Extended postoperative prophylactic antibiotic therapy in posterior instrumented spinal surgery: a pilot study

Introduction

Surgical site infection (SSI) following spinal surgery adversely affects individual patient outcomes and also constitutes a global healthcare burden (1). With reported rates of up to 10%, it is the third most common complication after spine surgery and accounts for more than 30% of all healthcare-associated infections (2-7). Indeed, Patel et al. found that SSI following spinal surgery leads to prolonged length of hospital stay and accounts for two-thirds of all causes for return to theatre (RTT) (8). Indeed, SSI was associated with a mortality rate of 1.1–2.3% (9-11). In addition to its impact on individual patients, SSI is a significant source of economic burden to the health care system. Kuhns et al. and Parker et al. have emphasised that SSI results in approximately doubling of health care cost for a patient following spinal surgery (12,13).

As such, there is growing emphasis on the need for efficacious prevention strategies against SSI following spine surgery (14). The potential role of routine pre-operative antimicrobial prophylaxis (AMP) in minimizing rates of SSI has long been recognised in the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) guidelines in particular (15-18). However, the optimal duration of post-operative AMP remains controversial in the face of conflicting evidence, and there has been increasing interest in the utility of extended anti-microbial courses (19,20). Hellbusch et al. and Maciejczak et al. argue that there is a reduction in SSI with the use of prolonged antibiotic use up to 72 hours, yet other authors such as Porter et al. and Abola et al. have found no benefit (21-24). The utility of a truly extended post-operative AMP in the spine surgical cohort therefore remains contentious.

We investigate the efficacy and feasibility of an extended 2-week regime of oral AMP in reducing the risk of SSI and overall complications in the post-operative period for patients undergoing posterior instrumented spinal surgeries. This study is crucial as any preventative strategy which has the potential to reduce the rate of SSI or post-operative morbidity is of particular importance in vulnerable subgroups such as the elderly or immunosuppressed. We present this article in accordance with the STROBE reporting checklist (available at https://asj.amegroups.com/article/view/10.21037/asj-25-73/rc).

Methods

Objective and outcomes

The objective of this study is to investigate whether a 2-week extended AMP therapy reduces the rate of postoperative gram-positive bacterial SSI and other postoperative complications in posterior instrumented spinal surgeries. As such, the outcome measures of the study were the rate of gram-positive SSI, RTT for gram-positive SSI, overall complication and overall infection (including pneumonia, urinary tract infection or sepsis).

Study design

The retrospective study was conducted between July 2018 and December 2019 in a level 1 trauma centre and complex spinal unit. All consecutive patients who underwent posterior instrumented spinal surgeries were included in the study. Patients who underwent surgeries for spinal infection, discitis, osteomyelitis or epidural abscess were excluded. A course of prolonged AMP was routine clinical practice for one surgeon, and given the patients were not randomized and this was a retrospective cohort study it was deemed that informed consent was not required.

Extended AMP therapy was administered to the intervention cohort. Postoperatively, these patients received 48 hours of intravenous cephazolin (2 g every 8 hours) and subsequently an extended regime of oral AMP (cephalexin 500 mg every 8 hours) for 2 weeks, which was standard practice by one surgeon. The control cohort was administered 24 hours intravenous cephazolin (2 g every 8 hours) only. All patients received routine pre-incisional intravenous first-generation cephalosporin as AMP (cephazolin 2 g). Stratification of intervention was surgeon specific. Standard infection prevention measures such as surgical site disinfection with alcohol-containing skin preparatory solutions and multilayered skin closures were applied to all patients. Follow-up was conducted in person where possible and by telephone for remote patients.

Baseline assessments included age, gender, body mass index (BMI), albumin level and the 11-variable modified frailty index (mFI), which was calculated from previously described methods (25). Surgical metrics recorded included diagnosis, revision spinal surgery, number of levels, spinal level (cervical, thoracic or lumbar) and surgical approach (one stage posterior, combined posterior and anterior or two staged posterior and anterior approached). The participants were followed up for signs of SSI and other markers of postoperative complications up to 90 days after surgery. SSI were classified according to the CDC SSI criteria (17).

Statistical analysis

Univariate statistical analysis was used to investigate demographics, surgical metrics, SSI and other post-operative complications between the extended AMP and standard AMP cohorts. Categorical outcomes were presented as frequencies (percentages). Continuous parametric outcomes were presented as mean (standard deviation), and non-parametric as median (interquartile range). Categorical univariate variables were analysed using the Fisher’s Exact test. Continuous data were tested using the Mann-Whitney U test.

