycin, if MRSA +
      7 days Induction60 (15.6)4 (5.0)3 (0.78)0.005
      Denotes statistical significance at p < 0.05.
      43 MRSA+ colonizations

      17 MSSA colonizations
      Arocho-Quinones et al,
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.


      2019
      No decolonizationNBody wash, chlorhexidine gluconate 2%

      nasal mupirocin 2%
      Evening before and morning of surgery

      Two times a day and morning of surgery
      11 (3.31)3 (0.01)S aureus and S epidermidis most common organisms

      Risk factors for infection in intervention group: obesity and previous implant-related SSI
      Yusuf et al,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      2017
      No decolonizationNBody wash, povidone-iodine



      Nasal mupirocin 2%
      Once preoperatively



      Three times a day for 1 day
      25 (10.0)3 (0.02)0.003
      Denotes statistical significance at p < 0.05.
      Operating room personnel limited to 5 at a time in intervention group

      S aureus most common organism
      Lefebvre et al,
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.


      2016
      Povidone-iodine shower night before and morning of surgeryY (nasal, preop consult)Body wash, chlorhexidine gluconate 4%

      Nasal mupirocin 2%
      Once daily for 5 days



      Three times a day for 5 days
      26 (36.5)13 (10.9)1 (1.6)0.04
      Denotes statistical significance at p < 0.05.
      S aureus most common organism in control

      E aerogenes infection in intervention
      Pepper et al,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.


      2016
      No decolonizationY (skin and nasal, preop assessment clinicBody wash, chlorhexidine gluconate 4%



      Hair wash, chlorhexidine gluconate 4%



      Nasal mupirocin 2%
      Once daily for 6 days





      Every other day for 5 days



      Three times a day for 5 days
      06 (7.5)00.003
      Denotes statistical significance at p < 0.05.
      Only decolonized if history of MRSA+, or missed screening (4 decolonizations)

      Vancomycin irrigation of the pocket was implemented in MRSA + patients

      S aureus most common cause of infection
      IV, intravenous; N, no; N/A, not applicable; Y, yes.
      Denotes statistical significance at p < 0.05.
      ∗∗ Detection method was performed via microbial cultures.
      Figure thumbnail gr2
      Figure 2Bar plot displaying the primary outcome result—total number of infections—in each of the five included studies over their duration. The treatment study arm consisted of either S aureus screening with subsequent decolonization or decolonization of all included subjects.

      Identified Pathogens

      All five of the included studies reported an instance of positive S aureus cultures, either through preoperative nasal swabbing or postoperative infection samples. There was one study that delimited positive nasal cultures by methicillin-resistant S aureus (MRSA) or methicillin-susceptible S aureus (MSSA) positivity;
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      71.7% were MRSA+, and 28.3% were MSSA+. One study performed 100 total preoperative nasal swabs and found zero MRSA colonizations.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      S aureus was identified as the most common cause of infection in the control group for three studies, with rates of 66.6%,
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      61.5%,
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      and 50%.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      In the intervention groups, one study reported three total infections, with one due to Staphylococcus epidermidis (S epidermis) and one due to Pseudomonas aeruginosa—the other culture grew no organisms.
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      Enterobacter aerogenes (E aerogenes) was the cause of the single infection in one study.
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      Two studies did not report infectious causes in the intervention group, and one study observed zero infections.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.

      Nasal Swabbing and Decolonization Effectiveness

      Three studies used preoperative nasal swabbing to screen for S aureus colonization. Rate of colonization for any form of S aureus was imputed at an overall S aureus colonization rate of 19.3% across all studies. Two studies
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      ,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      identified S aureus colonization on the basis of methicillin sensitivity, observing MRSA+ at an imputed overall colonization rate of 9.1%. Infection rate in the control groups ranged from 3.31% to 10.9%, and from 0% to 1.6% in the intervention groups. All five studies reported decreased rates of infection with either swabbing and decolonization as intervention or decolonization as intervention. The absolute number of infections seen in the intervention groups ranged from zero to three. Of these, in only two of five studies can the S aureus contribution to infection be determined
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      ,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      —there were no infections due to S aureus in either study after decolonization. Of the four studies that reported statistical analysis between groups, all reported a statistically significant decrease in infection, with the intervention group at an α of 0.05.