Multivariate logistic regression analysis was performed for identification of independent predictors of adverse surgical outcomes. Best-fit models were constructed with the dependent variables being: (i) gram-positive SSI; (ii) RTT for gram-positive SSI; (iii) overall complication and (iv) overall infection. Selection of baseline covariates as independent variables in the model was based on the univariate p value (<0.20). A dichotomized cutoff of mFI ≥0.27 was utilized in keeping with previous literature examining frail patients undergoing spine surgery (26). The backward elimination method was utilized in creation of models. Statistical significance was defined as a P value of less than 0.05. All statistical analyses were performed using STATA/IC version 14.2 (StataCorp, Texas, USA).

Ethical considerations

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Alfred Health Institutional Human Research Ethics Committee (approval No. 595/18) and individual consent for this retrospective analysis was waived.

Results

Two hundred and fifty-five consecutive posterior instrumented spinal surgeries were identified from the institutional registry (Figure 1); 61 patients (24%) received extended 2-weeks postoperative AMP. The remaining 194 patients (76%) received the standard 24 hours AMP.

Figure 1 Flowchart depicting the total cohort being stratified into SSI and gram-positive infection subgroups. SSI, surgical site infection.

Baseline and surgical characteristics

The baseline characteristics and surgical metrics of the cohorts are summarised in Table 1. Slightly over half of patients were male (55%; n=142) and 45% (n=114) were female. The extended AMP cohort had a greater median age of 63 years when compared to the standard AMP cohort (median age =57 years, p=0.05). The average mFI was greater in the extended AMP cohort (0.059) than the standard AMP cohort (0.089) (p=0.040). The groups were similar with respect to mean BMI, proportion who were morbidly obese (BMI >30 kg/m²) and those with hypoalbuminemia (albumin level <35 g/L).

The majority of the patients underwent posterior instrumented spinal surgeries for trauma (49%, n=125), followed by degenerative spine condition (38%, n=84) and tumour (12%, n=30). There were no significant differences in surgical pathology, proportion of revision spine surgery, number of surgical levels, location of spinal surgery (cervical, thoracic or lumbar) and surgical approaches between groups.

Outcome measures

The rate of gram-positive bacterial SSI in the extended AMP cohort was zero. In contrast, five patients (2.5%) in the standard AMP cohort were diagnosed with gram-positive bacterial SSIs. Isolated gram-positive organism was cultured from four cases [3 cases of methicillin-sensitive Staphylococcus aureus (MSSA) and 1 case of Staphylococcus hominis]. Polymicrobial SSI with a mixture of gram-positive and gram-negative organisms were cultured from the other patient (Enterococcus faecalis and Klebsiella oxytoca). All five of these patients required RTT for surgical wound washout. Despite this difference, no statistical significance was reached comparing the extended AMP and standard AMP cohort in the rate of gram-positive SSI, due to the small sample size and inherent low rate of infection within the unit. Using the current SSI rate of 2.5%, approximately 6,152 participants are required to provide an 80% power to demonstrate an absolute risk reduction of 1%, with a 5% significance level.

The rate of overall complication was lesser in the extended AMP cohort in comparison to the standard AMP cohort (34% vs. 55%, p=0.008). The extended AMP regime was also associated with a trend in lower rate of overall infection (11% vs. 21%, p=0.09) (Table 2). Finally, the overall SSI incidence was one patient who experienced a gram-negative Pseudomonas aeruginosa infection in the extended anti-microbial prophylaxis cohort, compared to six patients in the routine prophylaxis cohort. None of the patients in the extended cohort suffered opportunistic infections, such as Clostridium difficile, or adverse side effects from antibiotics necessitating early cessation of the regimen.

Independent predictors of surgical outcomes

Multivariate logistic regression analyses were conducted using predictive factors associated with outcome (P<0.2) in the univariate analysis. By virtue of their univariate p values, extended AMP usage, elderly age of >65 years, mFI of ≥0.27 (3/11 variables), obesity (BMI >30 kg/m²), hypoalbuminemia (albumin level <35 g/L), aetiology of pathology (trauma or non-trauma), revision surgery, location of surgery (cervical or thoracolumbar) and number of spinal levels (<5 or 5) were incorporated into the multivariable analyses.

Multivariate analyses revealed that the extended AMP regimen conferred lower risk of overall complication [odds ratio (OR) 0.41, 95% confidence interval (CI): 0.21–0.79, p=0.008]. The extended AMP regime also associated with reduction in risk of overall infection (OR 0.37, 95% CI: 0.14–0.99, p=0.050).