      Decolonization Protocol

      Every study used a unique protocol (Table 3). Nasal mupirocin 2% was incorporated in all five studies, most commonly three times a day for five days (2/5 studies), followed by three times a day for one day (1/5 studies) and twice a day for one day in conjunction with once in the morning of surgery (1/5 studies), and finally, for seven days (1/5 studies). One study
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      used nasal mupirocin for seven days as the sole decolonization agent in the days before surgery if patients were colonized at all, adding intravenous vancomycin on induction if MRSA+.
      Table 3Additional Infection Prevention Measures Employed in Each Study in Addition to Targeted Staphylococcus Aureus Antimicrobial Decolonization
      StudyAdditional infection prevention measures
      Hill et al,
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      2020
      N/A
      Arocho-Quinones et al,
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      2019
      IPB : 1) preoperative patient counseling regarding safe infection prevention practices 2) postoperative wound care education 3) postoperative 24-hour antibiotics for overnight patients, or else one dose of antibiotics on discharge.
      Yusuf et al,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      2017
      Performing the neuromodulation procedure in the earliest OR time slot; ensuring a minimal amount of OR personnel; providing home care nurses with SCS wound care instruction; providing wound care instruction to patients orally.
      Lefebvre et al,
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      2016
      N/A
      Pepper et al,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      2016
      Vancomycin/saline wash was used to irrigate the IPG wound pocket (only in the intervention arm).
      IPB, infection prevention bundle; IPG, implantable pulse generator; N/A, not applicable.

      Surgical-Site Infection Criteria

      The definition of and detection of SSI varied between all studies, when reported. Hill et al
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      defined it as any device explant with signs and symptoms of infection. Arocho-Quinones et al
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      defined it using the Centers for Disease Control and Prevention (CDC) guidelines for deep SSI,
      Surgical site infection event (SSI). The National Healthcare Safety Network.
      which, briefly, use clinical suspicion of infection or purulent exudate from suspected site of infection or microbiological evidence or skin erosion with any of the above. Yusuf et al
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      defined it as the presence of positive culture from the site or signs and symptoms of SSI as determined by a neurosurgeon or medical microbiologist. Pepper et al
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      used only infections in direct relation to the hardware. Lefebvre et al
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      did not report their working definition of SSI.

      Qualitative Assessment

      All five studies were therapeutic observational studies with prospective intervention groups matched with retrospective control. According to the Oxford Centre for Evidence Based Medicine, this constitutes level IV evidence throughout.
      OCEBM levels of evidence. The Centre for Evidence-Based Medicine.
      The JBI Critical Appraisal Tool for Cohort Studies
      • Munn Z.
      • Moola S.
      • Riitano D.
      • Lisy K.
      The development of a critical appraisal tool for use in systematic reviews addressing questions of prevalence.
      was used to assess risk of bias. This is an 11-item questionnaire wherein an answer of “no” to any question increases the risk of bias for the study. Two of the same questions were not applicable across all studies. Ultimately, every study yielded a “no” rate of three of nine (33.3%), all in response to the same questions. The study groups were not strictly from the same population given the combined prospective/retrospective nature of the studies. In addition, identification of confounding factors and methods to address these were not addressed. At this risk of bias, it was deemed all studies were suitable for inclusion in this review.