Overall complication rate was also positively associated with hypoalbuminemia (OR 3.18, 95% CI: 1.80–5.63, p<0.001) and surgery involving five or more spinal levels (OR 2.26, 95% CI: 1.31–3.92, p=0.004). Hypoalbuminemia (OR 2.53, 95% CI: 1.24–5.17, p=0.01), trauma diagnosis (OR 2.89, 95% CI: 1.33–6.26, p=0.007), cervical spine surgical site (OR 2.22, 95% CI: 1.01–4.91, p=0.049) and surgery involving five or more spinal levels (OR 2.78, 95% CI: 1.34–5.78, p=0.006), also predicted post-operative complications (Table 3). Multivariate analyses were ineffective in identifying the independent predictors for gram-positive SSI and RTT due to gram-positive infection due to the small number of positive outcomes.

Discussion

SSI has an estimated incidence of between 2–4% and several accepted modifiable as well as non-modifiable risk factors (27). Accepted known preoperative hazardous variables include age greater than 60 years, diabetes, obesity and smoking which all likely result in a degree of immunosuppression as Fang et al. noted (28). In the setting of a burgeoning elderly population who are increasingly being considered for instrumented spinal surgery, interventions to reduce post-operative morbidity and mortality carry greater relevance (29-32). Current consensus is that antibiotics are administered 30–60 minutes before skin incision, and discontinued 24 hours after spine surgery. Prolonged courses of antibiotics have been purported to propagate antimicrobial resistance, cost and paradoxically a higher incidence of postoperative infection. There is also the proposed risk of Clostridium difficile infection colonization. For this reason, standard observed surgical preventative measures include preoperative methicillin-resistant Staphylococcus aureus (MRSA) colonization, adequate skin preparation, minimizing operative time and appropriate patient selection. In addition to this though, further ideal preventative measures should be simple, easily implemented and efficacious (33,34).

Our unique proposal of a 2-week course of extended anti-microbial prophylaxis (AMP) satisfies all three criteria. This antibiotic prophylaxis regimen consisting of a cephalosporin for 2 weeks postoperatively is specifically designed to minimize SSI during the highest risk period, given most infections occur in this critical early postoperative period rather than in a delayed fashion (28). Furthermore, Zhou et al. conducted a meta-analysis of 22,475 patients and found that patients who underwent instrument surgery had a higher rate of SSI than non-instrumented operations (4.4% vs. 1.4%) (35). The consequences of infection in the setting of implants is also greater given the risk of colonization requiring removal of hardware, loss of mechanical stability and need for further delayed surgery once the infection has been treated (1). Indeed, to our knowledge this is the first study that demonstrates the potential effectiveness of a prolonged course of anti-microbial prophylaxis in reducing the absolute risk of gram-positive SSI, RTT rate and overall complication rate.

The concept of an extended microbial prophylaxis course has demonstrated great success in other surgical subspecialties including the orthopaedic field with Dasari et al. demonstrating patients were 35% less likely to develop a prosthetic-joint infection (36). Despite this, there is still diametrically opposing views in the spine surgery literature as to the role of extended courses of antibiotics. On one hand, Porter et al. argue that longer courses lead to unnecessarily lengthened hospital stays but not lower odds of SSI (24). In support of this, Shawky Abdelgawaad et al. compared 108 patients undergoing spinal surgery with half receiving up to 1 week of first generation cephalosporin compared to another group only receiving a single day of postoperative antibiotics (37). These authors concluded given there was only one SSI infection in the former group there was therefore no significant difference in infection rate regardless of whether an extended course of antibiotics was utilized (37). It is however clear that initial cohort studies were underpowered given the relatively low rate of SSI in the first instance as a testament to evolving contemporary sterilization processes and rising attention to the importance of sterility in improving healthcare outcomes. For example, Abola et al. who evaluated 4,454 patients of whom 60% received 24 hours of postoperative antibiotics and 40% received nil postoperative antibiotics (23). This study was still forced to conclude there was no difference in postoperative infection rate (OR 1.17, 95% CI: 0.62–2.23, p=0.63) (23).

For this reason and to overcome the low statistical power or individual studies, Barker performed a meta-analysis of six randomized controlled trials and determined that antibiotic use does result in a reduced rate of infection (5.9% vs. 2.2%) (16). This was despite the fact that none of the individual studies actually demonstrated a benefit to prophylactic antibiotics (16).

As an extension of this, Xia et al. interrogated the role of a longer course of antibiotics to determine if this resulted in a proportional decrease in infection (38). Pooling 1,003 patients, these authors concluded there was no significant difference in rates of SSI in patients receiving 24 hours of postoperative antibiotics compared with those receiving 72 hours (38). Marimuthu et al. supported this finding by comparing 72 vs. 24 hours dosage and finding nil difference in their study of 326 patients (39).

However, when specifically examining cases of instrumented surgery as in our study, Maciejczak et al. have importantly confirmed that the incidence of SSI was reduced (2.2% vs. 5.3%, p<0.01) with a 72-hour postoperative course of antibiotics (22). Hellbusch et al. support Maciejczak et al. by also discovering a reduction in SSI from 4.3% to 1.7% with a 72 hours postoperative antibiotic prophylactic course (21). The literature is evidently conflicted and the cost of patients remaining in hospital for a lengthier stay must be balanced against this possible benefit of reducing infection in a specific cohort of patients undergoing instrumented surgery. This is especially true given increasing the duration of antibiotics up to 1 week post-operatively, previous studies such as Kanayama et al. in a study of 1,597 patients undergoing lumbar spine surgery compared patients receiving either a single day or 5 to 7 days of postoperative antibiotics and found no significant difference in SSI rate (0.4% vs. 0.8%) (40).

We elected to focus our study on instrumented posterior spinal surgeries alone because the consequences of SSI are especially devastating in this cohort. Beyond the short-term sequelae of pain and erythema, patients are at risk of sepsis and instrumentation failure leading to correction losses (41,42). This is significant given these patients likely underwent surgical fixation because it was deemed necessary for their biomechanical stability. Not only does infection compromise the current construct, but it also jeopardises the ability to place new instrumentation into a pre-existing infective site. Our trial demonstrated that extended anti-microbial prophylaxis was effective in preventing the most frequent culprit organism of SSI: gram-positive bacteria. Despite the fact that the extended AMP group had a greater average mFI score, there were nil cases of gram-positive SSI. In stark contrast, there were five patients (2.5%) in the standard AMP cohort who were afflicted by gram-positive bacterial SSIs with the unfortunate need for surgical washout.

Finally, a reduction in SSI rate is apparently observed when the length of postoperative antibiotics was even further extended. Menendez Garcia et al. conducted a retrospective cohort study of 901 patients to determine rate of SSI 12 months following surgery with half of the patients administered 500mg oral cefuroxime every 12 hours until removal of sutures (43). This culminated in the group receiving extended antibiotics experiencing less SSIs (0.8% vs. 4.1%, p<0.01) (43). This is actually in contradiction to Warren et al. who found no difference even with post-discharge antibiotics (44). Nonetheless, our pilot study has determined that a prolonged course of anti-microbial prophylaxis confers an absolute risk reduction in overall complication rate. Intuitively, frail patients who undergo the physiological challenge of an operation are at greater risk of post-operative infections elsewhere as well. It would seem that this longer-term coverage has the additional protective benefit not just against local site infection, but distant infection as well. In turn, this translates a cost-effective strategy minimising the need for prolonged hospital stay or readmission, RTT for wound washout and debridement, prolonged antibiotic and wound care therapies, deconditioning, and further disability (45,46).

Perhaps ultimately a quantifiable risk stratification score is required in the future to develop a more nuanced approach to the role of antibiotics (47,48). Rechtine et al. (2) have identified that patients with a neurological deficit are at higher risk of injury compared to those who were neurologically intact (49-52). More than this, Zhang et al. also highlighted patients undergoing surgery for lumbar spinal stenosis rather than scoliosis or kyphosis (p<0.01) were more likely to experience a postoperative infection (1). To resolve this, Phillips et al. astutely noted that surgeons should evaluate each individual patient on an individual basis of their comorbidities, patient and surgical risk factors for SSI before devising a postoperative course of antibiotic plan (20). Interestingly, clinicians should also be cautious when cephalosporin which covers the most common skin organisms of the Staphylococcus species cannot be utilized due to adverse reaction. Nagy et al. demonstrated cefazolin rather than clindamycin was associated with a lower rate of infection (p=0.02) regardless of duration of prophylaxis (53). Herrington et al. found a similar finding with vancomycin rather than cefazolin prophylaxis associated with a 2.5 times higher risk of SSI (54).