      Random-Effects Meta-Analysis

      Overall, implementation of S aureus decolonization with or without the addition of preoperative nasal swabbing was associated with a decreased risk of postoperative SSI when compared with no specific infection prevention measures. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09–0.37; p < 0.001) Effect sizes for each study included in the random-effects model are displayed in Figure 3. Heterogeneity between studies was nonsignificant (I2 = 0.45%, τ2 = 0.00, χ2 = 1.64, df = 4, p = 0.80). Meta-regression analysis evaluating the effect of moderator variables in the form of nasal swabbing and additional infection prevention measures in some studies, such as the “infection prevention bundle” in Arocho-Quinones et al, yielded nonsignificant differences on odds of infection. Assessment of publication bias was performed with funnel plot analysis (Supplementary Data Supplementary Material 1), which indicated no focal paucity of studies, indicating a low likelihood of publication bias.
      Figure thumbnail gr3
      Figure 3Forest plot comparing log odds of infection between patient receiving intervention (screening and/or decolonization) or no intervention in a random-effects model. Patients receiving intervention were less likely to experience postoperative infection (OR = 0.19 [95% CI, 0.09–0.37]; p < 0.001).

      Discussion

      This study yielded five studies for final inclusion.
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      The intervention group in the studies included a mix of nasal screening/decolonization and decolonization for all patients. The control group mostly consisted of no screening and/or decolonization. Overall, postneuromodulation infection rates in the control groups were observed at 6.86% (59/860), which fell to 0.95% (10/1054) in the intervention groups—an 86% reduction. These results are echoed in the overall infectious disease literature, with one randomized, double-blind placebo-controlled, multicenter trial demonstrating a significant reduction in SSI when performing rapid screening and subsequent decolonization for nasal carriers of S aureus.
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      A nearly 60% reduction in SSI was seen in the decolonization group compared with the placebo group. This reduction in SSI, achieved through preoperative screening and decolonization, has been further established by a prospective cohort study with two-year follow-up in the orthopedic literature.
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections.
      Despite the inclusion of just five studies in this meta-analysis, a strong pooled effect size in favor of decolonization was obtained (OR = 0.19). This can perhaps be explained by the previous establishment of the effectiveness of decolonization in reducing SSI, as evidenced by a 0.21 relative risk of deep SSI in surgical patients who received preoperative mupirocin-chlorhexidine treatment.
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      This constant statistical evidence in favor of treatment points toward a reliable biological effect in reducing SSI.
      In a randomized, double-blind, placebo-controlled trial, Perl et al show that SSI is only significantly reduced with prophylactic intranasal decolonization in S aureus carriers.
      • Perl T.M.
      • Cullen J.J.
      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      In this systematic review, there were four studies that reported on significance for infection rate between groups. Three studies reported a significant reduction in the intervention group; however, they followed the screen-then-decolonize approach, whose efficacy is bolstered by the findings of Perl et al.
      • Perl T.M.
      • Cullen J.J.
      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      There was one study by Yusuf et al