It would therefore seem that the administration of perioperative AMP is logical given it has been demonstrated to reduce the incidence of SSIs even with various regimes across differing institution protocols (16). The causative organism in majority of SSIs is Staphylococcus aureus, a gram-positive coccus (11,55-57). Cefazolin (administered intravenously) and cephalexin (administered orally) are first-generation cephalosporins widely used for AMP due to their effectiveness against gram-positive bacteria, including Staphylococcus aureus (56,58,59). However, perhaps one reason for lack of widespread use of long-term suppression antibiotics is the fear of cultivating antibiotic-resistant bacteria. This is countered by previous studies on topical vancomycin powder usage in spine surgeries which have shown that long-term prophylactic antibiotics usage was not associated with increased antibiotic resistance bacteria despite the single case of Pseudomonas in this extended anti-microbial cohort (60). A previous large cohort study of 22,138 patients involving multidisciplinary elective surgeries has also shown that the use of surgical antibiotic prophylaxis, predominantly cephalosporins is not linked to the development of antibiotic-resistant infections (32). As Llor et al. noted, inappropriate antibiotic prescription for unnecessary indications leads to antibiotic resistance (61). However, our study demonstrates that prolonged AMP after posterior instrumented spinal surgery appears to be an effective and evidence-based targeted use of this therapy but should be considered on a risk vs. benefit ratio in individual patients.

We showed that an extended AMP protocol has the potential to reduce gram-positive SSI and RTT in posterior instrumented spinal surgeries, especially in high-risk patients who have non-modifiable risk factors for SSI such as increasing age and mFI. To further reduce our SSI rates, this extended AMP protocol could be implemented as part of an enhanced recovery after surgery (ERAS) pathway for posterior spinal instrumentation surgeries in high-risk patients. This standardised regime entails a combination of pre-operative, intra-operative and post-operative protocols standardising elements of surgical care, which have been shown to reduce rates of perioperative morbidity, infection and cost (62). This is not to say that all patients undergoing posterior instrumented spinal surgery shoulder receive an extended AMP course, but rather a risk stratification instrument could be utilised to determine which patients may potentially benefit from this prolonged regime.

A limitation of our original study was that patients were not randomised into different treatment arms which translates into the possibility of selection bias. The study had a relatively small study group size which precluded some of the variables from achieving statistical significance given the lack of adequate power. The retrospective nature of this study is also less desirable than a prospective multi-centre randomized trial. We also acknowledge the potential for confounders to include the intervention consisted of a longer intravenous antibiotic course rather than a purely antibiotic course given we wanted to maximize bioavailability and determine if there was a real treatment effect. It is also important to recognize that a single surgeon conducted the operations in the treatment arm which also carries risk of bias given the difference in individual operative technique or intraoperative measures. Conversely, strength of this study is a robust study protocol lending an excellent degree of internal validity that the absolute risk reduction rate observed in the outcomes measures were significant.

Our retrospective study was also conducted at a tertiary institution giving rise to generalisable results and reasonable external validity. The lack of statistical power is likely to be an inherent study flaw in many studies on this subject. In this case, our spinal unit already has a relatively low baseline SSI rate. The rarity of our outcome measure therefore means an extremely large cohort size would be necessary to perform a study to adequately power a multivariate analysis to definitively evaluate the use of an extended antibiotic prophylaxis protocol in preventing SSI. What we did find was an absolute risk reduction gram-positive SSI and overall complication rate. Future investigation would ideally focus on a prospective blinded randomized study design of a large sample size across multiple centres to enhance both internal and external validity.

Conclusions

In posterior instrumented spine surgeries, extended AMP has a favourable impact on lowering the risk of overall complication and infection and has the potential to reduce gram-positive bacterial SSI and its RTT rate. This protocol may be considered for use in high-risk patients with significant frailty and multiple non-modifiable risk factors for SSIs.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://asj.amegroups.com/article/view/10.21037/asj-25-73/rc

Data Sharing Statement: Available at https://asj.amegroups.com/article/view/10.21037/asj-25-73/dss

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-25-73/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-25-73/coif). B.T.S.K. serves as an unpaid editorial board member of AME Surgical Journal from May 2024 to June 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Alfred Health Institutional Human Research Ethics Committee (approval No. 595/18) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Zhang T, Lian X, Chen Y, et al. Clinical outcome of postoperative surgical site infections in patients with posterior thoracolumbar and lumbar instrumentation. J Hosp Infect 2022;128:26-35. [Crossref] [PubMed]
2. Rechtine GR, Bono PL, Cahill D, et al. Postoperative wound infection after instrumentation of thoracic and lumbar fractures. J Orthop Trauma 2001;15:566-9. [Crossref] [PubMed]
3. Blam OG, Vaccaro AR, Vanichkachorn JS, et al. Risk factors for surgical site infection in the patient with spinal injury. Spine (Phila Pa 1976) 2003;28:1475-80. [Crossref] [PubMed]
4. Smith JS, Shaffrey CI, Sansur CA, et al. Rates of infection after spine surgery based on 108,419 procedures: a report from the Scoliosis Research Society Morbidity and Mortality Committee. Spine (Phila Pa 1976) 2011;36:556-63. [Crossref] [PubMed]
5. Lee MJ, Cizik AM, Hamilton D, et al. Predicting surgical site infection after spine surgery: a validated model using a prospective surgical registry. Spine J 2014;14:2112-7. [Crossref] [PubMed]
6. Saeedinia S, Nouri M, Azarhomayoun A, et al. The incidence and risk factors for surgical site infection after clean spinal operations: A prospective cohort study and review of the literature. Surg Neurol Int 2015;6:154. [Crossref] [PubMed]
7. Magill SS, Hellinger W, Cohen J, et al. Prevalence of healthcare-associated infections in acute care hospitals in Jacksonville, Florida. Infect Control Hosp Epidemiol 2012;33:283-91. [Crossref] [PubMed]
8. Patel H, Khoury H, Girgenti D, et al. Burden of Surgical Site Infections Associated with Select Spine Operations and Involvement of Staphylococcus aureus. Surg Infect (Larchmt) 2017;18:461-73. [Crossref] [PubMed]
9. Veeravagu A, Patil CG, Lad SP, et al. Risk factors for postoperative spinal wound infections after spinal decompression and fusion surgeries. Spine (Phila Pa 1976) 2009;34:1869-72. [Crossref] [PubMed]
10. Núñez-Pereira S, Pellisé F, Rodríguez-Pardo D, et al. Implant survival after deep infection of an instrumented spinal fusion. Bone Joint J 2013;95-B:1121-6. [Crossref] [PubMed]
11. Maruo K, Berven SH. Outcome and treatment of postoperative spine surgical site infections: predictors of treatment success and failure. J Orthop Sci 2014;19:398-404. [Crossref] [PubMed]
12. Kuhns BD, Lubelski D, Alvin MD, et al. Cost and quality of life outcome analysis of postoperative infections after subaxial dorsal cervical fusions. J Neurosurg Spine 2015;22:381-6. [Crossref] [PubMed]
13. Parker SL, Shau DN, Mendenhall SK, et al. Factors influencing 2-year health care costs in patients undergoing revision lumbar fusion procedures. J Neurosurg Spine 2012;16:323-8. [Crossref] [PubMed]
14. Yao R, Zhou H, Choma TJ, et al. Surgical Site Infection in Spine Surgery: Who Is at Risk? Global Spine J 2018;8:5S-30S. [Crossref] [PubMed]
15. Spina NT, Aleem IS, Nassr A, et al. Surgical Site Infections in Spine Surgery: Preoperative Prevention Strategies to Minimize Risk. Global Spine J 2018;8:31S-6S. [Crossref] [PubMed]
16. Barker FG 2nd. Efficacy of prophylactic antibiotic therapy in spinal surgery: a meta-analysis. Neurosurgery 2002;51:391-400; discussion 400-1.
17. Goldner JL. CDC guideline for the prevention of surgical site infection. Surg Infect (Larchmt) 2000;1:249-50; author reply 250-3. [Crossref] [PubMed]
18. Solomkin J, Gastmeier P, Bischoff P, et al. WHO Guidelines to prevent surgical site infections-Authors' reply. Lancet Infect Dis 2017;17:262-4. [Crossref] [PubMed]
19. Tan T, Lee H, Huang MS, et al. Prophylactic postoperative measures to minimize surgical site infections in spine surgery: systematic review and evidence summary. Spine J 2020;20:435-47. [Crossref] [PubMed]