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      that reported a significant decrease in SSI between the control and the indiscriminate decolonization group. However, there were uncontrolled variables between groups; most notably, decolonization was simply one aspect of the intervention, added within a larger effort to stymy SSI termed a “care-bundle.” This included performing the neuromodulation at the earliest scheduled operating-room time, limiting operating-room personnel, educating home-care nurses on methods to limit SSI, and educating patients on proper wound care. Therefore, the veracity of the previous conclusions made through randomized, placebo-controlled trials in the study by Yusuf et al cannot be taken as strong evidence against the conclusion by Perl et al. Nevertheless, randomized, controlled inquiry evaluating the efficacy of swabbing and decolonization for neuromodulation-related SSI remains an unexplored avenue. Taken as such, the Neurostimulation Appropriateness Consensus Committee (NACC) only recommends decolonization if S aureus screening returns positive results, which is recommended to be performed in all patients who undergo neuromodulation.
      • Deer T.R.
      • Provenzano D.A.
      • Hanes M.
      • et al.
      The Neurostimulation Appropriateness Consensus Committee (NACC) recommendations for infection prevention and management.
      Specifically, they recommend decolonization with nasal mupirocin ointment and chlorhexidine baths.
      The NACC recommendations are partly derived from the protocols implemented in the two previously described RCTs.
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      ,
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections.
      In a study by Bode et al,
      • Bode L.G.
      • Kluytmans J.A.
      • Wertheim H.F.
      • et al.
      Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
      a 2% mupirocin ointment was used in combination with chlorhexidine gluconate soap, set at a schedule of ointment twice a day and the soap as a once-daily full-body wash, for five days. The RCT
      • Rao N.
      • Cannella B.
      • Crossett L.S.
      • Yates Jr., A.J.
      • McGough 3rd, R.
      A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections.
      by Rao et al used the same decolonization protocol. Interestingly, although all five studies included in this review incorporated 2% nasal mupirocin ointment in their protocol, there was a variety of schedules. Although three of the five studies used all the same decontaminants,
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      ,
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      ,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      none of these studies, nor the other two, followed the schedule of the RCT exactly. Three of the five studies opted for a protocol with either greater frequency or duration of application, with two implementing greater frequency of nasal mupirocin at three times a day for five days
      • Lefebvre J.
      • Buffet-Bataillon S.
      • Henaux P.L.
      • Riffaud L.
      • Morandi X.
      • Haegelen C.
      Staphylococcus aureus screening and decolonization reduces the risk of surgical site infections in patients undergoing deep brain stimulation surgery.
      ,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      and one with greater duration at seven days.
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      The other two studies used nasal mupirocin for just one day before and the morning of surgery.
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      ,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      Despite this variability, all the studies were effective in reducing SSI. Laboratory study has shown effective decolonization within a shorter duration of three days.
      • Walker E.S.
      • Vasquez J.E.
      • Dula R.
      • Bullock H.
      • Sarubbi F.A.
      Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective?.
      However, long-term decolonization with mupirocin can lead to treatment failure and subsequent relapse owing to the emergence of antibacterial resistance.
      • Walker E.S.
      • Vasquez J.E.
      • Dula R.
      • Bullock H.
      • Sarubbi F.A.
      Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective?.
      Correspondingly, the incorrect use of mupirocin or chlorhexidine in individuals who are not S aureus -colonized could potentially foster an environment for specific or generalized antibacterial resistance. In a study by Truong-Buldoc et al, mupirocin application against S aureus infection induced multidrug resistance response in the sensitivity of S aureus to ciproflaxin and chlorhexidine.
      • Truong-Bolduc Q.C.
      • Wang Y.
      • Reedy J.L.
      • Vyas J.M.
      • Hooper D.C.
      Staphylococcus aureus efflux pumps and tolerance to ciprofloxacin and chlorhexidine following induction by mupirocin.