20. Phillips BT, Sheldon ES, Orhurhu V, et al. Preoperative Versus Extended Postoperative Antimicrobial Prophylaxis of Surgical Site Infection During Spinal Surgery: A Comprehensive Systematic Review and Meta-Analysis. Adv Ther 2020;37:2710-33. [Crossref] [PubMed]
21. Hellbusch LC, Helzer-Julin M, Doran SE, et al. Single-dose vs multiple-dose antibiotic prophylaxis in instrumented lumbar fusion--a prospective study. Surg Neurol 2008;70:622-7; discussion 627. [Crossref] [PubMed]
22. Maciejczak A, Wolan-Nieroda A, Wałaszek M, et al. Antibiotic prophylaxis in spine surgery: a comparison of single-dose and 72-hour protocols. J Hosp Infect 2019;103:303-10. [Crossref] [PubMed]
23. Abola MV, Lin CC, Lin LJ, et al. Postoperative Prophylactic Antibiotics in Spine Surgery: A Propensity-Matched Analysis. J Bone Joint Surg Am 2021;103:219-26. [Crossref] [PubMed]
24. Porter MW, Burdi W Jr, Casavant JD, et al. Association between duration of antimicrobial prophylaxis and postoperative outcomes after lumbar spine surgery. Infect Control Hosp Epidemiol 2022;43:1873-9. [Crossref] [PubMed]
25. Leven DM, Lee NJ, Kothari P, et al. Frailty Index Is a Significant Predictor of Complications and Mortality After Surgery for Adult Spinal Deformity. Spine (Phila Pa 1976) 2016;41:E1394-401. [Crossref] [PubMed]
26. Veronesi F, Borsari V, Martini L, et al. The Impact of Frailty on Spine Surgery: Systematic Review on 10 years Clinical Studies. Aging Dis 2021;12:625-45. [Crossref] [PubMed]
27. Badia JM, Casey AL, Petrosillo N, et al. Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries. J Hosp Infect 2017;96:1-15. [Crossref] [PubMed]
28. Fang A, Hu SS, Endres N, et al. Risk factors for infection after spinal surgery. Spine (Phila Pa 1976) 2005;30:1460-5. [Crossref] [PubMed]
29. Kha ST, Ilyas H, Tanenbaum JE, et al. Trends in Lumbar Fusion Surgery Among Octogenarians: A Nationwide Inpatient Sample Study From 2004 to 2013. Global Spine J 2018;8:593-9. [Crossref] [PubMed]
30. Kweh BTS, Lee HQ, Tan T, et al. Risk Stratification of Elderly Patients Undergoing Spinal Surgery Using the Modified Frailty Index. Global Spine J 2023;13:457-65. [Crossref] [PubMed]
31. Kweh BTS, Lee HQ, Tan T, et al. Posterior Instrumented Spinal Surgery Outcomes in the Elderly: A Comparison of the 5-Item and 11-Item Modified Frailty Indices. Global Spine J 2024;14:593-602. [Crossref] [PubMed]
32. Kweh B, Lee H, Tan T, et al. Spinal Surgery in Patients Aged 80 Years and Older: Risk Stratification Using the Modified Frailty Index. Global Spine J 2021;11:525-32. [Crossref] [PubMed]
33. Daniels TL, Talbot TR. Infection control and prevention considerations. Cancer Treat Res 2014;161:463-83. [Crossref] [PubMed]
34. Farrell MS, Agapian JV, Appelbaum RD, et al. Surgical and procedural antibiotic prophylaxis in the surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document. Trauma Surg Acute Care Open 2024;9:e001305. [Crossref] [PubMed]
35. Zhou J, Wang R, Huo X, et al. Incidence of Surgical Site Infection After Spine Surgery: A Systematic Review and Meta-analysis. Spine (Phila Pa 1976) 2020;45:208-16. [Crossref] [PubMed]
36. Dasari SP, Kanumuri SD, Yang J, et al. Extended Prophylactic Antibiotics for Primary and Aseptic Revision Total Joint Arthroplasty: A Meta-Analysis. J Arthroplasty 2024;39:S476-87. [Crossref] [PubMed]
37. Shawky Abdelgawaad A, El Sadik MHM, Hassan KM, et al. Perioperative antibiotic prophylaxis in spinal surgery. SICOT J 2021;7:31. [Crossref] [PubMed]
38. Xia TC, Rainone GJ, Woodhouse CJ, et al. Post-operative antibiotic prophylaxis in spine surgery patients with thoracolumbar drains: A meta analysis. World Neurosurg X 2024;23:100373. [Crossref] [PubMed]
39. Marimuthu C, Abraham VT, Ravichandran M, et al. Antimicrobial Prophylaxis in Instrumented Spinal Fusion Surgery: A Comparative Analysis of 24-Hour and 72-Hour Dosages. Asian Spine J 2016;10:1018-22. [Crossref] [PubMed]
40. Kanayama M, Hashimoto T, Shigenobu K, et al. Effective prevention of surgical site infection using a Centers for Disease Control and Prevention guideline-based antimicrobial prophylaxis in lumbar spine surgery. J Neurosurg Spine 2007;6:327-9. [Crossref] [PubMed]