      A global systematic review observed a significant increase over the past decade and 13.8% prevalence of mupirocin-resistant methicillin-resistant S aureus.
      • Dadashi M.
      • Hajikhani B.
      • Darban-Sarokhalil D.
      • van Belkum A.
      • Goudarzi M.
      Mupirocin resistance in Staphylococcus aureus: a systematic review and meta-analysis.
      For the sake of retaining effectiveness of antibiotic agents and infection control, it is emphasized that antibiotic agents only be used in cases with obvious patient benefit.
      • Van den Poel B.
      • Saegeman V.
      • Schuermans A.
      Increasing usage of chlorhexidine in health care settings: blessing or curse? A narrative review of the risk of chlorhexidine resistance and the implications for infection prevention and control.
      In addition to nasal decolonization, four of the five studies included full-body decontamination with either chlorhexidine gluconate baths or preoperative povidone-iodine. These are used to eradicate S aureus from other sites of colonized anatomy, such as the perianal and groin regions.
      • Deer T.R.
      • Provenzano D.A.
      • Hanes M.
      • et al.
      The Neurostimulation Appropriateness Consensus Committee (NACC) recommendations for infection prevention and management.
      Two of the five studies
      • Arocho-Quinones E.V.
      • Huang C.C.
      • Ward B.D.
      • Pahapill P.A.
      Care bundle approach to minimizing infection rates after neurosurgical implants for neuromodulation: a single-surgeon experience.
      ,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      used decolonization as part of an overall “care-bundle” approach to limiting neuromodulation SSI. The efficacy of these approaches notwithstanding,
      • Manolis A.S.
      • Melita H.
      Prevention of cardiac implantable electronic device infections: single operator technique with use of povidone-iodine, double gloving, meticulous aseptic/antiseptic measures and antibiotic prophylaxis.
      • Polyzos K.A.
      • Konstantelias A.A.
      • Falagas M.E.
      Risk factors for cardiac implantable electronic device infection: a systematic review and meta-analysis.
      • Schweizer M.L.
      • Chiang H.Y.
      • Septimus E.
      • et al.
      Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery.
      they limit the conclusions that can be made regarding the effect size of the S aureus decolonization itself on the reduced SSIs observed. The care bundles often act as forcing functions that optimize health care professionals’ behavior toward reducing SSI.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      An international survey of 506 physicians performing neuromodulation demonstrated low compliance rates for infection-control recommendations made by the CDC, with only four of 15 recommendations having a compliance rate of greater than or equal to 80%.
      • Provenzano D.A.
      • Deer T.
      • Luginbuhl Phelps A.
      • et al.
      An international survey to understand infection control practices for spinal cord stimulation.
      Presumably, these recommendations would be more completely adhered to in a study implementing a comprehensive care-bundle approach, which would certainly play a role in reducing SSI.
      A single study differed from the other four by exploiting local vancomycin irrigation into the implantable pulse generator surgical pocket.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      The authors advocate for these methods owing to increased “intrawound concentrations than would be possible via IV administration alone,” which is especially advantageous in the fibrous pocket because of its reduced blood supply. In line with the NACC recommendations, this irrigation was only used in MRSA+ or high-risk patients.
      • Deer T.R.
      • Provenzano D.A.
      • Hanes M.
      • et al.
      The Neurostimulation Appropriateness Consensus Committee (NACC) recommendations for infection prevention and management.
      Despite the low complication profile of intrawound vancomycin, there are no official practice guidelines or recommendations for surgical wound irrigation.
      • Barnes S.
      • Spencer M.
      • Graham D.
      • Johnson H.B.
      Surgical wound irrigation: a call for evidence-based standardization of practice.
      In addition, vancomycin powder has shown promise in preventing SSI through systematic review and meta-analysis of the spine literature.
      • Bakhsheshian J.
      • Dahdaleh N.S.
      • Lam S.K.
      • Savage J.W.
      • Smith Z.A.
      The use of vancomycin powder in modern spine surgery: systematic review and meta-analysis of the clinical evidence.
      • Chiang H.Y.
      • Herwaldt L.A.
      • Blevins A.E.
      • Cho E.
      • Schweizer M.L.
      Effectiveness of local vancomycin powder to decrease surgical site infections: a meta-analysis.
      • Khan N.R.
      • Thompson C.J.
      • DeCuypere M.
      • et al.
      A meta-analysis of spinal surgical site infection and vancomycin powder.
      • Tubaki V.R.
      • Rajasekaran S.
      • Shetty A.P.
      Effects of using intravenous antibiotic only versus local intrawound vancomycin antibiotic powder application in addition to intravenous antibiotics on postoperative infection in spine surgery in 907 patients.
      • Xiong L.
      • Pan Q.
      • Jin G.
      • Xu Y.
      • Hirche C.
      Topical intrawound application of vancomycin powder in addition to intravenous administration of antibiotics: a meta-analysis on the deep infection after spinal surgeries.
      However, like irrigation, there is limited evidence to support the use of vancomycin powder in reducing neuromodulation-related SSI.
      • Amrani J.
      Intraoperative powdered vancomycin use with paddle lead placement.
      ,
      • Ghobrial G.M.
      • Thakkar V.
      • Singhal S.
      • et al.
      Efficacy of intraoperative vancomycin powder use in intrathecal baclofen pump implantation procedures: single institutional series in a high risk population.
      Given the success of Pepper et al in yielding a 0% intervention SSI rate,
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      and the low complication profile, further research into local vancomycin in neuromodulation procedures for positive carriers is certainly warranted.
      Infection rates for neuromodulation implants in the literature range from 0% to 10% for SCS systems,
      • Yusuf E.
      • Bamps S.
      • Thüer B.
      • et al.
      A multidisciplinary infection control bundle to reduce the number of spinal cord stimulator infections.
      ,
      • Pahapill P.A.
      Incidence of revision surgery in a large cohort of patients with thoracic surgical three-column paddle leads: a retrospective case review.
      3% to 15% for IT pump systems,
      • Ghobrial G.M.
      • Thakkar V.
      • Singhal S.
      • et al.
      Efficacy of intraoperative vancomycin powder use in intrathecal baclofen pump implantation procedures: single institutional series in a high risk population.
      ,
      • Malheiro L.
      • Gomes A.
      • Barbosa P.
      • Santos L.
      • Sarmento A.
      Infectious complications of intrathecal drug administration systems for spasticity and chronic pain: 145 patients from a tertiary care center.
      ,
      • Taira T.
      • Ueta T.
      • Katayama Y.
      • et al.
      Rate of complications among the recipients of intrathecal baclofen pump in Japan: a multicenter study.
      and 1% to 9% for DBS systems.
      • Deer T.R.
      • Provenzano D.A.
      • Hanes M.
      • et al.
      The Neurostimulation Appropriateness Consensus Committee (NACC) recommendations for infection prevention and management.
      ,
      • Frizon L.A.
      • Hogue O.
      • Wathen C.
      • et al.
      Subsequent pulse generator replacement surgery does not increase the infection rate in patients with deep brain stimulator systems: a review of 1537 unique implants at a single center.
      Overall infection rate in this study, including both controls and intervention groups, fell within the respective ranges, occurring in the following order from highest to lowest frequency: SCS (5.39%), IT pump (5.18%), DBS (2.49%), and sacral stimulation (1.51%). Indeed, SCS often has higher reported rates of infection than other types of implants, including joint replacement prostheses and pacemakers.
      • Darouiche R.O.
      Treatment of infections associated with surgical implants.
      S aureus has been shown to be the most common causative agent for SCS-related SSI, present in up to 48% of cases.
      • Follett K.A.
      • Boortz-Marx R.L.
      • Drake J.M.
      • et al.
      Prevention and management of intrathecal drug delivery and spinal cord stimulation system infections.
      ,
      • Fletcher N.
      • Sofianos D.
      • Berkes M.B.
      • Obremskey W.T.
      Prevention of perioperative infection.