41. Gerometta A, Rodriguez Olaverri JC, Bitan F. Infections in spinal instrumentation. Int Orthop 2012;36:457-64. [Crossref] [PubMed]
42. Kweh BTS, Lee HQ, Tan T, et al. The Role of Spinal Orthoses in Osteoporotic Vertebral Fractures of the Elderly Population (Age 60 Years or Older): Systematic Review. Global Spine J 2021;11:975-87. [Crossref] [PubMed]
43. Menendez Garcia M, Otermin Maya I, Librero Lopez J, et al. Effects of extended oral antibiotic prophylaxis on surgical site infections after instrumented spinal fusion: a cohort study of 901 patients with a minimum follow-up of 1 year. Acta Orthop 2023;94:80-6. [Crossref] [PubMed]
44. Warren DK, Nickel KB, Han JH, et al. Postdischarge antibiotic use for prophylaxis following spinal fusion. Infect Control Hosp Epidemiol 2020;41:789-98. [Crossref] [PubMed]
45. Calderone RR, Garland DE, Capen DA, et al. Cost of medical care for postoperative spinal infections. Orthop Clin North Am 1996;27:171-82.
46. de Lissovoy G, Fraeman K, Hutchins V, et al. Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am J Infect Control 2009;37:387-97. [Crossref] [PubMed]
47. Kweh BTS, Vaccaro AR, Schroeder G, et al. Craniocervical Junction and Upper Cervical Spine Fractures: Historical Systems and Advancements with the AO Spine Classification. Global Spine J 2026;16:759-70. [Crossref] [PubMed]
48. Kweh BTS, Vaccaro AR, Schroeder G, et al. Thoracolumbar Fractures: Historical Systems and Advancements With the AO Spine Classification. Global Spine J 2025; Epub ahead of print. [Crossref]
49. Kweh BTS, Tee JW, Oner FC, et al. Evolution of the AO Spine Sacral and Pelvic Classification System: a systematic review. J Neurosurg Spine 2022;37:914-26. [Crossref] [PubMed]
50. Kweh BTS, Khoo B, Asaid M, et al. Alexis retractor efficacy in transthoracic thoracoscopically assisted discectomy for thoracic disc herniations. Acta Neurochir (Wien) 2024;166:135. [Crossref] [PubMed]
51. Khoo B, Gonzalvo A, Kweh BTS. Spinal orthoses in osteoporotic vertebral fractures of the elderly. J Spine Surg 2023;9:224-8. [Crossref] [PubMed]
52. Kweh BTS, Gonzalvo A, Khoo B, et al. In defence of the efficacy and safety of braces in osteoporotic vertebral fractures. J Spine Surg 2023;9:506-8. [Crossref] [PubMed]
53. Nagy Z, Szabó D, Agócs G, et al. Antibiotic Prophylaxis in Instrumented Lumbar Spine Surgery: Cefazolin Outperforms Clindamycin Regardless of Duration. Antibiotics (Basel) 2025;14:830. [Crossref] [PubMed]
54. Herrington BJ, Urquhart JC, Rasoulinejad P, et al. Vancomycin Antibiotic Prophylaxis Compared to Cefazolin Increases Risk of Surgical Site Infection Following Spine Surgery. Global Spine J 2026;16:230-9. [Crossref] [PubMed]
55. Rao SB, Vasquez G, Harrop J, et al. Risk factors for surgical site infections following spinal fusion procedures: a case-control study. Clin Infect Dis 2011;53:686-92. [Crossref] [PubMed]
56. Schimmel JJ, Horsting PP, de Kleuver M, et al. Risk factors for deep surgical site infections after spinal fusion. Eur Spine J 2010;19:1711-9. [Crossref] [PubMed]
57. Chahoud J, Kanafani Z, Kanj SS. Surgical site infections following spine surgery: eliminating the controversies in the diagnosis. Front Med (Lausanne) 2014;1:7. [Crossref] [PubMed]
58. Weinstein MA, McCabe JP, Cammisa FP Jr. Postoperative spinal wound infection: a review of 2,391 consecutive index procedures. J Spinal Disord 2000;13:422-6. [Crossref] [PubMed]
59. Koutsoumbelis S, Hughes AP, Girardi FP, et al. Risk factors for postoperative infection following posterior lumbar instrumented arthrodesis. J Bone Joint Surg Am 2011;93:1627-33. [Crossref] [PubMed]
60. Bakhsheshian J, Dahdaleh NS, Lam SK, et al. The use of vancomycin powder in modern spine surgery: systematic review and meta-analysis of the clinical evidence. World Neurosurg 2015;83:816-23. [Crossref] [PubMed]
61. Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf 2014;5:229-41. [Crossref] [PubMed]
62. Chakravarthy VB, Yokoi H, Coughlin DJ, et al. Development and implementation of a comprehensive spine surgery enhanced recovery after surgery protocol: the Cleveland Clinic experience. Neurosurg Focus 2019;46:E11. [Crossref] [PubMed]