      Limitations

      This systematic review is not without limitations. None of the included studies is a prospective RCT; this allows for substantial heterogeneity of experimental variables among the five studies. This includes neuromodulation type, additional decontamination efforts surrounding S aureus decolonization, decolonization protocols, surgeon experience, and follow-up duration. Given these sources of heterogeneity and the limited study number of this review, it is difficult to discern the true effect of S aureus swabbing and decolonization as they relate to neuromodulation. Indeed, there was a wide variety of follow-up durations in the included studies, which would directly affect the number of postoperative infections captured and may underestimate this value if adequate follow-up duration is not implemented. These clear sources of heterogeneity notwithstanding, the meta-analysis model did not detect an overall significant source of heterogeneity. Although prospective studies should maintain consistency, this result highlights the potential external validity of the results of this study. According to the NACC, SSIs related to an implantable device are defined as infection within the region of the implanted device within one year postoperatively.
      • Deer T.R.
      • Provenzano D.A.
      • Hanes M.
      • et al.
      The Neurostimulation Appropriateness Consensus Committee (NACC) recommendations for infection prevention and management.
      Future studies investigating the use of these SSI-reducing efforts within neuromodulation should strive for this mark. Variability in surgeon experience may also significantly alter conclusions made, given that operative time is a risk factor for SSI and this operative time may decrease with greater experience in performing the neuromodulation procedure, as stated by one of the authors.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      This presents another possible limitation of a single-surgeon prospective observational cohort study with retrospective controls. The surgeon has necessarily accrued more experience, which, in the case of one study, contributed to significantly reduced operative times.
      • Pepper J.
      • Meliak L.
      • Akram H.
      • et al.
      Changing of the guard: reducing infection when replacing neural pacemakers.
      Moving forward, it would be of great value to the field of neuromodulation if greater efforts were taken to standardize study design in these infection-prevention studies. If the ideal of an RCT cannot be achieved, ensuring a balanced allocation of subjects between study arms would be ideal in observational cohort studies because large variability, as was the case in Hill et al,
      • Hill H.
      • Dukovac T.
      • Long A.
      • Conner J.
      • Goudelocke C.
      A novel sacral neuromodulation infection protocol is associated with reduction in device infection.
      limits the predictive validity of these data in inferential statistics. In addition, robust reporting of study design is essential to test for moderators in effect sizes. Although most studies were explicit in the decolonization protocol and reporting of swabbing location, time of swabbing and mean follow-up duration were not consistently reported. An adequate follow-up duration is critical because some of the shorter follow-up times seen in the included studies may very well have underreported the rate of SSI, given the CDC definition of deep SSI extends the cutoff to 90 days.
      Surgical site infection event (SSI). The National Healthcare Safety Network.
      In addition, standardization in confirming the presence of SSI is warranted because clinical and laboratory markers may be due to a systemic inflammatory response triggered by the implantation of a foreign neuromodulation device.
      • Davies M.G.
      • Hagen P.O.
      Systemic inflammatory response syndrome.
      Although this study analyzed the effects of screening and additional infection prevention measures on top of screening and/or decolonization as moderators, the observed nonsignificant difference in effect size between these groups in the meta-analyses is a tenuous conclusion, given the relative dearth in sample sizes comprising each group. Therefore, a greater number of these studies over time will contribute to a more adequately powered analysis, able to confidently detect these differences, if present, and strengthen the recommendations derived therein. Furthermore, although it can be argued that any such study ought to include preoperative swabbing in their methods given the previously established efficacy of swabbing and subsequent decolonization,
      • Perl T.M.
      • Cullen J.J.
      • Wenzel R.P.
      • et al.
      Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
      not nonselective decolonization, this distinction has yet to be proven in neuromodulation procedures specifically. Therefore, if clinical trials with both screened and nonscreened arms cannot be implemented, observational cohort studies using only nonselective decolonization maintain statistical value, given the present need for data in both groups to answer the question: to screen, then decolonize, or simply decolonize?

      Conclusions

      This systematic review and meta-analysis found five studies using S aureus screening and/or decolonization before neuromodulation procedures. All five studies reported reduced rates of infection in the intervention groups, with four of them reporting statistically significant differences. Overall infection rate in the control groups was 6.86% compared with 0.95% for intervention, a decrease of 86.2%. IT pump and SCS neuromodulation had the highest rates of both control and intervention infection rates, whereas DBS procedures had the lowest. In the meta-analysis, patients receiving intervention were less likely to experience postoperative infection. Of the studies reporting on infectious etiology, S aureus was identified as the most common infectious organism in the control group whereas no instances of S aureus infection were found in any intervention groups. Decolonization protocols contained a combination of nasal mupirocin ointment and full-body decolonization with either povidone-iodine or, most commonly, chlorhexidine gluconate soap. Taken together, the use of S aureus swabbing before neuromodulation procedures represents a promising method to decrease the incidence of SSI, further validating the usefulness of prospective RCTs to investigate the true utility of this measure.

      Authorship Statements

      Neal Patel, Justin Gold, and Nolan J. Brown were responsible for the conceptualization, data curation, formal analysis, methods, original draft, review, and editing of the manuscript. Mickey Abraham, Ryan S. Beyer, Shane Shahrestani, Julian Gendreau, and Antonios Mammis were responsible for the supervision, validation, review, and editing of the manuscript. All authors approved the final manuscript.

      Supplementary Data

      Figure thumbnail figs1
      Supplementary Material 1Funnel plots for assessment of publication bias. There were no focal paucity of studies indicating low likelihood of publication bias.

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